Abstract
Chronic wounds caused by pathogenic bacterial infections have been a worldwide medical threat and challenge, ZnO is a promising antibacterial agent to promote infected wound healing. However, ZnO particles need to be with a wound dressing material to improve low-dose antibacterial efficacy while reducing cytotoxicity. The natural polysaccharide, chitin-based hydrogels can be applied as a preferential supporting matrix for the deposition of ZnO. In this study, we developed chitin/ZnO composite hydrogels (CZG hydrogels), which were applied for the biofilm-infected full-thickness wound treatment. The three-dimensional hydrophilic network structure of chitin hydrogels provided a large number of absorption sites for Zn2+ ions, and CZG hydrogels were prepared by in situ synthesis of ZnO. CZG hydrogels had potent broad-spectrum and long-lasting antibacterial activity, good bacteriostatic ability against high concentration of bacterial fluids. The in vivo studies showed that CZG hydrogels have a significant effect of accelerating biofilm-infected wound healing. Collectively, this work confirmed that chitin hydrogels could be applied as a preferential natural supporting matrix for the deposition of inorganic metal and metal oxide nanoparticles, and provided alternative antibacterial dressing for treating microbial infections and promoting wound healing.
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References
Abbasabadi OR, Farahpour MR, Tabatabaei ZG (2022) Accelerative effect of nanohydrogels based on chitosan/ZnO incorporated with citral to heal the infected full-thickness wounds; an experimental study. Int J Biol Macromol 217:42–54. https://doi.org/10.1016/j.ijbiomac.2022.07.038
Alavi M, Nokhodchi A (2020) An overview on antimicrobial and wound healing properties of ZnO nanobiofilms, hydrogels, and bionanocomposites based on cellulose, chitosan, and alginate polymers. Carbohydr Polym 227:115349. https://doi.org/10.1016/j.carbpol.2019.115349
An H, Zhang M, Zhou L, Huang Z, Duan Y, Wang C, Gu Z, Zhang P, Wen Y (2023) Anti-dehydration and rapid trigger-detachable multifunctional hydrogels promote scarless therapeutics of deep burn. Adv Funct Mater 33:2211182. https://doi.org/10.1002/adfm.202211182
Anitha A, Sowmya S, Kumar PTS, Deepthi S, Chennazhi KP, Ehrlich H, Tsurkan M, Jayakumar R (2014) Chitin and chitosan in selected biomedical applications. Polym Sci 39:1644–1667. https://doi.org/10.1016/j.progpolymsci.2014.02.008
Brugnerotto J, Lizardi J, Goycoolea FM, Argüelles-Monal W, Desbrières J, Rinaudo M (2001) An infrared investigation in relation with chitin and chitosan characterization. Polymer 42:3569–3580. https://doi.org/10.1016/S0032-3861(00)00713-8
Cao H, Xiang D, Zhou X, Yue P, Zou Y, Zhong Z, Ma Y, Wang L, Wu S, Ye Q (2023) High-strength, antibacterial, antioxidant, hemostatic, and biocompatible chitin/PEGDE-tannic acid hydrogels for wound healing. Carbohydr Polym 307:120609. https://doi.org/10.1016/j.carbpol.2023.120609
Dhanalakshmi A, Palanimurugan A, Natarajan B (2017) Enhanced antibacterial effect using carbohydrates biotemplate of ZnO nano thin films. Carbohydr Polym 168:191–200. https://doi.org/10.1016/j.carbpol.2017.03.071
Ding B, Cai J, Huang J, Zhang L, Chen Y, Shi X, Du Y, Kuga S (2012) Facile preparation of robust and biocompatible chitin aerogels. J Mater Chem 22:5801–5809. https://doi.org/10.1039/C2JM16032C
Du T, Xiao Z, Cao J, Wei L, Li C, Jiao J, Song Z, Liu J, Du X, Wang S (2022) NIR-activated multi-hit therapeutic Ag2S quantum dot-based hydrogel for healing of bacteria-infected wounds. Acta Biomater 145:88–105. https://doi.org/10.1016/j.actbio.2022.04.013
Duan B, Huang Y, Lu A, Zhang L (2018) Recent advances in chitin based materials constructed via physical methods. Prog Polym Sci 82:1–33. https://doi.org/10.1016/j.progpolymsci.2018.04.001
Dutta RK, Nenavathu BP, Gangishetty MK, Reddy AVR (2012) Studies on antibacterial activity of ZnO nanoparticles by ROS induced lipid peroxidation. Colloids Surf B 94:143–150. https://doi.org/10.1016/j.colsurfb.2012.01.046
Falanga V, Isseroff RR, Soulika AM, Romanelli M, Margolis D, Kapp S, Granick M, Harding K (2022) Chronic wounds. Nat Rev Dis Primers 8:50. https://doi.org/10.1038/s41572-022-00377-3
Gaspar-Pintiliescu A, Stanciuc A-M, Craciunescu O (2019) Natural composite dressings based on collagen, gelatin and plant bioactive compounds for wound healing: a review. Int J Biol Macromol 138:854–865. https://doi.org/10.1016/j.ijbiomac.2019.07.155
George S, Yin H, Liu Z, Shen S, Cole I, Khiong CW (2022) Hazard profiling of a combinatorial library of zinc oxide nanoparticles: ameliorating light and dark toxicity through surface passivation. J Hazard Mater 434:128825. https://doi.org/10.1016/j.jhazmat.2022.128825
Hou F, Gong Z, Jia F, Cui W, Song S, Zhang J, Wang Y, Wang W (2023) Insights into the relationships of modifying methods, structure, functional properties and applications of chitin: a review. Food Chem 409:135336. https://doi.org/10.1016/j.foodchem.2022.135336
Huang L, Yang X, Deng L, Ying D, Lu A, Zhang L, Yu A, Duan B (2021) Biocompatible chitin hydrogel incorporated with PEDOT nanoparticles for peripheral nerve repair. ACS Appl Mater Interfaces 13:16106–16117. https://doi.org/10.1021/acsami.1c01904
Huang K-X, Zhou L-Y, Chen J-Q, Peng N, Chen H-X, Gu H-Z, Zou T (2023) Applications and perspectives of quaternized cellulose, chitin and chitosan: a review. Int J Biol Macromol 242:124990. https://doi.org/10.1016/j.ijbiomac.2023.124990
Jin Y, Wang C, Xia Z, Niu P, Li Y, Miao W (2023) Photodynamic chitosan sponges with dual instant and enduring bactericidal potency for treating skin abscesses. Carbohydr Polym 306:120589. https://doi.org/10.1016/j.carbpol.2023.120589
Kang X, Lei J, Yang C, Zhang P, Li X, Zheng S, Li Q, Zhang J (2022) A hybrid hydrogel composed of chitin and β-glucan for the effective management of wound healing and scarring. Biomater Sci 10:6024–6036. https://doi.org/10.1039/D2BM00935H
Liang J, Zeng H, Qiao L, Jiang H, Ye Q, Wang Z, Liu B, Fan Z (2022) 3D printed piezoelectric wound dressing with dual piezoelectric response models for scar-prevention wound healing. ACS Appl Mater Interfaces 14:30507–30522. https://doi.org/10.1021/acsami.2c04168
Liao W, Yang D, Xu Z, Zhao L, Mu C, Li D, Ge L (2023) Antibacterial collagen-based nanocomposite dressings for promoting infected wound healing. Adv Healthc Mater 12:2203054. https://doi.org/10.1002/adhm.202203054
Lin M-H, Wang Y-H, Kuo C-H, Ou S-F, Huang P-Z, Song T-Y, Chen Y-C, Chen S-T, Wu C-H, Hsueh Y-H et al (2021a) Hybrid ZnO/chitosan antimicrobial coatings with enhanced mechanical and bioactive properties for titanium implants. Carbohydr Polym 257:117639. https://doi.org/10.1016/j.carbpol.2021.117639
Lin X, Zhang L, Duan B (2021b) Polyphenol-mediated chitin self-assembly for constructing a fully naturally resourced hydrogel with high strength and toughness. Mater Horizons 8:2503–2512. https://doi.org/10.1039/D1MH00878A
Linju MC, Rekha MR (2023) Proline conjugated chitosan as wound healing material:in vitro studies on the influence of the scaffold on collagen production and wound healing. Int J Biol Macromol 242:124688. https://doi.org/10.1016/j.ijbiomac.2023.124688
Lu H-T, Lin C, Wang Y-J, Hsu F-Y, Hsu J-T, Tsai M-L, Mi F-L (2023) Sequential deacetylation/self-gelling chitin hydrogels and scaffolds functionalized with fucoidan for enhanced BMP-2 loading and sustained release. Carbohydr Polym 315:121002. https://doi.org/10.1016/j.carbpol.2023.121002
Ma K, Dong P, Liang M, Yu S, Chen Y, Wang F (2020) Facile assembly of multifunctional antibacterial nanoplatform leveraging synergistic sensitization between silver nanostructure and vancomycin. ACS Appl Mater Interfaces 12:6955–6965. https://doi.org/10.1021/acsami.9b22043
Mei J, Xu D, Wang L, Kong L, Liu Q, Li Q, Zhang X, Su Z, Hu X, Zhu W et al (2023) Biofilm microenvironment-responsive self-assembly nanoreactors for all-stage biofilm associated infection through bacterial cuproptosis-like death and macrophage re-rousing. Adv Mater 2303432. https://doi.org/10.1002/adma.202303432
Ning C, Wang X, Li L, Zhu Y, Li M, Yu P, Zhou L, Zhou Z, Chen J, Tan G et al (2015) Concentration ranges of antibacterial cations for showing the highest antibacterial efficacy but the least cytotoxicity against mammalian cells: implications for a new antibacterial mechanism. Chem Res Toxicol 28:1815–1822. https://doi.org/10.1021/acs.chemrestox.5b00258
Ogawa Y, Kimura S, Wada M, Kuga S (2010) Crystal analysis and high-resolution imaging of microfibrillar α-chitin from phaeocystis. J Struct Biol 171:111–116. https://doi.org/10.1016/j.jsb.2010.03.010
Pillai CKS, Paul W, Sharma CP (2009) Chitin and chitosan polymers: chemistry, solubility and fiber formation. Prog Polym Sci 34:641–678. https://doi.org/10.1016/j.progpolymsci.2009.04.001
Raguvaran R, Manuja A, Manuja BK, Riyesh T, Singh S, Kesavan M, Dimri U (2017) Sodium alginate and gum acacia hydrogels of zinc oxide nanoparticles reduce hemolytic and oxidative stress inflicted by zinc oxide nanoparticles on mammalian cells. Int J Biol Macromol 101:967–972. https://doi.org/10.1016/j.ijbiomac.2017.03.180
Rakhshaei R, Namazi H (2017) A potential bioactive wound dressing based on carboxymethyl cellulose/ZnO impregnated MCM-41 nanocomposite hydrogel. Mater Sci Eng C 73:456–464. https://doi.org/10.1016/j.msec.2016.12.097
Ranjbari A, Demeestere K, Kim K-H, Heynderickx PM (2023) Oxygen vacancy modification of commercial ZnO by hydrogen reduction for the removal of thiabendazole: characterization and kinetic study. Appl Catal B 324:122265. https://doi.org/10.1016/j.apcatb.2022.122265
Reyes PI, Yang K, Zheng A, Li R, Li G, Lu Y, Tsang CK, Zheng SXF (2017) Dynamic monitoring of antimicrobial resistance using magnesium zinc oxide nanostructure-modified quartz crystal microbalance. Biosens Bioelectron 93:189–197. https://doi.org/10.1016/j.bios.2016.09.011
Rosenberg M, Visnapuu M, Vija H, Kisand V, Kasemets K, Kahru A, Ivask A (2020) Selective antibiofilm properties and biocompatibility of nano-ZnO and nano-ZnO/Ag coated surfaces. Sci Rep 10:13478. https://doi.org/10.1038/s41598-020-70169-w
Rumbaugh KP, Sauer K (2020) Biofilm dispersion. Nat Rev Microbiol 18:571–586. https://doi.org/10.1038/s41579-020-0385-0
Sauer K, Stoodley P, Goeres DM, Hall-Stoodley L, Burmølle M, Stewart PS, Bjarnsholt T (2022) The biofilm life cycle: expanding the conceptual model of biofilm formation. Nat Rev Microbiol 20:608–620. https://doi.org/10.1038/s41579-022-00767-0
Shang Z, An X, Liu L, Yang J, Zhang W, Dai H, Cao H, Xu Q, Liu H, Ni Y (2021) Chitin nanofibers as versatile bio-templates of zeolitic imidazolate frameworks for N-doped hierarchically porous carbon electrodes for supercapacitor. Carbohydr Polym 251:117107. https://doi.org/10.1016/j.carbpol.2020.117107
Shi T, Lu H, Zhu J, Zhou X, He C, Li F, Yang G (2023) Naturally derived dual dynamic crosslinked multifunctional hydrogel for diabetic wound healing. Compos B Eng 257:110687. https://doi.org/10.1016/j.compositesb.2023.110687
Siddiqi KS, Rahman UR, Tajuddin A, Husen A (2018) Properties of zinc oxide nanoparticles and their activity against microbes. Nanoscale Res Lett 13:141. https://doi.org/10.1186/s11671-018-2532-3
Sirelkhatim A, Mahmud S, Seeni A, Kaus NHM, Ann LC, Bakhori SKM, Hasan H, Mohamad D (2015) Review on zinc oxide nanoparticles: antibacterial activity and toxicity mechanism. Nanomicro Lett 7:219–242. https://doi.org/10.1007/s40820-015-0040-x
Song Y, Wu H, Gao Y, Li J, Lin K, Liu B, Lei X, Cheng P, Zhang S, Wang Y et al (2020) Zinc silicate/nano-hydroxyapatite/collagen scaffolds promote angiogenesis and bone regeneration via the p38 MAPK pathway in activated monocytes. ACS Appl Mater Interfaces 12:16058–16075. https://doi.org/10.1021/acsami.0c00470
Tian B, Liu J (2023) Cyclodextrin-metal-organic frameworks in molecular delivery, detection, separation, and capture: an updated critical review. Carbohydr Polym 306:120598. https://doi.org/10.1016/j.carbpol.2023.120598
Wang L, Zheng W, Hou Q, Zhong L, Li Q, Jiang X (2022) Breathable and stretchable dressings for accelerating healing of infected wounds. Adv Healthc Mater 11:2201053. https://doi.org/10.1002/adhm.202201053
Wang L, Duan L, Liu G, Sun J, Shahbazi M-A, Kundu SC, Reis RL, Xiao B, Yang X (2023) Bioinspired polyacrylic acid-based dressing: wet adhesive, self-healing, and multi-biofunctional coacervate hydrogel accelerates wound healing. Adv Sci 10:2207352. https://doi.org/10.1002/advs.202207352
Wu T, Huang L, Sun J, Sun J, Yan Q, Duan B, Zhang L, Shi B (2021) Multifunctional chitin-based barrier membrane with antibacterial and osteogenic activities for the treatment of periodontal disease. Carbohydr Polym 269:118276. https://doi.org/10.1016/j.carbpol.2021.118276
Wu S, Yang Y, Wang S, Dong C, Zhang X, Zhang R, Yang L (2022) Dextran and peptide-based pH-sensitive hydrogel boosts healing process in multidrug-resistant bacteria-infected wounds. Carbohydr Polym 278:118994. https://doi.org/10.1016/j.carbpol.2021.118994
Wu H, Wei M, Hu S, Cheng P, Shi S, Xia F, Xu L, Yin L, Liang G, Li F et al (2023) A photomodulable bacteriophage-spike nanozyme enables dually enhanced biofilm penetration and bacterial capture for photothermal-boosted catalytic therapy of MRSA infections. Adv Sci 2301694. https://doi.org/10.1002/advs.202301694
Xing F, Chi Z, Yang R, Xu D, Cui J, Huang Y, Zhou C, Liu C (2021) Chitin-hydroxyapatite-collagen composite scaffolds for bone regeneration. Int J Biol Macromol 184:170–180. https://doi.org/10.1016/j.ijbiomac.2021.05.019
Xu D, Huang J, Zhao D, Ding B, Zhang L, Cai J (2016) High-flexibility, high-toughness double-cross-linked chitin hydrogels by sequential chemical and physical cross-linkings. Adv Mater 28:5844–5849. https://doi.org/10.1002/adma.201600448
Xu J, Younis MR, Zhang Z, Feng Y, Su L, Que Y, Jiao Y, Fan C, Chang J, Ni S et al (2023) Mild heat-assisted polydopamine/alginate hydrogel containing low-dose nanoselenium for facilitating infected wound healing. ACS Appl Mater Interfaces 15:7841–7854. https://doi.org/10.1021/acsami.2c21516
Yadollahi M, Gholamali I, Namazi H, Aghazadeh M (2015a) Synthesis and characterization of antibacterial carboxymethylcellulose/CuO bio-nanocomposite hydrogels. Int J Biol Macromol 73:109–114. https://doi.org/10.1016/j.ijbiomac.2014.10.063
Yadollahi M, Namazi H, Aghazadeh M (2015b) Antibacterial carboxymethyl cellulose/Ag nanocomposite hydrogels cross-linked with layered double hydroxides. Int J Biol Macromol 79:269–277. https://doi.org/10.1016/j.ijbiomac.2015.05.002
Yadollahi M, Farhoudian S, Barkhordari S, Gholamali I, Farhadnejad H, Motasadizadeh H (2016) Facile synthesis of chitosan/ZnO bio-nanocomposite hydrogel beads as drug delivery systems. Int J Biol Macromol 82:273–278. https://doi.org/10.1016/j.ijbiomac.2015.09.064
Yang C, Dawulieti J, Zhang K, Cheng C, Zhao Y, Hu H, Li M, Zhang M, Chen L, Leong KW et al (2022) An injectable antibiotic hydrogel that scavenges proinflammatory factors for the treatment of severe abdominal trauma. Adv Funct Mater 32:2111698. https://doi.org/10.1002/adfm.202111698
Yang F, Xue Y, Wang F, Guo D, He Y, Zhao X, Yan F, Xu Y, Xia D, Liu Y (2023) Sustained release of magnesium and zinc ions synergistically accelerates wound healing. Bioact Mater 26:88–101. https://doi.org/10.1016/j.bioactmat.2023.02.019
Yin X, Huang S, Xu S, Chang L, Zhao X, Chen Z, Mei X, Gao X (2022) Preparation of pro-angiogenic, antibacterial and EGCG-modified ZnO quantum dots for treating bacterial infected wound of diabetic rats. Biomater Adv 133:112638. https://doi.org/10.1016/j.msec.2021.112638
Zeng Q, Qi X, Shi G, Zhang M, Haick H (2022) Wound dressing: from nanomaterials to diagnostic dressings and healing evaluations. ACS Nano 16:1708–1733. https://doi.org/10.1021/acsnano.1c08411
Zhang Z, Shao C, Li X, Wang C, Zhang M, Liu Y (2010) Electrospun nanofibers of p-type NiO/n-Type ZnO heterojunctions with enhanced photocatalytic activity. ACS Appl Mater Interfaces 2:2915–2923. https://doi.org/10.1021/am100618h
Zhang M, Qiao X, Han W, Jiang T, Liu F, Zhao X (2021) Alginate-chitosan oligosaccharide-ZnO composite hydrogel for accelerating wound healing. Carbohydr Polym 266:118100. https://doi.org/10.1016/j.carbpol.2021.118100
Zhang H, Zhang X, Cao Q, Wu S, Wang X-Q, Peng N, Zeng D, Liao J, Xu H (2022) Facile fabrication of chitin/ZnO composite hydrogels for infected wound healing. Biomater Sci 10:5888–5899. https://doi.org/10.1039/D2BM00340F
Zhang H, Xu M, Luo H, Wu S, Gao X, Wu Q, Xu H, Liu Y (2023) Interfacial assembly of chitin/Mn3O4 composite hydrogels as photothermal antibacterial platform for infected wound healing. Int J Biol Macromol 243:124362. https://doi.org/10.1016/j.ijbiomac.2023.124362
Zhou L, Zhou L, Wei C, Guo R (2022) A bioactive dextran-based hydrogel promote the healing of infected wounds via antibacterial and immunomodulatory. Carbohydr Polym 291:119558. https://doi.org/10.1016/j.carbpol.2022.119558
Acknowledgments
Hongli Zhang, Mengqing Xu and Liang Wang contributed equally to this work. This study was financially supported by the National Natural Science Foundation of China (22005229, 22104116), Health Commission of Hubei Province Scientific Research Project (WJ2021Q052), Department of Education of Hubei Province Scientific Research Project (B2021018). We would like to thank the Analytical & Testing Center of Wuhan University of Science and Technology for the structure characterization.
Funding
This work was funded by the National Natural Science Foundation of China (22005229, 22104116), Health Commission of Hubei Province Scientific Research Project (WJ2021Q052), Department of Education of Hubei Province Scientific Research Project (B2021018).
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HZ: conceptualization, methodology, validation, formal analysis, investigation, data curation, and writing-original draft. MX: validation, formal analysis, investigation, data curation, methodology and investigation. LW: conceptualization, investigation, methodology, and writing-original draft. HL: investigation and methodology. SW: methodology and investigation. TG: conceptualization and supervision. QW: conceptualization, supervision, writing-review & editing, and funding acquisition. HX: conceptualization, supervision, resources, writing-review & editing, and funding acquisition.
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Zhang, H., Xu, M., Wang, L. et al. ZnO-incorporated chitin hydrogels for infected wound therapy. Cellulose 31, 3115–3127 (2024). https://doi.org/10.1007/s10570-024-05801-3
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DOI: https://doi.org/10.1007/s10570-024-05801-3