Abstract
An ideal wound dressing is highly desired for the repair of chronic wounds which should provide a moist environment, self-healing, antibacterial properties etc. Here, a novel injectable antibacterial chitosan hydrogel with good self-healing and improved mechanical properties has been prepared by dialdehyde bacterial cellulose (DABC) nanofibers as the non-toxic biocrosslinker. It is the first time to prepare the all-natural chitosan hydrogels by using ascorbic acid (VC) as solvent to dissolve chitosan and the natural fiber DABC as reinforcing and crosslinking agent. Then, the disadvantage of the use of acetic acid in the medical field was overcome and the other toxic crosslinking agents were abandoned. Accordingly, this work provides a new strategy towards fabricating the self-healing hydrogel with injectable and antibacterial properties. The new multifunctional hydrogels demonstrate strong potentiality in wound dressings or tissue engineering.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Abdel-Rahman RM, Hrina R, Abdel-Mohsen AM, Fouda MGM, Soliman AY, Mohamed FK, Mohsin K, Pinto TD (2015) Chitin and chitosan from Brazilian Atlantic Coast: isolation, characterization and antibacterial activity. Int J Biol Macromol 80:107–120. https://doi.org/10.1016/j.ijbiomac.2015.06.027
Anjum S, Arora A, Alam MS, Gupta B (2016) Development of antimicrobial and scar preventive chitosan hydrogel wound dressings. Int J Pharm 508:92–101. https://doi.org/10.1016/j.ijpharm.2016.05.013
Asoh T-A, Kawai W, Kikuchi A (2014) Alternating-current electrophoretic adhesion of biodegradable hydrogel utilizing intermediate polymers. Colloids Surf B 123:742–746. https://doi.org/10.1016/j.colsurfb.2014.10.014
Ballantyne B, Jordan SL (2001) Toxicological, medical and industrial hygiene aspects of glutaraldehyde with particular reference to its biocidal use in cold sterilization procedures. J Appl Toxicol 21:131–151. https://doi.org/10.1002/jat.741
Banerjee SL, Bhattacharya K, Samanta S, Singha NK (2018) Self-Healable aantifouling zwitterionic hydrogel based on synergistic phototriggered dynamic disulfide metathesis reaction and ionic interaction. ACS Appl Mater Interfaces 10:27391–27406. https://doi.org/10.1021/acsami.8b10446
Caló E, Khutoryanskiy VV (2015) Biomedical applications of hydrogels: a review of patents and commercial products. Eur Polym J 65:252–267. https://doi.org/10.1016/j.eurpolymj.2014.11.024
Calvini P, Gorassini A (2012) Surface and bulk reactions of cellulose oxidation by periodate A simple kinetic model. Cellulose 19:1107–1114. https://doi.org/10.1007/s10570-012-9717-1
Chen Y, Chung Y, Wang L, Chen K, Li S (2002) Antibacterial properties of chitosan in waterborne pathogen. J Environ Sci Health A 37:1379–1390. https://doi.org/10.1081/ese-120005993
Chen S, Wu Y, Mi F, Lin Y, Yu L, Sung H (2004) A novel pH-sensitive hydrogel composed of N,O-carboxymethyl chitosan and alginate cross-linked by genipin for protein drug delivery. J Control Release 96:285–300. https://doi.org/10.1016/j.jconrel.2004.02.002
Cheng C, Zhang X, Meng Y, Zhang Z, Chen J, Zhang Q (2017) Multiresponsive and biocompatible self-healing hydrogel: its facile synthesis in water, characterization and properties. Soft Matter 13:3003–3012. https://doi.org/10.1039/C7SM00350A
Chung Y, Chen C (2008) Antibacterial characteristics and activity of acid-soluble chitosan. Biores Technol 99:2806–2814. https://doi.org/10.1016/j.biortech.2007.06.044
Chung Y, Su Y, Chen C, Jia G, Wang H, Wu J, Lin J (2004) Relationship between antibacterial activity of chitosan and surface characteristics of cell wall. Acta Pharmacol Sin 25:932–936. https://doi.org/10.1016/j.jmb.2008.07.044
Dai L, Cheng T, Wang Y, Lu H, Nie S, He H, Duan C, Ni Y (2019) Injectable all-polysaccharide self-assembling hydrogel: a promising scaffold for localized therapeutic proteins. Cellulose 26:6891–6901. https://doi.org/10.1007/s10570-019-02579-7
Dimatteo R, Darling NJ, Segura T (2018) In situ forming injectable hydrogels for drug delivery and wound. Adv Drug Deliv Rev. https://doi.org/10.1016/j.addr.2018.03.007
Ding F, Shi X, Wu S, Liu X, Deng H, Du Y, Li H (2017) Flexible polysaccharide hydrogel with pH-regulated recovery of self-healing and mechanical properties. Macromol Mater Eng 302:1700221. https://doi.org/10.1002/mame.201700221
Eaglstein WH, Kirsner RS, Robson MC (2012) Food and drug administration (FDA) drug approval end points for chronic cutaneous ulcer studies. Wound Repair Regener 20:793–796. https://doi.org/10.1111/j.1524-475X.2012.00849.x
Gao C, Yan T, Dai K, Wan Y (2012) Immobilization of gelatin onto natural nanofibers for tissue engineering scaffold applications without utilization of any crosslinking agent. Cellulose 19:761–768. https://doi.org/10.1007/s10570-012-9698-0
Gupta A, Kowalczuk M, Heaselgrave W, Britland ST, Martin C, Radecka I (2019) The production and application of hydrogels for wound management: a review. Eur Polym J 111:134–151. https://doi.org/10.1016/j.eurpolymj.2018.12.019
Hamedi H, Moradi S, Hudson SM, Tonelli AE (2018) Chitosan based hydrogels and their applications for drug delivery in wound dressings: a review. Carbohyd Polym 199:445–460. https://doi.org/10.1016/j.carbpol.2018.06.114
Herskovitz I, Macquhae F, Fox JD, Kirsner RS (2016) Skin movement, wound repair and development of engineered skin. Exp Dermatol 25:99–100. https://doi.org/10.1111/exd.12916
Hessle CC, Andersson B, Wold AE (2005) Gram-positive and Gram-negative bacteria elicit different patterns of pro-inflammatory cytokines in human monocytes. Cytokine 30:311–318. https://doi.org/10.1016/j.cyto.2004.05.008
Hou Q, Liu W, Liu Z, Duan B, Bai L (2008) Characteristics of antimicrobial fibers prepared with wood periodate oxycellulose. Carbohyd Polym 74:235–240. https://doi.org/10.1016/j.carbpol.2008.02.010
Hu L, Cheng X, Zhang A (2015) A facile method to prepare UV light-triggered self-healing polyphosphazenes. J Mater Sci 50:2239–2246. https://doi.org/10.1007/s10853-014-8786-y
Jayakumar R, Prabaharan M, Kumar PTS, Nair SV, Tamura H (2011) Biomaterials based on chitin and chitosan in wound dressing applications. Biotechnol Adv 29:322–337. https://doi.org/10.1016/j.biotechadv.2011.01.005
Khorshidi S, Karkhaneh A (2018) A review on gradient hydrogel/fiber scaffolds for osteochondral regeneration. J Tissue Eng Regener Med. https://doi.org/10.1002/term.2628
Kim U-J, Lee YR, Kang TH, Choi JW, Kimura S, Wada M (2017) Protein adsorption of dialdehyde cellulose-crosslinked chitosan with high amino group contents. Carbohyd Polym 163:34–42. https://doi.org/10.1016/j.carbpol.2017.01.052
Kong M, Chen XG, Xing K, Park HJ (2010) Antimicrobial properties of chitosan and mode of action: a state of the art review. Int J Food Microbiol 144:51–63. https://doi.org/10.1016/j.ijfoodmicro.2010.09.012
Larsson PA, Berglund LA, Wågberg L (2014) Highly ductile fibres and sheets by core–shell structuring of the cellulose nanofibrils. Cellulose 21:323–333. https://doi.org/10.1007/s10570-013-0099-9
Li J, Wan Y, Li L, Liang H, Wang J (2009) Preparation and characterization of 2,3-dialdehyde bacterial cellulose for potential biodegradable tissue engineering scaffolds. Mater Sci Eng C 29:1635–1642. https://doi.org/10.1016/j.msec.2009.01.006
Li S, Li L, Guo C, Qin H, Yu X (2017) A promising wound dressing material with excellent cytocompatibility and proangiogenesis action for wound healing: strontium loaded silk fibroin/sodium alginate (SF/SA) blend films. Int J Biol Macromol 104:969. https://doi.org/10.1016/j.ijbiomac.2017.07.020
Li Z, Zhou F, Li Z, Lin S, Chen L, Liu L, Chen Y (2018) Hydrogel cross-linked with dynamic covalent bonding and micellization for promoting burn wound healing. ACS Appl Mater Interfaces 10:25194–25202. https://doi.org/10.1021/acsami.8b08165
Liu H, Li C, Wang B, Sui X, Wang L, Yan X, Xu H, Zhang L, Zhong Y, Mao Z (2018) Self-healing and injectable polysaccharide hydrogels with tunable mechanical properties. Cellulose 25:559–571. https://doi.org/10.1007/s10570-017-1546-9
Luo H, Xiong G, Hu D, Ren K, Yao F, Zhu Y, Gao C, Wan Y (2013) Characterization of TEMPO-oxidized bacterial cellulose scaffolds for tissue engineering applications. Mater Chem Phys 143:373–379. https://doi.org/10.1016/j.matchemphys.2013.09.012
Mahdavinia GR, Pourjavadi A, Zohuriaan-Mehr MJ (2008) Synthesis and properties of highly swelling PAAM/chitosan semi-IPN hydrogels. Macromol Symp 274:171–176. https://doi.org/10.1002/masy.200851423
Mansur HS, Costa E, Mansur AAP, Barbosa-Stancioli EF (2009) Cytocompatibility evaluation in cell-culture systems of chemically crosslinked chitosan/PVA hydrogels. Mater Sci Eng C 29:1574–1583. https://doi.org/10.1016/j.msec.2008.12.012
Mansur HS, Mansur AAP, Curti E, De Almeida MV (2013) Functionalized-chitosan/quantum dot nano-hybrids for nanomedicine applications: towards biolabeling and biosorbing phosphate metabolites. J Mater Chem B 1:1696–1711. https://doi.org/10.1039/C3TB00498H
Moon RJ, Martini A, Nairn J, Simonsen J, Youngblood J (2011) Cellulose nanomaterials review: structure, properties and nanocomposites. Chem Soc Rev 40:3941–3994. https://doi.org/10.1039/C0CS00108B
Mou K, Li J, Wang Y, Cha R, Jiang X (2017) 2,3-Dialdehyde nanofibrillated cellulose as a potential material for the treatment of MRSA infection. J Mater Chem B. https://doi.org/10.1039/c7tb01857f
Muzzarelli RAA (2009) Genipin-crosslinked chitosan hydrogels as biomedical and pharmaceutical aids. Carbohyd Polym 77:1–9. https://doi.org/10.1016/j.carbpol.2009.01.016
Nešović K, Janković A, Perić-Grujić A, Vukašinović-Sekulić M, Radetić T, Živkovićb L, Park SJ, Rhee KY, Mišković-Stanković V (2019) Kinetic models of swelling and thermal stability of silver/poly(vinyl alcohol)/chitosan/graphene hydrogels. J Ind Eng Chem 77:83–96. https://doi.org/10.1016/j.jiec.2019.04.022
Risbud MV, Hardikar AA, Bhat SV, Bhonde RR (2000) pH-sensitive freeze-dried chitosan–polyvinyl pyrrolidone hydrogels as controlled release system for antibiotic delivery. J Control Release 68:23–30. https://doi.org/10.1016/s0168-3659(00)00208-x
Sadeghi M, Hanifpour F, Taheri R, Javadian H, Ghasemi M (2016) Comparison of using formaldehyde and carboxy methyl chitosan in preparation of Fe3O4 superparamagnetic nanoparticles-chitosan hydrogel network: sorption behavior toward bovine serum albumin. Process Saf Environ Prot 102:119–128. https://doi.org/10.1016/j.psep.2016.03.005
Shao C, Wang M, Chang H, Xu F, Yang J (2017) A self-healing cellulose nanocrystal-poly(ethylene glycol) nanocomposite hydrogel via Diels–Alder click reaction. ACS Sustain Chem Eng 5:6167–6174. https://doi.org/10.1021/acssuschemeng.7b01060
Stashak TS, Farstvedt E, Othic A (2004) Update on wound dressings: indications and best use. Clin Tech Equine Pract 3:148–163. https://doi.org/10.1053/j.ctep.2004.08.006
Tan H, Chu CR, Payne KA, Marra KG (2009) Injectable in situ forming biodegradable chitosan–hyaluronic acid based hydrogels for cartilage tissue engineering. Biomaterials 30:2499–2506. https://doi.org/10.1016/j.biomaterials.2008.12.080
Taylor DL, Panhuis M (2016) Self-healing hydrogels. Adv Mater 28:9060–9093. https://doi.org/10.1002/adma.201601613
Toshikj E, Tarbuk A, Grgić K, Mangovska B, Jordanov I (2019) Influence of different oxidizing systems on cellulose oxidation level: introduced groups versus degradation model. Cellulose 26:777–794. https://doi.org/10.1007/s10570-018-2133-4
Tu Y, Chen N, Li C, Liu H, Zhu R, Chen S, Xiao Q, Liu J, Ramakrishna S, He L (2019) Advances in injectable self-healing biomedical hydrogels. Acta Biomater 90:1–20. https://doi.org/10.1016/j.actbio.2019.03.057
Voorhaar L, De Meyer B, Du Prez F, Hoogenboom R (2016) One-pot automated synthesis of quasi triblock copolymers for self-healing physically crosslinked hydrogels. Macromol Rapid Commun 37:1682–1688. https://doi.org/10.1002/marc.201600380
Wang T, Turhan M, Gunasekaran S (2004) Selected properties of pH-sensitive, biodegradable chitosan–poly(vinyl alcohol) hydrogel. Polym Int 53:911–918. https://doi.org/10.1002/pi.1461
Wang B, Huang C, Chen S, Xing X, Zhang M, Wu Q, Wang H (2018) Hybrid scaffolds enhanced by nanofibers improve in vitro cell behavior for tissue regeneration. Cellulose 25:7113–7125. https://doi.org/10.1007/s10570-018-2087-6
Weber P, Bendich A, Schalch W (1996) Vitamin C and human health—a review of recent data relevant to human requirements. Int J Vitam Nutr Res 66:19. https://doi.org/10.1016/0308-8146(95)00080-1
Wei Z, Yang J, Liu Z, Xu F, Zhou J, Zrínyi M, Osada Y, Chen Y (2015) Novel biocompatible polysaccharide-based self-healing hydrogel. Adv Funct Mater 25:1352–1359. https://doi.org/10.1002/adfm.201401502
Xiao F, Chen L, Xing R-F, Zhao Y-P, Dong J, Guo G, Zhang R (2009) In vitro cyto-biocompatibility and cell detachment of temperature-sensitive dextran hydrogel. Colloids Surf B 71:13–18. https://doi.org/10.1016/j.colsurfb.2008.12.040
Xu J, Liu Y, Hsu S-h (2019) Hydrogels based on Schiff base linkages for biomedical applications. Molecules 24:3005. https://doi.org/10.3390/molecules24163005
Yamane T, Nakagami G, Yoshino S, Muramatsu A, Matsui S, Oishi Y, Kanazawa T, Minematsu T, Sanada H (2013) Hydrocellular foam dressing promotes wound healing along with increases in hyaluronan synthase 3 and PPARα gene expression in epidermis. PLoS ONE 8:e73988–e73988. https://doi.org/10.1371/journal.pone.0073988
Yang B, Zhang Y, Zhang X, Tao L, Li S, Wei Y (2012) Facilely prepared inexpensive and biocompatible self-healing hydrogel: a new injectable cell therapy carrier. Polym Chem 3:3235–3238. https://doi.org/10.1039/C2PY20627G
Zhang M, Chen S, Sheng N, Wang B, Yao J, Wu Z, Wang H (2019) A strategy of tailoring polymorphs and nanostructures to construct self-reinforced nonswelling high-strength bacterial cellulose hydrogels. Nanoscale 11:15347–15358. https://doi.org/10.1039/C9NR04462K
Zhao R, Li X, Sun B, Tong Y, Wang C (2015) Nitrofurazone-loaded electrospun PLLA/sericin-based dual-layer fiber mats for wound dressing applications. Rsc Adv 5:16940–16949. https://doi.org/10.1039/C4RA16208K
Zhao X, Wu H, Guo B, Dong R, Qiu Y, Ma PX (2017) Antibacterial anti-oxidant electroactive injectable hydrogel as self-healing wound dressing with hemostasis and adhesiveness for cutaneous wound healing. Biomaterials 122:34–47. https://doi.org/10.1016/j.biomaterials.2017.01.011
Acknowledgments
This work was financially supported by the National Natural Science Foundation of China (51573024) and DHU Distinguished Young Professor Program.
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of interest
The authors do not have any conflict of interest to disclose.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Li, W., Wang, B., Zhang, M. et al. All-natural injectable hydrogel with self-healing and antibacterial properties for wound dressing. Cellulose 27, 2637–2650 (2020). https://doi.org/10.1007/s10570-019-02942-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10570-019-02942-8