Synthesis, drying process and medical application of polysaccharide-based aerogels

Journal Pre-proofs Synthesis, Drying Process and Medical Application of Polysaccharide-Based Aerogels Mehrez E. El-Naggar PII: DOI: Reference:

S0141-8130(19)37564-6 https://doi.org/10.1016/j.ijbiomac.2019.10.037 BIOMAC 13486

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International Journal of Biological Macromolecules

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17 September 2019 28 September 2019 3 October 2019

Please cite this article as: M.E. El-Naggar, Synthesis, Drying Process and Medical Application of PolysaccharideBased Aerogels, International Journal of Biological Macromolecules (2019), doi: https://doi.org/10.1016/ j.ijbiomac.2019.10.037

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Synthesis, Drying Process and Medical Application of Polysaccharide-Based Aerogels Mehrez E. El-Naggar Pretreatment and finishing of cellulosic fibers Department, Textile Research Division, National Research Centre, Dokki, Giza, Egypt Corresponding author: [email protected]; [email protected]; 01126018116

Abstract Aerogels are promisingly intended for the use in describing lighter solid materials with huge porous structures. The outcome of aerogels is of potential interest in biomedical purposes owing to many features such as high surface area, low density and porous structure, and so forth. There are numerous inorganic and organic materials employed in the preparation of aerogels. Many drying techniques are a fundamental part of their preparation such as supercritical, freeze-drying, vacuum, ambient pressure and microwave which have been utilized for drying the wet-gel via substitute the liquid inside the wet-gel pores with air. Three common lighter solid materials (i.e. aerogel, cryogel and xerogel) could be synthesized depending on the drying technique applied. This review focuses on aerogel definition, the steps for the preparation of aerogel, techniques used for drying the wet-gel platforms. Further it highlights the pros and cons of each drying technique for synthesizing a demanded material’s properties. As polysaccharide considered as one of the most prominent biocompatible and environmentally friendly polymers used for their preparation, thus we will present some examples (e.g.; cellulose, chitosan, starch, alginate, carrageenan and curdlan) and finally the potential biomedical applications of polysaccharidesbased aerogel are briefly emphasized. Keywords: Aerogel; Polysaccharides; Biomedical application

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1. Introduction This review overviews the approaches in current use for the formation of polysaccharide-based aerogels. The properties of polysaccharide-based aerogels are handled with respect to drying technique and application in various fields of medical domains including drug delivery [1], wound dressing [2], tissue engineering, medical implantable device, biosensor and bioimaging [3]. By definition, polysaccharides are carbohydrate polymers composed of a number of mono-saccharide units connected by glycosidic linkages [4-6]. The origin of polysaccharides is outlined according to the different sources like plants and as a by products from industrial processes [7-9]. Polysaccharides acquire structures that range from linear to greatly branched [4]. They comprise homo or hetero repeating units of monosaccharides. Aerogel has extraordinary physical properties and described as a lightest solid on earth [10]. It is characterized by high optical transparency, low thermal conductivity and low sound speeds. Such properties make its materials extremely convenient for many different applications such as medical fields, building, wastewater treatments, environmental pollution and so on [11-16]. The term “aerogel” refers to the component which is constituted of a gel scaffold and filling medium (air). According to Kistler in 1931, The solid materials with highly pores and highly surface area can be created by filling the air in the wet-gel instead of liquid by using advanced technique for drying [17]. The latter allows the reduction in shrinkage thereby resulting in the deformation of the network for the solid material during drying, maintain the huge porosity and thus maintaining the gel structure without degradation or collapsing [17]. Thus, Kistler has given the word “aerogel” for solid materials that have porous structure. This shed insight on, the discovery of a new era for the development of lightweight materials with unique properties [18, 19]. For example, inorganic aerogel, i.e. silica and their precursors have been significantly investigated due to their unique properties. Accordingly, the 2

prepared silica aerogels display porosities more than 99% and density value equal to 0.003 g/cm3. In addition, silica aerogel exhibited high surface area about 1200 m2/g with very low thermal conductivity and low sound velocity (~100 m/s) [2, 20] . Aerogel is generally man-made, ultralight, solid material which is categorized by a highly porous structure, highly specific surface area with low density as well [21] . The unique porous structure of aerogels depends on the type of aerogel-forming material as shown in Figure 1.

Figure 1: different shapes for the lightest aerogel In recent years, the materials in question comprise three common categories of materials, some materials termed aerogels, the others are called cryogel or xerogel. These categories depending upon the drying conditions and the final form of the produced materials. While, the solid material can be termed as “xerogel” when a vacuum oven was used for drying the samples of aqua-gel (wet-gel) at room temperature for 2 days or more [22, 23]. It is obvious that this type of materials has condense structure without pores as shown in Scheme 1. 3

Meanwhile, when the solvent inside the aqua-gels are evaporated using freezedrying, the resulted samples are called cryogels [24]. Particularly notable is that the resultant samples dried with freeze-drying have large pores. On the other hand, the term aerogel is related to the samples of aqua-gel dried using supercritical carbon dioxide (sc-CO2) [25]. The benefit of using this process is to obtain aerogel having small pores. All the shapes of aerogel, cryogel and xerogel are drawn in Scheme 1. 2. Chemical steps for the synthesis of aerogel Scheme 1 shows the processing steps used for the fabrication of aerogel [26]. The aerogel can be manufactures form inorganic compounds and organic polymers. There are many examples for the inorganic aerogel such as titania, zirconia, alumina and silica [27]. On the other hand, the organic aerogels may be composed of natural polymers (polysaccharides [28, 29] and proteins [30]) or synthetic polymers or mixture of natural and synthetic polymers [31, 32]. Concisely, the first step comprises the dissolution of the polymer or inorganic compounds in a desired solvent for specific time under stirring [33]. Later on, the wet gel (hydrogel) with a coherent network can be formed by making use of either chemical, enzymatic or physical crosslinking agent. The term “wet-gel” or “Hydrogel” is associated with the three-dimension network of polymers that has the ability to absorbs and holds a large amount of solvent [34]. The term “network” simulates the chemical, enzymatic or physical cross-links needed to maintain the polymeric structure of hydrophilic groups or domains to avoid the dissolution of polymer molecules in the aqueous phase [35, 36].

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ellowish,

were measured. The proportional to liquid/solid contact angle liq- in Table 1. m SEM images per formulation final values areand summarized m minimal resolution was0.1 l m. % mto microcrystalline m m uid/gas surf ace tension and inversely proportional Coagulation of dissolved cellulose we used network pore size. In the case of cellulose ‘‘ aquagel ’’ ,of up to 20 vol% at 3 wt% Results and discussion induces volume shrinkage % m ing from the first two components are high because cellulose is G in solution. ThisResultsand m discussion cellulose concentration value solutions hydrophilic and water surf ace tension is high. In Sample shrinkage, density and porosity decreases to around 5 vol% for all the other Sampleshrinkage, higherdensity and porosity overlap addition to capillary stresses, densificati on is due to cellulose concentrations. Additional volume shrinkicrocrysstrong hydrogen bonds that are formed between After coagulation in ethanol and several washing After coagulation in ethanol and several washing age are can bepresent observed after utions of numerous hydroxyl groups which on drying of the coagulated cycles in distilled water, white cellulose ‘‘aquagels’’ cycles in distilled water, white cellulose ‘‘ aquagels’’ cellulose: it is enormous for vacuum drying, followed wereobtained asshown in Fig. 1. Such wet aquagels andle due cellulose chain. As a result, the overall volume werethendriedby were obtained as shown in in Fig. 1. Such wet aquagels is close by rathertohigh shrinkage for sc CO2 drying and lowoneof thetechniquesmentioned in oting that shrinkage cellulose xerogels and above

after each step are shown in Fig. 2 as a function of 8 6 ( 2 0 1 1 )1 4 2 5 –1 4 3 8 cellulose concentration and drying method, and the final values aresummarized in Table 1. m Coagulationof dissolvedmicrocrystallinecellulose induces volumeshrinkageof up to 20 vol% at 3 wt% cellulose concentration in solution. This value m decreases to around 5 vol% for all the other higher cellulose concentrations. Additional volume shrinkage can be observed after drying of the coagulated cellulose: it isenormousfor vacuum drying, followed by rather high shrinkage for sc CO drying and low 8 6 ( 2 0 1 1 )1 4 2 5 –1 4 3 8 shrinkagefor freeze-drying. Methods section; the resulting dry samples are also Evaporative vacuum drying is slow and induces were then dried by one of the techniques mentioned in shrinkage for freeze-drying. shown in Fig. 1. Aerogels and both kindsof cryogels strong capillary pressure applied on pore walls: it is Methods section; the resulting dry samples are also Evaporative vacuum drying is slow and induces arewhiteandopaque,whereasxerogelsareyellowish, proportional to liquid/solid contact angle and liqtranslucentitand is much moreshrunk. uid/gas surface tension and inversely proportional to shown in Fig. 1. Aerogels and both kinds of cryogels strong capillary pressure applied on pore walls: To prepare aero- cryo- and xerogels we used network poresize. Inthecaseof cellulose ‘‘aquagel’’, are white and opaque, whereas xerogels are yellowish, proportional to liquid/solid contact angle and liqcellulose solutions with concentrations ranging from thefirst two componentsarehigh because cellulose is 123 translucent and much more shrunk. 3to11 wt%: monolithsarenot uid/gas surface tension and inversely proportional to formed from solutions hydrophilic and water surface tension is high. In with lower cellulose To prepare aero- cryo- and xerogels we used network pore size. In the case of cellulose ‘‘ aquagel’’ , content because the overlap addition to capillary stresses, densification is due to concentration is around 1–1.5 wt% forshrinkage microcrysstrong hydrogen bonds that are formed between low (almost surface tension and the liquid-vapour inby per using templates (surfactants) CTAB, SDS, Pluronic an aerogel by very our research group after a supercritical furt her processi ng st ages i l l ust rat ed may be combi nedisdependi ngsynthesized on speci fi cprocess, needs tzero) he appl i cat i on.this werewere obtained as shown such in Fig.as 1. Such wet aquagels eliminated by ant he evaporation aofxerogel is obtained, is thus, produced m shown ratherinhigh for%sc CO2 drying and low SEM images formulation measured. The after each step are Fig. 2 asbe aw function the large surface area presented by these aerogels, could used as of solutions with concentrations ranging from Fig. 3a correspond to alginate microparticles, Fig. 3b to silica in microthe two components are high because cellulose isandbyshrinkage Adapt ed fromcellulose Ref. [ 16] . terface disappears, this in turn,first forms an Any material that F127, P123 and can P65, work asone the structure's forming agents dryingdue process. are fragile and have bluish-white coloration then dried by of the techniques mentioned C r aerogel. y ogel mainly to theThey formation of a meniscus in athe liquid-vapour interfor freeze-drying. tallinecellulose(Gerickeet al.they 2009),andsolutionsof minimal resolution 0.1which lwere m. cellulose concentration and drying method, have andnumerous the hydroxyl groups which are present on carriers of drugs [ 22] . Further, alginate chitosan aerogels particles Fig. was 3c The be synthesized wet gels using the of sol-gel canand byto starch [ 17– 21] . be dried [ 14]where . Methodsmicroparticles. section; the resulting dryalginate, samples aresilica also and Evaporative vacuum drying is slow and induces face, a gradient of capillary tension isas formed on the walls the technique final values arehave summarized in Table 1. received great attention because they properties, starch microparticles haveshown a large surface area 359.54, 567.62 andmucoadhesive higher concentrationsarerather difficult tohandledue 3 to 11 wt%: monoliths are not formed from solutions cellulose water surface tension is high. In The in Fig. 1 was obtained through the hydrophilic sol-gel process, also and in Fig. 1. Aerogels andof both kinds of cryogels pores andaerogel can cause a collapse the entire structure. One way to elimstrong capillary pressure applied on porechain. walls:Asit aisresult, the overall volume Coagulation of and dissolved microcrystalline cellulose Fig. 1 Examples of an aquagel and samples after drying (aerogel, cryogels and xerogel) obtained from 7 wt% Forer mat i on of twith heed coldifferent lgel oi dal net sol uttechniques i 217.00 on m7 gat iwt% , respectively. The pore's diameter are 30.50, 25.60 chemiwith cal synt hesi s of aer ogeltechniques s, w hi ch st ar t s w i t(aerogel, h t he t r ansi t i on of a col l oi dal sol ut i on t o an i nt connect w or k (gel on). The known as wet chemistry technique. This process involves two stages: ing different cryogels and xerogel) obtained from are white and opaque, whereas xerogels aretoyellowish, inate meniscus is through a supercritical drying, which produces a proportional worth to liquid/solid angle and liqcellulose highDue viscosity. noting thatat contact v i a di sper si ng t he pol ymer s or any Results and discussion Sol utthis i on – solution sol t r ansi t i on induces their volume shrinkage up to 20 vol% 3 shrinkage wt% in cellulose xerogels is close to and above 2.1.1. for drug delivery t r at ed may be combi ned dependi ng on t he speci fi c needs of t he appl i cat i on. 9.40 nm Aerogels for the alginate, silica andand starch aerogel, respectively. to It isofalso with lower cellulose content because the solution and gelation. The fioverlap rsttension stage is thethus, sol formation, that is, incoltranslucent much more shrunk. very low (almost zero) surface and the liquid-vapour uid/gas surface tension and inversely proportional to

m g na om a a g na e M on o by nl i e n a se g m e h od ε =t 9 4 % ε ≈ 0 vel 13 cm M eh ng e a 2009 9.40 the alh gi nate, si ca and aerogel vel y. Due to 9.40 nm the gi nate, si,lmor irespecti ca and aerogel , respecti y.g Due to W possi bl e tfor o appr eci ifor calstarch paral t in cl es and e i ntstarch er nal ly he Fi g. i n 1.A eces of.e aer w i tC h rzero) anspar ent Ae bl ui sh appear ance. 2.1.1. rog etls for delive rymlnm M m0 m very most surface tensi on and thus, the qui d-vapour iat n-e quasi -spher SC = 1G 5 3 0 má e 1 9 boh cm i (al oni s oft he t hezero) sol aPi w et gel Ifl ow togel he l icol qui d tcont ai ned i and nsi de he por es very ow most tensi on and the l i qui d-vapour idrug nfi rfor st lmat st age sol forsurface mat i on, t hat i s,(al -thus, A a vol% a0 G on Ca d g a e Po me Result s iand discussion with observations all the samples were metallized induces volumeby shrinkage of up to 20 at 3 wt% g eVa = m P = 12 n m coul d be used as the lonal arge surface area these aerogel s, they iAny nt er connect t hr ee-di mensi net weased oraerogel k aspresented ws, el lthey as tcoul hei rV osi t y. m bi ocompat Mhas m % m M l arge surface area presented by these dxpor be used as Now adays, t he iaerogel nt er est. the about iy bl e aer ogel s ie ncr terface di sappears, thi s inm n turn, materi al ed that can i s el i di mi nat ed by thi an at ia on ocess, a xer ogel is obt aiforms ned, tan hi s i sacceleration Aturn, gol n o m C a . a g n a Bead s b d o n of m h od ε 99 % S = 3 00 580 m g A na e A za ou n e a 2011 Fi g.u 1.sPieces aerogel with transparent andconcentration bluish rerface sed in a sol vent bysevapor ysi sepr and conm m sappears, ihydr n forms an aerogel Any materi al that can cellulose in= = solution. This value ð 1Þ Volume shrinkageð %Þ¼ 100 1 appearance. 7 ofeplati num. The voltage used was Lean d o Ko n g Pek a a & Kasch m e T.A. Esquivel-Castro al. carri ers drugs [and 22] .Fi Further, gi nate chi s have 1 1tosan 1 2 aerogel cm g P = 13 19 n m M eh ng e a 2009 Qu gn a d m Fi g. 3a cor rdrugs espond t o al gi e mi cr opar t i cl es, g. tosan 3b t o al si l isol ca V miand cr odue ts ousi t hei retthe l iar ge sur face ar eaers and open por ous rnat uct e.of Those ar e V ae o ge 2 0 ech n o o gy R Us nze g h s em u carri [ogel 22] .sst al gi nate chi aerogel have be synthesi zed as gel ng sol -gel techni que can be dri m m % er i nt d-vapour i qui lkV. t he i nwet scus a meni of i on mat for t he to due nl mai ndex iat irve act efr rng t he . yFor l ow ar of i at i on var The . ur 15] [Further, aer n ed ai obt t o of ocess pr yi-ng dr cal i tdri cr super t3he 08 2010 ob e a 200 e nanopar t zed i clcompar es ar e i son, j oi ned by elthe ect ost-gel i c techni Sample shrinkage, densi tyby and porosity decreases to around 5 vol%sfor all the othermve higher bee synthesi as wet gel s usi sol que can be ed by m m pQ a c es am e e o 1 300 0 a m a great attenti on because mucoadhesi properti es, M pardr t i cl esdel and Fiy g.syst 3c ems t o strecei ar chved cr opar t i cl es. The al gi natthey e, si l have i ca and Ro bd ze Ren zo & Qu gn d 2 0 − 1 − 1 pr omi si ng char act er i st i cs for ug i ver [ee 22] .mi Fi g. 3 ishow s mucoadhesi face, w her e a gr adi ent of capi l l ar y t ensi on i s for med on t he w al l s of t he of t he ai r i s 1.004 and 0.0209 W m K t he i ni t i al pr ecur sor s, gel at i on t i me, cat al yst , degr of sol vat on, gerecei ved great attenti on because they have ve properti es, o n ase h0 p2 s u eo u aq an o g n s bui l d an i nt er connect ed t hr ee-di mensi onal an d V a en n e a 05 2 00 6 cellulose concentrations. Additional volume shrinkQ Average pore sizes were studied the image where V the sample volume at a given step (aquagel x is stogel ar chs using mi cr opar t i cl have a l ar ge sur face ar ea of 359.54, 567.62 and un h en ge a on o ou hn e d sed ph A g na e om Ca a g n a phol e M c o sp hes eas es b y n e n a It se ng S = 318 680 m g A a e A za e sp a e 2 011 tur he mor ogy of some aer t hat ar e used car r i er s of dr ugs. i s TM por es and can cause a col l apse t he ent i r e st r uct e. One w ay t o el i mthe supercritical drying process to obtain aerogels [ 15] . The variation of conductivity of aerogels are low. For comparison, the refractive index se for t he aer ogel s ar e 1.007– 1.24 and l at i on condi t i ons and gel pr ocessi ng can pr oduce aer ogel s w i t h di ffer ent mm e M m coagulation inInstruethanol anded several washing nt of gel at i on, see Fi g. 2. Thi s i s t he t r ansage can be observed after drying the coagul ated h1 o d co u p o em u sand on = 2 of 1 5 4 05 cm g P = 9 15 n m 2011 P op e es o he m c o sp h e es 2 − analysi s software ArchimedAfter (Microvision or after dryi ng) Vser the volume ofVcellulose ol is m m m 217.00 m gpar rcl espect i vel y.= The por e's di amet ar e 30.50, 25.60 and ech n ,t q u es D 7 5 5 4 7 m m possi bl e t o appr eci at e quasi -spher i cal i es and mor e i nt er nal l y t he a ea can b e a o ed b y co n o n g − 1 − 1 m i nat eg. t hi scus hr ough a super cr i tes i cal w hi ch prphol oduces a thermal vel y. 1sshow s t hei s physi cal of dr yi ng, por ous mor ogi es, por e si ze etthree c. [ 16] .airMesopor ous aer ogel sK can be cycles inof disti lled water, white cellul ose ‘‘ aquagels’’ t gel .Fi If he lmeni i qui d cont aitned ia nsiappear de t heance por cellulose: itAll is enormous for drying, followed C ageen an Bead s e1.004 m a ea m en w h a do em a 20 0 8 ε vacuum = 5 2 % ε ≈ 1 48 cm the initial precursors, gelation time, catalyst, ofgsolvation, geand conductivity the is and 0.0209 W m ments). At least 100 sizes on each different m % m degree Q an d chQu em gn ca u a o n Th e s ze g. 1. Pieces aerogel and bluish appearance. solution before coagul ation. volume shrinkages 9.40 nm forof t he alh gi nat e, las id ca and st arm ch aer ogel , rof espect iwith veltransparent y. Due o i nt er connect edusi t hr ee-di mensi onal net w ors) k as was el lsi t hei por tFiy. ca n c sa s or n S =t 2 00 230 m g m c es a e m a n y n fl u en ced by ag a ypr lr ow (alch most zer o) aft face t ensi on and t he l i qui d-vapour i nby our esear gr oup a super t i cal oduced by t empl at es (sur fact ant such CTAB, S DS , Plosi ur oni were obtained aso shown in Fig. 1.ad Such wet aquagels at iver on ocess, a xer ogel isur s er obt ai ned, tcr hiis i s t hus, pr 2588 Cellulose (2016)1 23:2585– 2595 byc rather high shri nkage for sc drying and low mg m V =CO 0 of 8 1 2 cm = 9 1 n m 2 SEM images per ng formul ation were measured. The after each step are shown Fig. 2 and asbe a lation conditions gelfunction processing can produce aerogels withP different respectively, while these fort i cl the aerogels areed 1.007– 1.24 and m a x p ecu so co n cen a on an d t he l ar ge sur face ar ea pre esent by hese aer ogel s, tin hey coul d used m % as m m FiF127, g. 3a cor espond t o al gi nat e mi crk opar 3b o simi l it ca mi cr oAga ge Bead b y hg. m a ge a on ε = 89% S = 320 m g V = 0 3 cmQ g Ro b ze Ren zo & Qu gn a d 20 er face di sappear hi n t ur n, msor aer mat er iral tand hat can agi l emeni and have at the bl s ui hi t for e col at i on P123 P65, w hi ch wdried or ass t he st rFi uct ur e'stmentioned for ngin agent s m then by one ofes, the techniques onfrtof a scus i ns, l iish-w qui d-vapour ian nt er - ogel . Any um e a os A na e & Sm n ov a 20 shrinkage for freeze-drying. P and = 1the 8 nm − 1 −were 1m. minimal resolution was 0.1 cellulose and drying method, m M , m car r irespectively. er s dr Fig. ugs [shows 22] b . the Fur t her alconcentration gi nat eof and chi trefractive osan aer ogel s par tp i cl21] es and Fi g. 3c oce stlMethods ar mi crof opar t i cl al gi nat e, siFor ld i ca and su ace aeea pn o ge e se ze o 20 h e esu canG=be5 Mesoporous .and 16]m [2 etc. size pore morphologies, appearance physical 1es. Kch m W 0.02 thehave supercritical drying process toaerogels obtain aerogels [ 15] variation conductivity of aerogels are low. comparison, the index es u o se o -gel eu ca y us u dr p S o M on o h s The y so v en sso uporous on ε ≈ 0 0 5 g cm S 0 . The 42 0 m of g nn oh a 0 6 m M % 0 m hesion zed et C gel usi ng t he sol t echni que can be i ed bytu [ 17– .p section; the resulting dry samples are also apibe l l arsynt y t ensi i sas forw med on tu he w al l s of tm he n Evaporative vacuum drying is slow induces no s gn fi can nfl u en ced b he p m Ce o se om a v e ce u o se M on o hs b y final so v en d sso u o nEmmett ε equation) = 9 5(Bru% ε direct ≈ 0 06 0 cmof the 3 wt% Gav on y an d Bu d o va 2y 008 freeze-drying led3to g breakage Brunauer, and (BET values are summarized in Table − 1 Teller −1. 1 oper ra ecei ved gr eat at t ent i on because t hey have mucoadhesi ve pr t i es, st ar ch mi cr opar t i cl es have l ar ge sur face ar ea of 359.54, 567.62 and m M m m the initial precursors, time, catalyst, degree of solvation, geandresearch thermal conductivity of the air is 1.004strong and 0.0209 W musing K templates a e aq u eo u s so u on o o a o su S = 20 0 3 0 gelation 0 g produced by (surfactants) such asm CTAB, SDS, Pluronic an aerogelshown synthesized by our group after of a supercritical w as obt ai ned hrst ough t he sol -gel pr al so in Fig. 1. Aerogels and b both kinds cryogels apse t he ent i rt e r uct ur e. One w ayocess, t o el i mcapill ary pressure applied on pore walls: it isprobably m O m m 2 − Ce u o se om b ac e a ce u1 o se M on o hs y b ac e a ea ed ε cellulose ≈ 0 0 08 g cm S = 200 m g n e m apo 2 0n o mQ a n yL beb y he e co s0 1o h e so sample most because precursor of low nauer et al. 1938). The samples were measured after Coagul ation of dissolved microcrystalline m m For m at i on of t he col l oi dal sol ut i 217.00 on m g , r espect i vel y. white Theand por e's di amet erxerogels ar e 30.50, 25.60 and are lation conditions andstructure's gel processing can respectively, while for theaq aerogels 1.24 and hopaque, e m a y an d wthese h 0 1 u eo u s 1.007– N aOH V = 0 5angle cm g liqP = 5produce n m aerogels with different m t echni que. cr Thi prdr ocess i nvol tw o st ages: are whereas are yellowish, c o ss nke A na e A za ou n e a ugh a super i t is cal yi ng, w hives ch pr oduces a proportional to liquid/solid contact and F127, P123 and P65, which work as the forming agents drying process. They are fragile and have a bluish-white coloration M m Result s and discussion via C dih spero sisan n g t he pol y m er s or an y Bead s b y d o p p n g ac d c ch o san S = 3 3 0 m g V = 0 4 cm g Kad b e a 2 0 1 1 an d Qu gn a d induces volume shri nkage of up to 20 vol% at 3 wt% cellulose concentration was unable to resist high and being degassed for 5 h at 70 °C. su ace a ea an d h e p o e s ze d s bu − 1 − 1 2.1.1. rog elsal for drug nm Ae for t he gi nat e, de si llive i cary and stu ar ch aer ogel rrespectively. espect i vel y.1 Due t o physical appearance of m m so omore n n a k a n e of so ushows on P = morphologies, 6 n m 008 porous pore size [ 16] . Mesoporous aerogels can bec es sh2 0.02 Wm K , Fi Fig. the e fi r st st age s t he sol for mat on, t hat i s, sor - ut i 9.40 translucent and much shrunk. face t ensi on iand t hus, t the l i qui d-vapour icol n- sol g. 1. Pieces aerogel with transparent and ace bluish appearance. uid/gas21] surf tension and inversely proportional to etc. ow s m a v a u es o h o se o b m par i cl es iio n t he pr ecur on [ 14] . er Ch an g e a 2008 Ch san M o no hi s c o ss n k n eased g as w [ 17– h in . solution. ε ≈ value 0 0 92 g m cm developed during water sublicellulose concentration This Now adays, he i nt est To about ocompat bland ebaer ogel s has i ncr M %3 8 heterogeneous stresses t he l ar ge sur face tar ea pr esent edprepare by tbi hese aer ogel s, ty hey coul d be used m on o h c ae o ge s A e ge a on h aerocryoxerogels we used er n, sed n aan sol vent oler ysi s tand cona d eh yd es n ac d by c our aqresearch u eo u snetwork so u pore on S = 6 m 84 5 m g V = 0 as 1 3 SDS, 5 cm g produced by using (surfactants) such CTAB, Pluronic an aerogel synthesized group after a supercritical ur fori ms aer ogel(by . Sol Any mat i al hat can size. In the case of 6 cellulose ‘‘templates aquagel ’’ ,m )hydr o m h e m x u e e g b y fi a o n o M m m porosity and ty densi shrinkage, Sample 2 5 decreases to around vol% for all other higher F g 4 Ae o ge m on o process, h a e h e h ap e o the h eP m = o d w hn em e h e the ge p were epmonolithic. a ed due o of t hei r ugs l ar ge sur ea and open por ous st r uct ur e. Those ar5e car r i erts dr [ 22] . face Fur t ar her ,Fig. al nat e and chi t osan aer ogel s also have The aerogel in 1gi was obtained through the sol-gel mation. All other samples Scanning electron microscopy (SEM) m h e su p e c y h9 e w a e co n cellulose solutions with concentrations ranging from se nanopar t i cl es tar e j oi ned by el ect ost by at i c usi ng t he sol -gel echni que can dr ired C h n be M oa no h s by so v en d sso u on ε = 8 4 92 % ε 0 2the0 2m 2 o g d cm Ts op sca as d e a ng 200 h ae o ge o b are a n ed b upe a d ng o m a h d o ge which p ≈ ep a1 ed n a F127, P123 and P65, work as structure's forming agents drying process. They fragile and have a bluish-white coloration the first two components are high because cellulose is T.A. Esquivel-Castro et al. Pol ym er sol of utdr i on em o v ed b y so v en ex ch an ge Th s m o h m aems o o S = 2 0 aerogels 3 6 3[ 15] m. The g P = 3 nm process to2 obtain variation of1to certain conductivity aerogels areC low. comparison, thee refractive cellulose concentrations. Additionaldrying volume shrinkpr omi si ng char act er st ias cs for ug del ihave ver yFor syst [involves 22] . solutions Fi g. 3index show r ecei ved gr eat at t ent iion because t hey mucoadhesi ve pr oper t i es, sthe supercritical Coagulation drying steps lead volume known chemistry technique. This two stages: 3wet to 11 wt%: notprocess formed from bui l d an i nt er connect ed ee-di mensi onal hydrophilic water Msurf ace is high. In and= Ch t hrn M monoliths o no h s b y so v en d u on oand S = 5 60 m g V 1 2 cm g R o b ze To u e e a 2o 0n 11 he p o d u c on o noe gan c ca b an [ 17– 21]& .tension [ 14] . are w G & w A T m − 1sso coagulation in some ethanol several washing age can be observed after dryi ng for of ofdrug the coagul ated y a ed ch o san P = 1 0 catalyst, nm tAfter he mor phol ogy of aerand ogel s eace tcellulose hat of ar e content used as car r iB er s of ugs. i Morphological s the initial precursors, gelation degree of solvation, ge- occupied by the and thermal conductivity the air is 1.004 and 0.0209 Wdr m K− 1Itaddition b ased ae o ge s F g 5c A na e A za 2.1.1. Aerogels delivery m mtime, was shrinkage compared toe the volume analysis the dry celluloses with lower because the overlap i nt of gel at i on, see Fi g. 2. Thi s i s t he t r anstoprocess, capill stresses, densificati on is due to The aerogel in Fig. 1 was obtained through the sol-gel also solution and The stage is the sol formation, that is,enormous cola as d ug ease m n o v aary S u A u en gw o n g p Se en a S m nT ov a 2011 L u Zh an g Fu D ess m m m w m u th o r 's e r s o a l coM p y cycles lled eci water, tegelation. cellul ‘‘first aquagels’’ TM gel possi blin e disti t o appr at e whi quasi -spher ige cal par cl es and mor emicrocrysie nta er nal l0 y0 tS he cellulose: it is for vacuum drying, followed lation conditions and processing can produce aerogels with different respectively, whileose these for the aerogels are 1.24 and 2 0 0 4 ti S m no v a e 2 5 Th sp eed o d are u g d sso u n o d u g m N N m m1.007– m F m & T O ay e e a 1996 W an g e a 2011 concentration is around 1– 1.5 wt% for Nowadays, the interest about biocompatible aerogels has increased initial solution ino the mold. The volume shrinkage was performed ine Zeiss Supra 40 N FEG scanning electron et gel . If t he l i qui d cont ai ned i nsib de t he por es strong hydrogen bonds that formed between known as wet chemistry technique. This process involves two T e M S a & Z b on d s e w een ch ns G a d n &− 1 Bdispersed w e 1 9hydrolysis 7 5 b u can be u dee a & dm Ab 1 9 Th u s ch n ge s can be o m ed o ad ed ae o ge m c rand opor p a c es co u stages: d be M o h o e Cellulose sd ou m ah agn u d9 e5 loidal nanoparticles in solvent by con2588 (2016) 23:2585– 2595 were obtained as shown in Fig. Such wet aquagels nta er connect ed t hr ee-di mensi onal net w or k as w el l and as tPhei osi t y. by rather high shri nkage for sc CO drying and low Fi g. 1.ack Pieces of aerogel with transparent and bluish appearance. 2 porous morphologies, pore size etc. [ 16] . Mesoporous aerogels can be m− 1 1. Ko respectively. Fig. 1 shows the appearance of 2.1.1. Aerogels for drug R T A N etso w or km For m at i on talline cellulose (Gericke et al. 2009), solutions as e h an dphysical u g o ad ed so d p a secondary c es Lee & Go udelivery d 2the 0 monolithic 0 6 S b ca or at i on pr ocess, a xerso ogel u i sb obt aized ned, t hi i s u s in bs y g e sp 0.02 ecWa gan c so v en s e gof co n cen b y s m p e ag n g o y d u ng he esu ng ch n so u numerous hydroxyl groups which are present on calculated for all samples as follows: microscope with electrons detector. Prior due to their large surface area and open porous structure. Those are solution and gelation. The fi rst stage ismi the solh formation, that is, m col- c a 4 ase s o u d a es on a de a an ca b o n ae o ge n h oe an o m o op a c es a e ad wo na were then dri by one the techniques mentioned in Fi g. 3a red espond tof o aerogel al gi nat eeh mi cr opar tare i research cl es, Fi g. 3b tby o si ls i ca cr a c ac ca c cor u m ch o d e d y d a e sa u a m e o ge ex cess o a e y yd ge co hp oo y sacch a co ge T shrinkage for freeze-drying. densation reactions. Those nanoparticles are joined electrostatic m at ied on d-vapour of o a m w et i nt gel i td h a 2 oC w Nowadays, thesuch interest about biocompatible aerogels hash increased higher concentrations rather difficul tm to handle due produced byC using templates (surfactants) as CTAB, Pluronic an synthesized byd our group after aed supercritical i on of a meni scus i n For t he l i qui er -we chain. As a result, theez overall volume o a n ed om o n o h scellulose b y n g Lee & Go u 2 0 0 6SDS, H o w ev e observations all the samples were metallized with um ch + N N d m e hy am d x u e F u a 1 9m 84 N agah am & To k u a Op on a y ch n hyd o ge s 14 3b 2 e .A. Gar cí a-for G on zál et d al . /a Car bohy at e P ol y m er s 2006 loidal nanoparticles dispersed in a l solvent by hydrolysis and conwdelivery promising characteristics drug systems [e 22] .dr Fig. 3 shows coherh en tp ns et w or k . o via d Cr osspar t i cl es and Fi g. 3c t oace st ar ch mi cr opar tan im cl es. The al gi nat e, si id ca and Methods section; the resulting dry samples are also V Evaporative vacuum drying is slow induces ST a ch o san a ack o p a c e sp h e c y (BET an d he ab and sen ce o bpa a c s ze u o x as Mt he ch a o S au pdrying o u to otheir s order & P an ay o o u 2 0 0 9 Zak a a cellulose o n ed o m eace y 4 a1ed ch n an aq u eo u s a w high viscosi ty. It is also noting that Brunauer, Emmett and Teller equation) (Brudirect freeze-drying led to breakage of the 3n wt% interactions in to build interconnected three-dimensional due to their large surface area and open porous structure. Those are shrinkage in xerogels is close ton and above capi l l ar y t ensi on i s forTs medo on t he w al l s of F127, P123 and P65, which work as the structure's forming agents They are fragile and have a worth bluish-white coloration the supercritical drying process obtain aerogels [a 15] .so The variation of conductivity of aerogelso are low. Forprocess. comparison, the refractive index Volume shrinkageð%Þ¼ 100 1To 7u nm ofto platinum. The acceleration used was m y eq u o nanoparticles m an y are d g d e v e y ap p ou s o a ep ex p ec ed o A th r's e rs o nIt a l c o p y ð1Þ electrostatic by joined Those reactions. densation T voltage l i n k i n g of sol par t i cl es so uca o n R o b ze u e e e a 2011 A e so v en ex Tab lof e face 2 st ar ch in mi cr opar t i cl es have a l ar ge sur ar n ea of ed 359.54, 567.62 and shown Fig. 1. Aerogels and both kinds cryogels the morphology of some aerogels that are used as carriers of drugs. is strong capill ary pressure appl on pore walls: it is Vsola Am y o se an d am y o p ec ne a e h be o b a ed w h en u s n g samples co n were v en o n a m n g ech n q u precursor es C l l apse t he ent i r e st r uct ur e. One w ay t o el i mpromising characteristics for delivery [ 22]co . Fig. ge 3 shows nauer al. 1938). The measured after sample probably because ofsystems low A (es H y dr ogel ) precursors, Tex t u rof al qua-gel pr o−p1er t i1 o f p o l yet sacch ar id e- b ased aer o gel s r ep o r t ed i nan l i tmost er at u rgee. 17– 21] . ied [y 14] .airreaching network, point gelation, see Fig. 2. This is the transo a co h odrug ch n s can h en be su p e c ca y d Pol m er gel at i onthe the initial gelation time, catalyst, solvation, and thermal conductivity ofwhereas the isxerogels 1.004 and 0.0209 W m K−e 2 − 1 3 [kV. interactions in order to build an interconnected % H ch GTh e s a e a ve p op o on o h An o h m an u ac u n g othree-dimensional p o n s degree o pof o cess h e ae o ge s n he 217.00 m g , r espect i vel y. The por e's di amet er ar e 30.50, 25.60 and are white and opaque, are yellowish, proportional to liquid/solid contact angle and liqo b a n ch n ae o ge s o h gh p o o s y h gh su ace a ea a possible to appreciate quasi-spherical particles and more internally the m ough a super cr i t i cal dr yi ng, w hi ch pr oduces a the morphology of some aerogels are used asr al carriers ofer drugs. is n c on o he s er a so u ce e g po m o b ead s m m cen e e an ge Th e u suthat aresist p o cess o gel t ype M orm pho l o gy Tex tu p r op t i esIt u Ref ench ce being degassed forand 5ehsee ate70 °C. cellulose concentration was unable to high and The aerogel inand Fig. 1o was obtained through the sol-gel process, also lation conditions gel can produce aerogels with different respectively, while these for are and contained Average pore sizes were studied using the image ofsiaerogels the sol in a Aer wet gel. If 1.24 the liquid inside the d en s y w ch an ges n v a d ep en d nc g y o h e y ch n network, point of gelation, Fig. 2. This is the transQ r formation where Vp isthe volume at agiven step (aquagel 9.40 nm for t he gimore natthe e,shrunk. l i ca st1.007– ar ch ogel , uid/gas rthe espect i vel y.pores Due tprocessing oso C.A. Gar cí a- Gonzál ez et . /o Carsample bohydr at e Pol ym er s 8 6 ( 2 0 1 1 ) 1 4 2 5 –1 4 3 8 u xalh ne fl u en ces he sn a n an dn mco o ec n g apaer p reaching o ach s o d o p1432 a u on co n a n n g h e y sacch a d e translucent and much surf ace tension and inversely to St ar ch ( p o t at o ) M o n o l i t h proportional ( b y tpossible ho ern m al gel at i o nquasi-spherical ) ε ≈o 0and .4 6so g/ cm S = the 7 2u msed / g; M eh ling et n al . (200 9) ye al P r face t ensi on and t hus, t he l i qui d-vapour i n− 1 − 1 an d h e so a co h v;en ne h e o g a w ge T toInstruappreciate more internally interconnected three-dimensional network well as their porosity. de E s a 199 8 J en k e ns & Do n ae o ge p of ecu so morphologies, b y stages: m ean s o etc. a [ sy n TM ge heterogeneous naerogels o zz e n as o a uparticles on co n stresses developed during water subliknown as wet chemistry technique. This process involves two 4 H.0.02 Maleki etW al.l m /ar Advances and Science 236 (2016) 1–esent 27 porous pore size 16] . pores Mesoporous can be Kin Colloid respectively. Fig. 1 shows the physical appearance d rInterface software Archimed (Microvision formation of the sol in a wet gel. Ifp the liquid contained inside the V = 00 .4 7 cm /g or after drying) and V is the volume of cellulose t he ge sur face ar ea pr ed by t hese aer ogel s, t hey coul d be used Tab las e analysis 2 is eliminated by an evaporation process, a xerogel is obtained, this is sol l To prepare aerocryoand xerogels we used Ts o p s as e a 2 0 9 network pore size. In the case of cellulose ‘‘ aquagel ’’ , ge a o n n a h ee s ep h e m a y ass a n n g h e ge n g o m o e agen Ge a o n ak es p ace u s a e a 2.1.1. for delivery t ur n, for ms an aer ogel . Any mat er i al t hat can F Q A Tex t u r al p r op er t Aerogels i es of p ol yl sacch ar( id ebased aerm ogel s r ep or t ed in l i tn er ) at u r e. St ar ch ( co r n : Eu r y l o n 7 ) M on o i t hdrug b y tinterconnected h er al gel at io ε ≈ as 0 .3 4 g/ cm S = 90 m / g; M eh l i n g et al . ( 2 0 0 9 ) three-dimensional network well as their; porosity. C hPluronic o san o b a ed b y d eace ysacch a oa n o ch n a o e po y d e n e w onk n h d o p o h eby so on co e n o co n ac w h Fig. hwere e s ge n g pn o solution andtgelation. The fiais rst stage is e the sol formation, that is,u colScanning electron microscopy (SEM) mation. All the other samples monolithic. Fig. correspond to alginate microparticles, 3b to silica microm w m w h t i c dr ugs produced using templates (surfactants) such as CTAB, SDS, an aerogel bymainly research group after supercritical eliminated bys an evaporation process, ahave xerogel is3a obtained, this is ments). Atm least 100 sizes on each of three different car r i er srsynthesized [ our 22] .due Fur her , al gie nat and chi tp osan aer ogel s solution before coagulation. volume shrinkages i of V rAll = 0 .3 7i es cm /g cellulose concentrations ranging from the first two high because cellulose is Aer ogel p t are ype e M or p h ol ogy Tex t uesen al pK rs op er teas Ref er en ce to the formation ae meniscus liquid-vapour interace y ad p o nac o w e H n he m oof e e g in the H an d components o em a u e co n o ed so u ohas nd p ce s usi ng t he sol -gel t echni que can be dr i ed by b ey o n d 5 0 % y p so u bbe n so d u e d sa p < 6 w H an C Nowadays, the about biocompatible aerogels increased c solutions with to alginate microparticles, 3b toM silica t ar ch ( f r o m n at i v e co r n gr an u l es) M i cr o sp hinterest er es Fig. (b y3a t hcorrespond er m al gel at i on S = 3Fig. 4– 1 11 m / g;microTh i s w o r k loidal nanoparticles dispersed in adue solvent by hydrolysis and conB m & A Coagulation and stepslead to certain volume er wt%: W o n & Bam u ced nua ach 19 7e 9 o ca o n s e su seq uten su e the c ca d y n g o ge ead s om a t ar ch (p ot at o) p M on ol ie t hThe (by t hB erdrying m al gel at ih on )e are ε ≈ in 0.46 g/ cm ; S = 72 / g; M eh la i no g et al . o (2009) r3ecei ved grThey eat at tfragile ent i on because tS hey have mucoadhesi ve oper iSes, mainly to theTh formation ofb apr meniscus in the liquid-vapour interF127, P123 P65, which work as forming drying process. are and have a bluish-white coloration p o o ch o san y nfl u en b ych h e d SEM images per formulation were measured. particles and Fig. 3c to microparticles. The alginate, silica and after each step shown Fig. as of e/w tou11 monoliths are not from solutions p m et h o d structure's co u p lstarch ed t op em uagents l si oes n V = 02 .1 2a– function 0 .3 7 cm g; m P = 2– n 9 nm hydrophilic and water surf ace tension is high. In V = 0.47 /g 0 er ogel o b seo v edha e s d sso b h e ae oA ge o m a walls on F gs 5to b their anlarge d 6surface Qu gn a d porous e a 2 0 0 8 2cm 0 1 face, where a formed gradient of capillary tension is are formed on the of the due area and open structure. Those are particles and Fig. 3c to starch microparticles. The alginate, silica eace y a o n an d h e so u and ce e ch s a nch p ecu sov edQu t ech n i q u es) , d D = 3 00 2 0 Sof t ar ch (cor n : the Eu r y lwalls on 7) M on i– t h1 (by t h0 er m alm gel at i volume on ) ε ≈ 0.34 g/ the cm % ; S = 90 m / g; eh l i n g et al . (2009) m densation joined by. to electrostatic face, whereo a gradient ofb capillary tension is formed on of the compared to the occupied byand Morphological analysis the dry celluloses was Dr y i n g [e 17– 21] [ 14] .S lower nM g os am ych o se o m o ecu es ev e s b Th enanoparticles s ze h ead s ob a n ed b y was h s mshrinkage e h ol o d s m a n y co ns o ed minimal resolution 0.1 l m.on with cellulose content reactions. becauseThose the Ev apor at i on cellulose concentration and drying method, and the addition capill ary stresses, is due to a 2 0 h y ca hy can e o a starch microparticles am large surface area of 567.62 V = 0.37 cm /0 g Pect i noverlap ( f r o m ci t r u s p eel ) P odensificati w d er ( b y have te h er al gel io n )1 0 ε ≈ 0 .2 g/ cm ; d S =o 4 8ge 5m m / g; o W h i tsan e, Bu d ar i n , et alb . (2 010 ) b F Qat P Con v er si on t h e w et gel i n t o aer ogel , promising characteristics for drug delivery systems [359.54, 22] .P Fig. 3S shows d es uc o n o ho e p gy an u e s uc u e by h eentire o fi ce d am e e o h sy n o zz e sed d u ng h e starch have a large surface area of 359.54, 567.62 and A u th o r 's r s o n a l c TM pores and can cause a collapse the structure. One way to elimSt ar ch (f r ome n at i v e cor n grn an uge l es) M i microparticles cr ospp h er esu (by t h er m al gel at i on o = 34– 111 m /ge g;cm Th i sp wo ore k p ec a o n an ac d c ch san so u o n n an a k a n V = 3 .6 2 / g m in order to build anand interconnected three-dimensional pores can aperformed collapse the entire One way 2n − to 1electron in Zeiss 40 FEG scanning solution the mold. The volume was The aerogel in Fig. was interactions obtained through the sol-gel process, concentration is 1around 1– 1.5 wt% for m et h od p l ed to em u l sin on g V = 0.12– 0.37 cm / g; P = 2– 9 n m m m mca m e& og ada on s ep he s a ch hyd o o microcrysm a oalso n cause Fstrong n a y a mSupra ostructure. d fi o h einitial p o cess u s p ushrinkage sed e 1. ec hydrogen bonds that are formed between final are summarized in Table 2 cou −at 1in x er ogel an d cr y ogel w values C Pect i n ( f rW o m ci t r u s p eel ) M og n ol t h ( b y aci d i c gel o n) ε ≈ and 0 .0 7C g/ cm Se = 200 m / g;2 0 0 8 WA h i t e, An i o , et n al g . ( 2 0 1o 0) 217.00 mo , ielimrespectively. The pore's diameter are 30.50, 25.60 o F g 6 b Qu gn a d; a e t o nag a the of some aerogels that are used carriers of drugs. It=is tn ech n i qg u es), = 300– as 1200 m 217.00 m ,Direspectively. The pore's diameter 30.50, 25.60 and co n g an d ag n g o o w ed by he e e dts he a olm n t oo h e aq u eo u s p ecu so u are o n Fi g. 2. Sol -gel pr ocess for t he chemi cal synt hesi s of ogel s, w hi ch stc arinate tfi s w i th he tdrying, ro ansi t2. i on ofais a col oi dal sol uto i morphology on an i nt er connect ed gel net w orgel k (gel atso i on). The A m o m inate this meniscus ism through aaquagel supercritical which produces a za 0 .3 8 /g network, reaching the point of gelation, see Fig. This the transthis meniscus isafter through supercritical drying, which a Pect i electrons n (f r om ci t r detector. uwhich s produces p eel ) Pow d eron (by all t hh er me almonolithic at i on ) ε V ≈ follows: 0.20 g/ cm ; Scm = 485 / g; W h i t e, Bu d ar i n , et al . (2010) m e ch o san ge sm a e ec w ash ed sev e a he p m es w h d Sol v en t ex t r act i on talline (Gericke etaer al. 2009), and solutions of known ascel wetlulose chemistry technique. This involves two stages: microscope with secondary Prior calculated for the samples hydroxyl groups are present Coagulation of) dissolved microcrystalline cellulose Fig. 1 process Examples of an and samples drying techniques (aerogel, cryogels and xerogel) obtained from 7 wt% ys a za o n o o0 9 y sacch a d h o u gh h e numerous n o zz ewith wdifferent as ep o ed o h e p ep a ti a oet n o m as c o s zed Vε = Due 3.62 /, grespectively. Al gi t n at e (f r o m Ca- al gi n at e)appl i cat i on. Mto on ol i t h ( bquasi-spherical yw i9.40 n ta er n al set n g m h od = 9cm 4 % ε ≈ 0s .1 3 g/ cm ; M eh ling et v al . n (20 ) fur t her pr ocessi ng st ages i l l ust r at ed may be combi ned dependi ng on he speci fi c needs of t he 9.40 nm for the alginate, silica and starch aerogel, respectively. to nm for the alginate, silica and starch aerogel, Due to possible appreciate particles and more internally the e u n n eu a p H each ed Kad b M o ge C acc Fi g. 1. Pieces of aerogel with transparent and bluish appearance. 2.1.1. Aerogels for drug delivery an a n za on em p e a u e a e a g gel. na e(almost ge contained p a surface c tension es Zh ao C a a ain- W o n Haci a s Pect i n the r om ci t r u sv p eel ) M on & ol i t h (by d i c gel at i on ) 2 0 0 7 ε S ≈ 0.07 g/ ; –S 3 =0 200 m / g; / g; V Wd h i t.9 e, ge An t on i o, al . (2010) cellulose solution liquid-vapour thus, and zero) very = 1cm 5ar 0 m = cm /et g; formation thezero) sol formation, inta a wet Iflow the liquid inside the pores higherand concentrations rather difficul to handle due low (almost surface tension thus, the liquid-vapour incellulose chain. As a(fwere result, the overall volume gelation. Thevery fiare rst stage isofthe sol that is,and colC .A. G cí azál ez et al . /1 Car bohy dr at e Pol y m er s u 8 6 ( 2 0 1 1 )1 4 2 5 –1 4 3 8 Results and discussion the samples metallized with volume shrinkage of up to 200 vol% atG 3on wt% Bo u a & b B u e 2 0 11 A ec a en a a e o V =n 0.38 cm /g nfl u en n g seq h e ge o m a w on F g 8 Ae o ge m observations c o spall he es F g 5c can b esm ob n ainduces n ed y co u p n g Adapt ed fr om Ref. [ 16]solution . P = 1 2 n m the large surface area presented by these aerogels, they could be used as interconnected three-dimensional as well as their porosity. Al s gi n the at e (flarge r ompo Caal giy n atm e) on ol network i tthese h (by ch in t er n al set t ich nthey g m etan h odM ) Vx ε = 94% , ε ≈ 0.13 g/ cm ; ge MC eh l ie na g et al . (2009) surface area presented by aerogels, could be used as Nowadays, the interest about biocompatible aerogels has increased ca p eoc su on up ed d s& a co a ge ex en v so M k 20 0 8 Al y zai o se ecu es a h e so ed v e s e e m u on edto on n qu e ay e S an disappears, this turn, forms an aerogel. Any material that can to their high viscosi ty. It is also noti ng 2015). Classical methods such as mercury porosimetry is eliminated by worth an aC xerogel is obtained, this is in cellulose xerogels is and above Al gi nterface at eprocess, (that fca r oconm a-shrinkage al gi n at Bead sclose (b y i fza fu si o n m ete h o d )cellulose = 9300 9 % ; S ==3 0cm 0 – /5 / g; nAm ai ef , Al t o u nm , et al . (2011 ), loidal nanoparticles dispersed indisappears, a solvent by evaporation hydrolysis and Sε = 150– m / g; V 1.9 g; 8 0 m terface this in turn, forms an aerogel. Any material that can concentration in solution. This value 7nin nm ofe) platinum. The acceleration voltage used was Volumeshrinkageð%Þ¼ 100 1 ð1Þ Xer ogel Lean d rd o,u Kon n g, g Pek alh a,e & Kasch m ia t t er , 1 and nitrogen adsorption (BJH approach) do not allow ead n g o v o u m e sh n k ages o 6 0 % o v e carriers ofThose drugsare [and 22] .Fig. Further, alginate and chitosan = 1 .1 – 1 .2 aerogels cm / g;have P = 13– 19 n m M eh l i n g et al . ( 2 0 0 9 ) , Qu i gn ar d et a PV = 12 nm Fig. 3a correspond to alginate microparticles, 3b togn silica microdue to their surface area and open porous Vsol a obtaini the nglarge pore size distribution in cellulose aerogel s: can aer ogel ta ech no oln ogy . Usi n g t h i s emca u l si o carriers of drugs [ 22] . structure. chitosan aerogels have be synthesized as using sol-gel be dried by F .g 6 d eother a 2 0Al 0 P ep a Al gi n at e (f r om al gi n at e) Bead (by d ib f f u si on m et Qu h od ) ε = 99% ; S = 300– 580 m / g; n ai8 ef , Al zai t ou n , et al . (2011) , (2 mainly due the ofelectrostatic a meniscus inwet the liquid-vapour interthe supercritical drying process toCaobtain aerogels [Further, 15] Thesalginate variation of conductivity of aerogels are low. For refractive index 12comparison, 3toasare 008, 2 0 1 0 ) ,o Ro b i ch t zer em et al . ( 2 0 0 8 ) densation reactions. Those joined by Sample inbe the first case, aerogels compressed under shrinkage, density and porosity decreases tosan around 5 vol% for all the higher 3gels kV. benanoparticles synthesized wetformation gelsthe using the sol-gel technique can dried by aretechnique V =n 1.1–mucoadhesive 1.2 cm / g; d P = 13– 19 nso m M eh l i n go et al . (2009) ,u Qu i gn dn et al . (d i ar t iar cl es am,o et er o of, 1 3 0i0 0 ard m )2 ar e received great attention because they have properties, o chThe o ac c u n s p s g d a d mercur y pressure and mercur y is not enteri ng pores, particles and Fig.systems 3c to ge starch microparticles. alginate, silica and Ro b i tm zer Rn en zo &–an Qu gn d ( 01 1o 1 promising characteristics for drug delivery [ 22]of.s Fig. 3 shows (2008, 2010) , Robi t zer et al . (2008) , F g 9 E ec o ge d yand ng m e conductivity od ge m on y h s o p ec oformed h e sam e of d m en s n s catalyst, and walls in the second, BJHthe does not allow obtaining pore o a1.004 gradient ofthree-dimensional capillary on the the initial precursors, gelation time, degree solvation, gethermal offace, the air iso and 0.0209 W tension m − 1n K−is received great attention because they have mucoadhesive st i r rC inh g of an aq u s.p h0 asen -0 oi l) ( or interactions in h order to e build anwhere interconnected an d Val en t iC neou et al (2 0& 5, i 2 0 6 ao J h en g an ed ep so ashrinke e w s properties, e n kconcentrations. o ss c as cellulose Additional volume Robi o t zer , Ren zo, & Qu i gn ar d (2011) Average pore sizes were studied using where V sample volume at a given step (aquagel sizes in a widesu range, from few tens of c nanometers to network p the ep a ed y he s m ge a on W h wi d a n eofa 2 0dal 1 0sol d ed u nd e p e ca the image xtisthe Fi g. 2. Sol -gel process for chemi calbsynthesi of a aerogel s, whi ch starts th Bu the transi ti on a gi col l oi on to an i few nterconnected gel (gel ati The starch microparticles have aylarge surface area of 359.54, 567.62 un t2006) il h th en gel at on of tu h e, d i sp sed p ase Al n at e (f r o m uti Caal gi n at e) M i cr o sp h er es (on). b in er n al It set t ig ng S and =v 31 8 – 6 8 0 ex m / g; Al ai o ef , iAl zai to n et al er . (2 011 ) hp an d Val en t i n et al o . (2005, the morphology some aerogels that are used as carriers of drugs. is A e ag n an d so en ch an ge e an a o o m em e microns. As roughly estimated from SEM images, d y ng ae o ge an d u n de a d y these n gpores xe ge TM andocan cause entire structure. One way to of elimlation conditions and gel processing can aerogels with different respectively, while for the aerogels 1.007– 1.24 and Al gi n at e (f rcoagulation om m Ca-et n at e) osp h u er es (by iage n t er n al set t i observed ng SV = drying 318– mthe g;coagulated Al n ai , Al t ou n ,m et . (2011) After inproduce ethanol and washing network, reaching the point of gelation, see Fig. aare 2.collapse This isthe the transthe average distanceArchimed between the cellulosic fibrils in be after h d co u p l ed tM oi cr em l si on = 680 2 of .1 5/– 4 .0 5 cm / g; P =ef 9 – zai 15 n 2al0 1 1 ) . Pr op er t i es of t h e m i cr osp h er es ( p a 2al gi− 1o analysis software (Microvision Instruorseveral after drying) and Vsolucan is the volume of cellulose urther processi ng stages i l l ustrated may be combi ned dependi ng m et h od cou pdiameter t o em l si on V = 2.15– 4.05 cm / g; P = 9– 15 n m the beads is of the order of tens of nanometers and 217.00 g respectively. The pore's are 30.50, 25.60 and − 1 on − 1 the speci fi c needs of the appl i cati on. tm ech n i, q u es) , D = 7 5– 5 4 7 l edthe m possible to appreciate quasi-spherical particles and more internally ar ea) can b e t ai l or ed b y con t r ol l i n g of t aerogels ech n i q u es), can D = 75– 547 m fibrils’produces thi ckness is arounda 20– 30pore nm.cycles average inate meniscus through aageen supercritical drying, which porous morphologies, size etc. [ 16] .t Mesoporous be 0.02 s, Ww mof K sol Fig. shows theis physical appearance ofi on in.an water, ‘‘ aquagels’’ formation in s a wet gel. If this the liquid contained inside the sol pores cellulose: ithis enormous vacuum drying, followed arlr an Bead s ((gel hwhite er m al t rThe eat m it h ε52% = ;5 ; ε ≈ 1 ; i gn ar d et al . (2008) i gn ar d et al 20 0 8.) Th e si ze d i s Fi g. 2.from Sol -gel process hithe ch strespectively. art with t he t1 ransi t i on of a- C col oi dal ut to an i nt ed gel w ork at icellulose on). ments). At least 100 sizes onThe each ofdistilled three different - Car r ageen (t hen er m t al tw r eat m en t w i tAll = ε2 ≈% 1.48 g/ cm ; .4 8 g/ cm Qu sizeerconnect of the beads is of few micrometers in diameternet an d chQu em i cal f or m u.l ( at i on solution coagulation. volumeεfor shrinkages Adapted Ref. [ 16] . for t he chemi cal synt hesi s of aerogel 9.40 nm for the alginate, andsbefore starch aerogel, respectively. Due to interconnected three-dimensional network as wellsilica as Bead their porosity.

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cat i o n i c sal t s ad d icat t iio Image anal ysis of aerogels prepared from solutions of onn i c) sal t s ad d i t i on ) different cellul ose concentr ations shows that bead’ s size decreases with increasing cellulose Agar concentration gel Bead s (by t h er m al gel at i on ) Bead s ( b y t h er m al gel at i o n ) from approxim ately 2.3 l m for aerogel s from 3 wt% cellulose solution to 1.3 l m for Cel 11 wt% l u lsolution. ose (f r om eu cal y p t u s p u l p , Sol u cel l ) M on ol i t h s (by sol v en t d i ssol u t i on ) kinds of , cryogels the same ogy ( f r o m eu cal y p t u s Both pu lp Sohave lu cel l ) (f M o n l liutl ose) h s ( b y so l M v on en i sso len utt d i io nu )t i on ) Cel l u lmorphol ose r om n at iv eo cel ol itt hd s (by sol v ssol which is typical for freeze- dried polysaccharide-based ( f r o m n at i v e cel l u l o se) M o n o l i t h s ( b y so l v en t d i sso l u t i o n ) samples (M attiasson et al. 2009) and very differ ent Cel l u l ose (f r om bact er i al cel l u l ose) M on ol i t h s (by bact er i a, t r eat ed from aerogel s obtained via drying with sc CO2 t h er m al l y an d w i t h 0.1 aq u eou s N aOH ) (Fig. Freez 2 − 1 (5 f r om b act er i al a cel u la o se) M on on l i ted h s (b yd b act er i(by a, dtr op r eat ed Ca u m gl4). n e ae ge o b a n e ap a m Ch i to osan Bead sen ph ing aci de i c ch i t osan

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= 2 00 –/ g; 230 m / g; SaS =a 200– 230 m2 cl es ar e m ai n l y i n fl u en ced b y agi t at i on VpV =p 0.8– cm–3 /1 g; .2 Pr =cm 9– 113 n/ mg; Pr = 9 – 1 1 n m =1.2 0 .8 m at r (2011) i x p r ecu r sor con cen t r at i on an d aq ε = 89%; Sa = 320 m 2 / g; Vp = 0.3 cm 32 , Ren zo, & Qu i gn ar d ε = 89% ; Sa = 3 2 0 m / g; / g; Robi Vpt zer = 0 .3 cm 3 / g; Ro b i t zer , Ren zo , & Qu i gn ar d ( 2 0 1 1 Pr = 18 n m u m e r at i os ( Al n ai ef & Sm i r n ov a, 2 0 1 1 = 1 8 g/ ncm m 3 ε P ≈ r 0.02– 0.5 ; Sa = 50– 420 m 2 / g In n er l oh i n ger et al . (2006) (2 su ar ea, p or e si ze) h r esu l t i n g 3 cm 3 ; ε95% ≈; 0 .0 2 – 0.3 0 .5 g/ Sa Gav = 5 4d2 0d tm / gr f ace In n er l oh in ger et al .of ( 2t 0 0e 6) ε = ε ≈ 0.06– g/ cm ; i l l0 on– an Bu ov a (2008) n ot si gn i fi can t ly nfl u en ced t8 h)e p r oc Saε = 200– 300 m / g ≈ 0 .0 6 – 0 .3 g/ cm 3 ; = 95% ; 2ε Gav i l l on anid Bu dt o v a (b 2y 00 ε ≈ 0.008 g/ cm 3 ; Sa = 200 m 2 / Li ebn er et al . (2010) r at e, aq u eou s sol u t i on - t o- oi l r at i o, su r f Sa = 2 0 0 – 3 0 0 m 2g; /g Vp = 0.5 cm 3 / g; Pr = 5 n m 3 2 ≈ 02.0 0 g/ cm = 2 0 0a m g; et al . osi (20 0 ) ofo o n om h M eh n e 009 bar b ead an d m a sol i t e 3 m aii gn n ly beb y. tn her e com p t1 i on tp he sel a g Saε = 330 / g; V8 / g; ; S Kad ib et al/ .2 (2011) an d Qu dLi et al p = 0.4 cm 3 / g; Pr = 5 n m PrV =6 m 0 .5 cm (2008) p n= cr ossl i n k er ) ( Al n ai ef , Al zai t ou n , et al ., 2 0 3 et al . (2008) ε S ≈ a 0.38– 0.92 g/ m cm 32 ; / g; Vp = 0 .4 cm Ch an g = 3 30 / g; Kad i b an et d al t .h (2 1or 1 )ean Qu gn ar d tet su r f ace ar ea e0p si d ze d iist ri bu io Sa = 66– 845 m 2 / g; Vp = 0.1– 3.5 cm 3 / g; Pr = 6 n m (2008) t i cl es sh ow si m i l ar v al u es t o t h ose ob t ai n Pr = 2– 5 n m ε ≈ 0 .3 8 – 0 .9 2 g/ cm 3 ; Ch an g et al . ( 2 0 0 8 ) ε = 84– 92%; ε ≈ 0.12– 0.22 g/ cm 3 ; Tsi op t si as et al . (2009) m on ol i t h i c aer ogel s. Af t er gel at i on , t h e m 2 2 = 6 6– 4P 5 m /m g; Vp = 0 .1 – 3 .5 cm 3 / g; SaS =a 220– 363 m8 / g; 1– 3 n r = om t h e m i x t u r e ( e.g., b y fi l t r at i on or ce 2 3 SaP = 560 g; Vn =m 1.2 / g; Robi t zer , Tou r r et t e, f etral . (2011) per =m 2 5h t he m ol d –/w e cm t he gel i s p r ep ar ed : r Prε = 10 m er cr it t si i cal in g, t0 h9 e)w at er con t a =n 8 4– 92% ; ε ≈ 0 .1 2 – 0 .2 2 g/ cm 3 ; t h e su p Tsi op as d etr y al . ( 20

Ch i t o san o n oaerogels, l i t h s ( baerogels y cellulose cr could oM ssl in k i ng w i t h in u t solution. This value Nowadays, about biocompatible has Ch i t i n on ol be i tconcentration hincreased s used (by solas v en t d i ssol i on ) the large surface the areainterest presented byM these they To prepare aero-y dcryoxerogels used loidal disappears, in aansolvent and can conal d eh es iand n aci d i c we aq u eo u snetwork so l u t i on ) terface thisdispersed in turn, forms aerogel.by Any material that ( Sol )hydrolysis pore size. In the case of cellulose ‘‘ aquagel’’ , 12 3 nanoparticles itin M on th h s (by sol v en d t i on of Sample density and porosity decreases 5t ht)vol% all the other higher Fi g. 4 . and Aer ogel m on olol i tito saround t ak e ei ssol shufor ap e of due to shrinkage, their large surface area solutions and open porous structure. Those are carriers of drugs [ 22] .ChFurther, alginate chitosan aerogels have r eacet at ed ch i t osan cellulose with concentrations from densation reactions. Those nanoparticles are joined electrostatic be synthesized as wet gels using the sol-gel technique can dried by Ch i t iby n be Mst oar no lit h s ( b yob so lranging v en tlb d i su sso lthe ucr tfirst iio ) components ch aer ogel t ai n edy y p er t in cal d r y i n g f rare om a because h y d r ogel p r ep two high cellulose is ar ed i n a m ol d Pol ymer sol utdrug i onthey r em ov ed b y sol v en t ex ch an ge. Th i s m et f or C h r i stmucoadhesive m as cook i es. S shrink= 220– 363 m / g; P = 1 – 3 n m cellulose concentrations. promising characteristics for delivery systems [ 22] . solutions Fig. 3 shows Additional volume received great attention because have properties, 3 to 11 wt%: formed interactions in order to build an interconnected three-dimensional water Msurface tension is high. In = 1 .2 cm / g; Ch i t in M monoliths o n o l i t are h snot (b y sofrom l v en t d i sso lhydrophilic u t i o n oand f S = 5 60 m / g; V Ro b i t izer Toiu r et t e, iet . (b 2on 011 ) d t h e p r od u ct on , of nror gan c (al car an bon d s bet w een ch ai n s ( Gar d n er & Bl ack w el l , 1975), bu t can be u d a, & Abd u l l ah , 1995). Th u s, ch i t i n gel s can be f or m ed ei t h er Aftermorphology coagulation of in some ethanol and by several washing y lused at ed ch it o san ) P = 10 n m age can be observed after drying of thebycoagulated the aerogels that are asbecause carriers of drugs. It is s ( Fi g. 5 c) ( Al n ai ef , Al zai t o sol u bi l i zed u si n g som e sp eci al or gan ic sol v en t s (e.g., con cen si m p l e agi n g or by d i l u t i n g t h e r esu l t i n g chb i t ased i n sol u taer i on s ogel in with lowerr eacet cellulose content the overlap network, reaching the point of gelation, see Fig. 2. This is the transaddition tohov capillary stresses, densificati on is due to(hei get au m f ast reu rd el S mm ir n a, S u t tge iru en gw g, l rer , )et S m ir 2 0 1 1 ; Li u , Zh an g, Fu , Dr essel h t r at ed f or m i c aci d , cal ci ch l ord id dg eh y r at e- sat u r( at ed et an ol , l ar ex cess ofon w at er S yd ogel or al al ., coh ol (al cogel )n ( ov Tama, u r a, cycles in to distilled water, white cellulose ‘‘ aquagels’’ possible appreciate quasi-spherical particles more internally the cellulose: itease isxenormous for vacuum drying, followed 2+ 0N,N0 4; m iand r ov a microcryset 0 5 ). Th e sp eed of dam r ua, g d iTok ssol u t2006 i on).f Op ort id r al ulgl i t h i uconcentration m ch l or i d e d iS m et h ywt% ln acet am i d e al m i., t2 u0 r e) ( Fu rd a, 1984; Nagah & u r a, on y , ch i t i n h y day r ogel s et can al be., 1 9 9 6 ; W an g et al ., 2 0 1 1 ) . M er is around 1– 1.5 for formation of the sol in a wet gel. If the liquid contained inside the pores strong hydrogen bonds that are formed between Tsi op t si& as, M i ch ai l of ,w St au rl op l os, & i ot ou 2009; ar ila, so t obt n ed f rd om eacet at ed ch i1 tu osan in ) an s al ch coh ol i ci n b on d s b et w een ch ai obtained n s ( Gar dn er Bl ack el , ou 1 97 5Pan ) , ay b uar t ,tcan be M u a, & Ab d uy ll l ah ,i t 9 . aqu Theou u s, it gel s can b e f or m ed e l wet oad ed aer ogel m i cr op i cl esZak cou d b eal of hd rai ee or err s of m agn d9 e5 were as ishown in Fig. 1. Such aquagels interconnected three-dimensional network as well as their porosity. by rather high shrinkage for sc CO drying and low 2 sol u t i on ( Robi t zer , Tou r r et t e, et al ., 2011 ). Af t er sol v en t ex ch an ge Net w or k For mat on tallineor cellulose (Gericke 2009), solutions ofedcon f ast er sol tet hal. an d rand goad sol i d phydroxyl ar Lee &are Gou , 00 . Si lb i ca is eliminated by an evaporation process, a xerogel isbobtained, sol u i l i zed this b yis u si n g som e sp eci al gan ic v en tu s (le.g., cen - t i cl es b( y si m ppresent le ld agi g6 )or y d i l u t i n g t h e r esu l t i n g ch i t i n sol u t i o numerous groups which on2n t o an al coh ol , ch i t i n al cogel s can t h en be su p er cr i t i cal l y d r i ed t o an d car b aer ogel s m ifreeze-drying. n t hh e an f or ol m ,of m i cr op ar t i ex cl es ar e t r ad iw t i on l y (h y d 4r . ogel Case u d i al escoh on p ol y ar i ) d e(aer o were then dried one of the mentioned inon to microparticles, Fig. 3b to silica microt r mat c cal3a ci correspond u m by ch l or ialginate dtechniques e d eh y d r at esat u r at ed et l ar ge cess of atal er ) stor ol (sacch al cogel Tam shrinkage for ied on off or a m w et iintergelaci w i td h ,aFig. ai n ch n aer ogel s of h i gh p or osi t y , h i gh su r f ace ar ea an d l ow higher concentrations are rather difficult to handle due mainly due to the formation of a meniscus in For theat liquid-vapour As aobt result, thei t ioverall volume ai n ed om m( on ol th s cellulose b ichain. ll & Gou ld, 2 0 0 6 )Tok . H ow ev er , 0 0 6 ) . Op t i on al l y , ch i t i n l i t h i u m ch l or i d e + N ,N - d i m et h y l acet amob i dte m i xftru r e) Fu rid a, 1y 9m 84 ;i n g ( Lee am uen r a, h y d r ogel s ca dN en agah si t y w i t h ch ana, ges & i n v al u e d ep d i n g2 on t h e ch i t i n con cen t r acoher ent tnet was, or k . M v i ai ch Cr ai ossparticles and Fig. to starch microparticles. The alginate, silica and Solwhere -gel t r aansi t i on of capillary tension is formed Methods section; the3c resulting dry & samples are also Evaporative drying slow induces a lan ack of p ar t i cl e sp h er i ci t y an d t is he abtand sen ce of p ar n tol i cl e si un or ar ch Tsi op si walls l of , St au r op ou lto os, P ay ou , 2 0 0 9 ; vacuum Zak ar i in a, ob t ai ed fr om rfteacet at ch it osan i n an aq u eou s al co ial on so an d close t h e al sol v en tze u sed i ni he or i gi ny al l4.1. w et ed gelS (tTabl e 2) their high viscosi ty. It iisot also worth noting that shrinkage cellulose xerogels is tocoh and above face, gradient on the of the m i t y , r eq u i r ed f or m an y d r u g d el i v er y (ap p ltisi i on s, ar). e ex p ect ed t o link ing of sol par t i cl es Tsi op et al .,( 2009 sol ucat tas iis on R ob i t zer , Tou r r et t e, et al ., 2 0 1 1 ) . Af t er sol v en t ex ch starch microparticles have a large surface area of strong 359.54, 567.62g and shown in Fig.at 1.iAerogels and both kinds of Aqua-gel cryogels capillary applied on400 pore walls: it b e ob t ai n ed w h en con v en t i on al m i l li tiosan n g t iech q u es. ose an d am y l op ect i n e ar e t h e Ch s obtn aiin ed by d eacet y l at i on of ch i t i n Am in a y dl egr ee e chemi cal synt hesi s of aer ogel s, w hi ch st ar t s w i t h t he t r ansi on can of acause col l oi dal sol ut t o structure. an i nt er connect gel net w or k (gel on). The porest iand a collapse thei on entire One way ed to elim( Hydr ogel ) u si npressure t o an al coh ol , ch i t i n al cogel s can t h en b e su p er cr i t i cal l y d r i Pol ymer gel at i on 2 − 1 bey d 50% anxerogel easi l y sol Aerogel us bli en i ntd i le u t e aci d s (par H < 6)..Gel lin g r el at i v e p r op or t i on An ot h er are m an u f act i and n g op t i on i s t o pon r ocess tdhi tei saer ogel h st ch Th e of t h es Cryogel 217.00 , respectively. The pore's diameter 30.50, 25.60 are whitemandgopaque, whereas xerogels are yellowish, proportional tou rliquid/solid contact350angle and liqst r at ed may be combi ned dependi ng on t he speci fi c needs t he appl i cat i on. a supercritical drying, which produces a t ai nofch t i n ar aer ogel s h iby gh p or osi t y , h i gh su r f ace ar ea an d pob r op er t ge) i es ch ii te osan e m ai ly in fl uof en ced he of inateof this meniscus is through f or m of b ead s ( m i l l i m et er – cen t i m et er r an . Th u su al p rn ocessf utn ctd i egr onee of t h e st ar ch sou r ce ( e.g., p ot at o t y tan w it h ch an ie n u den en ncr gy on ch i td in ce dd eacet ysi liat i on tp h e sou r ce ofges tar h ei d ch i t i nvpal r ecu re sor ( ep Quces i gn ar d ralginate, 9.40 nm for silica andi nstarch respectively. Due tosol g apaerogel, p r oach i s t surface o d r op a t i on con ten ai n n g hd e ol y sacch i n flu td hie st altl h i ne it y an mcon ol ecu la translucent andthe much more shrunk. uid/gas tension and uinversely proportional to ye et ., 2010 ). Ph y cal h y dcoh r ogel s ol of ch i t osan can be obt ai n ed very low (almost zero) surface tension and thus, the liquid-vapour int ial on an tsi h e sol al sol ue sed nby t hal e.,or i9 gi gel ( Tab aer ogel p r ecu r sor b y m ean s of a sy r i n ge/ n ozzl ed int o a u t i on con - v en t rid ( El l i is et 19 8n ; al Jenw k i et ns & Don al d dr p r eci p i t at i on of an aci d i c ch i t osan sol u t i on i n an al k al i n e sol u theTo large surface area presented bytthese aerogels, be used as prepare we used (‘‘Tsi op,ttak si es as p et al .,u2 0af 09 ). 300Gel network pore In the case of cellulose aquagel’’ ai n in g t h e they gel lcould ing p rsize. om ot er agen t. at on l ace t on a t h r ee- st ep t h er m al l y assi st e al aero- cryo- and xerogels terface disappears, this in turn, forms an aerogel. Any material that can t i on (iFi g. 6b) ( Qu i gn ar d et jal .,st 2008 ).er Af t er agigel n g fat or ia ceritn ai n hch iw ti tosan ai ed y eacet ysacch l at i on of i t or i nk .i ( n e t h e d r op l et s of t haerogels e sol u thave i on com e i n t o tcon act i t h tgel he gel l iash nt g pn r oof t ih e dp ol y ar i d e nch et w i) a In d th i m e, ttC he osan si s ar e ob w ed sev er al tb im es d w th i st i l l ed t i c drugswith carriers of [ 22] . Further, alginate and chitosan i cellulose solutions concentrations ranging from the two are high because cellulose is r m ot er ( e.g., p Hfirst - an d components / or t em p er at u r e- con t ru ol sol t ian , pied rtesen p l,ace b yeriad tt i on of d w erHi n th hy be synthesized as wet gels using the sol-gel technique can be dried by b ey on 0u % d s easi sol u bagu le d i lp u e aci sat (p < 6 )e . Ge w at er n tli ed l d n eu5 t r al pH ion s r each (iKad ice b, M ollvy i n ger Cacci rn a, sor r c great attention because of 250 m Bou sm i n a, & Br u n el , 2011 ). Af t er a sequ en t i al w at er t oet h an ol e cat i on s) . Th e su b seq u en t su p er cr i t i cal d r y i n g of t h e gel l ead s t o ( W oot t on & Bam u n u ar ach ch i , 1 9 7 9 ) . received they have mucoadhesive properties, p op er t i es of ch i t osan ar e m ai n l y i n fl u en ced by t h e d egr 3 tou11 solutions p wt%: monoliths are not formed from hydrophilic and water surface tension is vrhigh. In sol en t techniques(aerogel, ex chd anet ge, cryogelsandxerogel) al cogel s0ar e dr u p su pob crser i t i cal dr yi n g t er Aer ogel 1 iExamplesof anaquagel andsamplesafter obtainedfrom7 wt% t h e aer ogel f or mFig. at on ( F i gs. 5 b an d dryingwithdifferent 6) ( Qu i gn ar al ., 2 0 8d , 2 0 10 ) .on v ed st ar is d i ssol v ed b yi g d eacet y l at i on an ti ed h e sou rer ce of t haf e ch i ti nch pr ecu r sor ( Qu S m ead ing t o v ol um e ai shn r il ny k ages of dur i ng t he ov al l pam r ocess Dr yi ng si ze of t h e b ead s ob t ai n ed bdensificati y t h i s lon m et h od m con t r60% ol l ed n ger of ych l ose m ol ecu l es, b i re r ev er t si bl ee with lower cellulose content becauseTh thee overlap at i on Evapor addition to capillary stresses, is due to ii s et al ., 0 1 ) .al P h y si cal h yd riogel s hof i t osan can ob ai n ( Fi g. 6b) (Qu2 gn ar d0 et ., 2008 ). Pr ep ar at i on of ch em i cal y d r o200 Conv er si on t he w et gel int o aer ogel, b y t h e or i fi ce d icellulose am et er of t h e sy r i n ge/ n ozzl e u sed d u r i n g t h e gel d est r u ct i on of t h e gr an u l e st r u ct u r e. ( i solution

mm

m

Aer ogel -Gel t r ansi t i on

m

Solv ent ex t r act i on

r

p

3

r

Cellulose (2016) 23:2585– 2595

2591

2591

Fig. 4 SEM images of cellulose aero-, cryo- and xerogel made from 5 wt% cellulose solution

123

ps r eci i t at i on aci co-ch i tdosan sol u t gel of chp i t osan in aci d i c of sol u tan i on s u si n g d mion an d i al d eh y d es

i on

in

an

al k al i n e

to their high viscosity. It is also worth noting that shrinkage in cellulose xerogels is close to and above Xer ogel 123 50

sol en t ex ch s& ar d i0 ed on su p er cr i t il cal t h e so- cal ed i n v er2015). se em u l siporosimetry on pol m er zat iv on t echn i qu ean ( Mge, ay er al , Scogel an Cle ar k , r2 0 8 )u . p Am y l ose m ol ecu es ard e not seem be mesoporous or withismall macropores Classical methods such asmercury Cellulose l (2016) 23:2585– 2595 2591toy ascan beseen from theimages of higher and nitrogen adsorption (BJH approach) do not allowsmall macropores lmagnification ead i n g t o v ol u m e sh r i n k ages of 6 0 % d u r i n g t h e ov er al l p r 2015). Classical methods such asmercury porosimetry not seem to be mesoporous or with (Fig. 4), and also deduced from low specific surface obtaini ng pore size distribution in cellulose aerogel s: magnification nitrogen (BJH approach) do not allow ascan beseen from theimages of higher Fig. 4and SEM images adsorption of ( Fi g. 6 b ) ( Qu i gn ar d et al ., 2 0 0 8 ) . Pr ep ar at i on of ch em i cal h y areasurface values(Table 1). All finestructure formed during in aerogels: the first case,(Fig. aerogels under obtaining poreand size distribution in cellulose 4), andare alsocompressed deduced from low specific cellulose aero-, cryogel ch i t osan i n aci d i c sol u t i on s u si n g m on o- an d d i al d eh cellulose coagulation and preserved when drying with s of mercury pressurearea and values(Table mercury is not1).enteri ng structureformed pores, xerogelinmade wt% aerogels are compressed the from first 5 case, under All fine during Fi g. 9 . Ef f ect o f gel d r y i n g m et h o d : gel m o n o l y t h s o f p ect cellulose in o f t h e sam e cellulose d i coagulation m en si odrying n sc COs is completely lost during freeze-drying. The and inpores, the second, BJH does not allow obtaining porewhen solution 2with mercury pressure and mercury is not entering and preserved as cr ossl i n k er s w er e al so r ep or t ed ( Ch an g, Ch en , & Ji ao, 2 pressureThe generated during ice crystal growth and The sizes inpore a widesu range, from fewer tens of cr nanometers to pr ep ar ed bsynthesis y t h er m gel atwhich i o n (starts W h iwith t e, Bu ar i n , et ., 2 0 1 0solution ) and d rsecond, i ed n obtaining d er p it inetwork cal in the BJHto doesu not allow sc CO freeze-drying. for the chemical of al aerogels, thed transition ofal a colloidal an interconnected gel (gelation). 2 is completely lost during t er agi n g an d sol v en t ex ch an ge t o et h an ol at r oom t em p er a applied and on pore walls compresses theAf fibrils together few microns. fromduring SEM images, d r y i n g ( aer o gel ) an d u n d er ai r d r y i n g ( x er o gel ) . sizes in a wide range, from few tens of nanometers to Asroughly pressureestimated generated ice crystal growth

m

dr

m m

r ye

m

ze ee

m

2

a

concentration is around wt% for Fi g.1– 9 . 1.5 Ef f ect of gel dor r y imicrocrysnm g m at et h od : gel on ol y t hs of n ofod t hbonds ei sam e dthat i mien si onof s formed f i on .m F i n al ly ,p ect a im fi cat on th e p r ocess u si n g pu l sed el(Ch ecr et r ogr adat i on st ep , t h e st ar ch h y d r ogel strong hydrogen are between xer ogel and cr yogel as ossl i n er w er eb al) so ( r ep or t i ed and g, Ch en , al & J i ao,2 2008 t icr on (kF is g. 6 Qu gn ar et ., 0 0). 8 ) . Af t er agi n g f or a ce r ep ar ed by t h er m al gel at i on (W h i t e, Bu d ar i n , et al ., 2010 ) d r i ed u n d er su p er cr i t i cal t r starts i c fiwith el dthe s ftransition or t h e om i zat i on toof t h e Af aq eou s d psol r ecu sor sol i on cool in an d agi n g, f ol l ow ed b y t h e r eor Fi g. 2. Sol-gel process for the chemical synthesisdpof aerogels, which of at a colloidal solution an interconnected gel (gelation). The t eruagi n g network an v en trex ch an ge tu o tet h an ol at r oom t em pg er at u r e, ing (aer ) an d usolutions d er ai r d rof y i n g (x er ogel ). 150 tpresent im e, t he ch i t osan gel s ar e w ash ed sev er al t i m es w i t h dis talline cellulose (Gericker yet al. 2009), and hydroxyl groups which are on Fig. 1ogel Examples ofnran aquagel drying techniques cryogels obtained 7 wt% th ou ghand t samples h e numerous nafter ozzl ewith wdifferent as r ep or t (aerogel, ed f or t hand e xerogel) p r ep ar atfrom i on of m i cr osi zed r ecr y st al l i zat i on of t h e p ol y sacch ar i d e s further processing stages illustrated may be combined dependingal on the speci fi c needs of the application. w at u nr tiis, l n eu t) r.al p H i s r each Kad i bi,on M ol v ip ner ger , rC n at e gel p ar t i cl es ( Zh ao, Car v aj al , W on , er & H ar 20 07 an d ed gel ( at i n i zat t em at u eacci ar e agu t he cellulose solutionto gi higher concentrations are rather difficult handle due cellulose chain. As a result, the overall volume & bBr n el Af t er a seq u en t im alat w at - t8 oAer ogel m i cr osp h er es ( Fi g. 5 c) can b esm obitn aia, n ed y u cou p l,i n2 g0 1 1 )i. nfl u en ci n g t h e gel f or i on ( er Fi g. ) (et Bah Adapted from Ref. [ 16] . 100 Bou Fr

m

Cellulose (2016) 23:2585– 2595

Fig. 4 SEM images of cellulose aero-, cryo- and xerogel made from 5 wt% cellulose solution

2

a

BET Sur f ace ar ea ( m 2 / g)

concentration is around 1– 1.5 wt% for microcrystalline cellulose (Gericke et al. 2009), and solutions of higher concentrations are rather difficult to handle due to their high viscosity. It is also worth noting that

Fi g. 2. Sol-gel process 0 resulting in ‘‘flat’’ non-porous walls. the average between the walls cellulosic fibrils inthe fibrils microns. As roughly estimated from SEM images, distance applied on pore compresses together further processing stages illustrated may be combined depending on the specific needs of the application. thefew average 1 2 Supposing that the majority of 0 pores in cryogels are the fibrils beads inis of the order of tens ofnon-porous nanometerswalls. and distance between the cellulosic resulting in ‘‘flat’’ ‘‘seen’’ with SEM, we measured fibrils’ thickness is Supposing around 20–that 30 the nm.majority The average the beads is of the to order ofan tens of interconnected nanometers and of pores in cryogels are a high-resolution Fi g. 2.from Sol-gel process network (gelation). The their diameter. This approach is acceptable because size of the beads is of few micrometers gel in diameter. Adapted Ref. [ 16] . for the chemical synthesis of aerogels, which starts with the transition of a colloidal solution fibrils’ thickness is around 20– 30 nm. The average ‘‘seen’’ with a high-resolution SEM, we measured cryogels have only very large macropores as it will be Image analysis of aerogels prepared from solutions of size of the beads is of few micrometers in diameter. their diameter. This approach is acceptable because further processing stages illustrated may be combined depending on the specifi c needs of the application. Image demonstrated further with BET analysi s. For cryogels different cellul ose concentrations shows that bead’s analysis of aerogels prepared from solutions of cryogels have only very large macropores asit will be of each type and of each cellulose concentration pore size decreases with increasing cellulose concentration different cellulose concentrations shows that bead’s demonstrated further with BET analysis. For cryogels Adapted from Ref. [ 16] . sizes were analyzed at different distances from sample from approximately 2.3 l m for aerogel s from 3 wt% Crsize yogel decreases with increasing cellulose concentration of each type and of each cellulose concentration pore

3 4 5 6 cellulose concentration ( wt%)

7

8

9

bottom in order to check the influence of temperature cellulose solution to 1.3 l m for 11 wt% solution. from approximately 2.3 l m for aerogels from 3 wt% sizes were analyzed at different distances from sample gradient in the unidirectionall y frozen samples. An Both kinds of cryogels have the same morphol ogy cellulose solution to 1.3 l m for 11 wt% solution. bottom in order to check the influence of temperature example of pore size distribut ion for cryogels made which is typical for freeze-dried polysaccharide-based Both kinds of cryogels have the same morphology gradient the unidirectionall y frozen samples. An ional freezing and frozen directly in the with unidirect samples (Mattiasson et al.in2009) and very different which is typical for freeze-dried polysaccharide-based example via of pore size with distribution made is shown in Fig. 5. freeze-dryer from aerogel s obtained drying sc COfor cryogels

Fig. 1 Examples of an aquagel and samplesafter drying with different techniques(aerogel, cryogels g. 2. Sol-gel process for the chemical synthesis of aerogels, which starts with the transition of a colloidal solution to an interconnected gel network (gelation). The and xerogel) obtained from 7 wt% Fig. 1 Examplesof an aquagel andFifurther samplesafter drying with different techniques(aerogel, cryogelsand xerogel) obtained from 7 wt% cellulose solution processing stages illustrated may be combined depending on the speci fi c needs of the application. Adapted from Ref. [ 16] . cellulose solution 2

Fi g. 5 .

samples (Mattiasson et al. 2009) and very different with unidirectional freezing and frozen directly the In in cryogels prepared without pre-freezing Freeze-drying to sheet-li ke cellulose Cal ci u m - al(Fig. gi4).n at e leads aer ogel ob t ai n ed in d i fno f er en t sh ap es: ( a) m on ol i t h s ( M eh l i n g et al ., 2 0 0 9 ) , ( b ) b ead s an d ( c) m i cr op ar t i cl es ( Al from aerogels obtained via drying with sc CO is shownporesof in Fig. several 5. 2 largefreeze-dryer noticeable influence of pore location (either in the network with and interconnected (Fig. 4). Freeze-drying leads to sheet-li ke cellulose in diameter In cryogels no in horizontal direction) on its size was vertical or micrometers due to prepared ice growthwithout during pre-freezing network with large and interconnected poresof noticeable influence of pore in theIt was already reported that ice crystals detected. waterseveral freezing. The pore walls in cryogels are location much (either micrometers in diameter due to ice growth verticals, around or in horizontal size ly wasgrown from the bottom-cooled surface thickerduring than in aerogel 80 nm, anddirection) they do on itsvertical water freezing. The pore walls in cryogels are much detected. It was already reported that ice crystals thicker than in aerogels, around 80 nm, and they do vertical ly grown from the bottom-cooled surface

Scheme 1. General pathway of synthesis of bio-aerogels 123

123

2015). Classical methods such asmercury porosimetry and nitrogen adsorption (BJH approach) do not allow obtaini ng pore size distribution in cellulose aerogel s: in the first case, aerogels are compressed under mercury pressure and mercury is not enteri ng pores, and in the second, BJH does not allow obtaining pore sizes in a wide range, from few tens of nanometers to few microns. As roughly estimated from SEM images, the average distance between the cellulosic fibrils in the beads is of the order of tens of nanometers and fibrils’ thickness is around 20– 30 nm. The average size of the beads is of few micrometers in diameter. Image analysis of aerogels prepared from solutions of different cellulose concentrations shows that bead’s size decreases with increasing cellulose concentration from approximately 2.3 l m for aerogel s from 3 wt% cellulose solution to 1.3 l m for 11 wt% solution. Both kinds of cryogels have the same morphol ogy which is typical for freeze-dried polysaccharide-based samples (Mattiasson et al. 2009) and very different from aerogel s obtained via drying with sc CO2 (Fig. 4). Freeze-drying leads to sheet-li ke cellulose network with large and interconnected pores of several micrometers in diameter due to ice growth during water freezing. The pore walls in cryogels are much thicker than in aerogel s, around 80 nm, and they do

not seem to be mesoporous or with small macropores 123 ascan beseen from the images of higher magnification (Fig. 4), and also deduced from low specific surface area values (Table 1). All fine structure formed during cellulose coagulation and preserved when drying with sc CO2 is completely lost duri ng freeze-drying. The pressure generated during ice crystal growth and applied on pore walls compresses the fibrils together resulting in ‘‘flat’’ non-porous walls. Supposi ng that the majority of pores in cryogels are ‘‘seen’’ with a high-resolution SEM, we measured their diameter. This approach is acceptable because cryogels have only very large macropores as it will be demonstrated further with BET analysi s. For cryogels of each type and of each cellulose concentration pore sizes were analyzed at different distances from sample bottom in order to check the influence of temperature gradient in the unidirectionall y frozen samples. An example of pore size distribut ion for cryogels made with unidirect ional freezing and frozen directly in the freeze-dryer is shown in Fig. 5. In cryogels prepared without pre-freezing no noticeable influence of pore location (either in the vertical or in horizont al direction) on its size was detected. It was already reported that ice crystals vertically grown from the bottom-cooled surface

123

Gels are titled for the hydrogels when the solvent is water. Chemical crossFi g. 2. Sol-gel process for the chemical synthesis of aerogels, which starts with the transition of a colloidal solution to an interconnected gel network (gelation). The

Fig. 4. Schematic presentation of the sol– gel synthesis of aerogels and typical parameters that are involved in each synthesis step.be TEMcombined image is taken from the initial step on of gelation further processing stages illustrated may depending the speci fi c needs of the application. procedure. The figure is partially reproduced with permission from Ref. [71,75]. Adapted from Ref. [ 16] .

linking methods involve the introduction of permanent linkages (covalent starts with the preparation of the gel (e.g. hydrogel, if prepared in an aqueous solution, and alco(aceto)gel, if prepared (or undergone a solvent exchange) in an alcohol or acetone. The gel itself is prepared from a solution of precursors, water, and a catalyst, which is termed as a “sol”, usually by the addition of a chemical cross-linker or by changing the physical conditions of the reaction (e.g. pH, temperature). The following steps are washing, and/or solvent exchanging with an appropriate solvent. In the case of a hydrogel, the w ater contained in the pores w ill be replaced by alcohol, affording an alcogel. In the end, the solvent that fills the pores ( usually ethanol or m ethanol) is

evacuat ed from the gels by a chosen suitable drying technology, w hich in most cases is supercrit ical assisted drying to obtain the aerogel material [31]. Fig. 4 summarizes some synthesis parameters of all the aerogel production stages that influence the gel network formation and, subsequently, its properties at the macroscopic level. Since aerogelsare prepared from a wet chemical synthesisapproach, the “sol– gel chemistry”, several parameters affect the evolution of the microstructural pattern of the aerogel network, such as the type and amount of precursors, catalyst concentration, type of solvent, reaction

123

bonding) by means of cross-linking agent for example glyoxal (dialdehyde), glutaraldehyde, butane tetracarboxylic acid, citric acid, epichlorohydrin, sodium tripolyphosphate and

N,Nʹ-methylenebisacrylamide, etc [35, 37]. On the

contrary, the physical cross-linking causes noncovalent interactions or combination of hydrogen bonding, van der Waals, and electrostatic interactions [38]. Apparently, the main goal of the characterized hydrogels is to have the ability to retain a significant amount of water or biological fluids under physiological conditions and behavior similar to soft, living tissues, which make them interesting materials [39, 40]. Preparation of hydrogels can be accomplished consuming natural polymers, synthetic polymers or mixture of natural and synthetic polymers. Natural polymers, in particular, polysaccharides are given much attention by virtue of their biosafety, availability and biodegradability in addition of being economical [41]. Inter and intra crosslinks can be formed for many of polysaccharides that dissolve in aqueous solutions [1]. Such polysaccharides are 5

able to undergo the formation of van der waals forces or hydrogen bonding due to the existence of functional groups localized on their backbones [42]. These functional groups are represented by the hemiacetal oxygens, hydroxyls, or methyl groups thereby leading to formation of viscous solutions or gel. Of course, all native polysaccharides do not form a gel; they can be cross-linked using various cross-linking techniques to induce gel formation [43-45]. Returning to the steps of aerogel formation, the final step is to convert the wet gel to aerogel using drying technique. As shown above, there are three types of the solid material, viz., aerogel, xerogel and cryogel which are formed depending on the drying method [46-49]. By and large, the aerogel term is used for both lyophilized and supercritically dried material because the two methods of drying; Lyophilization and supercritical carbon dioxide (Sc- CO2) are widely used for aerogel formation. 3. Different techniques used for gel drying It is well known that the porosity and surface area of the formed aerogel is mainly affected by the drying techniques. In aerogel production, the drying step is the last and the most critical step [50]. It is worthy reporting that the wet-gel of polysaccharide polymers have heterogeneous structure with high porosity filled with liquid, mainly water [51, 52]. The function of drying step is intended to remove the liquid located inside the pores. It is known that, the traditional drying techniques tend to the formation of capillary tensions, as the vapor-liquid interface withdraw into the porous structure increasing the shrinkage and finally leading to the formation of cracked solid material [19, 53]. Thus, the objective of using the advanced drying techniques such as freezedrying, supercritical drying (CO2, acetone, methanol or ethanol), ambient pressure drying, vacuum drying, and microwave drying are aimed to remove the existed solvent inside the pores of the wet-gel maintaining the highly porous 6

structure and keeping the aerogel volume protected from disintegration, breakdown and collapsing. Below are the most advanced drying techniques used for wet-gel drying. 3.1.

Supercritical drying process Supercritical drying as shown in Figure 2 is an alternative drying

technique to the traditional drying, which has the capability to fabricate aerogel while preserving the porosity. In addition to preventing the collapsing of the pores, it also keeps the excellent textural properties of the wet-gel in the solid form (drying state) [54]. Supercritical drying system obstructs the formation of a liquid-vapor meniscus that move away upon the voiding of the pores in the wet gels. Practically, supercritical drying involves heating of wet-gel in a closed container, with the goal that the pressure and temperature exceeds the critical temperature and pressure of the solvent caught in the pores of the gel [55]. Liquid and vapor phase become indistinguishable, just like supercritical fluids. Furthermore, there is no capillary forces present in suck process. The aerogel can be taken away from the autoclave upon the release of the fluid through the outlet valve followed by consequent cooling. It is very critical that enough solvent has to be provided throughout the entire drying process not only to ensure the consistency of supercritical conditions but also to inhibit the shrinking and cracking of the aerogel solid material. Low temperature supercritical drying and high temperature supercritical drying are two kinds of supercritical drying technique [56]. In low temperature supercritical drying, the organic solvents such as ethanol, methanol, acetone in gel can be replaced by using soluble CO2. Followed by transforming into supercritical carbon dioxide (Sc-CO2). This transformation can be occurred only at the critical temperature which is very close to the room temperature and subsequently leads to the formation of aerogel. Nonetheless, capillary pressure

7

can be eliminated with using supercritical drying and thus keep up the original shape of materials [57]. the critical point can be reached with controlling the pressure and temperature at which gas and liquid co-exist with high productive hydrogel drying technique has the preferred position that surface tensions in pores can be evaded to keep up the pore structure of aerogels. In high temperature supercritical drying, the hydrogel should be substituted with an organic solvent (ethanol, methanol, acetone) and after that set in an autoclave for heating and pressurization. The solvent vents out from the gel when the solvent reaches the supercritical state [56].

Figure 2: photo image of supercritical CO2 drying device. Reproduced with permission form [58]

3.2.

Freeze-Drying Process Bearing in mind, the simplicity, environmentally friendly and

economically cost, freeze-drying technique can be used for the production of aerogel with high porosity and reduced shrinkage [56]. Figure 3 represent the photo image of freeze-drying instrument.

8

Figure 3: Photo image of freeze-drying device. Reproduced with permission form [58]

The procedure for removing the liquid using freeze drying technique can be carried out as pursue: Firstly, the liquid in the wet-gel is frozen and subsequently under low pressure, the frozen wet-gel is dried by sublimation [59, 60]. This is the reason for nominated the prepared materials with cryogels. The prepared cryogels using this technique have high porosity (more than 80%) and only half the inner surface of practically identical cryogel. Specific securities for freeze-drying are necessary for two reasons; (1) to act as stabilizing technique for the body of the gel, and (2) to facilitate the exchange of solvent in order to provide high sublimation pressure and low expansion coefficient as well [61, 62]. The properties exhibited with freeze dying technique such as the more macroporous structures obtained with large shrinkage and high value of BET when compared with that of the aerogels prepared with Sc-CO2 drying. 3.3.

Ambient Pressure Process Ambient pressure drying process is a promising method used in industrial

scaling up [63]. This current procedure playing the role to passive the pore surface 9

of the wet-gel. By passivation, there is no chance for the formation of newly chemical bonds to be created during the drying of the wet-gel. By then, the solvent was exchanged with organic solvent; acetone or ethanol followed by drying under ambient pressure condition [64]. The ambient pressure drying approach is a facile technique leading to the preserving the consumed energy by other techniques and tend to prepare such aerogels. But using this technique leads to the formation of the solid material (like aerogel) which may have insufficient porosity and large shrinkage [65]. 3.4.

Additional Drying techniques The other drying methods contain microwave drying and vacuum drying

techniques. These techniques have been used for drying the wet-gel to attain specific aerogel that acquired high specific surface area with considerable porous structure. 3.4.1.

Microwave drying Process Microwave drying strategy is one of the efficient ways because it is time-

saving in the preparation of three dimension (3D) interconnected meso- and microporous structures [54]. The aerogel formed by this technique is almost similar to that of the resulted aerogel by means of freeze-drying procedure but the formed macropores have significant small size [66]. 3.4.2.

Vacuum drying Process This technique was designed to save energy and time owing to the

utilization of less heat at a short time [67, 68]. Vacuum drying procedure techniques was carried out under reduced pressure. Such as, microporous aerogels were prepared with high surface area and a narrow-distributed pore size less than 6 angstrom dried using vacuum process.

10

4. Benefits and drawbacks of the different drying processes 4.1.

supercritical drying method Supercritical drying system is an efficient technique to prevent the drying

shrinkage or collapse of mesopores in order to attain well-characterized structures [48]. However, the utilization of high temperature and pressure in the drying step, the usage of large volume of the solvent and the consumed long time during solvent exchange, which significantly limiting their chance of scaling up into a pilot or industrial scale. This limitation could be attributed to energy and time consumption which increases the high overall cost process [69]. 4.2. Freeze-drying method Freeze-drying technique is extensively utilized and more favorable than supercritical drying technique owing to some features such as easy application, environmentally friendly and cost economically [70] and favorable for the production of highly ordered and controlled porous aerogels [71]. 4.3. Ambient pressure drying method The advantage for utilizing this technique for drying the wet-gel at ambient pressure. This method of drying can be used for the preparation of many aerogels at industrial scale. While, one of its drawbacks is the production of pollution for the environment, human and animals during the evaporation of solvents [54]. 4.4. Vacuum drying and microwave drying methods Vacuum drying and microwave drying methods are being used for drying the wet-gel during the development of aerogel for many years. However, those techniques are industrially undesirable as they tend to formation of large pores and leading to collapse of the polymer-based aerogel molecules, consequently, aims to reduce the surface area of the produced solid material [72, 73]. 11

5. Different Polysaccharides used for the production of aerogels There are many numerous of polysaccharides used in the production of bioaerogels. The abundance, biodegradability, biocompatibility and cost effective of polysaccharides provides the highly attention for their potential application [32]. Thus, the current features are considered as more than important for utilizing the polysaccharides in biomedical fields. Cellulose, chitosan, alginate, carrageenan (CAR), cellulose nanocrystals (CNC), starch and curdlan (CURD) are considered as the abundant polysaccharides used for the production of safe and cost-effective aerogel. They are maintainable materials that appropriately replace the utilization of silica-based aerogels in pharmaceutical development [74-76]. Some of the polysaccharides used for the aerogel formation are highlighted below. 5.1. Cellulose-based aerogel Cellulose is an insoluble polysaccharide comprised repeated D-glucose rings. D-glucose units containing cellulose are connected via ß-(1→4) bonding. The insolubility of cellulose in the common solvents is outstanding to the creation of its various inter and intramolecular bonds. Cellulose-based aerogels in literature is created by using two ways of drying; supercritical and freeze-drying methods. The first one is nominated cellulose II aerogels which formed by the direct dissolution of cellulose in a common solvent. The second one is to prepare cellulose aerogel by using cellulose nanofibres. The latter was obtained from nanofibrillated cellulose (NFC) or bacterial cellulose (BC). Nanofibrilated cellulose (NFC) was mechanically prepared by making use of mechanical disintegration of native cellulose followed by chemical or enzymatic treatments. In addition, Ninofibrillated cellulose (NFC) aerogel with high porosity and high surface area was obtained via two steps [77]. The first step is to dissolve NFC in water and then mixed this aquous solution was an organic solvent of ethanol or butanol. The second step is designed to prepare NFC aerogel by submitting the dissolved NFC to centrifugation and finally to freeze drying technique.

12

In the recent work reported by zeng et al., [78], cellulose-based aerogel was prepared from different sources for cellulose such as cotton linter, denim fabrics, and MCC. They reported that each type of these sources was dissolved in ionic solvent at 100 C and the produced suspension was immersed in water for gelation step (formation of hydrogel). The formed hydrogel from each type was dried in order to remove the liquids from wet-gel pores by three types of drying; supercritical, freeze drying and vacuum drying) to fabricate cellulose aerogels. In this work, zeng et al., examined the influence of drying technique on the structure of cellulose aerogel (surface area and pore volume) [79]. Figure 4 shows the different shapes of the solid material (inner texture); aerogel, xerogel and cryogel - that formed depending on the drying techniques. As presented in Figure 4 that the formed cellulose aerogel via using Sc-CO2 as drying technique have cauliflower-like arrangement, with the observation of an agglomerated small shaggy beads that contain fine nanostructured fibrillated texture. In brief, this morphology is considered as the typical form for the aerogel formation with high surface area and highly ordered small pores. on the contorary, cellulose cryogel which formed by drying cellulose hydrogel using freeze-drying technique have different morphology as compared with that of aerogel formed with Sc-CO2. It may very well be plainly observed the freeze-drying strategy prompts to the development of aerogel based on sheets of cellulose with very small and huge pores because of the ice growing throughout freezing step. On the other hand, the pores shape was changed with the utilization of freeze-drying technique. The pore walls of the as-produced cryogel is thicker than that of aerogel (produced via ScCO2). The formed cryogel have a low value of specific surface area. In addition, the formed structure of cellulose aerogel is completely different from that of freeze-drying technique because these fine structures are completely lost with the formation of cryogel. 13

Figure 4: SEM of cellulose aerogel, cryogel and xerogel. Reproduced with permission form [79].

Figure 5: BET of the three solid materials of cellulose (aerogel, cryogel and xerogel) Meanwhile, using vacuum technique for hydrogel drying tends to the formation of xerogel. The appearance of xerogel is like a thin film without any

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noticeable pores. the disappearance of pores structure could be attributed to that the generation of pressure throughout the growth of ice crystal. This action tends to compress the fibrils of walls and finally leads to producing a solid material with nonporous structure. In another explanation for the formation of xerogel, the strong pores are contracted during slow vacuum drying leading to the formation of very dense porosity. Thus, the macro- and/or mesopores cannot be observed in the solid material (xerogel) as confirmed from the SEM image. In a short, by investigate the images for the three different shapes. From these three drying techniques for the preparation of cellulose solid material, the application of vacuum as drying system is for the production of spongy solid materials is not recommended and not favorable. The effect of morphological structure of aerogel, cryogel and xerogel on the surface area (BET) is highly appreciated. In my lab, these types of cellulose solid materials (aerogel, cryogel and xerogel) were prepared using the three nominated drying processes and their BET were evaluated. As shown in Figure 5, the BET of cellulose aerogel is very high as compared with those of cryogel and xerogel which, in turn, related to the activity and efficiency of aerogel in many different applications [79]. 5.2. Chitosan-based aerogel Chitosan aerogel was prepared by the formation of gelation and subsequently drying. Chitosan hydrogel was prepared via using different methods such as polyelectrolyte complexes, ionically cross-linked hydrogels, entangled gels, and electrorheological fluids. In a common method, chitosan solution was prepared by dissolving chitosan in a queues solution and using sodium hydroxide solution for the formation of gel [80]. The formed chitosan gel was submitted to different ways of drying; Sc-CO2 and traditional drying [81]. The morphological structure of the obtained dried chitosan is displayed in Figure 6. It was observed that the air drying tends to the formation of chitosan like film without noticeable

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pores (Figure 6A), hence the surface area is very low. This issue can be ascribed to that air drying collapsing the structure of chitosan and hence, manifestation of huge shrinkage. While by using Sc-CO2 in drying (Figure 6B), the formed chitosan aerogel has 3D structure with excellent surface area and huge pores [82].

Figure 6: SEM of Chitosan based aerogel prepared from native chitosan dried using (A) air and (B) Sc-CO2. Therefore, for inclusion, swelling and exploiting the existence pores, it is advocated that the best drying method of chitosan hydrogels is Sc-CO2. 5.3. Pectin-based aerogel Pectin is described as polysaccharide acquired from the primary cell walls of terrestrial plants. In aerogel formation, firstly, the wet-gel (gelation step) can be obtained by means of acidic or thermal due to the creation of intra hydrogen bonds [83]. The accessibility of these hydrogen bonds is originated from the available carboxyl groups located on the molecules of pectin and also between the hydroxyl groups of the nearby molecules [84]. Secondly, the solvent of wet-gel was exchanged with absolute ethanol using supercritical drying CO2 to gain high surface area and high porosity pectin aerogel either using acidic or thermal in case of gelation process [85].

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5.4. Alginate-based aerogel There are many methods used for the preparation of alginate aerogel as follow: (1) by dissolving sodium alginate in water and the wet gel of sodium alginate or alginic acid was formed by drop-wise addition of dissolved sodium alginate to a solution of calcium chloride or hydrochloric acid solution. Then the formed wet-gel was dried using freeze drying technique. (2) by dissolving the sodium alginate in water and added drop-wise to a solution of calcium chloride to form wet-gel alginate. The as originated hydrogel was turned to alcogel by replacing the water existed into the pores with ethanol. After that, the aerogel was formed by drying the alcogel using Sc_CO2 drying technique [86]. Recently, it was reported that alginate/clay aerogel was prepared by dissolving the same weight of clay and sodium alginate into water and sodium salt. The formed solutions of clay and alginate were mixed together. After complete mixing, the pH (6 or 8) of the resultant mixture was achieved by adding drops of toluene sulfonic acid monohydrate. Then, alginate/clay aerogels were prepared by freezing the resultant mixture for 6 h in a freezer at -80 C and dried at low pressure at -80C using freeze-drying technique. Figure 8 displays the formation of alginate and alginate/clay aerogel. It was observed that the color of the formed aerogel was changed to brown with the addition of clay to alginate solution.

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Figure 7: SEM of alginate (left) and alginate/clay (right). Reproduced with permission form [87].

It was also clearly seen that at pH =6, the as prepared alginate/clay-based aerogels acquired an specific density around 400 cm3 /g. While at pH=8, the formed alginate/clay aerogel have an specific density equal to 232 ± 20 (cm3 /g) [87]. By and large, it was inferred that, dissolution of sodium alginate in water was occurred using magnetic stirring at about 85 °C. the formation of hydrogel was carried out by dropwise addition of the dissolved alginate to a salt solution of calcium chloride. At the end, the water in hydrogel pores was replaced by ethanol leading to the formation of alcogel. At the end, the alginate aerogel was acquired by drying the alcogel by means of Sc-CO2 or freeze-drying techniques [86]. 5.5. κ -Carrageenan-based Aerogel It was reported that κ-carrageenan aerogel was prepared via two three steps. The first step is to dissolve κ-carrageenan in water 80 C under magnetic stirrer for 12 h. The second step is to form κ-carrageenan hydrogel by emulsion

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method using ions such as potassium carbonate in which potassium is cation and carbonate is anion [88]. The second step is the gelation process in which potassium carbonate solution was added dropwise to carrageenan solution to obtain carrageenan hydrogel. The final step is to produce carrageenan aerogel by drying carrageenan hydrogel by making use of freeze-drying technique [89]. The resultant obtained that carrageenan aerogel has high specific area equal to 167 m2/g and pore volume of about 0.54 cm3/g and the diameter size of the pores is about 13 nm [88]. 5.6. Starch-based Aerogel Particles Starch is mainly composed of amylose and amylopectin. The relative proportion of these two components varies depending on the source of the starch and influences its characteristics such as crystallinity and molecular order [90, 91]. Starch gelation occurs in three-step thermally assisted process in which the hydration and plasticization of the network happens simultaneously. Firstly, the granules of the hydrophilic starch and be swelled due to the adsorption of water [92, 93]. Secondly, after raising the temperature of starch cooking, the gelatinization can be happened, leading to discharge of amylose molecules. This change is irreversible and leads to destruction of the granule structure. Finally, a retrogradation step takes place. Up on cooling and aging the gelatinized starch to room temperature, the starch hydrogel structure is formed and thus, the reorganization and the partial re-crystallization of starch structure can be occurred. Gel formation in starch is greatly controlled by Amylose content and gelatinization temperature. During starch gelatinization, Amylose molecules separate from starch granules, re-associate, and deposit on the amylopectin portion upon retrogradation. Amylose is the linear component that provides an amorphous property to the obtained gel of starch. This contributes to the creation of mesoporosity in starch. Furthermore, the retrogradation rate can be happened quickly

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along with the higher content of amylose. High gelatinization temperatures stimulate amylose discharge from starch granules. All things considered, over a specific worth, an increase in the crystallinity, inflexibility and density of the resultant starch-based aerogel will occur. Throughout the retrogradation process, low cooling temperatures are probably for obtaining aerogel with high surface area and subsequently, the nucleation rate is preferred. In starch gel, water-toethanol solvent exchange system is required to prevent collapsing the pores of aerogel structure during drying [10, 94]. Similarly, in the case of starch gel particles, the solvent system based on water and ethanol is critical to avoid particles coalescence. When gelatinization of starch gels takes place at low temperatures and lower amylose content, by the means of solvent exchange, extensive shrinkage occurs. 5.7. Curdlan-based aerogel Curdlan is carbohydrate linear polymer. Its structure consists of D-glucose linked by (1 → 3) glycosidic bonds. Curdlan is used for different applications especially and food and medical purposes due to its biocompatibility, biodegradability and safety compound. In medical, it can be used as drug carrier, anti-tumor, tissue repairing and wound healing as well. It is insoluble in water which limits its activity in biomedical domains. The insolubility of CURD can be ascribed to its structure (triple-helical) and the enormous number of the formed hydrogen bonds (intra-/ inter-molecular bonds). To improve its solubility of curdlan (like starch and soy protein), sodium hydroxide is used to open the coiled structure [95-101] and hence facilitate its solubility in cold water [95, 97, 102104]. Thus, CURD can be used for aerogel formation after its solubility in water. Unfortunately, the mechanical properties of the formed CURD cryogel is fragile and weak. In general, all polysaccharides have the same point (fragile properties) however, they have huge numbers of pores [100]. To overcome and improve the

20

mechanical properties, synthetic polymers such as polyethylene oxide (PEO) has been added with different ratios to act as supporting aerogel formation [100, 105]. To improve the mechanical properties more and more, reinforcement agent such as cellulose nanofibrils (CNF) has been added. Scheme 2 and figure 8 represent the graphical abstract and photo image for the formation of Curdlan cryogel respectively.

Scheme 2: graphical steps for the preparation of CURD-based cryogel. Reproduced with permission form [105]

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Figure 8: Image photos of cryogel based PEO and CURD, the concentration of each polymer is written on the front of the bottle. Reproduced with permission form [105]

Figure 9: SEM micrographs of PEO/CURD cryogel prepared at different concentrations of PEO and CURD and crosslinked with glyoxal. Reproduced with permission form [105]

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The morphological structure illustrate that the CURD aerogel is formed with cellular structure contains huge pores (Figure 9) depending on the concentrations of PEO and CURD. While Figure 10 shows the swelling properties of CURD cryogel when blended with different concentrations of PEO. Figure 11 displayed the stress-strain properties of CURD/PEO cryogel without NFC (Figure 11a) and with NFC (Figure 11b). It is obviously observed that the stress-strain properties of CURD/PEO cryogel is density dependent. The cryogel based on CURD have 20% of strain and this value was increased with the addition of PEO (20% and 40%) respectively with respect to the ration of CURD. In addition, the stress value was also decreased from 0.11 MPa to CURD cryogel to 0.02 and 0.04 with the addition of different ratios of PEO as supporting cryogel formation.

Figure 10: Photo images of PEO/CURD cryogels immersed in phosphate buffer saline after 24 h. Reproduced with permission form [105]

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Figure 11: Stress-strain profile of (a) PEO/CURD cryogel, (b) PEO/CURD/CNF (0.5%) cryogel. Reproduced with permission form [105] Increasing the concentration of PEO above 40% leads to sharply increasing the strain percent but with increasing the stress value as clearly observed from Figure 11b. On the other hand, the addition of NFC to the mixture solution of PEO and CURD and freeze dried leading to marginally effect on the data obtained for stress and stress values of PEO/CURD cryogel. However, by comparison with the data obtained for cellulose aerogel, it can be clearly seen that the value of compression modulus are 10 times higher than the compression modulus of some cellulose based aerogel (0.038 MPa) [37]. 6. Biomedical applications of bio-aerogels Aerogel formulations with their intrinsic properties as discussed earlier have attracted considerable attention in the biomedical field. Biocompatibility, biodegradability and lacking of toxicity are the most essential features making them appealing candidates in biomedical applications [70, 106]. As well as, the development of bioaerogels to mimic extracellular matrices (ECM) in body has enabled their different biomedical applications such as drug delivery [84, 107, 108], tissue engineering scaffolds [109-111], antibacterial [70, 112-114],

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biomedical devices [115] , biosensing [32, 116] and wound dressing [32, 117119] as discussed here. 6.1. Aerogel for Drug delivery application In the last few decades, wide arrays of novel delivery systems have been improved and reported for the prolonged and controlled release of such therapeutics. The good biocompatibility, high surface area, huge porous structures, and ease of preparation of aerogel-based polysaccharides (bioaerogels) making them as efficient carrier system for loading many of hydrophilic and hydrophobic drugs [120]. There are three different procedures described for loading drugs into bio-aerogels [121] encompassing i) loading before gelation, ii) during the aging step, and iii) throughout adsorption-precipitation process as displayed in Scheme 3.

Scheme 3: Schematic illustrates the three types for drug loaded aerogel before gelation or during aging step or during adsorption/precipitation step.

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6.2. Aerogel for tissue engineering application Tissue engineering involves the use of a tissue scaffold for the formation of new viable tissue (e.g. blood vessels, bone, cartilage, skin, bladder, muscle etc.) for a medical purpose [120]. Due to the desirable physical properties of aerogels over various other types of organic polymer scaffolds, they have been utilized as unique scaffolds in regenerative medicine and have made possible to conduct a growth substrate for cell culture and tissue engineering technologies [77]. Due to aerogels’ properties such as highly 3D porous structure for cell attachment with a tunable network of interconnected pores for the nutrient, oxygen supply to the cells and the elimination of cellular metabolic by-products make them highly appropriate for regenerative medicine purposes [77]. It has been found that swollen 3D nanocellulose aerogels with surface area of 308 m2/g and porosity up to 99.7%, have been reported as efficient scaffolds in cell growth and proliferation [122]. Another study showed that dual-porous cellulose aerogels with improved mechanical properties and biocompatibility when seeding with fibroblast cells on the surface of the prepared scaffolds. Among different aerogel formulations, microsphere aerogels have been shown as excellent candidate in tissue engineering [123]. It was also reported that the highly porous cellulose nanofibril aerogel microspheres provided large surface area, high-water absorption capacity, and low bulk density for cell growth and differentiation [123]. 6.3. Aerogel in wound dressing application Wound healing is a complexed and dynamic process in which devitalized and missing cellular structures and tissue layers are altered. physiological reaction that occurs when tissue integrity is conceded owing to pathologies, surgical involvements and disasters. The ultimate outcome of such route is the replacement of typical skin structures with scare tissue (Figure 12).

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Polysaccharide loaded AuNPs aerogel

Wound dressing aerogel

Human skin

Figure 12: different shapes for aerogel based wound dressing material Healing process comprising a great number of cells, extra cellular elements, mediators such as cytokines and other molecules. It can be promoted for chronic wounds; venous leg ulcers, diabetic foot ulcers and pressure ulcers. Voluminous microbes can be grown in chronic wounds which in turn, leads to spread the infection and ultimately leading to fetal consequences like amputation or even mortality. Thus, it is necessary to develop solid material capable of wound healing, stimulate tissue repair, and remove exudates. Moreover, they should have the ability to act as a barrier for microorganisms and facilitate the action of inflammatory step. Because of the porous structure of aerogel, they are able to absorb higher amounts exudates which prevent the wounds from infections. polysaccharidesbased aerogels, in particular, have been extensively applied in wound dressing due to high stability, low toxicity, non-allergenic with good biological performance. The solid structure of polysaccharide aerogel swells and prevents the formation of water-filled pockets that act as a culture medium to organisms. They can also be encapsulated with such active principal ingredient to easily facilitate and accelerate the healing action such as antimicrobial drug. Overall, aerogel platforms ought to be viewed as a rising elective that are still a work in progress.

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6.4. Aerogel as biosensor Biosensors are identified as analytical devices have the ability to make a combination between the biological component and a physicochemical detector [124]. It can be used to distinguish the analyte even when it is presented in very small amounts. Polysaccharides-based aerogel as 3D host matrices used as biosensors to detect the proteins or large biomolecules. Edwards et al. used cellulose nanocrystals (CNC) platform as a detector for healing chronic wounds. In addition, they also reported that the aerogel based on CNC is more favorable than other materials to detect human neutrophil elastase (HNE) [125]. Likewise, it was reported that chitosan-based aerogel is promising in this regard because of i) scaffolds properties, ii) bio-adhesivity, and iii) availability of the functional groups for further bioconjugation with other molecules [126]. 6.5. Aerogels in medical implantable device Biomedical implants are quickly growing up of research in materials science and biomedicine. In order to implant blood device, it must be compatible with endothelial cells in human in which they must be stable and protected from any noticeable degradation or decomposition for slightly potential types. Otherwise, they can cause immune hemostatic/thrombotic response [69]. Since the limitation of using of synthetic polymers implants in heart valves are cavitation formation, higher degradation rate and poor mechanical strength [69], the low density and high mechanical strength of aerogels are highly contributed in overcoming these issues. Furthermore, the aerogel improved the listing issue of the implant and its flexible permeable structure invested the exchanging of fluid between the implant and surrounding tissues as well as neurons growth on aerogel surface. Most interestingly, the versatility of sol–gel synthesis approaches allowed color-coding of aerogel implants during preparation with oxide-based pigments for easy tracking and better post-surgical identity. 28

6.6. Aerogels in bioimaging Medical imaging is assuming a significant role in healthcare improvement via early prognosis of such disease thus providing ideal treatment. Ability to image an implant located in the peripheral region of the body with least damages to the patient is a significant step of designing an implant-based biomaterial [127]. The acoustic absorption of aerogels has been a significant feature for noninvasive and quick imaging of aerogel-based implants situated in the peripheral region of the body, particularly, in peripheral nervous system. 7. Conclusions

and

perspectives

on

the

potential

production

of

polysaccharides-based aerogel As concluded, aerogel is a porous ultralight material derived from a gel, in which the liquid component for the gel has been replaced with a gas. Aerogel has outstanding characteristics such as high surface area, huge porosity and low density making it potential for wide range of applications. Accordingly, the goal of the present review is to highlight the advantage of utilizing polysaccharides in the production of environmentally benign aerogel. The natural polysaccharides are favorable for aerogel formation due to their biocompatibility, biodegradability and their low cost when compared with other synthetic polymers. My future work is designed to prepare carrageenan blended with cellulose nanocrystals that contain silver nanoparticles (AgNPs) with high concentrations. This future work will be considered to probing the preparation of AgNPs in solid state without using any hazard solvent or water extended to scaling up production and commercialization. Afterwards, AgNPs will be mechanically blended with carrageenan and CNC with varied ratios. CNC will be utilized to enhance the mechanical properties of carrageenan aerogel. The as prepared mixture of CAR/CNC/AgNPs will be conducted to freeze-drying technique. after successful preparation of CAR-based aerogel, it well be used for further applications such

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as anti-biofouling, antimicrobial wound dressing, and wastewater treatments. Thus, for the aerogel production, characterization and the various application, we are aiming to move the aerogel production from bench scale to pilot scale. 8. References [1] C. Alvarez-Lorenzo, B. Blanco-Fernandez, A.M. Puga, A. Concheiro, Crosslinked ionic polysaccharides for stimuli-sensitive drug delivery, Advanced drug delivery reviews 65(9) (2013) 1148-1171. [2] J. Stergar, U. Maver, Review of aerogel-based materials in biomedical applications, Journal of Sol-Gel Science and Technology 77(3) (2016) 738-752. [3] C. Vilela, R.J.B. Pinto, S. Pinto, P. Marques, A. Silvestre, C.S.d.R.F. Barros, Polysaccharide Based Hybrid Materials: Metals and Metal Oxides, Graphene and Carbon Nanotubes, Springer2018. [4] A. Ghafar, NOVEL FUNCTIONAL MATERIALS FROM UPGRADED BIOPOLYMERS: POLYSACCHARIDE AEROGELS, EKT-series (2018). [5] J. Pérez, J. Munoz-Dorado, T. De la Rubia, J. Martinez, Biodegradation and biological treatments of cellulose, hemicellulose and lignin: an overview, International microbiology 5(2) (2002) 53-63. [6] M. Söderqvist Lindblad, A.-C. Albertsson, E. Ranucci, M. Laus, E. Giani, Biodegradable polymers from renewable sources: rheological characterization of hemicellulose-based hydrogels, Biomacromolecules 6(2) (2005) 684-690. [7] H.V. Scheller, P. Ulvskov, Hemicelluloses, Annual review of plant biology 61 (2010). [8] R. Schoevaart, T. Kieboom, Galactose dialdehyde as potential protein cross-linker: proof of principle, Carbohydrate research 337(10) (2002) 899-904. [9] S. Van Vlierberghe, P. Dubruel, E. Schacht, Biopolymer-based hydrogels as scaffolds for tissue engineering applications: a review, Biomacromolecules 12(5) (2011) 1387-1408. [10] C. García-González, M. Alnaief, I. Smirnova, Polysaccharide-based aerogels—Promising biodegradable carriers for drug delivery systems, Carbohydrate Polymers 86(4) (2011) 1425-1438. [11] W. Ren, J. Gao, C. Lei, Y. Xie, Y. Cai, Q. Ni, J. Yao, Recyclable metal-organic framework/cellulose aerogels for activating peroxymonosulfate to degrade organic pollutants, Chemical Engineering Journal 349 (2018) 766-774. [12] Y. Han, X. Zhang, X. Wu, C. Lu, Flame retardant, heat insulating cellulose aerogels from waste cotton fabrics by in situ formation of magnesium hydroxide nanoparticles in cellulose gel nanostructures, ACS Sustainable Chemistry & Engineering 3(8) (2015) 18531859. [13] J. Liu, X. Ge, X. Ye, G. Wang, H. Zhang, H. Zhou, Y. Zhang, H. Zhao, 3D graphene/δ-MnO 2 aerogels for highly efficient and reversible removal of heavy metal ions, Journal of Materials Chemistry A 4(5) (2016) 1970-1979. [14] H. Bi, Z. Yin, X. Cao, X. Xie, C. Tan, X. Huang, B. Chen, F. Chen, Q. Yang, X. Bu, Carbon fiber aerogel made from raw cotton: a novel, efficient and recyclable sorbent for oils and organic solvents, Advanced Materials 25(41) (2013) 5916-5921. [15] R. Baetens, B.P. Jelle, A. Gustavsen, Aerogel insulation for building applications: a stateof-the-art review, Energy and Buildings 43(4) (2011) 761-769. 30

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