A chitosan-based antibacterial hydrogel with injectable and self-healing capabilities

Abstract

The presence of bacteria directly affects wound healing. Chitosan-based hydrogel biomaterials are a solution as they offer advantages for wound-healing applications due to their strong antimicrobial properties. Here, a double-cross-linking chitosan-based hydrogel with antibacterial, self-healing, and injectable properties is reported. Thiolated chitosan was successfully prepared, and the thiolated chitosan molecules were cross-linked by Ag–S coordination to form a supramolecular hydrogel. Subsequently, the amine groups in the thiolated chitosan covalently cross-linked with genipin to further promote hydrogel formation. In vitro experimental results indicate that hydrogel can release Ag⁺ over an extended time, achieving an antibacterial rate of over 99% against Escherichia coli and Staphylococcus aureus. Due to the reversible and dynamic feature of Ag–S coordination, an antibacterial hydrogel exhibited injectable and self-healing capabilities. Additionally, the hydrogel showed excellent biocompatibility and biodegradability.

Keywords

Hydrogel / Chitosan / Silver ion / Cross-linking / Antibacterial

References

[] Alshameri AW, Owais M. Antibacterial and cytotoxic potency of the plant-mediated synthesis of metallic nanoparticles Ag NPs and ZnO NPs: a review. OpenNano, 2022, 8,

[] Bapat RA, Chaubal TV, Joshi CP, Bapat PR, Choudhury H, Pandey M, Gorain B, Kesharwani P. An overview of application of silver nanoparticles for biomaterials in dentistry. Mater Sci Eng C, 2018, 91: 881-898,

[] Chen K-Y, Liao W-J, Kuo S-M, Tsai F-J, Chen Y-S, Huang C-Y, Yao C-H. Asymmetric chitosan membrane containing collagen I nanospheres for skin tissue engineering. Biomacromol, 2009, 10: 1642-1649,

[] Dai X, Guo Q, Zhao Y, Zhang P, Zhang T, Zhang X, Li C. Functional silver nanoparticle as a benign antimicrobial agent that eradicates antibiotic-resistant bacteria and promotes wound healing. ACS Appl Mater Interfaces, 2016, 8: 25798-25807,

[] Ellman GL. Tissues sulfhydryl groups. Arch Biochem Biophys, 1959, 82: 70-77,

[] Gao Y, Li Z, Huang J, Zhao M, Wu J. In situ formation of injectable hydrogels for chronic wound healing. J Mater Chem B, 2020, 8: 8768-8780,

[] Hamedi H, Moradi S, Hudson SM, Tonelli AE. Chitosan based hydrogels and their applications for drug delivery in wound dressings: a Review. Carbohydr Polym, 2018, 199: 445-460,

[] Klein MP, Hackenhaar CR, Lorenzoni ASG, Rodrigues RC, Costa TMH, Ninow JL, Hertz PF. Chitosan crosslinked with genipin as support matrix for application in food process: support characterization and β-d-galactosidase immobilization. Carbohydr Polym, 2016, 137: 184-190,

[] Kong L, Wu Z, Zhao H, Cui H, Shen J, Chang J, Li H, He Y. Bioactive injectable hydrogels containing desferrioxamine and bioglass for diabetic wound healing. ACS Appl Mater Interfaces, 2018, 10: 30103-30114,

[] Krauland AH, Hoffer MH, Bernkop-Schnürch A. Viscoelastic properties of a new in situ gelling thiolated chitosan conjugate. Drug Dev Ind Pharm, 2005, 31: 885-893,

[] Li Q, Lu F, Zhou G, Yu K, Lu B, Xiao Y, Dai F, Wu D, Lan G. Silver inlaid with gold nanoparticle/chitosan wound dressing enhances antibacterial activity and porosity, and promotes wound healing. Biomacromol, 2017, 18: 3766-3775,

[] Liang D, Lu Z, Yang H, Gao J, Chen R. Novel asymmetric wettable AgNPs/chitosan wound dressing: in vitro and in vivo evaluation. ACS Appl Mater Interfaces, 2016, 8: 3958-3968,

[] Mohamed Salleh NAB, Tanaka Y, Sutarlie L, Su X. Detecting bacterial infections in wounds: a review of biosensors and wearable sensors in comparison with conventional laboratory methods. Analyst, 2022, 147: 1756-1776,

[] Morones JR, Elechiguerra JL, Camacho A, Holt K, Kouri JB, Ramírez JT, Yacaman MJ. The bactericidal effect of silver nanoparticles. Nanotechnology, 2005, 16: 2346,

[] No HK, Young Park N, Ho Lee S, Meyers SP. Antibacterial activity of chitosans and chitosan oligomers with different molecular weights. Int J Food Microbiol, 2002, 74: 65-72,

[] Pan X-F, Gao H-L, Su Y, Wu Y-D, Wang X-Y, Xue J-Z, He T, Lu Y, Liu J-W, Yu S-H. Strong and stiff Ag nanowire-chitosan composite films reinforced by Ag–S covalent bonds. Nano Res, 2018, 11: 410-419,

[] Rinaudo M. Chitin and chitosan: properties and applications. Prog Polym Sci, 2006, 31: 603-632,

[] Rosen H. A modified ninhydrin colorimetric analysis for amino acids. Arch Biochem Biophys, 1957, 67: 10-15,

[] Somayajula D, Agarwal A, Sharma AK, Pall AE, Datta S, Ghosh G. In situ synthesis of silver nanoparticles within hydrogel-conjugated membrane for enhanced antibacterial properties. ACS Appl Bio Mater, 2019, 2: 665-674,

[] Sun Y, Sun G. Synthesis, characterization, and antibacterial activities of novel N-halamine polymer beads prepared by suspension copolymerization. Macromolecules, 2002, 35: 8909-8912,

[] Tchemtchoua VT, Atanasova G, Aqil A, Filée P, Garbacki N, Vanhooteghem O, Deroanne C, Noël A, Jérome C, Nusgens B, Poumay Y, Colige A. Development of a chitosan nanofibrillar scaffold for skin repair and regeneration. Biomacromol, 2011, 12: 3194-3204,

[] Tran NQ, Joung YK, Lih E, Park KD. In situ forming and rutin-releasing chitosan hydrogels as injectable dressings for dermal wound healing. Biomacromol, 2011, 12: 2872-2880,

[] Verlee A, Mincke S, Stevens CV. Recent developments in antibacterial and antifungal chitosan and its derivatives. Carbohydr Polym, 2017, 164: 268-283,

[] Wang X, Zheng C, Wu Z, Teng D, Zhang X, Wang Z, Li C. Chitosan-NAC nanoparticles as a vehicle for nasal absorption enhancement of insulin. J Biomed Mater Res B Appl Biomater, 2009, 88B: 150-161,

[] Wang N, Xu X, Li H, Yuan L, Yu H. Enhanced selective adsorption of Pb(II) from aqueous solutions by one-pot synthesis of xanthate-modified chitosan sponge: behaviors and mechanisms. Ind Eng Chem Res, 2016, 55: 12222-12231,

[] Wu J, Hou S, Ren D, Mather PT. Antimicrobial properties of nanostructured hydrogel webs containing silver. Biomacromol, 2009, 10: 2686-2693,

[] Wu F, Meng G, He J, Wu Y, Wu F, Gu Z. Antibiotic-loaded chitosan hydrogel with superior dual functions: antibacterial efficacy and osteoblastic cell Responses. ACS Appl Mater Interfaces, 2014, 6: 10005-10013,

[] Xu Z, Zhang C, Wang X, Liu D. Release strategies of silver ions from materials for bacterial killing. ACS Appl Bio Mater, 2021, 4: 3985-3999,

[] Zeng M, Fang Z. Preparation of sub-micrometer porous membrane from chitosan/polyethylene glycol semi-IPN. J Membr Sci, 2004, 245: 95-102,

[] Zhang M, Yang M, Woo MW, Li Y, Han W, Dang X. High-mechanical strength carboxymethyl chitosan-based hydrogel film for antibacterial wound dressing. Carbohydr Polym, 2021, 256,