Advances in porous chitosan-based composite hydrogels: Synthesis and applications

Journal Pre-proof Advances in porous chitosan-based composite hydrogels: Synthesis and applications

Ecaterina Stela Dragan, Maria Valentina Dinu PII:

S1381-5148(19)30813-2

DOI:

https://doi.org/10.1016/j.reactfunctpolym.2019.104372

Reference:

REACT 104372

To appear in:

Reactive and Functional Polymers

Received date:

8 August 2019

Revised date:

16 September 2019

Accepted date:

25 September 2019

Please cite this article as: E.S. Dragan and M.V. Dinu, Advances in porous chitosanbased composite hydrogels: Synthesis and applications, Reactive and Functional Polymers (2018), https://doi.org/10.1016/j.reactfunctpolym.2019.104372

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© 2018 Published by Elsevier.

Journal Pre-proof Advances in porous chitosan-based composite hydrogels: Synthesis and applications

Ecaterina Stela Dragan*, Maria Valentina Dinu* “Petru Poni” Institute of Macromolecular Chemistry, Aleea Grigore Ghica Voda 41A, 700487 Iasi,

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Romania; Tel.: +40.232.217454; Fax: +40.232.211299; [email protected]; [email protected]

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Abstract Chitosan (CS) as the only polycation coming from renewable resources is endowed with intrinsic valuable properties, such as: biocompatibility, biodegradability, low cost, easy availability, and high reactivity due to plenty of the reactive functional groups (-NH2 and –OH). Therefore, CS and its derivatives have been involved in numerous applications, either alone or as components in

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composite materials. This review aims to present an overview on the most recently published information on the preparation of porous CS based composite hydrogels such as: porous

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chitosan/synthetic polymer as beads and monoliths, CS/inorganic particles, porous semi- and full-

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IPN hydrogels, and on their applications either as very efficient composite sorbents for heavy metals and dyes, or as hemostats, smart drug delivery systems, wound dressings. The techniques

freeze-drying

(lyophilization),

and

imprinting/leaching

will

be

especially

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freeze-thawing,

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currently applied to prepare porous CS-based composites, including ice-templating (cryogelation),

highlighted. Using cryogelation in tandem with IPN strategy led to composite cryogels with high

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mechanical properties and high performances in separation processes of ionic species. Main factors

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which control the separations of dyes and heavy metal ions by porous CS-based composite sorbents are discussed based on the recently published articles and own results. Keywords: chitosan, dyes, heavy metal ions, porous composite sorbents, biomedical applications Abbreviations: AAm – Acrylamide; Agrs – Agarose; ALG – Alginate; AMX – Amoxicillin; BAAm – N,N’-methylenebisacrylamide; BC – Bacterial cellulose; β-CD – β-cyclodextrin; BSA – Bovine serum albumin; CAM – Clarithromycin; CEC - N-(2-carboxyethyl)chitosan; CEL – Cellulose; CMC – carboxymethyl cellulose; CMCS – Carboxymethyl chitosan; COF - Covalent Organic Framework; Col – Collagen; CNTs – Carbon nanotubes; CNW – chitin nanowiskers; CPL – Clinoptilolite; CS – Chitosan; DA – dopamine; DDS – Drug delivery system; DMAPS - 3Dimethyl-(methacryloyloxyethyl) ammonium propane sulfonate; DNC – Double network cryogel; ECH – Epichlorohydrin; EGDGE

– Ethyleneglycol diglycidyl ether; F-T – Freezing–thawing; GA

Journal Pre-proof – Glutaraldehyde; GEL – Gelatin; GO – Graphene oxide; HAP – Hydroxyapatite; HECS – Hydroxyethyl chitosan; HEMA – 2- hydroxyethyl methacrylate; HPMC – Hydroxypropyl methylcellulose; HA – Hyaluronic acid; IBU – Ibuprofen; IIPs – Ion-imprinted polymers; II-CCs – Ion-imprinted cryo-composites; IDM – Indomethacin; IPNs – Interpenetrating polymer networks; LYS – Lysozyme; MMT – Montmorillonite; MSNs - Mesoporous silica nanoparticles; NPs – Nanoparticles; PAA – Polyacrylic acid; PAAm – Polyacrylamide; PAN – Polyacrylonitrile; PDA – Poly(dopamine);

PEI –

Poly(ethyleneimine); PMAA –

Poly(methylmethacrylate); PVA –

Poly(methacrylic acid); PMMA –

Polyvinyl alcohol; PVP – poly(vinylpyrolidone); rGO –

Reduced graphene oxide; SGF - Simulated gastric fluid; SIF - Simulated intestinal fluid; SNC –

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Single network cryogel; TAC – Tetra-amine Cu; TPP - sodium tripolyphosphate; UF –

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Unidirectional freezing.

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1. Introduction

Chitosan (CS) [(14)-2-amino-2-deoxy-D-glucose] is a cationic polysaccharide obtained by the

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alkaline deacetylation of chitin, that consists of D-glucosamine and N-acetyl-D-glucosamine units, linked by -(14) glycoside linkages [1,2]. When CS is dissolved in acidic solutions below pH <

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6.0, the –NH2 groups are protonated, and can effectively inhibit the activity of various microorganisms by neutralizing the negative charges of the cell membranes [3]. Besides the from its biodegradability,

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biomedical applications derived

biocompatibility and

antibacterial

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properties [3,4], chelation properties have also been described for transition metal cations (Cu2+, Pb2+, Zn2+), soft-acid metals (Hg2+, Cd2+, Au3+, Ag+) or hard-acid metals (Sr2+, La3+, etc.) [5]. The degree of acetylation, and the molecular weight are the main parameters with a direct impact onto the solubility behavior, acid/base characteristics, and sorption properties of CS. In fact, it is considered that when the degree of acetylation is lower than 70 %, the apparent pK a varies between 6.3 and 6.8, CS becomes soluble in an aqueous acidic medium (pH ≤ 5.0) because more than 90 % of –NH2 groups are protonated. The physicochemical and biological properties of CS are determined by the presence of various functional groups on its backbone, such as: hydroxyl, amino, and acetamido groups. The presence of these groups constitutes a great advantage in improving the CS properties by introducing other suitable functional groups. Among various techniques presently in use to tailor the characteristics of CS for desired applications, graft copolymerization is of the utmost relevance [6]. Acidic solutions of CS when exposed to alkaline pH result in a decrease of the apparent charge density of the polymer, and thereby in the formation of physical gels due to hydrogen bonding and

Journal Pre-proof hydrophobic interactions [7]. To obtain CS-based homogeneous hydrogels or porous materials endowed with chemical stability at pH < 5.5, CS has been cross-linked by glutaraldehyde (GA), epichlorohydrin (ECH), genipin, and diglycidyl ethers of ethylene glycol or polyethylene glycol [24,7,8]. Furthermore, in order to modulate the mechanical properties, the water content of hydrogels, the response to an external stimulus, and chelating performances, composite hydrogels as interpenetrating polymer networks (IPNs) composed of CS and synthetic polymers [9], or CS/inorganic particles [10] have been designed. CS hydrogels with well-defined porous morphology (ordered structure) and interconnected pores have been also developed [11,12]. Depending on the pore sizes, porous hydrogels are classified as nanoporous (pores size below10

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nm), microporous (pore sizes in the range 10 nm – 10 μm) and macroporous or superporous (pores

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size above 10 μm) [6].

In this review, we focus on CS-based composite hydrogels having interconnected macroporous

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morphology introduced by freezing strategies (cryogelation – chemical cryogels, freeze-thawing – physical cryogels, freeze-drying – lyophilization), porogen leaching and gas foaming strategies.

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The working principle, the advantages and drawbacks of each technique used for building porous

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composite hydrogels based on CS will be presented in the first section. We then describe different types of cryogels, especially novel approaches to generate composite and stimuli-responsive materials by IPN approach and molecular imprinting methodology. We emphasize the properties of

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CS-based composite hydrogels, including swelling, porosity, mechanical strength, biocompatibility

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and biodegradability. In the subsequent sections, we aim to provide a detailed account of applications of 3D porous CS-based materials as sorbents for metal ions, dyes, other contaminants,

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catalysts, and biomedical applications such as: hemostasis, reservoirs for loading/release of active molecules (drugs, enzymes), and wound healing. 2. Preparation of porous CS-based composite hydrogels 2. 1. Techniques for building porous materials based on CS Over the last decade, CS-based porous hydrogels have been prepared through various techniques, including the freezing strategies [7-17], IPN approach [7,9,14,17,18-21], imprinting/leaching strategies [22-24], layer-by-layer technique [11,25], and gas foaming [26]. These methods have been applied for building porous CS-based composite materials either alone [8,13,16] or in combination of at least two methods [14,18-24,27,28]. The steps involved in the preparation of CSbased materials by above-mentioned methods will be described in the next subsections, some of their advantages and limitations being also highlighted.

Journal Pre-proof 2.1.1. Cryogelation – chemical cryogels In cryogelation technique, porous materials with highly interconnected pores are mainly obtained in an aqueous medium via free-radical polymerization of monomers/prepolymers/cross-linkers and initiator system concentrated in a partially frozen state where the ice crystals act as template [12,29,30]. Due to highly cross-linked polymer walls, this technique generates elastic and spongelike cryogels with shape memory features [12]. CS/clinoptilolite (CPL) biocomposite cryogels [13], cryogels based on methacrylic acid copolymers and CS [20], and CS/poly(ethyleneimine) (PEI) double network cryogels [21] have been successfully prepared by this technique. For example, the CS/CPL composite cryogels have been obtained by conducting the cross-linking of CS with GA in

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the presence of CPL particles [13]. A heterogeneous morphology with interconnected pores has been observed for the CS/CPL composite cryogels, with an average pore diameter of 52 ± 2 m

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(SEM image, Figure 1A).

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Figure 1

The pore morphology could be controlled using the unidirectional freezing (UF) approach

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[22,23,31-33]. Various aqueous mixtures or dispersions consisting of water-soluble polymers, inorganic particles have been unidirectional frozen in liquid nitrogen (−196

o

C), and thus

CS/polyacrylamide

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generating CS-based composites with micro-honeycomb or lamellar structures [22,32, Figure 1B]. (PAAm)/zeolite cryogels [22],

CS/poly(vinyl amine) cryogels embedding

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strong base anion exchanger microspheres [32] and CS/gelatin (GEL) scaffolds [31] with aligned

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porous structures have been recently prepared. The crystallization speed, the molecular weight of CS as well as the initial monomer or polymer concentration were found to be the key parameters affecting the size between the channels and the pore wall thickness [22,31,32]. To create 3D networks with two generation of pores, a strategy combining cryogelation and phase separation induced by the addition of n-butanol has been developed [24]. The schematic representation of this strategy is depicted in Figure 1C. CS-based cryogels exhibited larger pores with sizes in the range of 25–50 μm generated by cryogelation, and smaller pores between 4–10 μm produced by phase separation [SEM image (a) of Figure 1C]. Combining the cryogelation with porogen leaching technique, CS-based hydrogels with less compact walls between the large pores have been also successfully prepared [27]. Poly(methylmethacrylate) (PMMA), as fractionated particles, has been used as polymer porogen. The CS-based cryogel morphology was influenced by the crystallization rate, the weight ratio between CS and PMMA and the mesh of fractionated PMMA particles [27]. The internal morphology of the CS-based cryogels prepared in the presence of fractionated PMMA particles with mesh below 32 m revealed hierarchical porosity where larger pores with sizes in the

Journal Pre-proof range 75–90 μm have been formed via cryogelation, whereas smaller pores between 10–15 μm have been produced by PMMA leaching [SEM image (a) of Figure 1C]. These cryogels would be of interest as potential scaffolds for cell growth, the presence of less compact walls (small pores) between the large pores being favorable for the diffusion of low-molecular substances. 2.1.2. Freeze-thawing – physical cryogels Physical cryogels can be obtained by single or repeated cycles of freezing–thawing (F-T) of a concentrated aqueous solution containing polymers able to form physical cross-links by weak interactions, such as ionic interactions, crystallization, and hydrogen bonds [34-40]. Polyvinyl

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alcohol (PVA) was mainly combined with CS, because PVA crystallites act as junction points and

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stable 3D hydrophilic networks can be obtained [34,36,39,40]. During the F-T process, polysaccharides can readily bind to PVA owning to a high number of polar carboxyl and hydroxyl

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groups, giving rise to hydrogen bonds that form a 3D structure [34]. The gel fraction yield, the porosity, water vapor transmission rate, the wound fluid absorption, and the mechanical properties

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of the 3D physically cross-linked porous materials obtained by F-T process depended on the

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freezing and thawing temperature, time, and the number of F-T cycles [34,36,39,40]. In the case of PVA/CS/zinc oxide cryogels an increase of the F-T cycles resulted in a decrease of the pore sizes and an increase of the elastic modulus and tensile strength [34]. The improved water vapor

cryogels [34],

heparinized

PVA/CS/ZnO

cryogels [39], and

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properties of PVA/CS/ZnO

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permeability, the presence of highly interconnected porous structure, and the enhanced swelling

PVA/CS/honey/clay responsive nanocomposite cryogels prepared by F-T process [40] indicated

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their potential as wound dressings. Cryogel scaffolds can be also generated by F-T, but the resulted macropores in the range of 50 m could be a limiting factor for tissue engineering applications. 2.1.3. Freeze-drying (lyophilization) Freeze-drying (lyophilization) is another technique to build macroporous materials and consists in freezing of the aqueous polymeric solutions followed by the solvent sublimation under vacuum [41-54]. Sodium carboxymethylcellulose (CMC)/CS [43], cellulose (CEL)/CS [44], dextran/CS [45],

carboxymethyl

(HPMC)/glycerol [48],

konjac and

glucomannan/CS

[47],

CS/hydroxypropyl

GEL/carboxymethyl CS/hydroxyapatite

(HAP)

methylcellulose [50]

composite

scaffolds have been prepared using this technique [42-52]. The porosity, the thickness of pore walls, and the pore sizes have been mainly affected by the freeze-drying pressure, polymer concentration and cross-linking degree [41-54]. For example, by increasing the CS concentration, GEL/carboxymethyl CS (CMCS)/HAP hydrogels with thicker pore walls have been obtained [50]. Freeze-drying technique has been also applied to create pores within the non-porous PAAm/CS

Journal Pre-proof hydrogels after their synthesis; thus, the hydrogel has been first swollen in water, then lyophilized [18] (Figure 2A). The hydrogels morphology has been influenced by the cross-linker ratio and by the pH of the synthesis mixture. Thus, the hydrogel formed at pH 5 with a cross-linker ratio of 1/80 has pores with sizes in the range of 25–30 m (SEM image, Figure 2A). Figure 2 An increase in the cross-linker ratio from 1/80 to 1/20 led to a more stable porous morphology for PAAm/CS hydrogels with pores sizes of about 45–50 m [18]. In another study, new porous GEL/CS/Ag composites (Figure 2B) have been obtained by freeze-drying of swollen gels prepared

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by blending GEL/Ag with CS and cross-linked with tannic acid. The SEM micrographs indicated

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that GEL/CS, GEL/CS/Ag1, GEL/CS/Ag2, and GEL/CS/Ag3 (1, 2, and 3 represent the concentrations of Ag, i.e. 0.01%, 0.03%, and 0.05%, respectively) had a dense porous structure

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with interconnected pores [46]. The pore sizes of all GEL/CS/Ag composite materials have been comparable, being in the range of about 100–250 μm.

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By combining the freeze-drying method with chemical cross-linking and porogen leaching

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technique (SiO 2 particles, as porogen), novel hydrogel scaffolds with bubble-like porous structure based on hydroxyethyl chitosan (HECS) and CEL have been prepared [41]. The HECS/CEL scaffolds displayed a highly interconnected biporous structure. The bubble-like macropores of 100–

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250 m in size have been produced by leaching of SiO 2 particles, while the micropores of 10 m in

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size have been the result of water sublimation under vacuum, i.e. lyophilization [41]. These scaffolds have great potential for bone tissue engineering regeneration due to the highly

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interconnected porous structure which would provide an easy exchange of nutrients, and oxygen through 3D matrix. Nevertheless, there are some drawbacks associated with the freeze-drying (lyophilization) process, including (i) the difficult control of the pore sizes; (ii) the low mechanical strength of the resulted hydrogels; (iii) the formation of a skin surface due to the collapse of the hydrogel matrix at the scaffold–air interface [12]; (iv) the complete solvent removal is timeconsuming and cost-effective. 2.1.4. Porogen leaching In this technique, the free radical polymerization or the cross-linking processes are conducted in the presence of various porogens including polymers, inorganic particles, solvents, or salts, which are removed from the 3D matrices after reaction [53]. The pore sizes within the resulted 3D matrices could be easily controlled through the particle size and the concentration of porogen. However, the reduced number of the interconnected pores, the difficult removal of all porogen particles from

Journal Pre-proof matrix, and the toxic organic solvents used for porogen leaching are some major limitations associated with this technique. To address these issues and to optimize the synthesis of porous CSbased materials with controlled pore architecture, the porogen leaching strategy has been combined with cryogelation [24], and freeze-drying method [41,54]. N-butanol [24], PMMA particles [27,28], or SiO 2 particles [41,54], as porogens have been involved in the preparation of porous CSbased hydrogels especially for applications as scaffolds in tissue engineering. 2.1.5. Gas foaming Gas foaming is another simple method to generate macropores within 3D matrices using gas

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foaming agents, such as NaHCO 3 or NH4 HCO 3 [55,56]. For example, CS/HAP scaffolds have been

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fabricated as superporous hydrogels by combining microwave irradiation and gas foaming methods using NaHCO 3 as blowing agent [26]. SEM photographs indicated homogenous HAP coating

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through the 3D CS scaffolds. The use of supercritical carbon dioxide (scCO 2 ) as ‘green’ medium to induce porosity inside of CEL/CS scaffolds [57,58] has been also reported. The morphology of

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CEL/CS scaffolds prepared at room temperature and high-pressure conditions (50 bars) was

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compared with that of CEL/CS scaffolds obtained by gas foaming. The CEL/CS hydrogels formed at room temperature exhibited closed pore structures with sizes around 10-30 m, while those prepared by gas foaming had an interconnected porous structure with pore sizes 10-fold higher

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[58,59]. In conclusion, several strategies have been extensively utilized to fabricate CS-based

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porous hydrogels, including cryogelation, freeze-drying, porogen leaching, and gas foaming techniques. It is worth noting that the self-assembly technique provides a new and simple route for

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designing porous gels. Recently, this self-assembly strategy has also been utilized to develop graphene oxide (GO)-based macroporous composite hydrogels by integrating GO nanosheets within CS-based hydrogel networks [60]. Surprisingly, an extremely low amount (0.05–0.30 wt%) of GO can remarkably affect the architecture of hydrogel networks, leading to the formation of microporous composite hydrogels (Figure 3). To study the microstructure and formation mechanism of GO/CS-g-polyacrylic acid (PAA) composite hydrogels, the morphologies of wet hydrogel samples have been directly observed by optical microscope, as shown in Figure 3. Figure 3 The CS-g-PAA hydrogel exhibited a dense microstructure, while by increasing the amount of GO from 0.05 wt% to 0.30 wt%, the GO/CS-g-PAA composite hydrogels showed interconnected microporous structures, with pore sizes in the range of about 10–100 μm [60]. As Figure 3a shows, with increasing the amount of GO, the pore sizes increased gradually and parallel-aligned

Journal Pre-proof interconnected pores appeared, indicating a strong interaction between GO sheets and polymer chains. However, as the amount of GO further increased (> 0.30 wt%), the GO/CS-g-PAA composite hydrogels became non-porous again, which might be attributed to both the increased cross-linking density of hydrogel networks and the apparent aggregations of excessive GO sheets in the matrix. Therefore, a proper amount of GO addition can result in the formation of self-assembled macroporous structures in the composite hydrogel networks. 2.2. Porous CS-based IPN hydrogels IPNs are defined as a combination of two or more polymers in network form, where at least one of

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them was synthesized and/or cross-linked within the presence of the other(s) [61-63]. According to

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the synthesis procedure IPN hydrogels can be classified as: (1) sequential IPN hydrogels which consist in the synthesis of a first network followed by the synthesis of the second network; (2)

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simultaneous IPN hydrogels when the precursors of both networks are mixed and they are synthesized at the same time [9,63], semi-IPN hydrogels which are obtained by embedding a linear

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or branched polymer, either synthetic or natural, during the formation of a first network [9,17-

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23,32,63]. Various IPN hydrogels composed of CS and synthetic polymers have been recently designed [18-20,32,64,65]. In our group, ionic composite cryogels consisting of two independently cross-linked networks have been prepared [19]. Semi-IPN cryogels have been obtained first by

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cross-linking polymerization of acrylamide (AAm) with N,N’-methylenebisacrylamide (BAAm) in

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the presence of CS, by cryogelation. The cross-linking degree and the CS molar mass influenced the fraction of CS trapped in the semi-IPN cryogels. By cross-linking the CS chains trapped in the

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semi-IPN cryogels with ECH, PAAm/CS IPN cryogels were designed. The decrease of the crosslinker ratio from 1/40 to 1/60, for the same molar mass of CS, conducted to about twice larger pores (average pore size 34 m compared with 75 m), and to less compact pore walls [19]. The fabrication of novel chemically cross-linked double network cryogels (DNC), with an abundant number of NH2 groups, based on CS cross-linked with GA, as the first network, and PEI, cross-linked with ethyleneglycol diglycidyl ether (EGDGE), as the second network (Figure 4), has been recently synthesized by cryogelation, at -18 o C [21]. Figure 4 As SEM micrographs from Figure 4 shows, both single network cryogel (SNC) and DNC present a sponge-like morphology, the pores in the first network being much larger (Figure 4B) than those displayed by the DNC (Figure 4D). The average diameter of pores has been 90 ± 5 μm, and 51 ± 5 μm for SNC and DNC, respectively. The pore walls of DNCs become much thicker than those of

Journal Pre-proof the SNCs, as follows: 15 ± 6 µm, and 28 ± 4 µm, for SNC and DNC, respectively [21]. The decrease in pore sizes after the formation of the second network has been also observed by Wahid and coworkers [66]. The pure CS hydrogel exhibited large pore sizes, while the pore sizes decreased by introducing bacterial cellulose (BC) within CS matrix. The presence of pores plays an important role in the properties of hydrogels such as, compressibility, swelling, cell adhesion and nutrient diffusion, as will be shown in the following sections. 2.3. Porous ion-imprinted CS-based composite hydrogels Ion-imprinted polymers (IIPs) have been increasingly developed during the last 15 years on the

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principle of molecularly imprinted polymers [22,23,67-75]. The imprinted materials are designed to

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mimic the binding sites of biological entities and to recognize the template species [76]. The general procedure for IIP elaboration consists of the preparation of a ligand-metal complex and its

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copolymerization with a cross-linker in order to create 3D recognition cavities inside the polymer network [76]. A novel Dy3+ ion-imprinted CS membrane with interconnected 3D macroporous

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structure has been prepared by a simple immersion-precipitation-evaporation method for the

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selective solid liquid extraction of Dy3+ [71]. Zhang et al. [72] have reported the synthesis of a 3Dordered macroporous ion-imprinted CS film to adsorb Cu2+ ions from aqueous solutions; polystyrene (PS) micro-spheres and Cu2+ templates have been added to form a three-dimensional

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ordered macroporous structure and ion-imprinted sites, respectively. An original strategy has been

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also proposed to design CS-based ion-imprinted cryo-composites (II-CCs) with preorganized recognition sites and tailored porous structure by combining ion-imprinting and ice-templating

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techniques. The Cu2+-imprinted cryo-composites have been prepared according to the process depicted in Figure 5. Figure 5

First, Cu2+ ions were chelated by the amino and/or hydroxyl groups of CS chains to generate a Cu2+/CS complex and thereafter GA, as cross-linker for CS chains, CPL microparticles, the monomers mixture (AAm+BAAm), and initiators have been added for the in situ cross-linking of CS and simultaneous polymerization of AAm (Figure 5A). The geometry of pre-organized Cu2+/NH2 imprinted sites has been preserved throughout the cross-linking of CS chains by GA, while the leaching step (Cu2+ removal by ethylenediaminetetraacetic acid disodium salt dihydrate) generated well-defined 3D cavities, which form the favorable environment for selective rebinding of template

ions

(Figure

5B).

CPL

microparticles

have been added

into

the initial

polymer/monomers mixture to design cryo-composites with controlled swelling features. To further

Journal Pre-proof improve the overall chelating performance of cryo-composites, carboxylate groups have been introduced by partial hydrolysis of amide moieties from PAAm (Figure 5B). The Cu2+-imprinted cryo-composites with oriented porous morphology have been obtained by UF technique to ensure the facile access of ions to the binding sites [22]. In addition, it has been recently shown that the porous ion-imprinted CS-based composite materials have a chance to a “NEW LIFE” after Cu2+ ion binding, as catalysts for dyes decolorization [73]. 3. Properties of macroporous hydrogels The

properties

of

the

macroporous

hydrogels,

such

as

swelling,

porosity,

elasticity,

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biodegradability and biocompatibility could be tailored by controlling (i) the synthesis parameters

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(gel preparation temperature, cross-linking degree, monomer/polymer concentration, pH, molecular weight of polymers); (ii) the polymer type natural or synthetic; (iii) the monomer nature, ionic or

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non-ionic; (iv) the technique for pore generation and the drying method [13,22,49,51,77-91]. Some

discussed in detail in the subsequent sections.

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Table 1

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properties of porous CS-based composites with various compositions are listed in Table 1, and

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3.1. Swelling

Swelling is considered one of the most important properties of hydrogels which determines their

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wide variety of applications [22,49,51,77-79]. Generally, during the swelling process, the pores are

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rapidly filled with solvent and, at the same time, the polymeric region of hydrogel takes up solvent molecules from the environment. The water absorption depends on the affinity of the solvent molecules for the polymer chains (Table 1). The swelling ratio (SR, Eq. 1) [13,14,20-22,32,39], the water uptake (WU, Eq. 2) [13,26,38,40,84,87,88], the equilibrium water content (EWC, Eq. 3) [21,50,81], and the water retention (WR, Eq. 4) [34,38] and the water vapor transmission rate (WVTR, Eq. 5) [34,40] have been mainly used to describe the swelling behavior of porous CSbased composite hydrogels. 𝑊

𝑆𝑅 = 𝑊𝑡

(1)

𝑑

𝑊𝑈 =

𝑊𝑡−𝑊𝑑 𝑊𝑑

𝐸𝑊𝐶 = 𝑊𝑅 =

× 100

𝑊𝑒−𝑊𝑑 𝑊𝑒

𝑊𝑡 −𝑊𝑑 𝑊𝑒−𝑊𝑑

× 100

× 100

(2) (3) (4)

Journal Pre-proof 𝑊𝑉𝑇𝑅 =

𝑊𝑖 −𝑊𝑓

(5)

𝐴𝑡

where Wt and Wd represent the weights of the hydrogel in swollen state at time t, and respectively in dried state; We is the weight of swollen hydrogel at equilibrium; Wi and Wf are the water amounts within the

hydrogel before and after being placed in thermostatically controlled chamber, t in Eq. 5 is 24 h, and A is the area of each sample in m2 . The swelling of porous CS-based composite hydrogels is highly dependent on the pH of the aqueous media [13,22,36,40,87], on the initial monomer/polymer concentration [22], and on the cross-linking density [18,19,81]. For example, the SR values of porous semi-IPN and IPN PAAm/CS composite hydrogels decreased with the increase of the cross-linker ratio [18,19],

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because the relaxation of polymer chains are hindered with the increase of the cross-linker ratio. The entrapment of a natural zeolite within CS network and the presence of carboxylate groups,

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generated by partial hydrolysis of amide moieties from PAAm, led to composite hydrogels (NICC15.H or II-CC15.H) with controlled swelling ratios (25–40 g/g, depending on pH) [22]. The SR

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values of II-CC15.H have been higher than those of NI-CC15.H at low pH (pH < 4), the swelling feature in this pH range is dominated by the cationic character of CS network. The optical images

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taken on NI-CC15.H and II-CC15.H swollen in aqueous solutions with various pH values indicated

Figure 6

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the influence of pH on their size and shape (Figure 6A).

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The diameters of II-CC15.H discs are higher than those of NICC15.H at pH 3 and 4.5, indicating

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the presence of more primary amine groups available for protonation. Since Cu2+ ions have been involved in the imprinting step of II-CC15.H, a part of the NH2 groups of CS participated into the chelation process (Figure 5A), and thus, the II-CC15.H network has been less cross-linked by GA. At pH > 6, the shape of both cryo-composites has been not affected, the swelling process being controlled by the electrostatic repulsion between COO − groups (Figure 6A). The swelling behavior of hydrogels has also an important influence on the seeding effect, distribution and growth of seeded cells when they are used as scaffolds for 3D cell culture [41]. As seen in the swelling kinetics of the freeze-dried CEL and HECS/CEL scaffolds (Figure 6B), the two kinds of scaffolds could reach equilibrium swelling state in water within 20 s and the swelling kinetics of HECS/CEL scaffolds have been faster than that of CEL scaffolds. Moreover, the value of SR of HECS/CEL scaffolds (26.9 ± 0.6) has been much higher than that of CEL scaffolds (21.4 ± 0.5). These results indicated that HECS/CEL scaffolds have been more hydrophilic than CEL scaffolds, which is consistent with the result of contact angle measurements (insets of Figure 6B).

Journal Pre-proof Since the target application of the majority CS-based composite hydrogels is biomedical, their swelling behavior is also investigated in PBS (pH 7.4). In Figure 6C is presented the swelling kinetics of CS/Agarose (Agrs) scaffolds in PBS at 37 °C. All scaffolds absorbed large quantities of PBS, ranging from 800 to 1200% after 15 min, followed by a gradual increase at a rate of 0.75-l.25 % per min to reach saturation levels after 6 h. The inset bar chart shows the percentage of scaffold swelling after saturation (6 h). The CS100 and CS75-Agrs25 scaffolds demonstrated the highest swelling ratio (ca. 1500 %) and CS50-Agrs50 scaffolds the lowest. The CS100 scaffolds were unstable in PBS and fully disintegrated after 24 h, while the CS-Agrs scaffolds remained intact until the end of the swelling experiment, showing the stabilizing effect of Agrs incorporation. The

f

high swelling capacity of these scaffolds was attributed to the existence of hydrophilic functional

oo

groups (-OH and -NH2 ).

pr

An adequate hydration capacity is also essential to achieve controlled and uniform release of the therapeutic agents and to enhance the mucoadhesive properties of buccal CS-based composite

e-

sponges [51]. For this purpose, CS was blended with five polymers known with mucoadhesive properties, namely Carbopol (CRB), CMC, HPMC, sodium alginate and hyaluronic acid (HA).

Pr

Among all fabricated sponges CS/CRB and CS/HPMC showed higher hardness values, porosity, swelling degree and enhanced muco-adhesion compared to other sponges.

al

The swelling properties of porous hydrogels are also strongly influenced by the ratios of components, and the number of F-T cycles [39]. By increasing the amount of PVA in the structure

rn

of porous PVA/CS/ZnO hydrogels, due to the high hydrophilicity of this polymer, the swelling

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ratio values increased. By increasing the number of F-T cycles, crystallinity increases and stronger intermolecular forces are formed among polymer chains which results in the reduction of swelling ratio. The WVTR of PVA/CS/ZnO composite hydrogels has been also evaluated. The WVTR values decreased by adding ZnO nanoparticles and by increasing the number of F-T cycles [39]. By contrast, the incorporation of HAP nanoparticles within CS networks improved the swelling properties of hydrogels [78]. The high rate of swelling capacity of CS-based composite hydrogels containing HAP has been attributed to the hydrophilicity offered by the free –OH groups of HAP. In conclusion, the water content within hydrogels have a key role because influences the water diffusion coefficient, the surface mobility, the mechanical properties and chemical stability of the hydrogel. 3.2. Porosity The pore size and porosity of hydrogels could be tuned by changing various parameters, such as concentration of polymers or monomers, cross-linking degree, temperature, freezing rate, addition

Journal Pre-proof of organic solvents or inorganic particles [19-22,24,32,53,73,77,80]. The swollen state porosity, Ps (%), and total porosity, P (%), of porous CS-based hydrogels have been generally calculated according to the Eqs. (1) and (4), respectively, listed in Table S1 [27,28,73]. The volume fraction of pores (Vp ) within composite hydrogels was calculated by Eq. (7) (Table S1). The porosity, and the average pore diameters and distribution have been also evaluated by mercury intrusion porosimetry [36,86]. Another technique frequently used to determine the porosity within CS-based composite scaffolds is by immersing of the samples in various solvents such as ethanol [39,89], isopropanol [84], and xylene [86]. In this case, the porosity has been calculated by Eq. (9)

f

(Table S1).

oo

In another study, Bayrak et al. [26] determined the void fraction of the CS/HAP composite scaffolds by immersing the dried samples in PBS (pH 7.4) at 37 °C. The volume of PBS absorbed

e-

fractions were calculated by Eq. (10) (Table S1).

pr

by the CS/HAP composite scaffolds was evaluated using Burette Digital III apparatus, and the void

The porosity values estimated using all the above-mentioned procedures are listed in Table 1, the

Pr

porosity was mainly influenced by the synthesis technique selected for pore generation, and by the

3.3. Mechanical properties

al

initial monomer/polymer concentration [19-22,24,32,53,77,83].

rn

The mechanical strength of porous CS-based composite hydrogels was mainly investigated by tensile and compression tests [24,44,45,81-83]. The specific parameters which describe the

Jo u

mechanical properties of hydrogels such as Young’s modulus, tensile strength and yield strength are usually obtained from the stress-strain charts. In the compression tests, the CS-based composite hydrogels are placed between two plates and compressed [15,24,41,45,65]; the variable pressure applied to the hydrogel surface allows the calculation of different mechanical parameters using various theoretical models. The compressive elastic modulus and compressive strength of physically cross-linked pH-responsive hydrogels in swollen state at pH 7 have been found to vary with the gel composition from 3 to 11 kPa, and 178 to 206 kPa, respectively. The swollen gels had a viscoelastic behavior and encountered deformation from 70% to 85% before failure, indicating the formation of robust 3D hydrogel structures. The mechanical properties of porous materials could also be modulated by selecting the co-monomers and synthesis temperatures (RT or cryogelation) [24]. Mechanical properties of porous CS-based hydrogels can be also influenced by the morphological parameters, such as porosity, pore shape, and pore size [44,90]. To improve the mechanical properties of porous materials, various strategies have been applied, including the

Journal Pre-proof addition of other molecules (such as GO) or polymers [8,37,44,60,81,87,91], the use of various cross-linking agents and different cross-linking ratios [7], variation of polymer concentration [88]. The compression modulus of hydrogels prepared using these strategies ranged from 0.005 to 20 MPa (Table 1). However, these modifications could also induce chemical toxicity and impaired nutrient diffusion within the polymer matrix [82]. Typical stress-strain curves of PVA/CS hydrogels prepared with different weight ratios of CS to PVA (from 0 to 60%) and different GA ratios (from 0.1% to 1.0%) are shown in Figure 7a and 7b, respectively [88]. Some optical pictures of PVA/CS hydrogels under compression by a thumb in

f

comparison with those of pure PVA hydrogel are presented in Figure 7c-h.

oo

Figure 7

pr

As Figure 7a shows the pure PVA hydrogel was very weak with a compressive stress at fracture of about 1.55 MPa. The stress at fracture for the PVA/CS hydrogels increased gradually from 1.55 to

e-

26.59 MPa as the ratio of CS to PVA increased from 0% to 40%; at a CS/PVA weight ratio higher than 40% the stress at fracture decreased to below 20.22 MPa being ascribed to the inhomogeneity

Pr

of the structure. When the GA concentration was increased, the stress at fracture for the CS/PVA hydrogels increased gradually (Figure 7b). The stress at fracture reached maximum values of 3.7

al

MPa at 20% CS (to PVA) and 1.0% GA. The optical pictures of the PVA/CS hydrogel (30% CS, 1.0% GA, Figure 7c-e) and of the pure PVA hydrogel (Figure 7f-h) show that the composite

rn

hydrogel was very tough during compression without being broken (Figure 7g), whereas the pure

Jo u

PVA hydrogel was very fragile and easily crushed by a gently pressing of a thumb (Figure 7h). Thus, the mechanical properties of the PVA/CS hydrogels could be controlled by changing the weight ratio of CS to PVA and GA concentration. The elastic properties of carbon nanotubes (CNTs)/CS composite foams were investigated by cyclic compression tests (Figure 7i and j) [91] in comparison to the pure CS foams. In the first compression cycle, the stress–strain curve showed two distinct stages during the loading process (Figure 7i). The stress increased linearly at strain ≤ 13% which belonged to a linear-elastic region, recording the elastic deformation of lamellas in the CNTs/CS composite foam. In the second cycle, a positive stress response appeared at a strain of 6%, indicating the sample recovered up to 94% of the original length after the first cycle. In all of the subsequent cycles, hysteresis loops were observed and obvious linear-elastic and plateau regions appeared on loading curves. However, in these cycles, recovery ratio of sample, maximum compressive stress and area of hysteresis loop became smaller and tended towards stability after 10 cycles (Figure 7i), suggesting a viscoelastic

Journal Pre-proof behavior under compression. Even being compressed for 50 cycles, the CNTs/CS-L-0.5 composite foam still could recover to over 80% of its original length and keep its original macroscopic shape without bend or crack. By contrast, the pure CS foam exhibited a poor compressibility (Figure 7j). As shown in Figure 7j, the sample only recovered 62% of its original length after 5 compression cycles, and since the second cycle the loading curves rapidly reached densification region almost without elastic and plateau regions. Therefore, the addition of CNTs can obviously improve the elasticity of CS foams [91]. 3.4. Biodegradability and biocompatibility

f

Hydrogel biodegradability is a required feature in biomedical applications demanding controlled in

respect,

temperature

or

pH

could

act

as

oo

vivo resorption or local dissolution to support cell activities and promote tissue regeneration. In this local environmental parameters,

which can

pr

accelerate/decelerate the hydrogel degradation by chain disentanglement, hydrolysis or even

e-

proteolysis. Several strategies have been involved in controlling the degradation rate of naturally derived hydrogels, including the change in deacetylation degree of material, modification of

Pr

molecular weight, concentration, combination with other polymers, and incorporation of additives [34,78,92]. It has been reported that the hydrogels with lower porosity or larger pore sizes degraded more rapidly than those with higher porosity or smaller pore sizes [50,93-97]. This behavior is

al

attributed to the thicker pore walls, associated self-catalyzed hydrolysis and domination of bulk

rn

degradation over surface degradation. The hydrogel structure (the mesh size of cross-linked network) also affects the degradation profile, a highly cross-linked hydrogel (smaller mesh size)

Jo u

exhibiting longer degradation times [95,96]. Maji et al. [50] evaluated the biodegradation profile of GEL/CMCS/HAP composite 3D macroporous scaffolds against collagenase type I and lysozyme. Similar to the swelling profile, GEL/CMCS/HAP composite 3D macroporous scaffolds showed a faster rate of degradation in the presence of both enzymes. The weight loss of PVA/CS/β-CD membranes over 21 days was investigated by Morgado and colab. [36] in aqueous solutions of different pHs. A weight loss of 40% and 60% was observed during the first 7 days for PVA/CS/β-CD_4 min and PVA/CS/βCD_10 min, respectively. In general, the biodegradability of a material is a requirement for wound treatment, otherwise it may induce the formation of new lesions and increase the pain felt by the patient when the dressing is changed. The cytocompatibility of PVA/CS membranes loaded with βCD was evaluated through in vitro studies. The cells adhered and grew in the presence of the membranes and

in the negative control (cells seeded without materials), highlighting the

membranes biocompatibility.

Journal Pre-proof

4. Applications of 3D porous chitosan-based materials 4.1. Sorbents (metal ions, dyes, other pollutants) Among polysaccharides, CS represents a pivotal component in the fabrication of porous composite sorbents with high sorption performances for heavy metal ions, various dyes and other organic pollutants [5,9,98-104]. Sorption performances, such as equilibrium sorption capacity and sorption kinetics are strongly influenced by the sorbent composition, the presence of ligands and the pH [98]. As it will be shown below, the presence of numerous reactive functional groups such as -OH

f

and -NH2 constitutes a generous platform for chemical transformations of CS into plenty of

oo

modified CS having attached various chelating groups required to enhance the selectivity for certain ionic species. CS and its derivatives can be manufactured readily to obtain polymers with

pr

different shapes, such as gel beads, fibres, nanoparticles, powders, membranes, flakes, hollow fibres, and foams. According to the conventional methods, the main parameters which allow the

e-

control of sorption process are: pH, temperature, sorbent dosage, contact time, and co-existing ions

Pr

[100,101,104]. The biosorption performances and sorption mechanism are also depending on the accessibility of the sorbate molecules to the active sites of the biosorbent, which is intimately connected on both the size of molecules and the sorbent porosity [105]. A porous composite

rn

with a fast adsorption rate.

al

sorbent can provide strong mechanical properties and a large surface area, intimately connected

The biosorption process is of great interest not only for the waste waters remediation but also for

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the potential of CS based sorbents loaded with metal ions to be used as novel advanced materials for various applications such as: new sorbents, supported catalysts, sensors, antimicrobial supports [5]. 4.1.1. Metal ions There are different types of interactions between heavy metal ions (HMIs) and the CS-based sorbents including electrostatic attraction, ion-exchange, complexation and chelation, and van der Waals forces. The functional groups of the sorbent and the medium pH will determine the dominance of a certain type of interactions and finally the sorption mechanism [98,104,106]. Among the HMIs usually present in the wastewaters, much attention has been focused on Cu2+, Co2+, and Ni2+ [107-119]. All these metal ions are essential for living organism, within permissible limits [14]. On the other hand, exciding the allowable concentrations of 2.0 mg/L for Cu2+ can cause nausea, vomiting, gastrointestinal illness, muscle pain, liver poisoning, kidney failure, and

Journal Pre-proof Wilson’s disease. The tolerance limit for Ni2+ in drinking water is 0.01 - 0.02 mg/L, but exposure to high concentrations of Ni2+ may cause dermatitis, gastrointestinal disturbances, liver or kidney failure, dysfunctions of central nervous system, cancer of the lungs and bones, and may have mutagenic effects. High concentrations of Co2+ in water, food, and as radioactive cobalt in environment may cause low blood pressure, paralysis, diarrhea, lung irritation and bone defects [118]. Novel composite biosorbents have been developed in our group as cryobeads by dual cross-linking of a mixture of CS and starch coming from different botanical sources, such as potato, wheat, and rice, grafted with poly(acrylonitrile) (PAN), to enlighten the influence of the origin of native

f

starches on the removal of Cu2+, Co2+, and Ni2+ by the CS/(starch-g-PAN) composite sorbents [14].

oo

As can be seen in Figure 8a, a remarkable level of reusability was found for the composite cryobeads based on CS and rice starch-g-PAN (GRS), no decrease of the sorption capacity being

pr

observed after five consecutive sorption/desorption cycles. Even if all HMIs investigated in this work were adsorbed by the novel composites, the qm values were in the order: Cu2+ > Ni2+ > Co2+.

e-

Usually, the difference in the adsorption extent on the same sorbent is correlated with the metal ion

Pr

characteristics. Covalent index, which reflects the degree of covalent interactions in the metal ligand complex relative to ionic interactions, Xm2 .r, which values have been 3.39, 2.62, and 2.61 for

Figure 8

rn

composite cryobeads.

al

Cu2+, Ni2+, and Co2+, respectively, could explain the order of sorption capacity onto these

The values of atomic radius, which are 1.45 A, 1.62 A, and 1.67 A, for Cu2+, Ni2+, and Co2+,

Jo u

respectively, support the same order of preference. A possible mechanism of binding of the Cu2+, Ni2+ and Co2+ onto the composite cryobeads is proposed in Figure 8b. As can be seen, N from primary amine groups in CS and in the nitrile groups in PAN, and O atoms in the secondary hydroxyl groups are involved in the complex formation. Many recently published studies have demonstrated that the sorption performances of porous CSbased sorbents for HMIs could be augmented by the presence of inorganic particulate sorbents such as zeolites [107-113]. Thus, CS-zeolite Na-X composite beads with open porosity and different zeolite contents have been prepared by an encapsulation method [109]. It was found that the drying method of the adsorbent dramatically affected the textural properties of the composite and the metal sorption capacity. Subsequent gelation of the zeolite suspensions in alkaline solution has allowed the preparation of composite beads with different zeolite/CS ratios, while supercritical CO 2 drying has allowed the formation of highly porous aerogels with significant Cu2+ sorption capacity when rehydrated. Thus, the Cu2+ sorption capacity of CS hydrogel has been about 190 mg/g, more than

Journal Pre-proof 70% of this capacity being retained when CS has been dried with supercrititcal CO 2 , and only 10% of the capacity has been kept when a xerogel has been obtained by the evaporative drying. While a CS coating diminishes the accessibility of the zeolite microporosity, the presence of zeolite improves the stability of the dispersion of CS upon supercritical drying and increases the affinity of the composites for Cu2+ cations. Tsai et al. have investigated the removal of Cu2+, Ni2+, Pb2+, and Zn2+, from aqueous solution in single and multi-metal system using CS-coated montmorillonite (MMT) beads, either cross-linked with ethylene glycol diglycidyl ether (EDGE), or non-cross-linked [111]. An increase in ionic strength caused a decrease in % removal of all HMIs. Adsorption of the four metals followed the

f

pseudo-second-order (PSO) kinetic model. In single metal system, the equilibrium sorption data of

oo

Cu2+ and Zn2+ fitted well the Freundlich model, while Ni2+ and Pb2+ followed the Langmuir model, the cross-linked composite beads having a higher maximum adsorption capacity compared with the

pr

non-cross-linked ones. The calculated Langmuir adsorption capacities for Cu2+, Ni2+, Pb2+, and Zn2+ using the composite sorbent in single metal system have been 13.04, 12.18, 29.85, and 13.50

e-

mg/g, respectively. The adsorption capacity in single- and multi-metal system followed the order:

Pr

Pb2+ > Cu2+ > Zn2+ > Ni2+. A maximum removal of 94.08, 92.42, 88.28, and 42.04% for Pb2+, Cu2+, Ni2+, and Zn2+ has been achieved in groundwater system. Ordered porous zeolite/CS (Zel/CS) monoliths have been prepared by a unidirectional freeze–

al

drying method [112]. The adsorption of Cu2+ and Pb2+ onto the porous Zel/CS monoliths has been

rn

studied. The metal ion adsorption capacity of the Zel/CS monoliths has been related to the concentration of the metal ions, the adsorption time and the Zel/CS ratio. An experimentally

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maximum adsorption of 89 mg/g has been achieved for Cu2+ ions with the monolith having a 1:1 ratio between Zel and CS. Furthermore, the Zel/CS monoliths with adsorbed Cu2+ ions behaved as an effective catalyst in the reduction of 4-nitrophenol to 4-aminophenol and had presented a good recyclability.

To increase the CS surface area, mechanical strength and recyclability, Tu et al. have mixed CS with layered silicate rectorite (REC) and the mixtures were subsequently electrosprayed to nanosized spheres, which were immobilized on the surface of electrospun polystyrene (PS) mats with the final aim the adsorption of Cu2+ [113]. Small Angle X-ray diffraction patterns showed that the interlayer distance of REC in composite mats was enlarged by the intercalation of CS chains, such structure being very helpful for metal adsorption. The Cu2+ ions adsorption of composite mats has been tested at different conditions and the results have demonstrated that PS mats coated with CS-REC nanospheres had the adsorption capacity up to 134 mg/g. Moreover, the addition of REC containing Ca2+ could also improve the metal adsorption because of cation exchange. The PS mats

Journal Pre-proof immobilized with CS-REC nanospheres still kept 78% of the initial adsorption ability after three adsorption-desorption cycles. A novel approach has been developed by Verma et al. [114] who have synthesized arginine functionalized magnetic CS beads for the removal of Cu2+, Co2+and Ni2+ ions from aqueous solution. The adsorption capacity of the composite beads has been the highest at pH 6 and followed the order Cu2+> Co2+> Ni2+. The adsorption isotherm data have been well fitted with the Freundlich isotherm model. The maximum removal percentage by the composite beads has been 86, 82, and 71%, with the maximum adsorption capacity of 172.4, 161.2, and 103.0 mg g-1 , for Cu2+, Co2+, and Ni2+ ions, respectively. The possible mechanism of adsorption of metal ions by the arginine

oo

f

functionalized magnetic CS beads is shown in Figure 8c. The regeneration of the composite beads with 0.1 M EDTA solution has shown the fourth time of the adsorbent regeneration performed very

pr

well, up to 70% of adsorption capacity being preserved.

Mesoporous-high surface area CS/poly(ethylene oxide) PEO nanofibres, stabilized by hydrogen

e-

bonding, have been recently fabricated by Shariful et al. by electrospinning process [115]. The

Pr

effect of CS/PEO weight ratio on the adsorption capacity of the composite nanofibres for Cu2+, Zn2+ and Pb2+ ions has been investigated. It was found that the formation of beadless fibres has been achieved at CS:PEO ratio of 60:40. Average fiber diameter, and the specific surface area of these

al

composite fibres have been 115 ± 31 nm, and 218 m2 /g, respectively. PSO kinetic model has fitted

rn

the experimental data, while the equilibrium adsorption data have been the best fitted with the Langmuir isotherm. The maximum adsorption capacity for Cu2+, Zn2+ and Pb2+ ions were found to

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be 120, 117 and 108 mg/g, respectively. Moreover, the beadless nanofibres can be reused without significant loss of adsorption capability, this being unchanged in the first three cycles, and slightly reduced in the fourth and fifth cycle. Porous composite sorbents, very efficient in the sorption of Cu2+ ions, have been developed in our group by the ice-templating strategy [22,23,116]. Thus, novel CS-based cryogel composite sorbents, endowed with high selectivity for Cu2+ ions, have been synthesized by combining the ionimprinting methodology with UF technique [22,23]. The sorption selectivity of ion-imprinted composite (II-CC) sorbents has been studied in comparison to non-imprinted (NI-CC) ones using binary or multicomponent mixtures of Cu2+ with Co2+, Ni2+, Zn2+ or/and Pb2+ ions. It was found that Cu2+ ions have been bound onto both II-CC and NI-CC sorbents, when they were in mixtures with Pb2+, Zn2+, or Co2+ ions (Figure 9A). Figure 9

Journal Pre-proof The more intense blue and the darker green color of II-CC compared to NI-CC sustained the high affinity and selectivity of this sorbent for Cu2+ ions. These observations have been further supported by the high values of the selectivity coefficients obtained for the II-CC sorbents [22]. The ionic radius of template ion (Cu2+ ions) and the electronegativity of the metal ions involved into the competitive sorption studies were found to have a major role into Cu2+ ion recognition and its selective capture by these composite sorbents. In addition, a fast sorption of Cu2+ ions was observed for II-CC sorbents, the sorption equilibrium being reached after 20 min (Figure 9B) [23]. The rapid sorption process was most probably induced by the combined effect of Cu2+ complexation rate, the presence of recognition sites within the II-CC structure, and its oriented,

f

highly porous morphology. The desorption process was also very fast, the complete elution of Cu2+

oo

ions being achieved in about 30 min. Furthermore, the almost constant sorption capacity of Cu2+ ions at equilibrium after five sorption/desorption cycles, as well as the unaffected disc shape of the

pr

composite, without cracks and defects (optical images in Figure 9B), revealed their remarkable chemical and mechanical stability upon successive sorption/desorption cycles [23].

e-

The adsorption properties of Co-imprinted magnetic 8-hydroxychinoline (HQ)-CS for Co2+ ions

Pr

from aqueous solutions have been investigated by Beyki et al. [118]. Maximum sorption capacity has been obtained at pH 8–9. It was demonstrated that the 8-HQ has been the main functional group in the composite structure which had paramount role for Co2+ adsorption. The efficiency of

al

imprinting process was investigated by comparing the performance of imprinted with non-

rn

imprinted sorbents. It was found that at initial Co2+ concentration of 1.0 mg/L, adsorption removal was 75% using non-imprinted, while 99.5% removal of Co2+ was performed by imprinted sorbent.

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Competitive adsorption of Co2+, in the presence of Cd2+, Ni2+ and Pb2+ ions, has been studied. The results indicated that the distribution factors of Co2+/Cd2+, Co2+/Ni2+ and Co2+/Pb2+ have been 11, 42 and 2, respectively.

Le et al. have recently used industrial wastes and natural materials as starting materials (steel slag, shrimp shell wastes, and bovine bone) to obtain magnetite, CS, and HAP, respectively, to prepare cross-linked magnetic HAP/CS composite for Ni2+ removal [119] (Figure 9C). The composite has been cross-linked with green tea extract. The adsorption of Ni2+ was fast, 60 min being enough to ensure the saturation with Ni2+ of the HAP/Fe3 O4 /CS composite sorbent. The authors have explained the adsorption mechanism of Ni2+ ions by the following processes: (i) adsorption of Ni2+ ions onto the surface of HAP particles by exchanging them with Ca2+ ions, (ii) adsorption of Ni2+ ions onto the surface of CS through complexation interactions with the amine and hydroxyl groups, and (iii) the ion exchange and/or complexation between Ni2+ and phenolic groups on the composite surface (Figure 9C). In another approach, Guo et al. have prepared novel macroporous Ni2+-

Journal Pre-proof imprinted chitosan foam adsorbents (F-IIP) using NaHCO 3 and glycerine to obtain a porogen [120]. The use of the IIP technique has increased the selectivity for Ni2+ and the adsorption capacity. The adsorption process has been described best by Langmuir monolayer adsorption model, and the maximum adsorption capacity was 69.93 mg/g. The analysis of selective adsorption demonstrated the excellent preference of the IIP foams for Ni2+ ions compared with other coexisting metal ions. Furthermore, tests over five sorption/desorption cycles have suggested that the IIP foam adsorbents had good durability and efficiency. Removal of Cd2+ by various porous composite sorbents having CS as polycation is of an actual concern [121-124]. In this context, the development of macroporous bionanocomposites has been

oo

f

performed by the intercalation of CS in the natural vermiculite (VU) or organically modified vermiculite (OVU) involving ultrasound irradiation, with the final aim the removal of Cd2+ ions

pr

from aqueous solution [121]. The composites have been processed as foams by freeze-drying resulting in materials with interconnected elongated macropores with average diameter around

e-

150–200 μm (Figure 10a). A FESEM image of the sample containing 65% CS (Figure 10b) shows a better detail of the inner structure of these bionanocomposite foams, the estimated porosity being

Pr

about 97% for this sample. The adsorption equilibrium data of Cd2+, carried out in batch mode, has been described with the Langmuir, Freundlich and Prausnitz–Radke isotherm models. The

al

adsorption capacity of the composite consisting of VU and 65%CS bionanocomposites towards Cd2+ has been three times higher than that of the pristine VU. The adsorption mechanism includes

Figure 10

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pH of the Cd2+ solution.

rn

electrostatic interactions, cation exchange and chelation, and depends on the amount of CS and the

A novel adsorbent has been recently designed by grafting poly(maleic acid) onto CS microspheres cross-linked with GA [123]. The effects of pH, contact time, and initial concentration on Cd2+ adsorption have been investigated, and the maximum adsorption capacity was 39.2 mg/g, which is much higher compared with that of cross-linked CS microspheres (14.5 mg/g). The experimental data have been well fitted with PSO kinetic and Langmuir isotherm models. The composite microspheres could be reused up to five sorption-desorption cycles with a small loss of the adsorption capacity (<15%). Very recently, Quirola-Flores et al. have developed a nanoparticlebased mesoporous composite consisting of silicate-titanate nanotubes (STNTs) dispersed in the walls of hollow CS beads with the aim to be used for Cd 2+ adsorption [124]. It was found that the maximum adsorption capacity of the composite beads has been 2.3 times higher than that of STNTs alone. The composite was used for Cd2+ adsorption in batch solutions and to treat real leachate by

Journal Pre-proof using packed columns. The maximum sorption capacity has been 172 ± 37 mg Cd2+/g and 656 ± 27 mg Cd2+/g, with CS beads and STNTs/CS composite beads, respectively. The composite beads have been successfully reused four times, demonstrating high potential for wastewater treatment. Among the numerous HMIs, Pb2+ ions, which are widely used in metal finishing, electroplating cable manufacturing, and battery manufacture, can cause brain damage, vomiting, and kidney dysfunction and therefore must be removed from the wastewaters [125-129]. In the context of the World

Health

Organization

(WHO)

drinking

water

guideline,

the

maximum acceptable

concentration of Pb2+ is 0.048 M [129]. Highly porous magnetic CS hydrogel beads have been prepared by a combination of in situ co-precipitation and ionic cross-linking with sodium citrate

oo

f

[125]. Laser confocal microscopy revealed highly uniform porous structure of the composite beads, which contained high moisture content (93%). Batch adsorption experiments and adsorption kinetic

pr

analysis revealed that the adsorption process of Pb2+ obeys a PSO model. Isotherm data have been well described by the Langmuir equation, and the maximum adsorption capacity has been 84.02 mg

e-

Pb2+/g sorbent. The magnetic composite beads have been formed by chelating Fe2+ and Fe3+ ions with CS followed by the formation of Fe3 O4 through the in situ co-precipitation reaction and cross-

Pr

linking of CS with citrate ions. The multilayer onion-like structure has been clearly observed. The adsorption capacity for Pb2+ presented a small decrease after 5 cycles.

al

A novel CS/PEG/PAA hydrogel adsorbent containing hard Lewis base adsorption sites (i.e., amino group, hydroxyl group, ether linkage, carboxylate ions) has been prepared by glow-discharge

rn

electrolysis plasma (GDEP) technique and then applied for the selective adsorption of Pb2+ [126].

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The sponge-like structure has facilitated the diffusion of metal ions into the three-dimensional network, increasing the adsorption rate. Competitive adsorptions of Pb2+ and Cd2+ have been carried out and the results showed that the maximum adsorption capacities have been 431.7 Pb2+/g, and 265.0 mg Cd2+/g. The CS/PEG/PAA adsorbent has presented good adsorption selectivity for Pb2+ in the presence of Cd2+, even if according to the ionic radii of the metals (Cd2+ 109 pm; Pb2+ 133 pm), Cd2+ ions can move more quickly in solution, while Pb2+ ions are larger, making their mobility in the solutions more difficult. The preference for Pb2+ ions has been explained by the authors by the hard and soft acids and bases (HSAB) principle. Polydopamine-modified-chitosan

(CS-PDA)

aerogels

have

been

synthesized

through

simultaneously dopamine self-polymerization and GA cross-linking reactions to enhance the adsorption capacity and acid resistance of CS [127] (Figure 10c). CS-PDA exhibited superior adsorption performances in the removal of Cr6+ and Pb2+. Adsorption isotherms and kinetic data were well fitted by Langmuir isotherm and PSO kinetic model, respectively. The maximum adsorption capacities of CS-PDA for Cr6+ and Pb2+ have been 374.4 and 441.2 mg/g, respectively.

Journal Pre-proof After eight cycles, adsorption capacity of CS-PDA showed no obvious decline. The interior network structure of CS-PDA aerogels was not destroyed after adsorption of Pb2+and Cr6+, which demonstrated the stability and tolerance of adsorbent (Figure 10d and e). The cross-linked amino groups could also remove Pb2+and Cr6+through electrostatic attraction or chelation. After eight cycles, the adsorption capacities of CS-PDA for Pb2+and Cr6+ still remained approximately 80%. A novel adsorbent consisting of PAN-CS mats was successfully prepared via the shoulder-toshoulder electrospinning and electrospraying techniques [128]. Furthermore, CS nanospheres and PAN nanofibers have been alternately arranged which could enlarge the space between the

f

nanofibers, facilitating the diffusion of heavy metal ions in solution. Afterwards, REC was

oo

introduced into the mats to achieve the predesigned intercalated structure between the CS chains and the interlayer of REC. The PAN modification of as prepared mats can be carried out by

pr

immersion into a DETA-Na2 CO3 solution to form aminated composites with more amine groups, to enhance the adsorption performance. The adsorption experiments results showed that the aminated

e-

composite mats exhibited at least 2.0 times increase in the adsorption capacity of Pb 2+ compared to

Pr

the original PAN-CS composite mats. The maximum adsorption capacities of PAN-CS, PANCS/REC and aminated PAN-CS/REC mats have been 77.40 ± 4.5 mg/g, 162.95 ± 8.6 mg/g and 500.95 ± 21.4 mg/g, respectively. These results have confirmed that both the incorporation of REC

al

and the amination process could increase the adsorption performance of the composite sorbents.

rn

A freeze-drying method has been used to fabricate HAP/CS porous materials for the removal of Pb2+ ions from aqueous solutions [129]. The Pb2+adsorption performances of the HAP/CS and CS

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porous materials have been investigated by the flow of Pb2+ aqueous solutions through the adsorbents at 25 o C, at pH 5.5. The adsorbed amount of Pb2+on the HAP/CS porous sorbent has reached a maximum of 264.42 mg Pb2+/g after 7 days. Adsorption kinetic results exhibited a good fit to the PSO kinetic model. The HAP/CS porous material possesses interconnected threedimensional macropores with pore sizes of 100–400 m. The remarkable changes in the morphology and phase of the HAP/CS porous material after the adsorption of Pb2+ions suggested that the HAP nanoparticles were converted into PbHAP via a dissolution–precipitation reaction. The PO 4 3- ions and OH- ions from the HAP nanoparticles tended to increase the local ion concentrations around the crystals. Pyromellitic

dianhydride-modified

nanoporous

magnetic

CEL–CS

microspheres

have

been

synthesized to introduce abundant carboxyl groups onto the basic microstructure [130]. Due to its nanoporous structure and large quantity of carboxyl groups, the CEL/CS-based bioadsorbent exhibited excellent adsorption performance for removal of Pb2+ions with maximum adsorption

Journal Pre-proof capacity of 384.6 mg/g. Increasing the pH value up to 6.0, the adsorption capacity first increased then reached adsorption equilibrium at pH 6.0. Furthermore, the adsorption kinetics and isotherms of Pb2+ ions on the composite sorbent obeyed the PSO kinetic model and Langmuir isotherm, and the rate of adsorption has been found to be controlled by film diffusion. The sorbent microspheres loaded with Pb2+ could be easily regenerated with HCl, the removal capacity being almost 89% after six sorption/desorption cycles. Among the HMIs, Hg2+ is one of the most hazardous and toxic element that contaminates our water and air supplies [131-134]. The WHO considers mercury as one heavy metal of great concern to public health, the limit of detection in drinking water being less than 1 g/L [131]. The CS–PVA

oo

f

hydrogel with three-dimensional network structure has been developed via a GA cross-linking method in combination with an alternate freeze–thawed process (three cycles) [132]. Adsorption

pr

experiments and comparative studies showed that the hydrogel adsorbent has superior adsorption capacity and selectivity for Hg2+ ions. Its adsorption capacity for Hg2+ ions has reached 585.90

e-

mg/g, at pH 5.5. The selectivity coefficient of the composite hydrogel for Hg2+ has been 487.7, 36642.5, 284298.5 times higher than that for Cu2+, Pb2+, and Cd2+ ions, respectively. The SEM

Pr

images of the hydrogel before and after the loading with Hg2+ ions presented in Figure 10i, and 10j, respectively, show that the hydrogel loaded with metal ions looks much more dense and presents

al

many ‘‘particles’’ compared with the pristine hydrogel, and this support the high affinity of the sorbent for Hg2+ ions. Even in the presence of Cu2+, Cd2+, Pb2+, the CS–PVA hydrogel still

rn

displayed a higher adsorption capacity for Hg2+ ions, the adsorption capacity being in the order:

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Hg2+ > Cu2+ > Pb2+ > Cd2+. The regeneration of the CS–PVA hydrogel loaded with Hg2+ ions could be performed with HCl, HNO 3 and NaCl solutions. A new hybrid sorbent has been prepared with CS and poly(glycidyl methacrylate) (GMA) coating magnetite microparticles (MCGMA-I) [133]. The concentration of amine groups on the sorbent has been increased by the reaction with diethylenetriamine (DETA). These materials showed high affinity and selectivity for Hg2+ uptake from aqueous solutions. The selectivity of the sorbents in Hg2+ sorption has been evaluated in multicomponent solutions containing Hg2+, Co2+, Cu2+, Fe2+, Ni2+, Zn2+and Mg2+, at pH values of 0.4–1.6. Irrespective of pH, the maximum sorption capacities of competitor metal ions by the modified sorbents has been less than 5.0% of sorbed amounts of Hg2+ ions. The selectivity of the sorbents for Hg2+against other HMIs has been explained by the sorption mechanism which has been attributed to ion-exchange of Hg2+ chloro-anions on protonated amine groups in acid conditions, while the competitor metal ions are not supposed to form stable chloro-anions under the selected experimental conditions. KI has been used for Hg2+

Journal Pre-proof desorption, and found the desorption yielded 99%, and the sorbent could be efficiently recycled for minimum three sorption/desorption cycles. A strong affinity for Hg2+ has been also reported by Lone et al. for the cross-linked gelatin/CS composite hydrogel [134]. The freeze-dried hydrogel behaved like a “sponge”. Cr6+ is one of the most dangerous ions present in the wastewaters, which must be adequately removed, the most often used technique being the sorption on various reusable sorbents, either synthetic [135,136] or composite sorbents having CS as the polycation coming from renewable resources [32, 137-142]. Novel composite sorbents have been designed in our group consisting of a combination between CS and a synthetic polycation, poly(vinyl amine) (PVAm), in a ratio of

base

anion

exchangers

(IEx)

having

(vinylbenzyl diethyl 2-hydroxyethyl)ammonium

oo

strong

f

80:20, w/w, dual cross-linked with GA and EGDGE, in which the microspheres of some porous chloride functional groups, and sizes in the range 90-200 m, have been evenly dispersed.

pr

Macroporous CS/PVAm/IEx composites as cryobeads or monoliths have been applied to the sorption of Cr6+ from synthetic aqueous solutions, in batch mode. The results revealed that the

e-

sorption of Cr6+ oxyanions was high in the range of pH 3 - 6, and abruptly decreased when pH was

Pr

> 6 (Figure 11). The PFO kinetic equation well fitted the kinetics profiles indicating that electrostatic interaction dominated the sorption process. Equilibrium sorption results of Cr6+ onto composite cryobeads were the best described by the Sips, Langmuir, and Temkin isotherm models.

al

The maximum sorption capacity evaluated by the Langmuir model at 25 o C was in the range 200-

rn

320 mg Cr6+/g sorbent. The composite cryogels could be repeatedly used in the sorption of Cr6+, a low decrease of the adsorption capacity being observed after five consecutive sorption/desorption

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cycles. The remarkable sorption capacities and the high reusability of the CS/PVAm/IEx composites suggest the promising potential of these novel sorbents in the removal of Cr6+. Figure 11

The values of mean free energy, evaluated by the Dubinin-Radushkevich isotherm, which were higher than 40 kJ/mol, support chemisorption as the most probable mechanism. The sorption process has been endothermic (ΔH° > 29 kJ/mol) and spontaneous (the increase of the negative values of ΔG° with the increase of temperature). The large domain of pH where the composite effectively adsorb the Cr6+ oxyanions, the fast sorption rate, the high sorption capacities (qe in the range 200-320 mg Cr6+/g composite, at 25 o C), and the convenient level of reusability of the novel composite cryogels recommend them as potential alternative in the removal of Cr6+ ions. An environmental-friendly biocomposite of CS and lysozyme (LYS) has been recently prepared by Rathinam et al., using GA as cross-linker [139]. This composite sorbent has showed excellent removal of Cr6+ along with concurrent removal of other heavy metals such as Cd 2+ and Ni2+ ions

Journal Pre-proof from aqueous solutions. The maximum adsorption capacity for Cr6+ has been 216 mg/g sorbent. The Cr6+ removal has been driven by a combination of electrostatic interactions coupled with reduction, hydrogen bonding, and chelation. The sorption capacity did not change after three sorption/desorption cycles. To further increase the adsorption capacity of the CS beads, Zhang et al. have modified them with malic acid and further freeze-dried [140]. The maximum equilibrium adsorption capacity of the novel composite for Cr6+ has been 383.2 mg/g, reached within 2 h. For comparison, the chemisorption of Cu2+ onto these beads formed a monolayer with a maximum equilibrium adsorption capacity of 183.8 mg/g, reached within 24 h. A novel adsorbent of CS-1,2-

f

cyclohexylenedinitrilotetraacetic acid–GO (CS/CDTA/GO) nanocomposite has been successfully

oo

prepared in the presence of GA as cross-linker [142]. The effects of adsorbent chemical composition, CDTA/GO concentration, adsorbent dose, pH, temperature, contact time and initial

pr

metal ion concentration on Cr6+ sorption have been investigated. The results showed that the optimum pH was 3.5 and equilibrium time 60 min. The adsorption kinetics of Cr6+ followed the

e-

PSO kinetic model and the adsorption isotherm has been fitted by the Langmuir model. The

Pr

maximum adsorption capacity of the adsorbent has been 166.98 mg/g, and the composite adsorbent could be regenerated more than three times.

Arsenic is one of the most harmful pollutants present in the surface water and groundwater [143-

al

146]. A high amount of arsenic in groundwater has been reported in Southeastern Asia, North and

rn

South America [144]. In many regions, arsenic contaminated water is served as the primary drinking water source [143]. To minimize the risk of arsenic, the WHO lowered the maximum

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concentration of arsenic in drinking water to 10 μg/L. Arsenic exists mostly in two inorganic forms as oxyanions of arsenite As3+ and arsenate As5+, the dominant arsenic species in groundwater being As3+, which is 60 times more toxic than As5+ [143-145]. Thus, it is obvious the need to develop low-cost and highly efficient sorbents to remove arsenic species from water environment. Fe-CS beads constitute a promising sorbent for arsenic removal, but usually have shown slow kinetics due to the low porosity. Porous Fe-CS beads represent a new solution for the efficient removal of arsenic due to the speeding the internal diffusion, more adsorption sites being accessible for adsorption. In this context, Wei et al. have fabricated a porous Fe-CS sorbent as beads by freezecasting technique [143]. The composite beads have been chemically cross-linked with ECH to improve their acid resistance. A heterogeneous catalytic oxidation process has been also developed by using H2 O2 to promote and accelerate the As3+ removal. The maximal adsorption capacities of porous Fe-CS beads for As3+ has been 52.7 mg/g at pH 7.0, coexisting sulfate, carbonate, silicate and humic acid having no influence on As3+ removal, especially when H2 O2 has been added. The

Journal Pre-proof porous Fe-CS beads could be readily separated and regenerated, and the adsorption efficiency maintained above 90% throughout five consecutive sorption/desorption cycles. In another approach, 3D honeycomb-like structured nanoscale zero-valent iron/CS composite foams have been developed and tested for effective removal of inorganic arsenic in water [144]. It was found that the composite foams obtained at -80 o C exhibited oriented porous structure with better mechanical properties than those prepared at -20 o C, the removal capability of As3+ and As5+ being up to 114.9 mg/g and 86.87 mg/g, respectively. The adsorption kinetics of As3+ and As5+ could be described by PSO kinetic model and their adsorption isotherms follow Langmuir adsorption model. The superior removal performance of the composite foams on As3+ and As5+ ions

f

has been ascribed to its oriented porous structure with abundant adsorption active sites [144].

oo

Neeraj et all. have investigated the removal of As3+ via the adsorption onto mesoporous CS coated iron-oxide nanocomposites [145]. The maximum monolayer adsorption capacity, at pH 6.0,

pr

calculated using Langmuir model was found 267.2 mg As3+/g sorbent. After five repeated adsorption cycles, only 13% loss over the initial adsorption capacity has been observed.

e-

Sorption/recovery of precious metals with CS based composite sorbents has been also reported last

Pr

years [147-149]. Thus, Song et al. have developed PEI-loaded CS hollow beads by the ionotropic gelation with sodium tripolyphosphate (TPP) as counter polyanion [147]. The composite beads have been loaded with PEI by pre- and/or post-loading methods, making the sorbent reach in amine

al

groups able to recover Pt4+ metal ions. The maximum Pt4+ uptake by the PEI-loaded CS hollow

rn

beads has been 815.2 ± 72.6 mg/g, which was much higher than that of a commercial ion exchange resin, Lewatit®MonoPlus TP214 (330.2 ± 16.6 mg/g). A sequential metal scavenging fill-and-draw

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process has been operated using the PEI-loaded CS hollow beads for ten cycles and the Pt4+ recovery efficiency was kept above 97.4% even after the last cycle [147]. Petrova et al. have investigated methods for correction of selectivity of sorbents based on N-(2-sulfoethyl) CS towards Pt4+ and Pd4+, in HCl solutions [149]. An increase in the degree of sulfoethylation of CS led to the significant increase in the selectivity of sorption of Pd4+ over Pt4+. Application of the N-(2sulfoethyl)CS with the highest degree of sulfoethylation permitted the selective separation of Pd4+ from Pt4+ (рН = 5.0). It was established that the highest removal of Pt4+ has been achieved when the рН was equal to 2.0, and the highest removal degree of Pd4+ was achieved in the рН range from 4 to 5. The demand for rare earth elements (REEs) is lately more and more expending by the increased interest in the green energy (electric vehicles, wind turbines) as well as photonics and electronic devices, magnets and catalysts. As the sources of REEs are located in few countries, mainly in China and Australia, the recovery of REEs from the secondary resources, including low-grade ores,

Journal Pre-proof mining residues, waste materials, has received lately an enormous interest. Such wastes are usually acidic and contain traces or low concentrations of REEs, biosorbents being an attractive alternative for their treatment [150]. In this context, Guibal et al. have recently investigated the sorption of Er3+ [150] and Nd3+ [151] by composite biosorbents based on CS and CEL. Thus, CEL containing SH groups and CS cross-linked with GA, and functionalized by poly(aminocarboxymethylation) (PCM-CS) have been tested for their performances in the sorption of Er3+, and found the highest sorption capacity for PCM-CS, up to 117–145 mg Er3+/g. Sorption capacity increased with pH due to the progressive deprotonation of reactive groups (amine functions, thiols groups and carboxylic groups). Acidic solutions of thiourea efficiently desorb Er3+and allows the recycling of the sorbents

f

for minimum five sorption/desorption cycles.

oo

In another approach, CEL and CS have been modified by chlorination first with POCl3 , aspartic acid being then immobilized, the sorption capacity for Nd3+ being thus almost doubled compared to

pr

the raw materials, mainly due to the carboxylate groups [151]. The equilibrium of sorption has been reached in 3 h of contact, the kinetic results being well fitted by the PFO kinetic model. The

e-

sorption isotherms have been described by the Freundlich and the Langmuir models and the

Pr

maximum sorption capacities have been up to 77–80 mg Nd3+/g, at pH 5. Desorption of Nd3+ could be successfully performed with 0.5 M HNO 3 and the sorbents could be recycled at least five sorption/desorption cycles without significant loss in sorption/desorption performances.

al

Table 2 presents some of the sorption results reported in the last five years obtained with porous

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Table 2

rn

CS-based composite sorbents against the main HMIs.

Uranium, thorium, radium, polonium, strontium (Sr-90), cesium (Cs-137) or cobalt (Co-60) are investigated for their environmental impact and human health effects [152]. Uranium is a nuclear fuel resource as well as one of the main radioactive elements in the radioactive liquid wastes. Thorium is used for industrial purposes, and medical applications. Long lived radionuclides such as Cs-137 (half life of 30.17 years), Sr-90 (half life of 28 years) and Co-60 (half-life of 5.27 years) are considered as the most dangerous to human health because of their high solubility, long half-lives and easy assimilation in living organisms [152]. Therefore, the removal of radionuclides from the radioactive liquid wastes is a central concern for scientists [153-156]. Incorporating a magnetic core in the micro- or nano-particles of sorbents not only facilitates the solid/liquid separation, but also ensure the safe recovery of spent sorbents at the end of the process when applied in nuclear industry. Thus, Elwakeel et al. have prepared a composite sorbent enriched in amine groups via cross-linking CS with GA in the presence of Fe 3 O4 , and then the sorbent functionalized with chloride moieties, by the reaction with ECH, has been further reacted with tetraethylenepentamine

Journal Pre-proof (TEPA) [154]. This sorbent has shown a high affinity towards the UO 2 2+ ions from aqueous medium, with the maximum sorption capacity of 1.8 mmol/g at pH 4 and 25 o C. The SEM images have shown a surface with several small pores inside suggesting interconnected macropores within the resin. However, the surface has been changed to smooth, while the formerly existing pores disappeared, these being the first evidence of the strong interactions occurring between UO 2 2+ ions and the adsorbent. Hydrochloric acid (0.5 M) was used for desorbing UO 2 2+ from loaded resin, a desorption yield as high as 98% being reported. Anirudhan et al. have recently reported the synthesis of a novel composite sorbent consisting of poly(amidoxime)-g-CS/bentonite [P(AO)-g-CS/BT] by in situ intercalative polymerization of

f

acrylonitrile (AN) and 3-hexenedinitrile (3-HDN) onto CS/BT composite using ethylene glycol

oo

dimethacrylate (EGDMA) as cross-linking agent [155]. The adsorption efficiency of U6+ from the seawater increased by the amidoximation reaction of nitrile groups. The pH 8.0 and the sorbent

pr

dose of 2.0 g/L have been reported as optimum for the complete removal of U6+. The equilibrium of sorption has been attained within 60 min and the kinetic data have been well fitted by PSO model,

e-

supporting chemisorption as the mechanism of sorption. The well agreement of equilibrium data

Pr

with Langmuir adsorption model confirms monolayer coverage of U6+ onto the P(AO)-g-CS/BT, the maximum adsorption capacity being 49.09 mg/g. The spent adsorbent has been effectively regenerated with 0.1 M HCl and the adsorption capacity has been not significantly decreased after

al

six adsorption–desorption cycles. Highly porous magnetic BT/CS composite beads have been

rn

prepared by immobilization BT within magnetic CS beads, ionically cross-linked with sodium citrate, to develop a novel sorbent efficient in the removal of

137

Cs from radioactive wastewater

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[156]. The adsorption kinetics has obeyed the PSO kinetic model, and the best fitted equation for equilibrium data has been the Langmuir isotherm model. The maximum adsorption capacity of the beads with BT to CS mass ratio of 5:1 has been 57.084 mg/g. The composite beads have retained good adsorption ability for Cs+ within a wide pH range, from 3.5 to 9.8, in the presence of Li+, Na+, K+ and Mg2+ cations. The adsorbent was able to be recycled by treating the beads with 0.1 mol/L MgCl2 to quantitatively desorb Cs+. 4.1.2. Dyes Owing to their high non-biodegradability, toxicity, as well as carcinogenic potential, dyes and pigments are probably the most difficult pollutants present in the wastewaters [10, 99, 157-159]. The large variety of dyes used in industries such as textile, plastic, paper, food or cosmetics makes the water pollution with dyes a very serious threat for human health and environment. The release of colored wastewaters in effluents can affect the photosynthetic activity of aquatic life by reducing

Journal Pre-proof the light penetration. Therefore, the dye removal from industrial wastewaters is usually performed by processes like biological treatment, coagulation/flocculation, adsorption, and oxidation. Among the known technologies for decontamination of the colored wastewaters, adsorption is considered an effective and economical method due to the flexibility in the selection of adequate sorbent and operation, and the production of effluents suitable to be reused. Furthermore, the adsorption process would have the advantage of allowing recovery of the dyes in a concentrated form. Numerous porous composite sorbents based on CS have been lately developed and tested for their abilities in the removal of cationic dyes [159-170]. Thus, methylene blue (MB) has been efficiently removed by the sorption on IPN composite hydrogels based on CS and PAAm prepared by freeze-

f

drying strategy [18], as well as CS/PAAm IPN cryogels [19]. It was found that the Sips isotherm

oo

fitted the best the experimental data and the maximum sorption capacity for MB has been 755.5 mg MB/g cryogel. The PAAm/CS IPN cryogels have presented excellent properties in separation of

pr

MB from its mixture with methyl orange (MO) and a very high level of reusability, no changes in the sorption capacity being observed after four consecutive sorption/desorption cycles [19]. Novel

e-

strategies for water desalination or removal of organic dyes, based on polymers coming from

Pr

renewable resources, such as composite membranes of CS-CEL nanocrystals have been synthesized through a freeze-dried technique and successfully used in the removal of cationic dyes [159].

al

High sorption capacity for MB has been lately reported for CS–clay composite [161], CS-crosslinked with -carrageenan bionanocomposites [162], poly(AA-co-VPA) hydrogel cross-linked with

rn

N-maleyl CS [163], GO-CS composite sorbent [164], porous β-cyclodextrin/CS/GO hydrogel

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[165], CS composite aerogels prepared through cross-linking and addition of GO nanosheets [166], CS graft poly (acrylic acid-co-2-acrylamide-2-methylpropane sulfonic acid) hydrogel [167], GO/CS composite sponge [170]. Magnetic CS composite cross-linked with GA has been used as biosorbent for removal of crystal violet [160]; GO/CS aerogel microspheres with honeycombcobweb and radially oriented microchannel structures have been used as a sorbent with a large spectrum of contaminants removal, among them being Rhodamine B and MB [168]. A novel magnetic nanocomposite hydrogel based on carboxymethyl chitosan (CMCS) efficient in the removal of Crystal Violet has been recently reported [169]. Finding novel sorbents for the decontamination of wastewaters containing anionic dyes has attracted a large participation of the scientists all over the world, as the numerous articles published in the last five years on the removal of these dyes demonstrate [168, 171-195]. Among organic dyes, azo dyes make up the majority of colorants used for dyeing processes because of their vast number of shades and fastness properties. Thus, the porous CS/HAP composite membranes with a

Journal Pre-proof sponge-like surface and a three-dimensional inter-penetrated porous structure of about mean pore size less than 10 m have been developed by Shi et al. and used in the removal of Direct Blue 15 [171]. The proposed membranes have an adsorption capacity 2.5 times higher as compared with non-porous CS/HAP membrane, and a high-speed in dynamic dye removal (98% in less than 15 min). Moreover, the porous membrane has featured repeated dye removal, the adsorption capacity being above 80% from the initial after five cycles of dynamic adsorption at a concentration of 150 mg dye/L. Calcon-imprinted magnetic chitosan nanoparticles have been synthesized as a novel adsorbent by using ECH and GA as cross-linkers for adsorption and removal of calcon from polluted solutions [172]. The adsorption isotherm and kinetics have been described by Langmuir

oo

ECH and GA have been 51.71 and 39.23 mg/g, respectively.

f

and PSO models, respectively. Maximum removal capacity by the nanoparticles creoss-linked with

pr

In another approach, Chen et al. have fabricated a composite cryogel from quaternized nanofibrillated CEL and CS by freeze-drying and cross-linking with ECH [174]. The experimental

e-

adsorption data at equilibrium have well fitted the Langmuir isotherm model, with the maximum adsorption capacity of Acid Red 88 of 473.9 mg/g. The adsorption kinetics well fitted the PSO

Pr

kinetic model. The removal percentage of Acid Red 88 has been still 96% even after five adsorption-desorption cycles. CS/REC/carbon nanotubes (CNTs) composite foams have been

al

fabricated by unidirectional freeze-casting technique and used as sorbents for MO removal [175]. The morphology of the composite showed well-ordered porous three-dimensional layers and

rn

horizontal stratum landform-like structure. When the mass ratio of CS to REC was 10:1 and CNTs

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content was 20%, the composite foam performed best in adsorbing low concentration of MO, the maximum adsorption capacity being 41.65 mg/g. The adsorption kinetics has been fitted to PSO kinetic model, and the adsorption isotherm was well described by Langmuir model [175]. Magnetic halloysite nanotubes (HNT) with CS nanocomposite sponges were prepared by combining solution-mixing and freeze-drying and used for the removal of Congo red (CR) in aqueous solution in batch mode [178]. The adsorption kinetics of CR removal followed the PSO kinetic model and the Langmuir adsorption isotherm best fitted the equilibrium data with maximum adsorption capacities of 41.54 and 54.49 mg/g on Fe3 O4 −HNT/CS and HNT/CS, respectively. Furthermore, the composite sorbent presented a high recyclability. Highly porous core-shell structured GO-CS beads have been recently fabricated by Ouyang et al. and tested for the sorption of MO [179]. Figure 12 illustrates the synthesis strategy and the morphology of these composite beads. Figure 12

Journal Pre-proof As can be seen in Figure 12a, GO beads have been first prepared in liquid nitrogen, dispersed then in CS solution, and after freeze-drying the porous core-shell composite beads have been obtained (Figure 12b and c). CS hydrogels with embedded porous hyper-cross-linked polymer (HCP) particles have been prepared by de Luna et al. as efficient adsorbents for removal of various dyes (indigo carmine, rhodamine 6G and sunset yellow) from water [180]. Adsorption experiments have revealed a synergistic effect between CS and HCP particles, the sorbent being able to remove both anionic and cationic dyes. Moreover, the samples could be regenerated and reused keeping their adsorption ability unaltered over successive cycles of adsorption, desorption, and washing. Hydrophobically

oo

f

modified chitosan (HMCS) sponge have been prepared by the Schiff base reaction of the amino groups of chitosan backbone with dodecylaldehyde, in order to enhance the interaction with

pr

hydrophobic adsorbates [188]. HMCS has been dissolved in mild acid solution, the stable foam obtained being freeze-dried to get a wettable sponge characterized by enhanced specific surface

e-

area. The composite sponge demonstrated a high adsorption capacity for MO (168 mg/g). The equilibrium adsorption of MO followed the Langmuir isotherm model, and the kinetic data have

Pr

been well described by PSO kinetic model.

Novel composite sorbents have been prepared by cross-linking CS with di-ammonium tartrate

al

(DAT) and urea/DAT and tested for the removal of CR dye from aqueous phase [188]. Equilibrium

rn

adsorption data have been the best fitted to Sips isotherm model, the maximum dye uptake being 1597 mg CR/g of CS cross-linked with DAT, and 1447 mg/g for CS cross-linked with urea/DAT.

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The adsorption kinetic data have been well described by PSO kinetic model. The sorption process has been spontaneous and endothermic. In another strategy, CS-based hydrogels have been prepared by cross-linking CS with GA adding activated carbon (AC) to the CS solution, with the final aim as the sorbent to be applied for removal of Food Blue 2 (FBL2) and Food Red 17 (FR17) from aqueous binary system [189]. It was demonstrated that the composite containing AC presented higher adsorption capacities, the maximum adsorption values reported being 155.1 and 133.9 mg/g for FBL2 and FR17, respectively. The best eluent has been NaOH 0.01 mol/L, the sorbent being efficient within 5 cycles of reuse [189]. Wang et al. have recently reported the synthesis of a novel eco-friendly porous adsorbent based on CEL and CS, by adjusting the mass ratios between CEL and CS, via sol-gel and freeze-drying technique, to be used for CR removal [190]. As can be seen in Figure 13a and b, it was possible to change the morphology of the aerogel by adjusting the mass ratio between CEL and CS. Figure 13

Journal Pre-proof Batch adsorption studies showed that aerogel exhibited maximum removal efficiency to CR at a CEL:CS ratio of 1:3, and sorbent dose of 2.5 g/l. CR adsorption on the composite aerogel fitted PSO kinetics and Langmuir isotherm. The maximum theoretical adsorption capacity of this composite aerogel for CR has been 381.7 mg/g, at pH 7.0, and 30 o C. The adsorption mechanism included electrostatic and chemical interactions. A novel composite biosorbent has been recently developed by Zheng et al. by blending CS with dialdehyde microfibrillated cellulose (DAMFC) nanofibrils, by solvent-casting, a Schiff base being formed between the aldehyde groups in DAMFC and the amine groups in CS [193]. The DAMFC/CS has shown excellent adsorption of CR. As can be seen in Figure 13c, the driving force

f

for the CR adsorption included the hydrogen bonding and the electrostatic attraction. The

oo

adsorption capacity of CR at equilibrium has been 152.5 mg/g, with a high removal efficiency of 99.95% in 10 min. The adsorption kinetics of CR onto DAMFC/CS composite followed PSO

pr

model, and the adsorption at equilibrium has been well fitted with the Langmuir model.

e-

GO/CS aerogel was prepared by a facile ice-templating technique for metanil yellow dye adsorption [195]. The composite aerogel exhibited large removal efficiencies (91.5–96.4%) over a

Pr

wide pH range (3–8) and a high adsorption capacity of 430.99 mg/g at 8 mg adsorbent dose, 400 mg/L concentration, and 35.19 min contact time. The adsorption equilibrium has been best

al

described by the Langmuir isotherm model. The sorbent could be easily separated and regenerated for reuse in five sorption-desorption cycles with 80% of its initial sorption capacity.

rn

Some of the lately published results obtained at the sorption of various dyes on the porous

Table 3

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composite sorbents based on CS are summarized in Table 3.

As can be seen in Table 3, many recently fabricated porous CS based composite sorbents contain GO nanosheets, which beside the increase of the mechanical strength allows to enlarge the sorption properties of the composites making them able to sorb both anionic and cationic dyes. An example of such composite is presented in Figure 14 and represents multifunctional GO/CS aerogel microspheres (GCAMs) with honeycomb-cobweb and radially oriented microchannel structures fabricated by combining electrospraying with freeze-casting strategies. Figure 14 This composite has been able to adsorb heavy metal ions, cationic dyes such as MB and Rhodamine B, anionic dyes such as MO and Eosin Y, and phenol. The equilibrium of sorption has been attained in only 5 min for Cr6+ (292.8 mg g-1) and MB (584.6 mg g-1), respectively. The adsorption capacity has been preserved for six cycles of adsorption-desorption.

Journal Pre-proof

4.1.3. Other pollutants Beside HMIs and dyes, many other pollutants could be removed by the porous composite sorbents based on CS, from simulated or real wastewaters, such as phosphate [21, 196-198], acetaminophen [199], patulin [200], humic acid [201], bilirubin [202], ciprofloxacin [203], ammonium [204]. Phosphate is an essential nutrient for living organisms, but the excess of phosphate in the municipal wastewaters coming from soaps, detergents, fertilizers, pesticides, and industrial activities causes eutrophication of rivers, water reservoirs and lakes [197, 198]. Recovery of phosphorus (P) from

f

the wastewaters is also strongly necessary, not only for the environment protection but also to

oo

provide a sustainable strategy for the P supply. Therefore, it is strongly required to find efficient

pr

methods and materials for phosphate removal to avoid its tremendous effects on the environment. Thus, Wan et al. have developed a composite sorbent with zirconium loaded into magnetic

e-

CS/PVA IPN hydrogels for the phosphorus recovery [197]. The maximum sorption capacity reached at pH 6.5 has been 50.76 mg P/g sorbent, at 22 o C. Isotherms and thermodynamics studies

Pr

showed that monolayer sorption was dominant, and the sorption process has been spontaneous and exothermic. The generated hydrogel beads have been reused for five cycles, without any loss of the

al

initial sorption capacity. The sorption mechanisms proposed by the authors have been inner-sphere complex and ligand exchange.

rn

In another approach, Kumar and Viswanathan have fabricated a composite sorbent for enhanced

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phosphate remediation by including tetra-amine Cu(II) (TAC) into CS beads [198]. The sorption reached the equilibrium in about 40 min. Langmuir isotherm fitted the best the experimental data. The mechanism proposed by the authors for the phosphate uptake by the TAC/CS biocomposite beads is presented in Figure 15a. Figure 15 Tests for the reusability of the TAC/CS composite beads have been carried out with 0.25 M NaOH as regenerant. A novel double network composite (DNC) cryogel, consisting of CS cross-linked with GA, as the first network, and PEI, with a concentration up to 15% cross-linked with EGDGE, as the second network, has been recently fabricated in our group [21]. As can be seen in Figure 4A, the composite cryogel is endowed with an abundant number of amine groups and has been successfully used in the removal of phosphate ions. The phosphate sorption has been fast (equilibrium in three hours), due to the presence of macropores (Figure 4C), and well modeled by the PSO kinetic model, supporting chemisorption as the main mechanism of sorption. The Langmuir and Sips isotherms

Journal Pre-proof have been the best in modeling the sorption process at equilibrium. The maximum sorption capacity given by the Langmuir isotherm for the DNC having the highest content of GA and the highest concentration of PEI has been about 343.23 mg phosphate/g DNC, which places this novel sorbent among the best sorbents for phosphate removal recently reported in literature. CS beads cross-linked with GA have been first modified with thiourea to get SH groups attached on the CS chain, and then used for the adsorption of patulin from aqueous solution, in batch mode [200]. The adsorption capacity of the CS beads for patulin has been 1.0 mg/g at pH 4.0, 25 o C. Adsorption process has been well described by PFO kinetic model, and Freundlich isotherm model. Removal of humic acid from aqueous solution using PAAm/CS semi-IPN hydrogel has been

f

recently reported [201]. The results have indicated that the semi-IPN hydrogel was successfully

oo

fabricated and could be applied as a biocompatible and biodegradable adsorbent in a wide pH range, from 3 to 9. Low ionic strength effectively enhanced the adsorption capacity. As the ionic

pr

strength increased, this enhancement was less obvious but still positive. The adsorption kinetics have been fitted to a PFO kinetic model, and the adsorption isotherm has been the best described by

e-

the Sips isotherm model. The maximum adsorption capacity has attained 166.30 mg/g, based on the

Pr

Sips isotherm at 25 o C. Experiments demonstrated that the humic acid adsorption process can be primarily attributed to electrostatic interactions, the hydrogen bonding being also involved. Ouyang et al. have used carbon nanotubes (CNTs) as nanofillers to fabricate CS beads with

al

controlled porous structure via dropping the mixed solution into liquid nitrogen, thus obtaining

rn

highly porous composite cryobeads containing radially oriented channels [202]. At 40 wt% CNT, the authors have observed small CNT agglomerates distributed in the CS matrix, while at a content

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of 80 wt% CNT, the nanofiller has been mainly dispersed in the channel walls. The adsorption capacity of bilirubin (a metabolic product of hemoglobin in red blood cells) has increased with the increase of the CNT content up to 43.6 mg/g within 2 h for the composite beads with the highest content in CNTs. Privar et al. have recently reported removal of ciprofloxacin (CIP) from aqueous solutions using metal-chelate sorbents fabricated via chelation of Cu2+, Al3+, and Fe3+ ions by supermacroporous cryogel of N-(2-carboxyethyl)chitosan (CEC) cross-linked with hexamethylene diisocyanate (HMDI) [203]. Modification of CEC cryogel with Cu2+and Al3+ ions improved the CIP recovery up to 98%, in the pH range 7–10, the maximum sorption capacity being 280 and 390 mg/g for Cu2+ and Al3+ -chelated cryogels, respectively. The metal-chelated CEC cryogels have been efficient for CIP removal from solutions with environmentally relevant concentration (50 μg/L), and have been applicable as monolith sorbents under dynamic conditions. The metal concentration in water after CIP recovery met drinking water quality standards, when Cu2+and Al3+ chelated but not for Fe3+-chelated.

Journal Pre-proof Natural zeolites are known for their capacity to adsorb ammonium, but because of their fine sizes (several nm to some m) it is difficult to separate them from the wastewaters and to reuse [204]. A large variety of composites having zeolites as fillers dispersed in natural or synthetic polymers have been lately developed. Among them, CS/zeolite composites have found numerous applications as efficient sorbents for HMIs, dyes and drugs [9, 10, 22, 23, 107-110,112]. A novel composite sorbent based on NaA zeolite and CS as porous beads, highly efficient in the removal of ammonium

ions from water, has been developed by in-situ hydrothermal method, using halloysite

as starting natural zeolite [204]. SEM images have evidenced that the porous composite beads have been composed of 6–8 m sized cubic NaA zeolite particles kept together by chitosan (Figure 15b).

f

A maximum adsorption capacity of 47.62 mg NH4 +/g has been achieved at 25 o C, according to the

oo

Langmuir model. The adsorption capacity of the composite beads still maintained 90% of the initial sorption capacity after 10 adsorption–desorption cycles (Figure 15c).

pr

A facile and environmentally-friendly approach has been developed by Cao et al., who have

e-

recently fabricated reduced GO (rGO)/polydopamine (PDA) composite aerogel reinforced with CS and after that modified with 1H,1H,2H,2H-perfluorodecanethiol (PFDT) [205]. As can be seen in

Pr

Figure 16a, a PDA film has been first anchored on rGO nanosheets via DA self-polymerization. By means of hydrothermal treatment, immersion and freeze-drying process, rGO nanosheets modified by PDA were self-assembled into a 3D porous structure, and the CS/rGO composite aerogel has

al

been thus obtained. Finally, to obtain perfluorinated superhydrophobic PDA/CS/rGO composite

rn

aerogel, PFDT has reacted with PDA film. Before the reaction with PFDT, the composite possesses

Figure 16

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super-amphiphilicity in air and superoleophobicity under water.

The high stability of the perfluorinated composite aerogel under repeated cycles is illustrated by the SEM images in Figure 16b and c, which present the perfluorinated PDA/CS/rGO composite aerogel before and after ten cycles of oil/water separation. A powerful approach has been recently developed by Li et al. for the fabrication of covalent organic framework (COF) loaded with Pd nanoparticles involved in 3D CS aerogels and their application for continuous flow-through aqueous dechlorination of chlorobenzenes (CBs), in water, at

room temperature

triformylphloroglucinol

[206].

COFs have been synthesized

with

diamines,

such

as

by the reaction of 1,3,5-

1,4-phenelynediamine,

2-nitro-1,4-

phenelynediamine, hydrazine, and terephthalohydrazide [206]. Pd NPs embedded in COFs has been prepared by the reduction of Pd2+ with NaBH4 , and the composite COF-CS aerogels have been prepared by mixing crystalline COF powders with acidic CS in water, followed by the addition of 1,4-butanediol diglycidyl ether as cross-linker, when the primary amino group of CS have

Journal Pre-proof interacted with epoxy moiety through amino-epoxy reaction. The composite aerogel monoliths have been stable and could be reused at least five cycles without evident loss of the catalytic activity in dechlorination (Figure 17a). Working with a variety of CBs it was found that the electronic effect of substituents had a dramatic influence on the reaction time but not on dechlorination efficiency. Figure 17 Starting from the imperative need for selective sorption and catalytic conversion of the atmospheric CO 2 to reduce and keep under control the greenhouse effect, new sorbents have been designed last years. In this context, a novel COF-CS composite aerogel has been fabricated by chemical cross-

f

linking between COF decorated with allyl-imidazolium ionic liquid (COF-IL) and thiol-attached

oo

CS via photoinduced thiol-ene reaction [207], which has exhibited a highly CO 2 selective adsorption over N 2 and CH4 under ambient conditions. The high selective CO 2 adsorption and

pr

catalytic conversion activity of the COF-IL have been preserved in the composite aerogel. As can be seen in Figure 17b, the COF-IL/CS aerogel could be readily shaped as the fixed-bed reactor

e-

model via a freeze-drying procedure, and the CO 2 cycloaddition with epoxides in a recycling way

Pr

has been achieved (no diminish of the catalytic activity after five cycles).

al

4.2. Catalysis

CS based materials as efficient heterogeneous catalysts, the main controlling parameters, and their

rn

behavior in various reactions have been described by Guibal in a comprehensive review [208]. This

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subsection of our review will present some examples of porous composites based on CS with performances as photocatalysts in the degradation of highly toxic dyes [209-212] and as catalysts in the reduction reactions [213-215], mainly reported in the last five years. Among many materials with potential as photocatalysts, TiO 2 is a promising one due to its good stability, low cost, and environmental friendliness [216]. However, because of its wide band gap (3.2 eV), it has a low photocatalytic efficiency. Natural polymers such as CS could be an attractive route to fabricate composites presenting a better optical response of TiO2 -based photocatalysts, in a wider range of the solar spectrum [209,210]. Thus, ice templating strategy has been adopted by Chen et al. in the fabrication of novel TiO 2 /CS/rGO composites with a highly aligned macroporous structure for photocatalytic applications [209]. As can be seen in Figure 17c and d, the composite morphology could be easily tailored by the TiO2 content from 45 to 77 vol%, when the lamellar pore width has decreased from 50–45 to 5–10 m, while the wall thickness increased from 2–3 to 20–25 m, the channels between the layers being more uniform distributed when rGO content has been 1.0 wt%.

Journal Pre-proof Pathania et al. have investigated the photocatalytic degradation of MO and CR dyes, two highly toxic azo dyes, from aqueous solution, with CS-g-PAAm/ZnS nanocomposite as photocatalyst, under simulated solar irradiation [211]. The authors have found 75% degradation of CR after 2 h of irradiation, and 69% degradation of MO after 4 h of irradiation. The catalytic performance of novel Cu2+-loaded macroporous ion-imprinted or non-imprinted CSbased composites, namely IICC-Cu2+, and NICC-Cu2+, for degradation of Methyl Orange (MO) in aqueous solutions has been recently reported [73]. The MO degradation by IICC-Cu2+ or NICCCu2+ catalysts has been studied either under ambient light (Figure 18A and B), or in a Fenton-like catalytic system (Figure 23 C, D). The MO solution shows a maximum absorption band at 464 nm,

f

whose intensity drastically decreased and almost disappeared after 360 min of reaction when IICC-

oo

Cu2+ was used as catalyst (Figure 18A), compared to NICC-Cu2+ (Figure 18B) under ambient light. As can be observed from the residual absorbance values (Figure 18C and D), the decolourisation of

pr

MO solutions was remarkably accelerated by the addition of H2 O2 ; thus, the maximum absorption band at 464 nm drastically decreased in time in the presence of both catalysts, and almost

e-

disappeared in the case of IICC-Cu2+ catalyst after 40 min of reaction (Figure 18C).

Pr

Figure 18

A decolorization efficiency of about 95.3% has been achieved within 360 min in the presence of IICC-Cu2+ compared to only 67.4% for NICC-Cu2+ under ambient light. When the IICC-Cu2+

al

catalytic activity has been tested in Fenton-like conditions (addition of H2 O 2 as co-catalyst), the

rn

decolorization efficiency increased up to 98.6% within only 40 min. The reusability results showed only a slight decline in the catalytic performance of IICC-Cu2+ catalysts after each reaction cycle,

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without significant depreciation or deactivation after four runs. In order to obtain the optimum working conditions for these catalytic systems, the effect of several parameters including catalyst dose, initial MO concentration, pH, and initial H2 O2 concentration on the MO degradation has been analyzed in detail [73].

Fabrication of a bionanocomposite based on CS-guar gum blended with silver nanoparticles, with potential in the catalytic degradation of environmental pollutants such as dyes (Reactive blue-21, Reactive red-141, and Rhodamine-6G), and 4-nitrophenol, has been recently reported [213]. By TEM analysis it has been shown that the silver nanoparticles, with an average diameter of about 50 nm, have been uniformly distributed in the CS-guar gum blend. The reduction of 4-nitrophenol to 4-aminophenol has been completed within 3 min and the catalyst has been efficient up to 3 cycles. 3D-macroporous CS-based cryogels with Pd and Pt nanoparticles (NPs) in situ formed in the cryogel walls by the reduction of noble metal complexes with GA used as cross-linker have been fabricated by Berillo and Cundy, in two steps [214]. The CS cryogel with CS chains chelated by the

Journal Pre-proof nobel metal complexes due to the cryoconcentration effect has been prepared first, and, after thawing at room temperature, the contact with GA led to both the cross-linking of CS chains by the formation of Schiff’s base groups, and to the reduction of metal complexes to metal NPs. Thus, the cryogelation of CS with Pd complexes led to 99.66% noble metal binding. The catalytic activity of the in situ generated PdNPs, at 2.6 - 21.0 μg total mass, has been studied utilizing a model system of 4-nitrophenol reduction. The kinetics of the reduction reaction under different conditions have been examined, with no decrease of the catalytic activity being observed over 17 treatment cycles. Supermacroporous Co(II)-chelated CEC monolith cryogels have been used by Bratskaya et al. for the fabrication of Co(II) ferrocyanide -containing composite for selective recovery of cesium ions, 137

Cs of 140,000 ml/g, and the adsorption capacity of ~1

f

with the distribution coefficient for

oo

mmol/g [215]. Composite Pd catalysts supported on CEC cryogel provided tenfold higher reaction rate in 4-nitrophenol reduction compared with Pd-catalyst supported on CS nonporous beads. The

pr

adsorption capacity of CEC cryogels toward transition metal ions decreased with the increase of

e-

cross-linking density and have reached 1.3 mmol/g and 1.0 mmol/g for Cu2+ and Co2+, respectively.

Pr

4.3. Biomedical applications 4.3.1. Hemostasis

al

Fast bleeding control and quick hemostats for non-lethal massive traumatic bleeding in battlefield

rn

and civilian accidents are strongly important for reducing mortality and medical costs. The commercial hemostatic materials hardly meet the requirements for rapid hemostasis, high

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biocompatibility, and easy to use. Current hemostatic devices focus primarily on time to hemostasis, but prevention of bacterial infection is also critical for improving survival rates [217]. Therefore, the interest in novel and highly efficient and biodegradable hemostatic materials, most of them based on CS sponges, became lately extremely important [218-228]. In this context, Lan et al. have fabricated spongy CS composites obtained from silk worm pupae and gelatin, in different proportions, which has been cross-linked with tannic acid and then freeze-dried under vacuum [218]. The best blood-clotting index has been achieved in vitro by a CS/gelatin sponge ratio of 5:5. Furthermore, the gel composite has presented the best hemostatic effect in the rabbit artery bleeding and liver model tests compared to the two components separately due to its ability to absorb blood platelets easily and to the higher liquid adsorption ratio. In addition, subcutaneous transplantation of the composite gel into rabbits resulted in its almost complete degradation after 6 weeks. The fabrication of porous CS microspheres with tunable pore size as a quick hemostat has been performed by microemulsion combined with thermally induced phase separation technique

Journal Pre-proof [220]. Their hemostatic property was characterized by blood clotting kinetics, adherence interaction between red blood cells/platelets and CS microspheres, in vitro and in vivo hemostasis, and histological analysis. To enhance the hemostatic efficiency of CS, Zn2+ALG has been introduced to CS to prepare porous CS/ZnALG microspheres [221]. Such microspheres have been prepared by successive steps of micro-emulsion, polyelectrolyte adhesion, and thermally induced phase separation. In another approach, the hemostatic performance of CS has been greatly improved by blending it with kaolin to fabricate porous composite microspheres through inverse emulsion method combining with thermally induced phase separation, as can be seen in Figure 19A [222]. Figure 19

f

The synergetic hemostatic competence of CS and kaolin contributed in increasing the hemostatic

oo

efficacy of the composite microspheres compared with the porous CS microspheres (CSMS). The CSMS-K shows highly porous internal structure with internal pore diameter of less than 2 μm

pr

(kaolin particles with size of 1–2 μm are indicated by arrows). The SEM images in Figure 19B support the interconnected porous structure of these composite microspheres, both in the inner and

e-

on the outer surface.

incorporating

mesoporous

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In a novel approach, Sun et al. have recently reported the fabrication of porous quick hemostats by silica

nanoparticles

into

CS

through

a

combination

of

the

microemulsion, thermally induced phase separation, and surfactant templating method [223]. As

al

can be seen in Figure 19 (a-f), a large number of mesoporous silica nanoparticles have been

rn

incorporated onto and within the composite microspheres. The synergetic two hemostatic mechanisms from CS and mesoporous silica nanoparticles let CSMS-S composite with proper

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amount of silica to display better hemostatic potential than the porous CSMS without silica. Wang et al. have developed CS/DA/diatom-biosilica composite beads with good biocompatibility, by the alkalization precipitation method, for rapid hemostasis [224]. The diameter of composite beads was about 15 mm, which could avoid the potential risk of vascular embolism due to the diffusion of small particles into normal vessels with the bloodstream. The porous structure of the beads led to rapid absorption of large amount of water, which contributed to the rapid aggregation and adsorption

of blood

biocompatibility

and

cells.

In addition,

non-cytotoxicity.

A

the composite beads have demonstrated biodegradable

collagen

sponge

reinforced

good with

CS/calcium pyrophosphate nanoflowers, endowed with performances, such as rapid water absorption ability, the positive surface rich in amino groups, and high specific surface area (952.5 m2 /g), has been developed for rapid hemostasis [225]. The composite sponge with optimized composition could activate the coagulation cascade, induce haemocytes and platelets adherence, promote the blood clotting and achieve hemorrhage control in vitro and in vivo.

Journal Pre-proof Composite sponges based on N-alkylated CS are promising candidates for very efficient hemostats, both in vitro and in vivo [226, 227]. Thus, a rapid and safe hemostatic sponge has been developed by mixing mesoporous silica nanoparticles (MSNs) with a glycerol-modified N-alkylated CS sponge (GACS) [226]. It was demonstrated that MSN–GACS exhibited unique hemostatic potency in vitro coagulation tests. In addition, MSN–GACS exhibited better biocompatibility than Combat Gauze (CG), which is popular in the US military. Furthermore, in rabbit femoral artery and liver injury in vivo models, MSN–GACS showed better hemostatic efficiency and lower cardiovascular toxicity than CG. In conclusion, MSN–GACS is an excellent prehospital hemostatic agent for firstaid applications. Zhang et al. have reported the preparation of novel safe and efficient hemostatic

f

dressing composite sponges using N-alkylated CS (AC) and GO (ACGS) with different ratios

composite sponges have exhibited

oo

between GO and AC, by a dilute solution freeze phase separation and drying process [227]. The excellent absorption capacity, mechanical stability, and

pr

biocompatibility. In vitro clotting tests have showed that increasing the GO content led to better coagulation efficiency. Moreover, the sponge containing 20% GO has accelerated erythrocyte and

antibacterial conductive

nanocomposite cryogels

based

on CNTs and

glycidyl

Pr

Injectable

e-

platelet adhesion, and promoted the release of intracellular Ca2+.

methacrylate functionalized quaternized CS for lethal noncompressible hemorrhage hemostasis, with rapid blood-triggered shape recovery and absorption speed have been fabricated by Zhao et al.

al

[228]. Cryogel containing 4 mg/mL CNT has demonstrated better hemostatic capability than gauze

rn

and GEL hemostatic sponge in vivo (mouse-liver injury model, mouse-tail amputation model, and

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rabbit liver defect lethal), and better wound healing performance than a commercial film.

4.3.2. Reservoirs for loading/release of bioactive molecules (drugs, enzymes) Owing to its intrinsic outstanding biocompatibility and antibacterial properties, CS is involved in a large platform of nano/micro/macro-hydrogel 3D networks for targetable drug delivery systems (DDSs) [4,20,229-247]. However, only the most recently published results will be discussed in this section. Because of the poor mechanical strength and high swelling ratio of the CS constructed DDSs, these systems lead to burst release of drugs by breaking down the network. To overcome this issue, the entrapment of aluminosilicates [13,231,232], HAP [233,234], or silica [235] into their structure with the formation of biocomposite hydrogels provided DDSs with improved delivery kinetics. 3D macroporous biocomposites based on CS and CPL have been prepared in our group by the cryogelation technique and their potential as drug carriers has been investigated [13]. It was found that the CPL content had a strong influence on the water uptake, as well as on the cumulative release of diclofenac sodium (DS) and indomethacin (IDM). It was demonstrated that

Journal Pre-proof the drug delivery preferentially takes place in phosphate buffer saline (pH 7.4) in comparison to simulated gastric fluid (pH 1.2). The drug release mechanism of DS has followed a pseudo-Fickian diffusion, but changed to non-Fickian release at a content of 33 wt.% CPL or when IDM has been loaded drug. These results suggest that the CS/CPL composite cryogels could be promising alternatives for the intestinal delivery of hydrophobic drugs. MMT was added in the preparation of novel composites based on oleic acid-g-chitosan for delivery a Ca2+channel blocker (diltiazem hydrochloride), by solvent casting and freeze drying of the polymer solution [231]. The drug released from the composite was 13% within 3 h in simulated gastric fluid (SGF) (pH 1.2), and in simulated intestinal fluid (SIF) (pH 7.4) has reached about 80%

f

of the loaded drug content, within 12 h. Semi-IPN nanocomposites composed of CS and acrylic

oo

acid (AA), acrylamide (AAm), and poly(vinylpyrolidone) (PVP) have been prepared by Panahi et al. by using MMT to increase the mechanical strength of the composite hydrogel and used it in the

pr

delivery of clarithromycin (CAM) [232]. In vitro drug release patterns showed that the composite containing MMT presented a sustained release of drug over an extended period of time compared

e-

with CS-g-poly(AA-co-AAm)/PVP/CAM formulation. The reason is that interconnected porous

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channels within superabsorbent nanocomposite network hinder penetration of aqueous solutions into hydrogel and subsequently cause a slower drug release. The time to achieve 50% release of drug in CS-g-poly(AA-co-AAm)/PVP/CAM formulation was about 6 h, while in the case of the

al

composite with MMT, 10 h were necessary to release 50% of drug. That is also because the drug

rn

molecules attached onto MMT layers by hydrogen-bonding interactions may release more slowly. A novel hybrid has been recently reported by Salama [233] who have used the CS-g-poly(3-

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sulfopropyl methacrylate) hydrogel as a template for biomimetic sponge like HAP mineralization. BSA has been loaded in the hybrid hydrogel and the release profile of protein suggested that the hybrid behaved as a controlled release vehicle of BSA. To increase the solubility and oral bioavailability of poorly soluble drugs, Zhang et al. have designed a novel 3D macroporous HAP/CS foam-polymer micelle supported composite [234]. Candesartan cilexetil has been selected as a poorly soluble model drug. HAP/CS foam has been synthesized first by a wet chemical coprecipitation technique using PMMA as a macropore template. After that, the drug-loaded polymer micelles have been encapsulated into the macropores of the HAP/CS foam and freezedried to produce drug-loaded composites. It was reported that the aqueous dissolution rate of the drug in the drug composite formulation significantly increased compared with the pure drug, in both simulated gastric and intestinal conditions. Zhao et al. have developed a dual-stimuli responsive composite film from CS hydrogel with embedded mesoporous silica nanoparticles (MSNs) of 2 mm thickness deposited on a titanium electrode and evaluated as a DDS for ibuprofen

Journal Pre-proof (IBU) as a model drug [235]. The IBU release has been studied as a function of pH and electrical conditions applied to the titanium plate, and found the IBU release rate followed a near zero-order profile. The release has been retarded when −1.0 V was applied, but at −5.0 V a faster kinetics has been observed. Composite sponge with different CMC/CS ratios and under different pH conditions were synthesized via a freeze-drying method and investigated by Cai et al. for in vitro drug release behavior and antibacterial property by using gentamicin, as a hydrophilic model drug, and two hydrophobic drugs, IBU and roxithromycin [43]. The results showed that the CMC/CS ratio and the pH influenced not only the sponge morphology, but also the degradation behavior, drug-loading capacity, and the antibacterial activity. The bacteriostatic experiment showed a strong antimicrobial

f

ability of sponges loaded with gentamicin on inhibiting E. coli. An antibacterial and biodegradable

oo

composite hydrogel, fabricated by the Schiff-base reaction between aldehyde and amino groups of oxidized ALG and CMCS, loaded with tetracycline hydrochloride and integrated within gelatin

pr

microspheres, has been developed for drug delivery and wound healing [237]. Furthermore, powerful bacteria growth inhibition effects against E. coli and S. aureus suggested that the

e-

composite gel dressing had a promising future in the treatment of bacterial infection.

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Farias and Boateng have developed composite freeze dried wafers for potential oral and buccal delivery of low dose aspirin to prevent thrombosis in elderly patients with dysphagia [238]. Wafers without drug have been formulated either from metolose (MET) and carrageenan (CAR), or with

al

MET and low molecular weight CS, in different weight ratios. SEM images confirmed the presence

rn

of pores within the initial wafers, while aspirin loaded wafers showed a more compact matrix with aspirin dispersed over the surface. Drug dissolution studies showed that aspirin was rapidly

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released in the first 20 min and then continuously over 1 h. Some lyophilized wafers seem to be promising systems for the administration of low dose aspirin for older patients with dysphagia. Perinelli et

al.

have

investigated

various

HPMC/CS

composite

hydrogels,

loaded

with

metronidazole (as an antimicrobial drug), regarding their antimicrobial efficacy against the pathogenic fungus Candida albicans and found that hydrogels containing 1% w/w CS, either as free polymer chain or assembled in nanoparticles, showed an improved mucoadhesiveness and an antiCandida effect after vaginal administration [241]. Partially deacetylated chitin nanowhiskers (CNW) have been used as a filler to design ALG composite hydrogels, by the polyelectrolyte complexation between alginic acid and the amine groups on the surface of CNW, for controlled delivery of tetracycline [242]. A honeycomb morphology was found for the freeze-dried gels. Inclusion of CNW prolonged the release of tetracycline owing to the changes in drug diffusion, making these composite hydrogels of interest for intestinal drug delivery. Novel smart composite hydrogels as semi-IPN hydrogels based on CS,

Journal Pre-proof DMAEMA and HEMA and the nanocomposites with silver (Ag NCs) and amoxicillin (AMX) have been formulated by Sivagangi Reddy et al. and evaluated for the release of AMX and silver nanoparticles [243]. It was observed that the drug release rate of AMX has been greater in SGF than in SIF, due to enhanced swelling of the gel in SGF, but lower from the gels containing both AMX and Ag (0) compared with the previous. Increasing the concentration of HEMA enhanced the drug release rate in SIF due to enhanced polymer-biofluid interaction, while the increase in the CS feed ratio, decreased the drug release rate due to rigidity of the network and less amount of pores to escape from the network. Antimicrobial and DNA cleavage studies revealed that the hydrogels with AMX-Ag (0) NCs have better ability to cleave DNA than pure AMX and nanosilver that means it

f

shows synergetic effect [243]. Lately, CS-based thermosensitive composite hydrogels have

oo

received considerable attention for local drug delivery [244, 245]. Thus, microspheres composed of tenofovi/Bletilla striata polysaccharide/CS have been loaded into a thermoresponsive hydrogel

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consisting of CS/ALG and ??,-glycerophosphate to form a double-component formulation for vaginal delivery systems [244]. Hydrogels based on CS/HA/β-glycerophosphate loaded with

e-

doxorubicin have demonstrated body temperature sensitivity, pH sensitive drug release, and

Pr

adhesion to cancer cells [245]. The mechanical strength, the gelation temperature, and the drug release behavior have been monitored by HA content.

The CS based porous composite hydrogels have been used as carriers not only for the small drugs

al

but also for macromolecular drugs, such as proteins [20,88,233,239]. Macroporous IPN composite

rn

hydrogels composed of MAA and either AAm or HEMA, cross-linked with BAAm, as the 1st network, and CS cross-linked with PEGDGE, as the second network have been developed in our

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group [20]. A strong difference during the loading and release of lysozyme (LYS) from either single network hydrogel and IPN composites hydrogel has been observed. Thus, while the amount of LYS loaded on SNCs was higher than that loaded on the IPNs, the release of LYS from SNCs occurred at pH 2, when the ratio between MAA and AAm was 50:50, and only at pH 1 when the ratio between MAA and AAm was 70:30. The 2nd network led to the decrease of the pore size of the IPNs, but the presence of CS facilitates the LYS release from IPNs, mainly at a concentration of monomer of 5 wt/v%, and when HEMA was used as nonionic comonomer. Highly porous and biocompatible PVA hydrogels containing partially deacetylated α-chitin nanowhiskers have been fabricated by chemical cross-linking with GA, and physically cross-linked by repeating freeze-thawing cycles, and tested as carrier for BSA used as model drug [88]. The presence of nanowhiskers increased the mechanical property of the hydrogels. The composite hydrogel containing 40% CNW has achieved the highest equilibrium swelling ratio, and could release more than 80% of the BSA, within 75 h. Composite gel beads have been prepared from

Journal Pre-proof ALG and CMCS by dual ionic gelation: (i) ionic gelation between SA and Ca2+, and (ii) CMCS with β-glycerophosphate [240]. The composite beads have been investigated in the delivery of BSA, and found that BSA has slowly released at pH 1.2, the release ratio being about 10 %, while at pH 7.4, the total release time has been extended up to 11 h, the largest cumulative release being 97 %. 4.3.3. Wound healing As the outermost layer, the skin, the largest organ of the human body, has a critical protective role as barrier against the environment, it helps to prevent infection, water loss, and electrolyte imbalance, and regulates body temperature [46,248]. Therefore, when the skin is damaged, its

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integrity has to be quickly restored and homeostasis should be re-established [46,248-251]. In recent years, wound dressing strategies have received a great deal of attention. The ideal wound

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dressing material should fulfill the following requirements: good biocompatibility, antibacterial activity, water absorbency, water retention, non-cytotoxicity, and biodegradability [46]. Through

e-

interacting with the wound where they cover, functional active dressings create and maintain a moist environment for wound healing [250]. Figure 20 summarizes the function of CS-based

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hydrogels in the complex process of wound healing [250]. Figure 20

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Maintaining a moist environment around a wound can accelerate recovery and decrease the risk of systemic infection. This can be achieved with wound dressings that have antibacterial and swelling

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properties and can inhibit bacterial growth and absorb exudate from the wound [251]. Finding

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novel biomaterials-based active wound dressings with enhanced properties for wound healing is nowadays a major task. As the main component of commercial dressings, CS sponge is an effective hemostatic

dressing

with

interconnected

porous

structures,

high

swelling

capacity,

good

antibacterial activity and quick hemostatic ability [249]. However, the poor hydrophilicity of sponges could not maintain the wound moist and cause secondary damage when applied and removed as a wound healing dressing. Up to now, there is almost no clinically used wound dressing satisfying with all the requirements of the ideal skin wound dressing. Composite sponges based on CS are lately among the most investigated wound dressing materials [46, 239, 248-268]. The modern wound dressings should keep the wound moist by absorbing excess from the wound or maintaining water. The sponges that contain sufficient amount of water provide a moist environment and protect wound from bacterial infection [255]. Composite sponges having in situ generated AgNPs have demonstrated high antibacterial effect and abilities to act as efficient wound dressings as an escape at the antibiotic resistance [46, 251, 264]. Green reducing agents such as gelatin [46], and polysaccharides [251, 264] have been used to prepare AgNPs instead of usual and

Journal Pre-proof toxic methods. Thus, Ye et al. have recently designed a novel composite hydrogel by using first gelatin as a reducing agent and stabilizer to generate AgNPs in situ, which has been mixed with CS, cross-linked with tannic acid, and then freeze-dried to obtain a new composite Gelatin/ CS/Ag [46]. The summary of their strategy is presented in Figure 2B. SEM images in Figure 2B show that materials had a porous structure and interconnected pores. GEL/CS/AgNP composites displayed better mechanical properties than those of GEL/CS and good water absorption and water retention, enabling the wound surface to be maintained in a humid environment for a long duration. More importantly, the material had a significant antibacterial effect, which enables the wound to remain in a clean, sterile environment without infection. The antibacterial capacity increased as the

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concentration of AgNPs increased. Spongy composites with AgNPs have been synthesized by

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freeze-drying a mixture of AgNO 3 and CS-L-glutamic acid derivative loaded with HA solution. The spongy composites had an interconnected porous morphology [251]. HA, used as a cross-

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linking agent for CS, plays an important role in human skin as a key component of the skin extracellular matrix, and has many beneficial properties such as hydrophilicity, biodegradability,

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and a unique viscoelastic nature. The spongy composites exhibited good mechanical properties,

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swelling, and water retention capacity. In vitro antibacterial activity has showed that the sponges have been effective in inhibition the growth and penetration of E. coli and S. aureus. The CS-Lglutamic acid/HA/AgNPs spongy composites promoted wound healing, as determined by in vivo

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tests, wound contraction ratio, and average healing time. Hu et al. have fabricated a hydrophilic

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composite sponge via the physical incorporation of CS into hydroxybutyl-CS, through vacuum freeze-drying technique [249]. Cytotoxicity tests revealed enhanced cell viability and proliferation,

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and growth of fibroblasts. It was also proved that the best composite sponge had a better ability to promote wound healing and helped for faster formation of skin glands and re-epithelialization than the separate sponges of reference.

Including other metal NPs such as Cu NPs [260, 266], and metal oxides NPs such ZnO NPs [258260] into biopolymers to fabricate novel wound dressings open up new windows for research in the improving the healing properties of these composite materials. The synthesis of metal oxides in the presence of CS not only increases the antibacterial activity of CS, but also constitutes a great potential to tune the structure and the morphology of metal oxides which is called biomineralization [259]. Among the metal oxide nanoparticles, ZnO-NPs exhibit some significant properties such as wide band gap (3.37 eV), UV absorption, photocatalytic activity, non-toxicity, antimicrobial activity, and potential to form different morphologies. PVA/CS/ZnO nanocomposite hydrogels have been prepared using the F-T method, the process parameters being optimized by employing response surface methodology [258]. Increasing the number of freeze-thaw cycles

Journal Pre-proof caused the decrease of pore size, the increase of porosity and wound fluid absorption, as well as the increase of elastic modulus and tensile strength. Antibacterial properties, biocompatibility, and invitro wound healing tests demonstrated the capacity of the composite system to treat wounds [258]. Zabihi et al. have prepared a CS/ZnO nano-hybrid by the use of ultrasound irradiation in the presence of a tri sodium citrate as nontoxic complexing agent [259]. The nano-hybrid has showed higher antibacterial activity, cell viability and UV absorption compared with ZnO-NPs. Multifunctional composite wound dressing materials which should respond to requirements such as conductivity, antioxidant ability and antibacterial property are lately investigated. In this context, Qu et al. have prepared conductive injectable hydrogels by mixing CEC and oxidized HA-g-aniline

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tetramer under physiological conditions, their synthesis strategy being presented in Figure 21a and b [254].

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Figure 21

The composite hydrogel exhibited stable rheological properties, high swelling ratio, suitable time,

electroactive

properties,

free

radical

scavenging

capacity,

and

in

vitro

e-

gelation

biodegradability. Comparative with the commercial wound dressing material, the OHA-AT/CEC

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composite hydrogels have showed faster wound healing rate with fewer inflammatory infiltration, higher density of fibroblasts and collagen deposition, and thicker granulation tissue thickness [254].

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Other composite sponges lately reported, having CS as the main component, are composed of: CS and carboxymethyl kognac glucomannan cross-linked by EDC/NHS strategy [(1-ethyl-3-(3(EDC),

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dimethylaminopropyl)-carbodiimide

N-hydroxysuccinimide

(NHS)]

[255],

bacterial

[267].

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CEL/CS semi-IPN hydrogels [261], CS and GEL loaded with tannins and platelet-rich plasma

Biocompatible tannic acid/CS

in citric acid/pullulan composite nanofibers, with synergistic

antibacterial activity against the Gram-negative bacteria E. coli, have been successfully developed [256]. The ternary nanofibrous membranes have been thermally cross-linked by the formation of amide bonds between CS and citric acid, to become water stable for potential applications as wound dressing. The novel composite membrane has supported the attachment and growth of fibroblast cells by the 3D environment, which mimics the extracellular matrix (ECM) in skin. Polyelectrolyte complexes formed between CS and other natural polymers have been used as effective wound healing materials [239, 252, 253]. Thus, in situ injectable hydrogels have been developed by mixing CMCS and ALG solutions [252]. The authors have added CS oligosaccharide into the polymer mixture to obtain stronger hydrogels and better biological activities. The injectable hydrogels have accelerated the wound healing process in a mouse skin defect model, and have

Journal Pre-proof showed an increase of the thickness and integrity of epidermal tissue, and of the formation of collagen fibers. Novel cytocompatible CS-based DN and triple-network (TN) hydrogels have been fabricated by physically-chemically crosslinking methods [262]. The second network has been constructed from the

zwitterionic

monomer

3-dimethyl-(methacryloyloxyethyl)

ammonium

propane

sulfonate

(DMAPS) owing to its good biocompatibility, antimicrobial and antifouling properties. The nonionic poly(2-hydroxyethyl acrylate) (PHEA) has been the third network due to its good biocompatibility, excellent antifouling and mechanical properties. The cross-section SEM images in Figure 21 show that both CS/PHEA (DN1, the molar ratio of GA to CS has been 0.2/3.0, Figure

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21C ), and CS/PDMAPS/PHEA (TN1, with the same molar ratio GA to CS, Figure 21D) hydrogels

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display a smooth and uniform porous morphology with pore sizes in the range 20∼100 μm. Besides the excellent mechanical properties, DN1 and TN1 gels exhibited good antimicrobial,

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cytocompatible and antifouling properties due to the presence of CS, PDMAPS and PHEA,

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4. Conclusions and perspectives

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properties which recommend them for biomedical applications in wound dressing [262].

To summarize, various porous CS-based composites with tailored morphologies and enhanced

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mechanical properties have been lately fabricated by freezing strategies (cryogelation – chemical cryogels, freezing-thawing – physical cryogels, freeze-drying – lyophilization), porogen leaching

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and gas foaming strategies. The porosity, the thickness of pore walls, and the pore sizes have been

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mainly affected by the initial monomer or polymer concentration, cross-linking degree, the molecular weight of CS, freezing and thawing temperature, the number of F-T cycles, the crystallization speed, and freeze-drying pressure. By combining the freezing strategies i.e. cryogelation or freeze-drying with porogen leaching or gas foaming technique, novel CS-based hydrogel scaffolds with two generation of pores have been designed. A huge attention has been lately given. on the macroporous CS-based composite biosorbents reinforced with inorganic materials including silica, zeolites (CPL, REC, metal oxides), clays (MMT, bentonite), natural or synthetic polymers (by IPN approach), endowed not only with enhanced mechanical properties, but also with high capacity of sorption for various pollutants (HMIs, anionic and cationic dyes, phosphate, ammonium, chlorobenzenes) and high reusability. Ion imprinting strategy has been used to design CS-based composite sorbents with high selectivity for certain HMIs. Among HMIs involved in the sorption processes using CS-based composite as sorbents, Cu2+, Co2+, Ni2+, Pb2+, Hg2+, Cd2+, Cr6+, As3+, As5+, precious metals (Pd2+, Pt4+), rare earth

Journal Pre-proof elements (Nd3+, Er3+) are the most investigated. The mechanism of sorption has been discussed as a function of the sorbent functionalities and parameters of the sorption environment. The biosorption process is of great interest not only for the wastewaters remediation but also for the potential of CSbased sorbents loaded with metal ions to be used as novel advanced materials for various applications such as: new sorbents, supported catalysts, and biosensors. Porous composites based on CS have been successfully used as photocatalysts in the degradation of highly toxic dyes as well as catalysts in the reduction reactions. The decolorization efficiency has been further increased when Cu2+-loaded macroporous ion-imprinted CS-based composites have been used as photocatalysts. It was demonstrated that porosity was very important in the catalytis

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reduction reaction. Thus, composite Pd catalysts supported on N-(2-carboxyethyl) CS cryogel has provided tenfold higher reaction rate in 4-nitrophenol reduction compared with Pd-catalyst

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supported on CS nonporous beads.

CS-based composite sponges, with enhanced hemostatic efficiency, having metal ions (Zn2+),

e-

kaolin, mesoporous silica, GO or CNTs incorporated have been lately investigated. CS is involved

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in a large platform of nano/micro/macro-hydrogel 3D networks for targetable DDSs, but because of the poor mechanical strength and high swelling ratio of the CS constructed DDSs, these systems lead to burst release of drugs by breaking down the network. By the entrapment of aluminosilicates,

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HAP, or silica with the formation of biocomposite hydrogels, the drug delivery kinetics have been

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dramatically improved. The modern wound dressings should keep the wound moist by absorbing water in excess from the wound. The sponges that contain sufficient amount of water provide a

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moist environment and protect wound from bacterial infection. Composite sponges having in situ generated Ag NPs have demonstrated high antibacterial effect and abilities to act as efficient wound dressings as an escape at the antibiotic resistance. Novel composite hydrogel has been designed by using first gelatin as a reducing agent and stabilizer to generate Ag NPs in situ, which has been then mixed with CS, cross-linked with tannic acid, and then freeze-dried to obtain a porous composite Gelatin/CS/Ag NPs. Including other metal NPs such as Cu NPs, and metal oxides NPs such ZnO NPs into biopolymers to fabricate novel wound dressings open up new windows for future research in the improving the healing properties of the CS-based composite materials. The synthesis of metal oxides in the presence of CS not only increases the antibacterial activity of CS, but also constitutes a great potential to tune the structure and the morphology of metal oxides which is called biomineralization.

Journal Pre-proof The applications of the CS-based porous biosorbents in the future will be further strengthened by the extending of the incorporation of inorganic nanofillers such as graphene oxide and reduced graphene oxides as well as carbon nanotubes, which will enlarge the sorption capacities and the selectivity in the separation of the multitude of pollutants. Incorporation of various covalent organic frameworks, as a special category of porous organic crystalline materials endowed with attractive physical and chemical properties, such as gas separating, catalysis, sensing, and heavy metal adsorption, in cross-linked CS aerogels, will gain considerable attention in the future due to the unique properties of the composites as highly reusable sorbents in difficult separation processes such as selective sorption and catalytic

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conversion of atmospheric CO 2 , and dechlorination of chlorobenzenes (CBs), in water, at room temperature.

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Conflict of interest

We declare that there is no conflict of interest concerning the manuscript "Advances in porous

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chitosan-based composite hydrogels: Synthesis and applications", by Ecaterina Stela Dragan and

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Maria Valentina Dinu, referenced by REACT_2019_757.

References

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Acknowledgements: This work was supported by a grant of Romanian Ministry of Research and Innovation (CCCDIUEFISCDI) PN-III-P1-1.1-TE-2016-1697 project [TE117/10.10.2018], and the European Social Fund for Regional Development, Competitiveness Operational Programme Axis 1 – Project “Petru Poni Institute of Macromolecular Chemistry-Interdisciplinary Pol for Smart Specialization through Research and Innovation and Technology Transfer in Bio(nano)polymeric Materials and (Eco)Technology”, InoMatPol (ID P_36_570, Contract 142/10.10.2016, cod MySMIS: 107464).

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hydrogels based on chitosan and hyaluronic acid for pH sensitive drug release, Carbohydr. Polym.

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[246] A.M. Craciun, L.M. Tartau, M. Pinteala, L. Marin, Nitrosalicyl- imine-chitosan hydrogels

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based drug delivery systems for long term sustained release in local therapy, J. Colloid Interface Sci. 536 (2019) 196-207.

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chitosan based hydrogels for potential application in local tumor therapy, Carbohydr. Polym. 179 (2018) 59-70.

[248] X. Chen, M. Zhang, X. Wang, Y. Chen, Y. Yan, L. Zhang, L. Zhang, Peptide-modified

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chitosan hydrogels promote skin wound healing by enhancing wound angiogenesis and inhibiting

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inflammation, Am. J. Transl. Res. 9 (2017) 2352-2362.

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[249] S. Hu, S. Bi, D. Yan, Z. Zhou, G. Sun, X. Cheng, X. Chen, Preparation of composite hydroxybutyl chitosan sponge and its role in promoting wound healing, Carbohydr. Polym. 184 (2018) 154-163.

[250] H. Liu, C. Wang, C. Li, Y. Qin, Z. Wang, F. Yang, Z. Li, J. Wang, A functional chitosanbased hydrogel as a wound dressing and drug delivery system in the treatment of wound healing, RSC Advances 8 (2018) 7533-7549. [251] B. Lu, F. Lu, Y. Zou, J. Liu, B. Rong, Z. Li, F. Dai, D. Wu, G. Lan, In situ reduction of silver nanoparticles by chitosan-L-glutamic acid/hyaluronic acid: Enhancing antimicrobial and woundhealing activity, Carbohydr. Polym. 173 (2017) 556-565. [252] X. Lv, Y. Liu, S. Song, C. Tong, X. Shi, Y. Zhao, J. Zhang, M. Hou, Influence of chitosan oligosaccharide on the gelling and wound healing properties of injectable hydrogels based on carboxymethyl chitosan/alginate polyelectrolyte complexes, Carbohydr. Polym. 2015 (2019) 312321.

Journal Pre-proof [253] M. Ishihara, S. Kishimoto, S. Nakamura, Y. Sato, H. Hattori, Polyelectrolyte complexes of natural polymers and their biomedical applications, Polymers, 11 (2019) 672. [254] J. Qu, X. Zhao, Y. Liang, Y. Xu, P.X. Ma, B. Guo, Degradable conductive injectable hydrogels as novel antibacterial, antioxidant wound dressings for wound healing, Chem. Eng. J. 362 (2019) 548-560. [255] Y. Xie, Z. Yi, J. Wang, T. Hou, Q. Jiang, Carboxymethyl konjac glucomannan - crosslinked chitosan sponges for wound dressing, Int. J. Biolog. Macromol. 112 (2018) 1225-1233. [256] F. Xu, B. Weng, R. Gilkerson, L.A. Materon, K. Lozano, Development of tannic acid/chitosan/pullulan composite nanofibers from aqueous solution for potential applications as

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wound dressing, Carbohydr. Polym. 115 (2015) 16-24.

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[257] Y. Zhou, H. Li, J. Liu, Y. Xu, Y. Wang, H. Ren, X. Li, Acetate chitosan with CaCO 3 doping form tough hydrogel for hemostasis and wound healing, Polym. Adv. Technol. 30 (2019) 143-152.

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[258] M.T. Khorasani, A. Joorabloo, H. Adeli, Z. Mansoori-Moghadam, A. Moghaddam, Design and optimization of process parameters of polyvinyl (alcohol)/chitosan/nano zinc oxide hydrogels

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as wound healing materials, Carbohydr. Polym. 207 (2019) 542-554.

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[259] E. Zabihi, A. Babaei, D. Shahrampour, Z. Arab-Bafrani, K.S. Mirshahidi, H.J. Majidi, Facile and rapid in-situ synthesis of chitosan-ZnO nano-hybrids applicable in medical purposes; a novel combination of biomineralization, ultrasound, and bio-safe morphology-conducting agent, Int. J.

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[260] T. Jayaramudu, K. Varaprasad, R.D. Pyarasani, K.K. Reddy, K.D. Kumar, A. AkbariFakhrabadi, R.V. Mangalaraja, J. Amalraj, Chitosan capped copper oxide/copper nanoparticles

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encapsulated microbial resistant nanocomposite films, Int. J. Biolog. Macromol. 128 (2019) 499-

[261] F. Wahid, X.H. Hu, L.Q. Chu, S.R. Jia, Y.Y. Xie, C. Zhong, Development of bacterial cellulose/chitosan

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semi-interpenetrating

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antibacterial properties, Int. J. Biolog. Macromol. 122 (2019) 380-387. [262] W. Zou, Y. Chen, X. Zhang, J. Li, L. Sun, Z. Gui, B. Du, S. Chen, Cytocompatible chitosan based multi-network hydrogels with antimicrobial, cell anti-adhesive and mechanical properties, Carbohydr. Polym. 202 (2018) 246-257. [263] A. Oryan, S. Sahvieh, Effectiveness of chitosan scaffold in skin, bone and cartilage healing, Int. J. Biolog. Macromol. 104 (2017) 1003-1011. [264] L. Ran, Y. Zou, J. Cheng, F. Lu, Silver nanoparticles in situ synthesized by polysaccharides from Sanghuangporus sanghuang and composites with chitosan to prepare scaffolds for the regeneration of infected full-thickness skin defects, Int. J. Biolog. Macromol. 125 (2019) 392-403.

Journal Pre-proof [265] F. Han, Y. Dong, Z. Su, R. Yin, A. Song, S. Li, Preparation, characteristics and assessment of a novel gelatin–chitosan sponge scaffold as skin tissue engineering material, Int. J. Pharm.476 (2014) 124-133. [266] S. Kumari, B.N. Singh, P. Srivastava, Effect of copper nanoparticles on physico-chemical properties of chitosan and gelatin-based scaffold developed for skin tissue engineering application, Biotech 9 (2019) 102. [267] B. Lu, T. Wang, Z. Li, F. Dai, L. Lv, F. Tang, K. Yu, J. Liu, G. Lan, Healing of skin wounds with a chitosan–gelatin sponge loaded with tannins and platelet-rich plasma, 82 (2016) 884-891. [268] A. Tchobanian, H.V. Oosterwyck, P. Fardim, Polysaccharides for tissue engineering: Current

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landscape and future prospects, Carbohydr. Polym. 205 (2019) 601-625.

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Figure Captions

Figure 1. Preparation steps of CS-based cryogels with tailored porous morphologies. SEM images

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for (A) cryogels with heterogeneous morphology (Reproduced with permission [13] Copyright

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2016, Elsevier), (B) cryogels with unidirectional oriented porous channels (Reproduced with permission [32] Copyright 2017, Elsevier (a); Reproduced with permission [22] Copyright 2018, Elsevier (b)), and (C) cryogels with two generation of pores (Reproduced with permission [24]

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(b)).

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Copyright 2018, Taylor and Francis (a); Reproduced with permission [27] Copyright 2013, Elsevier

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Figure 2. Preparation of porous CS-based composites by freeze-drying technique. (A) porous PAAm/CS composite hydrogels (Reproduced with permission [18] Copyright 2012, Elsevier), (B) porous GEL/CS/Ag composite hydrogels (Reproduced with permission [46] Copyright 2019, Elsevier).

Figure 3. (a) Optical images of CS-g-AA hydrogel and GO/CS-g-AA composite hydrogels containing different amounts of GO. (b) Microstructure changes of CS-g-AA hydrogel and GO/CSg-AA composite hydrogels from the swollen state to the dried state. (c) Possible microstructures of GO/CS-g-AA composite hydrogels with relatively low and high GO loadings (Reproduced with permission [60] Copyright 2016, Elsevier). Figure 4. Schematic representation of the DNC formation (A). SEM images of SNC (B) and DNC (C). (the insets of Figs. 3B and 3C represent the optical images of the cross-sectioned SNC and DNC in dried state). (Reproduced with permission [21] Copyright 2019, Elsevier).

Journal Pre-proof Figure 5. (A) Schematic representation for preparation of II-CCs. (B) Removal of template (Cu2+ ions) and partial hydrolysis of CONH2 groups from PAAm. (Reproduced with permission [22] Copyright 2018, Elsevier). Figure 6. (A) Optical images of II-CC15.H and NI-CC15.H swollen at various pH values (Reproduced with permission [22] Copyright 2018, Elsevier). (B) Swelling kinetics and water contact angles of 1.5 wt.% CEL and HECS/CEL scaffolds (Reproduced with permission [41] Copyright 2017, Elsevier). (C) Swelling kinetics of CS/Agrs scaffolds in PBS at 37 °C (Reproduced with permission [87] Copyright 2019, Elsevier).

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Figure 7. Typical compressive curves of PVA/CS hydrogels (a)(b). The pictures of PVA/CS (30%

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CS, 1% GA) hydrogels (c-e) and pure PVA hydrogels (f-h) compressed by a thumb [88]. Stress– strain curves of cyclic compressions on (i) CNTs/CS-L-0.5, and (j) pure CS foam [91].

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Figure 8. (a) Reusability of the composite cryobeads (initial concentration of Cu2+ ~ 200 mg/L; pH

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5.5; sorbent dose 1 g/L; contact time 24 h); (b) Possible mechanism of metal ion binding onto the

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CS/GRS composite (reproduced with permission from Ref. [14]); (c) The proposed mechanism of M2+ complexation on the arginine functionalized magnetic nanoparticle entrapped chitosan beads

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(reproduced with permission from Ref. [114]).

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Figure 9. (A) Optical images of II-CC and NI-CC before and after metal ion sorption using binary

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mixtures of Cu2+ ions with Pb2+, Zn2+ or Co2+ ions (Reproduced with permission from Ref. [22]). (B) Sorption and desorption kinetics cycles of Cu2+ ions onto/from II-CC sorbent. The optical images display the color difference between the cryo-composites as discs both before Cu2+ sorption and after the 5th cycle of elution (bottom images, yellowish discs), and after the 1st and the 5th cycle of Cu2+ sorption (top images, blue discs) (Reproduced with permission from Ref. [23]) (C) Schematic presentation of the composite beads fabrication based on CS and HAP (reproduced with permission from Ref. [119]). Figure 10. Optical microscope image of the VU65%CS (a) and a SEM image of the same sorbent (b) (Reproduced with permission from Ref. [121]); SEM images of CS-PDA before (c) and after loading with Pb2+ (d) and Cr6+ (e); EDX mapping micrographs (f, g, h) (Adapted with permission

Journal Pre-proof from Ref. [127]); SEM images of the CS–PVA hydrogel before (i), and after loading with Hg2+ ions (j) (Reproduced with permission from Ref. [132]) Figure 11. CS/PVAm/IEx composite beads before (a) and after loading with Cr6+ (b); SEM image of the interior of the beads loaded with Cr6+; influence of pH on the sorption capacity and on the removal efficiency (d); isotherm models fitted on the equilibrium sorption data of Cr6+ onto CS/PVAm/IEx composite beads (e) (Graphical abstract in Ref. [32]). Figure 12. (a) The two-step freeze-casting process to make GO beads and GO-CS beads; (b) cross-

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section of a bead showing a GO core embedded in the CS shell; (c) SEM image of the CS shell showing parallel and uniform channels (reproduced with permission from Ref. [179]).

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Figure 13. a) and b) Cross-sectional SEM images of two CEL/CS aerogels (reproduced with

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permission from Ref. [190]). c) Possible adsorption mechanism of CR onto DAMFC/CS

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composites (reproduced with permission from Ref. [193]).

Figure 14. SEM images of GCAM10 (a, b), and the cross-section of GCAM10 (c, d); schematic

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illustration of the adsorption mechanisms of various pollutants onto GCAMs composite beads (e)

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(reproduced with permission from Ref. [168]).

Figure 15. (a) Mechanism proposed for the phosphate removal by TAC/CS composite beads

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(reproduced with permission from Ref. [198]); (b) The inner morphology of the NaA zeolite/CS composite porous beads; (c) the reusability of NaA zeolite/CS composite beads in the removal of NH4 + ions (reproduced with permission from Ref. [204]). Figure 16. Schematic illustration of the preparation of CS/rGO aerogel and superhydrophobic aerogel. (a); perfluorinated PDA/CS/rGO composite aerogel before (b) and after ten cycles of oil/water separation (c) (reproduced with permission from Ref. [205]). Figure 17. a) COF loaded with Pd nanoparticles embedded in CS aerogel monolith and its application in dechlorination of CBs (reproduced with permission from Ref. [206]); b) graphical abstract of Ref. [207]; SEM images of porous TiO 2 /CS/rGO composites prepared with 1.0 wt%

Journal Pre-proof rGO and TiO 2 content of 71 vol% (c) and 77 vol% (d) (Reproduced with permission from: Ref. [209]). Figure 18. UV – Vis spectra of MO aqueous solutions in the presence of IICC-Cu2+ (A), NICCCu2+ (B), IICC-Cu2++H2 O2 (C) and NICC-Cu2++H2 O2 (D) catalytic systems. The corresponding color changes at various time intervals are presented as insets. Figure 19. (A) Strategy for the preparation of CS/kaolin porous microspheres (CSMS-K); (B) SEM images of CSMS-K3 (up) and SEM cross-section of CSMS-K3 ((1) and (2)). Kaolin particles with

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size of 1–2 μm (indicated by arrows) are observed on the CSMS-K surface (Reproduced with permission from Ref. 222); SEM images of (a) CSMS, (b) CSMS-S3, (c) CSMS-S4, (d) CSMS-S5,

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(e) CSMS-S6, and (f) cross-section of CSMS-S3. a-1, b-1, c-1, d-1, e-1, f-1 are the enlarged images

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of the corresponding sample. The inset is a TEM image of a silica microsphere (Reproduced with

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permission from Ref. 223).

Figure 20. Summary of the application of chitosan-based hydrogel dressings (Reproduced with

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permission from Ref. [250]).

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Figure 21. (a) Synthesis scheme of OHA-AT/CEC hydrogel. (b) Full-thickness skin defect model treatments involving multiple biological and physical functions (Reproduced with permission from

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Ref. [254]); (C) and (D) The cross-section SEM images of DN1 and TN1 composite gels (Reproduced with permission from Ref. [262].

Journal Pre-proof Table 1. Swelling, pore sizes, porosity and elasticity of various CS-based composites. 3D Matrix

Technique for pore generation

Properties a

SR, g/g

Pore

c

Refs.

P, %

d

G, kPa

sizes, m CS/CPL

Cryogelation

18-80

30-60

75-94

-

[13]

CS/Starch-g-PAN

Cryogelation

15-22

5-20

-

-

[14]

CS/PAAm as semi-IPN

Lyophilization

12-600

10-45

42-56

-

[18]

Cryogelation

25-160

89-95

-

[19]

Cryogelation

12-33

40-95

-

-

[20]

15-90

-

-

[21]

5-40

15-25

80-96

-

[22]

32.9

400-600

72

220

[26]

2.5-3.5

2-10

31-40

1000

[36]

CS/PAAm as semi-IPN

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f

or full-IPN

e-

CS/ PMAA-co-PAAm or

pr

or full-IPN

Cryogelation

Unidirectional

rn

CS/PAAm/CPL

0.880.97

al

cryogels

Pr

CS/PMAA-co-HEMA CS/PEI double network

30-75

CS/HAP

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freezing

Microwave irradiation and gas foaming

PVA/CS/-CD

ssCO2 and freezedrying

CS/GEL/PVA

Freeze-drying

20-40

50-100

-

2200

[38]

HECS/CEL

Freeze-drying and

0.269

100-250

-

150

[41]

-

20-50

-

0.781

[48]

porogen leaching CS/HPMC/glycerol

Freeze-drying

Journal Pre-proof GEL/CMCS/HAP

Freeze-drying

9.67-

190-600

90-93

12280

[50]

13.22 BC/CS/GA

Freeze-drying

-

100-500

-

0.4-2.5

[66]

CS/pectin/k- carrageenan

Freeze-drying

10-40

28-50

-

0.1-0.4

[81]

CS/Col/HA/HAP

Freeze-drying

0.06-

50-100

89-98

10-50

[84]

14-48

-

61-380

[85]

78-83

2240-

[86]

0.07 HAP/phosphorylated CS

Cryogelation and

-

GEL/CS/HAP

Cryogelation and

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f

freeze-drying -

94-120

Cryogelation and freeze-drying Freeze-thawing

CS/CB

Freeze-drying

CS/CMC/Ti-6Al-4V

Freeze-drying

al

-

350-

[87]

4500

10-100

-

3700

[88]

-

50-100

82

62.3

[89]

-

41-523

34-64

83-412

[90]

rn

a

150-300

3450

10-80

Pr

PVA/CS

12

e-

CS/Agrs

pr

freeze-drying

SR – Swelling ratio; cP – Porosity; dG – Elastic modulus; PAN – polyacrylonitrile; PMAA –

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poly(methacrylic acid); HEMA – 2- hydroxyethyl methacrylate; -CD – -cyclodextrin; HPMC – hydroxypropyl methylcellulose; CMCS – carboxymethyl chitosan; Col – collagen; HA – Hyaluronic acid; Agrs – Agarose; CMC – carboxymethyl cellulose.

Journal Pre-proof

Structure

Metal ion

Exp. Cond.

qm, mg/g

Kinetics

Isotherm

Ref.

CS/starches-gPAN cryobeads

Cu2+ Ni2+ Co2+ Cu2+

pH 5; 27 o C; 1 g/L pH 6; 27 o C; 1 g/L pH 6; 27 o C; 1 g/L pH 4.5; 25 o C; 1 g/L

100.6 83.25 74.01 259.56

PSO PSO PSO PSO

Langmuir, Sips Langmuir, Sips Langmuir, Sips Langmuir

[13] [13] [13] [23]

Cu2+

89

-

-

[112]

60

-

-

[112]

Cu2+

pH 6; 25 o C; 0.05 g/L pH 6; 25 o C; 0.05 g/L ???

134

PSO

Langmuir

[113]

Cu2+ Co2+ Ni2+ Cu2+ Zn2+ Pb2+ Co2+

pH 6; 30 o C; 1 g/L pH 6; 30 o C; 1 g/L pH 6; 30 o C; 1 g/L 25 o C; 2.5 g/L 25 o C; 2.5 g/L 25 o C; 2.5 g/L pH 8; RT; 0.2 g/L

172.4 161.2 103.0 120 117 108 100

PSO PSO PSO PSO PSO PSO PSO

Freundlich Freundlich Freundlich Langmuir Langmuir Langmuir Freundlich

[114] [114] [114] [115] [115] [115] [118]

Ni2+ Ni2+

pH 6; RT; 3 g/L pH 6; 40 o C; 1 g/L

112.36 69.93

PSO PSO

Langmuir Langmuir

[119] [120]

Cd2+

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Table 2. Sorption of some metal ions by porous CS-based composite sorbents (2015-2019).

pH 7; 25 o C; 1 g/L

102.15

PSO

Langmuir

[122]

39.2 656±27

PSO PSO

Langmuir Langmuir

[123] [124]

84.02 265.0

PSO PSO

Langmuir Langmuir

[125] [126]

431.7

PSO

Langmuir

[126]

441.2

PSO

Langmuir

[127]

composite CS

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Pb2+ Cd2+

Polydopamine modified CS aerogel (CSPDA) PNMCMs

Pb2+ Cr6+

pH 2.0; 1 g/L

374.5

PSO

Langmuir

[127]

Pb2+

384.6

PSO

Langmuir

[130]

MCGMA-II

Hg2+

pH 5.0; RT; 0.2 g/L pH 4; 20 o C; 2.5 g/L pH 5.5; 25 o C; 1.25 g/L

521.5

PSO

Langmuir

[133]

314.31

PFO

Langmuir

[32]

pH 7.0; 25 o C; 0.005 g/L

216

PSO

Langmuir and Freundlich

[139]

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PMCH Porous CS/PEG/PAA by GDEP

pH 5; 25 o C; 1 g/L pH 6.8; 22 o C; 0.24 g/L pH 6; RT; pH 4.8; 25 o C; 0.3 g/L pH 4.8; 25 o C; 0.3 g/L pH 5.5 ; 1 g/L

IEx embedded into CS/PVAm cryobeads Porous CS-LYS biocomposite

Cd2+ Cd2+

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CS/PEO nanofibers membrane Co2+ imprinted 8HQ--Fe2 O3 /CS HA/Fe3 O4 /CS Ni2+ imprinted macroporous CS CS/zeolite composite PMACCMS STNT-CS beads

e-

CS/REC coated PS mats AFMNPCBs

f

Pb2+

Pr

Porous Zel/CS monoliths (1:2)

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Cu2+ imprinted

Pb2+

Cr6+ Cr6+

Journal Pre-proof 3D honeycomblike Fe/CS composites CS coated Fe3 O4 nanocomposites PEI loaded CS hollow beads PCM-CS

As

3+

pH 6.0; 25 o C; 0.5 g/L

114.9

PSO

[144]

pH 6.0; 30 o C; 2 PSO Freundlich [145] 267.2 g/L Pt4+ pH 1.0; 25 o C; 815.2 ± PSO Langmuir [147] 1g/L 72.6 Er3+ pH 5.0; 27 o C; 0.2 117-145 PFO Langmuir [150] g/L AFMNPCBs – arginine functionalized magnetic nanoparticles entrapped in chitosan beads; GDPE – glowdischarge electrolysis plasma; PMACCMS – poly(maleic acid)-grafted on chitosan microspheres; STNT – silicate-titanate carbon nanotubes; PMCH – porous magnetic chitosan beads; PNMCMs – pyromellitic dianhydride-modified nanoporous magnetic cellulose-chitosan microspheres; MCGMA-II – CS and poly(glycidyl methacrylate) coating Fe 3 O4 core functionalized with ECH and then with diethylenetriamine; IEx- strong base anion exchanger; PVAm- poly(vinyl amine); LYS- lysozyme; PCM-CS poly(aminocarboxymethylated) chitosan.

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rn

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Pr

e-

pr

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f

As3+

Langmuir

Journal Pre-proof Table 3. Sorption of some cationic and anionic dyes by porous CS-based composite sorbents (2015-2019). Structure

Dye

Exp. Cond.

qm, mg/g

Kinetics

Isotherm

Ref.

Fe3 O4 /CS/GA nanocomposites CS-cross-linked-carrageenan bionanocomposites N-maleyl CS crosslinked P(AA-coVPA) hydrogel

Crystal Violet Methylene Blue

pH 11; 25 o C; 0.817 g/L pH 5.5; 26 o C; 2 g/L

105.41

PSO

Langmuir

[160]

123.1

PSO

Langmuir

[162]

Crystal Violet Methylene Blue Methylene Blue Methylene Blue Indigo Carmine Methylene Blue Rhodamine B Methylene Blue Methyl Orange Methylene Blue Methylene Blue Direct Blue 15 Acid Orange 7 Methyl Orange Congo Red

pH 7; 25 o C; 0.05 g/L pH 7; 25 o C; 0.05 g/L pH 7; 22 o C; ~0.7 g/L pH 12; 25 o C; 0.2 g/L 27 o C;

64.56

PSO

[163]

66.89

PSO

402.6

PSO

RedlichPeterson RedlichPeterson Langmuir Freundlich

[165]

376.8±32.3

Langmuir

[166]

27 o C;

168.6±9.6

Langmuir

[166] [167]

Methyl Orange Methyl Orange Congo Red

pH 5.0; 25 o C; 1 g/L pH 5.0; 25 o C; 5 g/L pH 5.0; 25 o C; 5 g/L pH 6.8; 30 o C; 0.17 mg/L

GO/CS sponge Sponge-like CS/HAP membrane Amine-shield porous CS beads Porous core-shell GO/CS beads Porous GO/CS fibers by etching silica nanoparticles CS/β-CD crosslinked with GA GA Cross-linked CS + Ni/Fe2 O4 nanocomposite GO/CS aerogel

Metanyl Yellow

[164]

f oo PSO

e-

pr

1134

556.9

PSO

936

PSO

272.23

PSO

Extended Freundlich Extended Freundlich Langmuir

584.6

PSO

Langmuir

[168]

275.5

PSO

Langmuir

[170]

369

PSO

Langmuir

[171]

2803.77

PSO

Langmuir

[177]

316

PSO

Langmuir

[179]

294.12

PFO

Langmuir

[181]

392

PSO

Langmuir

[182]

551.2

PSO

Langmuir

[192]

274.7

PSO

Langmuir

[192]

431

PFO, low conc.; PSO, high conc.

Langmuir

[195]

Pr

al

GO/CS aerogel microspheres

pH 3.0; 25 o C; 1 g/L pH 3.0; 25 o C; 1 g/L pH 7.5; 25 o C; 0.2 g/L pH 6.0; 25 o C; 0.2 g/L pH 8.0; 25 o C; ~0.33 g/L pH 7.0; 25 o C; 2 g/L pH 2.0; 45 o C; 6 g wet/L pH 7.0; 25 o C; 0.5 g/L pH 5.0; 20 o C; 0.7 g/L

rn

CS-g-P(AA-coAMPS)

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Cross-linked GO-CS (1:0.3) composite Porous GO/CS/β-CD hydrogel Cross-linked GO/CS aerogel

[163]

[167] [168]

Journal Pre-proof Highlights Porous chitosan-based composites with tailored morphology by freezing strategies



Porous composite chitosan-based sorbents effective in selective removal of metal ions



Porous composite sorbents endowed with high level of reusability



Porous chitosan-based composites as hemostats and smart drug delivery systems



Chitosan-based composite sponges are among the most effective wound dressings

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

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

Figure 9

Figure 10

Figure 11

Figure 12

Figure 13

Figure 14

Figure 15

Figure 16

Figure 17

Figure 18

Figure 19

Figure 20

Figure 21