Sodium carboxymethylation-functionalized chitosan fibers for cutaneous wound healing application

Abstract

A water absorption biomaterial, sodium carboxymethylation-functionalized chitosan fibers (Na-NOCC fibers) were prepared, applied for cutaneous wound repair, and characterized by FTIR and NMR. The water absorption of Na-NOCC fibers increased significantly with substitution degree rising, from 3.2 to 6.8 g/g, and higher than that of chitosan fibers (2.2 g/g) confirmed by swelling behavior. In the antibacterial action, the high degree of substitution of Na-NOCC fibers exhibited stronger antibacterial activities against E. coli (from 66.54% up to 88.86%). The inhibition of Na-NOCC fibers against S. aureus were above 90%, and more effective than E. coli. The cytotoxicity assay demonstrated that Na-NOCC2 fibers were no obvious cytotoxicity to mouse fibroblasts. Wound healing test and histological examination showed that significantly advanced granulation tissue and capillary formation in the healing-impaired wounds treated with Na-NOCC fibers, as compared to those treated with gauze, which demonstrated that Na-NOCC fibers could promote skin repair and might have great application for wound healing.

Keywords

sodium carboxymethylation-functionalized chitosan fiber / water absorption / wound healing / wound dressing

References

[1] Miraftab M, Masood R, Edward-Jones V. A new carbohydrate-based wound dressing fibre with superior absorption and antimicrobial potency. Carbohydrate Polymers, 2014, 101: 1184–1190

[2] Babu R, Zhang J, Beckman E J, . Antimicrobial activities of silver used as a polymerization catalyst for a wound-healing matrix. Biomaterials, 2006, 27(24): 4304–4314

[3] Kanokpanont S, Damrongsakkul S, Ratanavaraporn J, . An innovative bi-layered wound dressing made of silk and gelatin for accelerated wound healing. International Journal of Pharmaceutics, 2012, 436(1‒2): 141–153

[4] Lu S, Gao W, Gu H Y. Construction, application and biosafety of silver nanocrystalline chitosan wound dressing. Burns, 2008, 34(5): 623–628

[5] Sashiwa H, Aiba S I. Chemically modified chitin and chitosan as biomaterials. Progress in Polymer Science, 2004, 29(9): 887–908

[6] Muzzarelli R A A. Chitins and chitosans for the repair of wounded skin, nerve, cartilage and bone. Carbohydrate Polymers, 2009, 76(2): 167–182

[7] Chang J, Liu W, Han B, . Investigation of the skin repair and healing mechanism of N-carboxymethyl chitosan in second-degree burn wounds. Wound Repair and Regeneration, 2013, 21(1): 113–121

[8] Zhou Y, Yang H, Liu X, . Potential of quaternization-functionalized chitosan fiber for wound dressing. International Journal of Biological Macromolecules, 2013, 52: 327–332

[9] Anitha A, Divya Rani V V, Krishna R, . Synthesis, characterization, cytotoxicity and antibacterial studies of chitosan, O-carboxymethyl and N,O-carboxymethyl chitosan nanoparticles. Carbohydrate Polymers, 2009, 78(4): 672–677

[10] Kim I Y, Seo S J, Moon H S, . Chitosan and its derivatives for tissue engineering applications. Biotechnology Advances, 2008, 26(1): 1–21

[11] Qin Y, Hu H, Luo A, . Effect of carboxymethylation on the absorption and chelating properties of chitosan fibers. Journal of Applied Polymer Science, 2006, 99(6): 3110–3115

[12] Upadhyaya L, Singh J, Agarwal V, . Biomedical applications of carboxymethyl chitosans. Carbohydrate Polymers, 2013, 91(1): 452–466

[13] Rinaudo M. Chitin and chitosan: Properties and applications. Progress in Polymer Science, 2006, 31(7): 603–632

[14] Kong X. Simultaneous determination of degree of deacetylation, degree of substitution and distribution fraction of −COONa in carboxymethyl chitosan by potentiometric titration. Carbohydrate Polymers, 2012, 88(1): 336–341

[15] Chen X G, Park H J. Chemical characteristics of O-carboxymethyl chitosans related to the preparation conditions. Carbohydrate Polymers, 2003, 53(4): 355–359

[16] Zhou Y, Shi L, Li F, . Preparation and characterization of carboxymethyl-functionalized chitosan fiber. Journal of Natural Fibers, 2015, 12(3): 211–221

[17] Muzzarelli R A A, Tanfani F, Emanuelli M, . N-(carboxymethylidene) chitosans and N-(carboxymethyl) chitosans: Novel chelating polyampholytes obtained from chitosan glyoxylate. Carbohydrate Research, 1982, 107(2): 199–214

[18] Lv J, Zhou Q, Liu G, . Preparation and properties of polyester fabrics grafted with O-carboxymethyl chitosan. Carbohydrate Polymers, 2014, 113: 344–352

[19] Sweeney I R, Miraftab M, Collyer G. Absorbent alginate fibres modified with hydrolysed chitosan for wound care dressings — II. Pilot scale development. Carbohydrate Polymers, 2014, 102: 920–927

[20] Zeng X, Sun Y X, Qu W, . Biotinylated transferrin/avidin/biotinylated disulfide containing PEI bioconjugates mediated p53 gene delivery system for tumor targeted transfection. Biomaterials, 2010, 31(17): 4771–4780

[21] Li X, Kong X, Zhang Z, . Cytotoxicity and biocompatibility evaluation of N,O-carboxymethyl chitosan/oxidized alginate hydrogel for drug delivery application. International Journal of Biological Macromolecules, 2012, 50(5): 1299–1305

[22] Tao S, Gao S, Zhou Y, . Preparation of carboxymethyl chitosan sulfate for improved cell proliferation of skin fibroblasts. International Journal of Biological Macromolecules, 2013, 54: 160–165

[23] Zhou Z, Yan D, Cheng X, . Biomaterials based on N,N,N-trimethyl chitosan fibers in wound dressing applications. International Journal of Biological Macromolecules, 2016, 89: 471–476

[24] Huang Y, Zhang L, Yang J, . Structure and properties of cellulose films reinforced by chitin whiskers. Macromolecular Materials and Engineering, 2013, 298(3): 303–310

[25] Ong S Y, Wu J, Moochhala S M, . Development of a chitosan-based wound dressing with improved hemostatic and antimicrobial properties. Biomaterials, 2008, 29(32): 4323–4332

[26] Dowling M B, Smith W, Balogh P, . Hydrophobically-modified chitosan foam: description and hemostatic efficacy. The Journal of Surgical Research, 2015, 193(1): 316–323

[27] Upadhyaya L, Singh J, Agarwal V, . The implications of recent advances in carboxymethyl chitosan based targeted drug delivery and tissue engineering applications. Journal of Controlled Release, 2014, 186: 54–87

[28] Gong C, Wu Q, Wang Y, . A biodegradable hydrogel system containing curcumin encapsulated in micelles for cutaneous wound healing. Biomaterials, 2013, 34(27): 6377–6387

[29] Murakami K, Aoki H, Nakamura S, . Hydrogel blends of chitin/chitosan, fucoidan and alginate as healing-impaired wound dressings. Biomaterials, 2010, 31(1): 83–90

[30] Brugnerotto J, Lizardi J, Goycoolea F M, . An infrared investigation in relation with chitin and chitosan characterization. Polymer, 2001, 42(8): 3569–3580

[31] Zhao Y W, Liu L, Han X, . Preparation of N, O-carboxymethyl chitosan with different substitutional degree and its application for hemostasis. Advanced Materials Research, 2013, 798 ‒ 799: 1061–1066

[32] Kubota N, Tatsumoto N, Sano T, . A simple preparation of half N-acetylated chitosan highly soluble in water and aqueous organic solvents. Carbohydrate Research, 2000, 324(4): 268–274

[33] Patrulea V, Applegate L A, Ostafe V, . Optimized synthesis of O-carboxymethyl-N,N,N-trimethyl chitosan. Carbohydrate Polymers, 2015, 122: 46–52

[34] Zheng M, Han B, Yang Y, . Synthesis, characterization and biological safety of O-carboxymethyl chitosan used to treat Sarcoma 180 tumor. Carbohydrate Polymers, 2011, 86(1): 231–238

[35] Lim S H, Hudson S M. Application of a fiber-reactive chitosan derivative to cotton fabric as an antimicrobial textile finish. Carbohydrate Polymers, 2004, 56(2): 227–234

[36] Lim S H, Hudson S M. Review of chitosan and its derivatives as antimicrobial agents and their uses as textile chemicals. Journal of Macromolecular Science Part C: Polymer Reviews, 2003, 43(2): 223–269

[37] Lim S H, Hudson S M. Synthesis and antimicrobial activity of a water-soluble chitosan derivative with a fiber-reactive group. Carbohydrate Research, 2004, 339(2): 313–319

[38] Raafat D, von Bargen K, Haas A, . Insights into the mode of action of chitosan as an antibacterial compound. Applied and Environmental Microbiology, 2008, 74(12): 3764–3773

[39] Kong M, Chen X G, Xing K, . Antimicrobial properties of chitosan and mode of action: a state of the art review. International Journal of Food Microbiology, 2010, 144(1): 51–63

Acknowledgements

This work was supported by the Foundation of NSFC & SD (Grant No. 81271727), the China’s State Oceanic Administration Project (Grant No. 201505022), the Doctoral Fund of Ministry of Education of China (Grant No. 20120132110012), and the Taishan Scholar Program, China.

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2016 Higher Education Press and Springer-Verlag Berlin Heidelberg