Study on preparation and performance of PEG-based polyurethane foams modified by the chitosan with different molecular weight

International Journal of Biological Macromolecules 140 (2019) 877–885

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International Journal of Biological Macromolecules journal homepage: http://www.elsevier.com/locate/ijbiomac

Study on preparation and performance of PEG-based polyurethane foams modified by the chitosan with different molecular weight Haonan Qin, Kang Wang ⁎ Tianjin Key Lab of Membrane Science and Desalination Technology, Chemical Engineering Research Center, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300350, China

a r t i c l e

i n f o

Article history: Received 27 May 2019 Received in revised form 6 August 2019 Accepted 21 August 2019 Available online 22 August 2019 Keywords: Chitosan Molecular weight Polyurethane Foam Grafting degree

a b s t r a c t A category of polyethylene glycol-polyurethane (PU) foams were prepared by chitosan (CS) with different molecular weight as chain extender. The activity group, CS grafting degree, crystallization behavior, morphology, thermal stability, mechanical properties, hydrophilicity, protein adsorption and degradation in vitro of PU-CS composite foams were investigated. The experimental results indicated that better group reactivity (-NH2 and -OH) in CS with low molecular weight led to the higher CS grafting degree (78.9% and 98.3%) in the PU foams modified by aminoglucose (CA) and chito-oligosaccharide in 3000 g/mol (CS3K). The disordered crystallization behavior of PU-CA composite foams appeared due to both -NH2 and C6-OH in CA with high activity. However, a clear crystallization diffuse peak in PU-CS3K similar to that in pure PU was presented because the activity of -NH2 in CS3K was relatively high. The phase separation and disorder bubble holes appeared in PU-CS composite foam when CS with high molecular weight in 30,000 g/mol and 300,000 g/mol (CS30K and CS300K) were used. It was the high grafting degree of CS that PU-CS3K had relatively high thermal stability. With the increase of CS molecular weight, the tensile strength, the hydrophobicity, the protein adsorption and the degradation rate of PU-CS composite foam increased. Although pure PU and PU-CS composite foam with low molecular weight of CS (CA and CS3K) have similar hydrophilicity, the adsorption amount of BSA on the latter increases obviously owing to the electrostatic adsorption of amino groups, and the degradation rate of latter during the early stage of degradation is lower than that of former due to the relatively large number of chemical crosslinking sites. These experimental results presented new suggestions for the research and application of CS in PU based biomaterials. © 2019 Published by Elsevier B.V.

1. Introduction Polyurethane (PU) as an important medical device have good biocompatibility and cytotoxicity compared to other polymeric materials such as rubber and plastics [1]. This polymer is produced by the reaction of an isocyanate and a polyol in addition to other additives used to adjust the characteristics of the final product. Properties such as innocuity and biodegradation can be varied by modifying materials including biologic, synthetic and inorganic materials, such as collagen, starch, vegetable oil, alginate (SA), lignin and silica nanoparticles [2–10]. Especially, combination of chitosan (CS) with polyurethane has attracted considerable attention [11]. Due to the antibacterial property, the similar composition with the extracellular matrix, biodegradability, the low immunogenicity and unique properties of blood contact, CS has been regarded as a prominent candidate for clinical research and application [12]. The adsorption capacity, mechanical strength, flame retardant, thermal stability, and antibacterial activity of composites are improved by ⁎ Corresponding author. E-mail address: [email protected] (K. Wang).

https://doi.org/10.1016/j.ijbiomac.2019.08.189 0141-8130/© 2019 Published by Elsevier B.V.

introducing CS into PU [13–15]. PU/CS foam which showed a semicrystalline structure, high porosity and good mechanical characteristics can well remove Food Red 17 dye from aqueous media [13]. An eightbilayer chitosan/lignosulfonate based coating by layer-by-layer assembly method significantly improved the fire resistance of flexible polyurethane foam [14]. Thermal stability of PU samples increased with the addition of CS in the PU backbone because of quite thermal stable behavior of chitosan but did not affect at higher concentrations, while antibacterial activities increased with increasing CS concentrations [15]. At the same time, PU can be used as carrier and support of CS. Cell proliferation on the CS/SA and CS/SA/PU scaffold was found to be faster than on a pure CS scaffold, which suggested that novel ternary CS/SA/PU scaffolds potentially serve as an improved alternative to CS scaffolds for skeletal muscle tissue engineering [16]. There are many alternative methods for coupling CS with PU. CS powder can be directly blended during the preparation of PU [17,18]. CS small particles were introduced into cross-linked PU solution in N, N-dimethylformamide (DMF) after prepolymer extension and before foil formation [17]. The mixture of chitosan-graphite oxide composite particles and polyether polyol were used to synthesize modified PU foam materials as adsorbents [18]. In addition, CS can be immobilized

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H. Qin, K. Wang / International Journal of Biological Macromolecules 140 (2019) 877–885

onto the surface of PU [19–21]. To improve the hemocompatibility and biocompatibility of PU, PU films surface was modified by poly ethylene glycol (PEG) through acryloyl chloride and subsequently grafted on carboxymethyl-chitosan [19]. PU foam membrane filled with humic acid-chitosan crosslinked gels for dye removal was prepared by soaking the foams into humic acid-chitosan crosslinked gels and hot-pressing them into membranes [20]. Chito-oligosaccharide (COS) was modified onto the surface of PU membrane based on the self-polymerization of dopamine [21]. Moreover, CS can be introduced into the PU structure, such as a chain extender in PU synthesis [15,22–25]. Zia et al. proposed a step growth polymerization technique that the PU prepolymer was extended with chitin and 1,4-butane diol (BDO) [22]. Thermally stable PU elastomers were synthesized by the reaction of poly(ε-caprolactone) (PCL) and isophorone diisocyanate (IPDI), extended with different mass ratio of CS and BDO [23]. Thermo gravimetric analysis (TGA) of PU blends with 0.25 M:0.75 M of CS to curcumin as a chain extender indicated a better thermal stability and mechanical properties [24]. A series of chitosan and montmorillonite (MMT) clay based PU bionanocomposites were synthesized by step growth polymerization technique [15,25]. Javaid et al. presented that crystalline behavior of CS based PU bio-nanocomposites was influenced by varying diisocyanate structures [25]. The solubility pattern is important for the effective utilization of CS in biomedical applications. In order to improve the solubility of CS in solvents, CS with low molecular weight was prepared and used in PUCS composites synthesis [23,26–30]. Oligosaccharides obtained by treating CS with H2O2 dissolved in dimethyl sulfoxide (DMSO) and can be used for preparation of PU elastomer in solvent media [23]. PU prepolymer chain can be extended by low molecular weight CS (molecular weight 50,000 g/mol) or COS(number-average molecular weight 3000 g/mol) [28,29]. The addition of low molecular weight CS remarkably increases antimicrobial and UV protective properties of PU-CS composite [28]. The composite films of poly(ether-ester-urethane) (PEEU) and water-soluble COS were prepared by using a simple physical mixing method with DMF as solvent [30]. The thermal stability, the degradation rate and the surface blood compatibility of the PU-CS composites could be controlled by adjusting CS content [15,25,28–30]. Although CS with different molecular weights has been used in the preparation of PU-CS composites, the effect of molecular weight of CS on the properties of composites has not been analyzed and compared. In this work, D-glucosamine (CA), CS oligosaccharide with molecular weight of 3000 g/mol (CS3K), low molecular weight CS of 30,000 g/mol (CS30K) and high molecular weight CS of 300,000 g/mol (CS300K), were chosen as chain extender to preparation the PU-CS composites foams. PU foams are versatile polyporous polymeric products and widely used in many applications [31]. The present research work was focused to investigate the effect of CS with different molecular weights on the performance of PU materials. The PU-CS composites foams were synthesized in two steps. The copolymerization of IPDI with PEG (Mn = 2000) was produced and then mixed with different molecular weights of CS solution under catalysts to form PU-CS composites foams via a foaming process. The role of long-chain flexible PEG is the soft segment while the hard segments are made up of isocyanic acid and CS chains. Active group and crystalline structure of samples were confirmed using Fourier transform infrared (FTIR) spectroscopic method and X-ray Diffractometer (XRD) respectively. The grafting degree of CS was determined by the weight-loss method. Microstructure of foams was observed by scanning electron microscope (SEM). Thermal degradation behavior of samples was studied using thermogravimetric techniques (TG). Mechanical properties, surface hydrophilicity, water absorption capacity and moisture retention, were evaluated in detail. In addition, protein adsorption examination of foams was studied by bovine serum albumin (BSA) adsorption. Furthermore, the degradable behavior of PU-CS composite foams was researched in the simulated body fluid (SBF, pH = 7.4) during five weeks. The obtained results would be very useful for the application of CS in PU biomedical polymer material field.

2. Experimental 2.1. Materials CA and CS3K(Mn = 3000 g/mol) were supplied from Aldrich. CS30K (Mn = 30,000 g/mol) and CS300K(Mn = 300,000 g/mol) were purchased from Shanghai YuanYe Medical Chitosan GmbH. The degrees of deacetylation of CS with different molecular weights were all above 90%. Poly(ethylene glycol) (PEG, Mn = 2000 g/mol) was obtained from Aldrich and dried for 3 h at 110 °C under vacuum for 3 h prior to use. Isophorone diisocyanate (IPDI) was purchased from Fluka. Tin bis (2-ethylhexanoate) (T-9), triethylenediamine (DABCO), silicone(L580) and other reagents were AR grade. And Simulated body fluid (SBF, pH = 7.4) was homemade.

2.2. Preparation of PU-CS composites foams The process consisted, basically, of two steps: (1) preparation of PU prepolymers and (2) foam reaction, as shown in Fig. 1. Step 1: Preparation of PU prepolymers. The prepolymers were obtained through condensation reactions between 20 g PEG2000 and 4.444 g IPDI with the NCO/OH ratio of 2:1. The reactions were performed at 85 °C with a magnetic stirring rate of 350–400 rpm for 70 min. Step 2: Foam reaction. 10 mL5% CS solutions with different molecular weights CS were obtained by dissolving CA and CS3K in distilled water respectively and CS30K and CS300K in 1% acetic acid separately. Foaming agent that was prepared by dissolving 0.06 g T-9, 0.1 g DABCO and 0.35 g L-580 in 10 mL5% CS solutions was added to the freshly PU prepolymer in an open mould with stirring for 10s and then foams expanded freely in the vertical direction. After 24 h at room temperature, samples were dried under vacuum for 48 h to maintain the porous structure, subsequently foams were washed with distilled water and dried under vacuum for 48 h again. Prepared foams PU-CA, PU-CS3K, PU-CS30K and PU-CS300K were cut into shapes for testing. Control sample PU foam was produced by using foaming agent without CS solutions. 2.3. Characterization 2.3.1. FTIR FTIR were recorded by an infrared spectrophotometer (TENSOR 27, Bruker, Germany) from 4000 to 500 cm−1 at the resolution of 2 cm−1.

2.3.2. The grafting degree of CS The grafting degree of CS was determined by the weight-loss method. After the reaction, all samples were dried and weighed (W0). Then all the samples were put into distilled water or 1% acetic acid solution for 30 min to remove unreacted CS, and dried and weighed again (Wg). The grafting degree of CS (wt%) = [0.5-(W0-Wg)]/0.5 × 100%, where 0.5 was the addition amount of CS (g).

2.3.3. XRD The crystallization behaviors of polymer foams were measured by XRD (D8-Focus, Burke AXS, Germany) analysis in the dispersion range (2θ) of 5–45° with a scanning rate of 8°/min at 25 °C.

2.3.4. Morphological analysis The Morphological analysis was observed by and scanning electron microscope (SEM) (S-4800, Hitachi, Japan) with 3.0 kv gold-sprayed coating.

H. Qin, K. Wang / International Journal of Biological Macromolecules 140 (2019) 877–885 CH3

H3 C OH

n H

O

n

Step 1: prepolymerization reaction

N C O

H2 C

+ 2n

85°C

O C N

CH3

70mins

n

C O

N

O C N H2 C

H3C CH2

CH3 O

H3C

NH C

H3 C

O

C

n

H N

O

O

OH

C6

CH3

C4

CH3

C5

OH

O

n HN

O HO NH

C H3C CH3

O

O H3C

HN

C H3 C

NH

CH3

H3 C

H3 C

HN

HN

CH3

C O

C

O

O

O

n

C

CH3

CH2

CH2

CH2 NH

HO

NH2

C

O HN

OH

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OH OH

HO

n

n

HN

C1

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O

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NH2

OH

OH O

HO

C2 HO

CS-1%Acetic Acid Solution

GA-Aqueous Solution

C O

O O

C3

Step 2: chain extension and foam reaction

O

879

O n

O

C

C NH

NH

CH2

CH2 O

NH

NH

H3 C

C

C HN HN OH

HO

H3 C

HO

CH3 NH2 OH

O O

O

OH

O

OH

CH3 O NH C OH HN

O

HO

O

H3 C

H3C

CH2 CH3 O

C

O

NH CH3

H3 C

O

O

O

OH

O HO

n

HO

O C

O

n Fig. 1. Reaction scheme of PU-CS composites foams.

2.3.5. Thermal stability Thermogravimetric analysis (TGA) of foams was recorded using thermo gravimetric and differential thermal Analyze (Perkin Elmer Diamond Series, USA) under inert atmosphere (N2, gas) from room temperature up to 500 °C with a heating rate of 20 °C/min.

2.3.6. Mechanical properties The measurement of tensile strength and elongation at break of foams was based on GB/T 1040.3–2006 with a texture analyzer (TMSPro, Food Technology Corporation, USA). Each sample was carefully mounted and clamped between the tensile grips probes, and stretched at a speed of 5 mm/min at room temperature. Wet samples were obtained by immersing dry samples into SBF for 2 h. Tensile strength, Elongation at break and Young's modulus were calculated with averaged results of at least three samples.

2.3.7. Water contact angle Contact angle measurement was carried out by using a contact angle meter (DMe-201, Kyowa Interface Science, USA). A 5 μL drop of redistilled water was applied on the surface of sample for characterization. All surface contact angle values reported here were the average values of three measurements made on different positions of the sample surface. 2.3.8. Water absorption Based on the reported method [39], the water absorption capacity was tested by immersing a dry sample (W0) with 1 cm × 1 cm × 0.5 cm squares in SBF solution. The samples at different interval time were weighed as wet weight (Wt) after wiping off excess water with filter paper. The water absorption ratio (%) = (Wt-W0)/W0× 100. The equilibrium water absorption ratio was obtained until 120 min when the water absorption ratio remained constant.

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H. Qin, K. Wang / International Journal of Biological Macromolecules 140 (2019) 877–885 3546cm-1

2877cm-1

PU-CS300K

23.5o

19o

10.5o

1051cm-1

PU-CS300K 2898cm

-1

PU-CS30K

1105cm-1

3307cm-1

3413cm

-1

PU-CS30K

20.5o

2919cm-1

PU-CS3K

PU-CS3K 1124cm-1

PU-CA 21.20

PU

PU-CA

3382cm-1

1072cm-1

2875cm-1

10

15

20

25

30

35

2-Theta(o) 3340cm-1

2873cm-1

PU

Fig. 4. XRD characterization of samples.

C-O-C-1

1146cm

-NH

4000

3500

1715cm

-CH

3000

-1

1658cm

-1

-NHCOO -NHCONH

2500 2000 Wavenumber(cm-1)

1500

1000

500

Fig. 2. FTIR spectra of samples.

2.3.9. Protein adsorption assay The assessments were performed on PU-CS composite foam with Bovine serum albumin (BSA) according to previous papers [40–42]. Samples were cut into 1 cm × 1 cm × 0.5 cm squares and immersed in 3 mL of BSA solutions (1 mg BSA in 10 mL phosphoric buffer solution (PBS), pH = 7.4), followed by an incubation at 37 °C for 3 h. Then the substrates were rinsed twice with sufficient PBS. Then 1 mL of each adsorbed BSA suspension was obtained from solutions and determined by the staining method with Coomassie brilliant blue at a UV–vis absorption wavelength of 595 nm to measure the residue BSA. Each measurement was repeated at least three times. Results were given as μg protein/cm3.

110

98.3

100 90

78.9

Graft degree(wt%)

80 70 60

40.3

36.6

PU-CS30K

PU-CS300K

50 40 30 20 10 0

PU-CA

PU-CS3K

Fig. 3. Grafting degree of CS.

2.3.10. In vitro degradation The in vitro degradation tests were performed in simulated physiological conditions. Five kinds of the samples with 10 mm × 10 mm × 5 mm were weighed (W0), and then separately immersed in SBF (15 mL). The systems were cultured at 37 °C for 5 weeks. Sample in every week interval was transferred to a vacuum drying oven at 37 °C for 72 h and weighed (Wd). In the later stage of degradation, the sample was broken. The residue was filtered by filter paper and dried with the filter paper. After removing the weight of the filter paper, the residual weight of the degraded sample Wd was obtained. The degradation ratio = (W0-Wd)/W0 × 100%.

3. Results and discussion 3.1. FTIR characterization FTIR spectra of samples were presented in Fig. 2. In the spectrum of pure polyurethane, the absorption bands at 3340 cm−1, 2873 cm−1and 1146 cm−1 were attributed to the characteristic stretching frequencies of -NH, -CH and ester bonds C-O-C respectively [30]. After grafting with CA, CS3K, CS30K and CS300K, -NH absorption band shifted from 3340 cm−1 to 3382 cm−1, 3413 cm−1, 3307 cm−1 and 3546 cm−1 respectively. Stretching vibration peak of -CH and C-O-C in PU-CS composite foams also changed. It was demonstrated that prepolymer was chain-extended with CS. In addition, the -NHCOO around 1715 cm−1 is synthesized from -OH group and -NCO group [30]. The ureido (-NHCONH) at 1658 cm−1 band is not only a particularly important proof of reactions between -NCO groups and C2-NH2 groups of polysaccharides but also a demonstration for foam formation resulted from reactions of H2O and -NCO groups [32,33]. For polyols containing OH, primary alcohols could react with isocyanates immediately at room temperature, while the reaction rate of secondary alcohols is only 30% of that of primary alcohols, and all compounds with -NH2 groups can react with isocyanate theoretically [11]. Compared with pure PU foam, the adsorption peak of PU-CS composite foams at 1658 cm−1 were all strengthened, which indicated the formation of new ureido between residual amide linkage of CS and the prepolymer. In the preparation of PU prepolymers, the -NCO and -OH was 0.02 mol and 0.01 mol respectively. 10 mL 5% CS solutions with 0.0034 mol of -NH2 (CS unit C6H11O4, see Fig. 1) was added in the foam reaction. At this time, the -NCO can react with –OH of CS because the amount of former was much larger than that of -NH2.The sharp peak of 1715 cm−1 remarkable variety happened to PU-CA

H. Qin, K. Wang / International Journal of Biological Macromolecules 140 (2019) 877–885

PU(A)

PU(B)

1.00mm

PU-CA(A)

PU-CA(B)

1.00mm

PU-CS3K(A)

PU-CS3K(B)

1.00mm

PU-CS30K(A)

PU-CS30K(B)

1.00mm

PU-CS300K(A)

PU-CS300K(B)

1.00mm

Fig. 5. Morphological characterization of foams. Tail tag (A) and (B) refers to the photos by optical microscope and SEM respectively.

881

the steric hindrance, which could impact reactivity between CS and prepolymer, is bound up with the molecular weight [1]. It has been shown from FTIR characterization that –NH2 of CS have high activity with NCO groups. Besides amino groups, hydroxyl groups of CA were also available for chemical reaction with NCO groups (Fig. 1), which improved the degree of grafting of CA. Under high reactivity between -NH2 of CS and NCO groups, it is possible that the chemical crosslinking amount of CS can be enhanced by properly increasing the molecular weight of CS. Therefore, the highest grafting degree of CS was presented in PU-CS3K. When relatively high molecular weight of chitosan CS30K and CS300 K were used, lower grafting degree of CS were obtained due to the less reactivity of groups under high steric hindrance of polysaccharide long molecular chain which has been presented by FTIR spectra experimental results.

3.3. XRD characterization Generally, researchers considered that the amount of CS has an obvious influence on the crystallization behavior of PU composite. Barikani et al. reported that the increase in amount of COS obtained by H2O2 depolymerization favored the formation of more ordered structure and the phase segregation [23]. However, the XRD findings revealed by Zia et al. that the addition of CS into PU films caused a decrease in crystallinity [25]. Hou et al. suggested that the more crosslinking points in COSbased PU films formed with the addition of COS (number-average molecular weight 3000 g/mol), which makes it more difficult for COS to react with the prepolymer due to the steric effect, and the unreacted COS is physically mixed with COS-based PU films, resulting in slightly blunt peaks in the scattering patterns [29]. In here, XRD of samples were carried out in order to examine the effect of molecular weight of chitosan on the crystallinity of PU-CS composite foams. As shown in Fig. 4, a clear diffuse peak with a maximum at 2θ = 21.2° was observed in the pure PU, which indicated that pure PU was a hemicrystalline polymer [29]. This is due to the structural regularity and the thermodynamic in compatibility of the hard and soft segments. All the PU-CS composite foams with a little diffuse peak at 2θ = 10.2° that was attributed to -NH group of chitosan showed that chitosan has been successfully grafted with PU [25]. In addition, the new diffraction peak 2θ = 20.5° in PU-CS3K was considered to be ureido between chitosan and the prepolymer [29]. However, the crystal peak at 2θ = 20.5° in PU-CA almost disappeared. Two well oriented crystallinity peaks at 2θ = 19° and 2θ = 23.5°, which the former was attributed to hard segments and chitosan and the latter was related to the soft segment mobility, was observed in PU-CS30K and PU-CS300K [23,25]. 110

The chemical cross-linked amount of CS in PU-CS composite foam can be known by the grafting degree of CS that was displayed in Fig. 3. The grafting degree of CA and that of CS3K reached 78.9% and 98.3% respectively, while that of relatively high molecular weight CS30K and CS300K showed poor grafting activity with 40.3% and 36.6% respectively. It was shown that the molecular weight of polysaccharides has an important influence on the grafting degree of CS, which is related to the reactivity of groups and the steric hindrance of polysaccharides. In the PU-initiated graft polymerization process, structures of aliphatic hydroxyl groups determined the final grafting density [1]. Radically,

90 100

80

Enalrge

70

90

60 80

Mass(%)

3.2. The grafting degree of CS

100

Mass(%)

foams due to the highly reactivity in C6-OH group of CA (Fig. 1). The relatively strong peak of 1658 cm−1 appeared in PU-CS3K, which shown the highly reactivity between -NH2 and -NCO. With the increase of molecular weight of CS, both of 1658 cm−1 peak and 1716 cm−1 peak became weak in PU-CS30K and PU-CS300K because steric hindrance of polysaccharide long chain inhibited the reaction activity.

50 40

PU PU-CA PU-CS3K PU-CS30K PU-CS300K

70

30 20

60

10

240 260 280 300 320 340 360 380 o Temperature( C)

0 0

50

100

150

200

250

300 o

Temperature( C) Fig. 6. TGA curves of samples.

350

400

450

500

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H. Qin, K. Wang / International Journal of Biological Macromolecules 140 (2019) 877–885

Table 1 Mechanical properties of samples. Sample

Tensile strength (KPa) Dry/wet

Elongation at break (%) Dry/wet

Young's modulus (MPa) Dry/wet

PU PU-CA PU-CS3K PU-CS30K PU-CS300K

26.4 ± 0.2/2.95 ± 0.3 25.4 ± 0.2/3.59 ± 0.4 29.9 ± 0.1/4.69 ± 0.4 32.4 ± 0.2/10.4 ± 0.5 32.9 ± 0.3/16.4 ± 0.5

61.6 ± 1.1/21.6 ± 0.4 66.3 ± 1.1/25.3 ± 0.4 63.9 ± 1.2/26.2 ± 0.5 60.3 ± 1.7/29.3 ± 0.7 58.3 ± 1.8/39.2 ± 0.8

42.9 ± 0.5/13.7 ± 0.2 38.4 ± 0.8/14.2 ± 0.1 46.7 ± 0.7/17.9 ± 0.1 53.8 ± 1.3/35.6 ± 0.7 56.5 ± 1.3/41.2 ± 1.0

The crystallization behavior of PU-CS composite foams also involved in the reactivity of groups and the steric hindrance of polysaccharides. CA as extender, ordered structures of PU would be greatly destroyed and the disorder of PU composite was improved due to both -NH2 and C6-OH in CA with high activity. When CS3K was grafted, a clear diffuse peak in PU-CS3K similar to that in pure PU was presented because the activity of C6-OH was weaken by steric effect and the polymer tend to crystallize by interaction between -NH2 and -NCO. With the further increase of molecular weight of CS, the crosslinking points between -NH2 and -NCO began to decrease under the steric hindrance which lessened the interaction between CS and prepolymer. CS itself is a crystalline polymer and higher intensity of crystallinity. Two well oriented crystallinity peaks in PU-CS30K and PU-CS300K indicated that the phase separation between CS and soft segment appeared. 3.4. Morphological analysis The morphological photos of PU foams before and after grafting treatments were shown in Fig. 5. It was visible from optical photographs that the pure PU foams and PU-CA foams presented visually waterwhite transparent, uniform and porous, whereas PU-CS3K foams appeared pale yellow and high density porous structure. When relative high molecular weight of CS was grafted, foams became disorderly with uneven size of holes in PU-CS30K and PU-CS300K. SEM photos showed that all foams appeared a 3-D bubble hole structure and their hole wall becomes thicker with the increase of CS molecular weight. Especially for PU-CS3K foams, there were many cross holes and through holes with small size. XRD experimental results exhibited that crystallinity of PU-CS3K similar to that of pure PU was relative order which promoted the formation of uniform porous structure, and phase separation between CS and soft segment in PU-CS30K and PU-CS300K resulted in disorder bubble holes. In addition, high grafting degree of CS limited the growth of bubbles and produced small holes in PU-CS3K.

thermal insulators and the grafting sites in PU matrix hindered the further decomposition of composites. 3.6. Mechanical properties As an ideal biomedical material, which requires it to be in close contact with the skin surface or tissues, and its mechanical strength needed to be tested to determine the comfort of the materials. The mechanical properties of samples were shown in Table 1. For dry foams, the tensile strength increased with the increased molecular weight of CS, but the elongation at break decreased accordingly. Moreover, compared with the tensile strength of pure PU foam, that of PU-CA foams weakened. The variation of Young's modulus is similar to that of the tensile strength. It was demonstrated that using high molecular weight chitosan as chain extender can improve the tensile strength and the deformation resistance of PU-CS composite foam, but introduction of low molecular weight chitosan would decrease that. Zhang et al. reported that the addition of low molecular weight chitosan (3000 g/mol) was disadvantageous to the tensile strength of PEEU composite films [30]. In addition, Zia et al. suggested that the entanglement of polymer chains caused by higher molecular weight results in neck deformation that might be the reason of lower elongation values [24]. The mechanical properties of wet foams were different from that of dry foams. When the high molecular weight of chitosan was applied in PU-CS composite foam, both tensile strength and elongation at break increased, which was due to the strong hydration resistance of high molecular weight chitosan. The difference in Young's modulus between dry foam and wet sample shrank obviously when high molecular weight chitosan was added, which indicated that the deformation resistance of wet composite foam was enhanced apparently under the synergistic effect between intensive entanglement of high molecular weight CS chains and strong hydration resistance. 3.7. Surface and bulk hydrophilicity

3.5. Thermal stability The thermal stability of PU-CS composite foams was characterized by TGA measurement as shown in Fig. 6 with the local enlarged drawing of curves. Compared with pure PU, the addition of 5% CS has little effect on thermal stability of PU-CS composite foam. In addition, all samples showed two stage decompositions. The first decomposition happened in the temperature ranging from 100 to 340 °C was attributed to the water loss in foam and cleavage of urethane and substituted urea bond, and the second stage of mass loss extended up to 340–440 °C owing to the decomposition of diisocyanate [34]. PU-CS3K with relatively high decomposition temperature and remaining weight was due to the high grafting degree of CS. The well grafted CS3K as the

The surface and bulk hydrophilicity of biomaterials are related to the protein adsorption, biodegradability and even the mechanical properties of wet samples. As shown in Table 2, all materials showed acute contact angle, indicating that samples have good wettability due to the hydrophilicity of PEG. Comparing with the contact angle of pure PU, that of PU-CA was even smaller and that of PU-CS3K was slightly wider. Zhang et al. reported that the surface hydrophilicity of PEEU composite films increased gradually with the increase of the low molecular weight chitosan (3000 g/mol) content from 5 to 35 wt%, which was ascribed to the introduction of hydrophilic amino groups and hydroxyl groups in low molecular weight chitosan [30]. We considered that pure PEEU

Table 2 Hydrophilicity characterization and protein adsorption. Sample

PU

PU-CA

PU-CS3K

PU-CS30K

PU-CS300K

54.3 ± 0.3

53.2 ± 0.1

55.3 ± 0.1

62.9 ± 0.4

65.7 ± 0.5

934 ± 12 2.20 ± 0.07

1114 ± 11 14.2 ± 0.21

800 ± 16 19.6 ± 0.35

717 ± 19 23.6 ± 0.27

575 ± 19 23.8 ± 0.19

Water contact angle (°) Equilibrium water absorption ratio (%) BSA adsorption (μg/cm3)

H. Qin, K. Wang / International Journal of Biological Macromolecules 140 (2019) 877–885

3.8. Protein adsorption Protein adsorption could reduce the requirement for further support for keeping the materials in place due to the better adherence of the scaffold to the wound surface [36,37]. It was indicated from Table 2 that the adsorbed amount of BSA distinctly increased in PU-CS composite foams as compared to pure PU foam. In addition, with the increase of molecular weight of chitosan, the protein adsorption was improved. It is well know that protein adsorption is preferred on hydrophobic surfaces because the adsorption competition between water molecule and protein. With the increase of molecular weight of chitosan, the hydrophobicity of PU-CS composite foam increased, which improved the adsorption amount of BSA. However, there was no significantly difference in hydrophilicity between PU-CS composite foam with low molecular weight of chitosan (CA and CS3K) and pure PU foam. At this time, 1200 PU-CS300K PU-CS30K PU-CS3K PU-CA PU

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film with high water contact angle of 97° showed a hydrophobic surface and the hydrophilicity of PEEU composite films increased obviously by adding low molecular weight chitosan. Hou et al. reported that PEGbased PU film had good hydrophilicity [43]. In this paper, PEG-based PU foam with water contact angle much less than 90o also presented good hydrophilicity. Then, introduction of low molecular weight chitosan (5% addition) in PEG-based PU-CS composite foam had little effect on improving hydrophilicity of sample. In addition, when chitosan of high molecular weight (30KDa and 300KDa) was used, the contact angle of PU-CS composite foam increased obviously. It was demonstrated that addition of high molecular weight chitosan will obviously improve the hydrophobicity of foam. Lin et al. reported that the surface hydrophilicity of water-borne PUchitosan (200,000–400,000 g/mol) composites decreased with the increase of CS content, because high molecular weight CS with high crystallinity and the rigid chain hindered the polar groups to come to the polymer surface [35]. Our experimental results were similar to the analysis that the hydrophobicity of PU-CS composite foam improved with the increase of molecular weight of chitosan. It is a critical aspect for wound protection that polymeric spongy network had good liquid absorbing capability and moisture retention. As shown in Fig. 7, The water absorption ratio of pure PU was the highest and that of PU-CS3K was the lowest at 10 min, because high grafting degree of CS in PU-CS3K composite foam depressed the hydration of polymer chain in the initial stage. The behavior of the equilibrium water absorption (Table 2) corresponded to the hydrophilic property of composite foam. Higher hydrophilicity and larger equilibrium water absorption ratio.

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Weeks Fig. 8. Degradation rate of samples.

the electrostatic adsorption of amino groups in low molecular weight chitosan would lead to enhance the adsorption amount of BSA. 3.9. Degradation in vitro Degradation was a vital performance of biomaterials [44]. The in vitro degradation behavior of foam, which were incubated in SBF (pH = 7.4) at 37 °C for 5 weeks, was shown in Fig. 8. In the first three weeks of degradation, the degradation rate of pure PU foam reached to about 35% weight loss, but that of PU-CS composite foams were less than 30%. However, the PU-CS composite foams exhibited a fast degradation rate in the sequential two weeks. The degradation rate of PUCS3K, PU-CS30K and PU-CS300K were up to 70%, 85%, 98% and 98% respectively after five weeks, but that of pure PU foams was only 60%. Campos et al. thought that two factors should be considered in the degradation of PU microparticles [38]. One is the susceptibility of ester and urethane bonds to hydrolytic degradation. It is known that hard segments (consisting of urethane linkage) degrade slower than soft segments (consisting of ester linkage), since the urethane bond is much less susceptible to hydrolytic degradation than an ester bond. The other one is that the hydrophilicity of the polymer structure, which improve the degradation of polymers in aqueous solutions because water can more efficiently penetrate into the polymers and hydrolyze the esters bond. Zhang et al. reported that blending of PEEU with low molecular weight chitosan (3000 g/mol) could increase the degradation rate since the high surface and bulk hydrophilicity of the composite films, and the degradation time of composite films could be controlled by adjusting the chitosan content [30]. In this work, composite foam with high molecular weight chitosan (CS30K and CS300K) presented lower degradation rate due to their relatively strong hydrophobicity during the early stage of degradation. However, the hydrophilicity of composite foam with low molecular weight chitosan (CA and CS3K) was similar to that of pure samples, but the degradation rate of former was lower than that of latter. Here, it was the relatively large number of chemical crosslinking sites in PUCA and PU-CS3K composite foam that depressed the hydrolysis of ester bonds. In the late stage of degradation, the hard segment began to hydrolyze. The introduction of CS in the hard segment accelerated the chain scission by hydrolysis of urethane bonds. With the increase of molecular weight of chitosan, the degradation rate of composite foam increased. Lower grafting degree of CS was the main reason for faster degradation rate. Though the CS grafting degree of PU-CA was lower than that of PU-CS3K, the degradation rate of the former was the slowest, which should be due to the high activity of hydroxyl besides amino group in CA.

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4. Conclusion In this research, a category of PEG-based PU-CS composite foams were produced by CS with different molecular weight as chain extender. The experimental results showed that the differences in group reactivity (-NH2 and -OH) and steric resistance of CS with different molecular weight had an important influence on the crystallization behavior, morphology, mechanical properties, hydrophilicity, protein adsorption and degradation in vitro of PU-CS composite foams. CS with an appropriate lower molecular weight presented high reactivity, which enhanced the CS grafting degree and thermal stability. When CS of high molecular weight was used, the phase separation between CS and soft segment appeared due to steric hindrance, which caused disorder bubble holes in PU-CS30K and PU-CS300K. Both the tensile strength and the hydrophobicity of PU-CS composite foam increased with the increased molecular weight of CS. The contribution of PEG to the hydrophilicity of foams should be considered. The electrostatic adsorption of amino groups in low molecular weight CS improved the adsorption amount of BSA in PU-CS composite foam. The protein adsorption in PU-CS30K and PUCS300K was enhanced due to their relatively high hydrophobicity. In the early stage of degradation in vitro, the degradation rate of PU-CS composite foam was slower than that of pure PU, and in the following time, the former accelerated obviously. With the increase of CS molecular weight, the degradation rate of PU-CS composite foam increased, which related to the chemical crosslinking density of the composites. The obtained data gives viewpoints to the other important laws of CSmodified PU and encourage the further research of this foaming material for biomedical application.

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