Abstract
Hydrogels have attracted widespread attention in controlling bleeding due to their superiority in matching irregular defects. However, inadequate mechanical performance, insufficient adhesion and long gelation times still hinder their application for hemostasis. In this study, a novel hydrogel with self-healing and adhesive properties was designed and synthesized by introducing reversible borate ester bonds of polyvinyl alcohol-borax into tannic acid-modified bacterial cellulose (TA@BC). As demonstrated by tensile stress‒strain tests and rheological measurements, the hydrogels have excellent mechanical performance owing to the synergistic multiple crosslinked bonds among tannic acid-modified bacterial cellulose (TA@BC), polyvinyl alcohol polymer chains and borax in a covalent polymer network. The hydrogels show good self-healing properties and adhesion to different substrates. Moreover, blood loss from a wound treated with the designed hydrogel was approximately 1/5th that from an untreated wound, demonstrating the excellent hemostatic capacity of the hydrogels. Therefore, the designed hydrogels have potential applications in hemostasis and wound dressing.
Graphical abstract
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ai JY, Li K, Li JB, Yu F, Ma J (2021) Super flexible, fatigue resistant, self-healing PVA/xylan/borax hydrogel with dual-crosslinked network. Int J Biol Macromol 172:66–73. https://doi.org/10.1016/j.ijbiomac.2021.01.038
Alexander A, Khan J, Saraf S, Saraf S (2014) Polyethylene glycol (PEG)–poly (N-isopropylacrylamide)(PNIPAAm) based thermosensitive injectable hydrogels for biomedical applications. Eur J Pharm Biopharm 88:575–585. https://doi.org/10.1016/j.ejpb.2014.07.005
Brochu ABW, Craig SL, Reichert WM (2011) Self-healing biomaterials. J Biomed Mater Res A 96a(2):492–506. https://doi.org/10.1002/jbm.a.32987
Bu Y, Zhang L, Liu J, Zhang L, Li T, Shen H, Wang X, Yang F, Tang P, Wu D (2016) Synthesis and properties of hemostatic and bacteria-responsive in situ hydrogels for emergency treatment in critical situations. ACS Appl Mater Inter 8:12674–12683. https://doi.org/10.1021/acsami.6b03235
Bu YZ, Zhang LC, Sun GF, Sun FF, Liu JH, Yang F, Tang PF, Wu DC (2019) Tetra-PEG based hydrogel sealants for in vivo visceral hemostasis. Adv Mater 31:1901580. https://doi.org/10.1002/adma.201901580
Chen YJ, Zhang YN, Mensaha A, Li DW, Wang QQ, Wei QF (2021) A plant-inspired long-lasting adhesive bilayer nanocomposite hydrogel based on redox-active Ag/Tannic acid-cellulose nanofibers. Carbohyd Polym 255:117508. https://doi.org/10.1016/j.carbpol.2020.117508
Deng YD, Chen JY, Huang JY, Yang XS, Zhang XD, Yuan SJ, Liao WZ (2020) Preparation and characterization of cellulose/flaxseed gum composite hydrogel and its hemostatic and wound healing functions evaluation. Cellulose 27:3971–3988. https://doi.org/10.1007/s10570-020-03055-3
Deng ZY, Wang SS, Pei YQ, Zhou B, Li J, Hou XY, Li B, Liang HS (2021) Tuning of molecular interactions between zein and tannic acid to modify sunflower sporopollenin exine capsules: enhanced stability and targeted delivery of bioactive macromolecules. ACS Appl Bio Mater 4:2686–2695. https://doi.org/10.1021/acsabm.0c01623
Ding FY, Shi XW, Wu S, Liu XH, Deng HB, Du YM, Li HB (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
Fan C, Fu J, Zhu W, Wang DA (2016) A mussel-inspired double-crosslinked tissue adhesive intended for internal medical use. Acta Biomater 33:51–63. https://doi.org/10.1016/j.actbio.2016.02.003
Forooshani PK, Lee BP (2017) Recent approaches in designing bioadhesive materials inspired by mussel adhesive protein. J Polym Sci Pol Chem 55:9–33. https://doi.org/10.1002/pola.28368
Ghobril C, Grinstaff M (2015) The chemistry and engineering of polymeric hydrogel adhesives for wound closure: a tutorial. Chem Soc Rev 44:1820–1835. https://doi.org/10.1039/C4CS00332B
Guo TY, Wang WX, Song JL, Jin YC, Xiao HN (2021) Dual-responsive carboxymethyl cellulose/dopamine/cystamine hydrogels driven by dynamic metal-ligand and redox linkages for controllable release of agrochemical. Carbohyd Polym 253:117188. https://doi.org/10.1016/j.carbpol.2020.117188
Han JQ, Lei TZ, Wu QL (2014) High-water-content mouldable polyvinyl alcohol-borax hydrogels reinforced by well-dispersed cellulose nanoparticles: dynamic rheological properties and hydrogel formation mechanism. Carbohyd Polym 102:306–316. https://doi.org/10.1016/j.carbpol.2013.11.045
Han L, Yan LW, Wang KF, Fang LM, Zhang HP, Tang YH, Ding YH, Weng LT, Xu JL, Weng J, Liu YJ, Ren FZ, Lu X (2017) Tough, self-healable and tissue-adhesive hydrogel with tunable multifunctionality. Npg Asia Mater 9:e372. https://doi.org/10.1038/am.2017.33
He JH, Shi MT, Liang YP, Guo BL (2020) Conductive adhesive self-healing nanocomposite hydrogel wound dressing for photothermal therapy of infected full-thickness skin wounds. Chem Eng J 394:124888. https://doi.org/10.1016/j.cej.2020.124888
Huang SQ, Su SY, Gan HB, Wu LJ, Lin CH, Xu DY, Zhou HF, Lin XL, Qin YL (2019) Facile fabrication and characterization of highly stretchable lignin-based hydroxyethyl cellulose self-healing hydrogel. Carbohyd Polym 223:115080. https://doi.org/10.1016/j.carbpol.2019.115080
Lei H, Fan DD (2021) Conductive, adaptive, multifunctional hydrogel combined with electrical stimulation for deep wound repair. Chem Eng J 421:129578. https://doi.org/10.1016/j.cej.2021.129578
Li CP, Mu CD, Lin W, Ngai T (2015) Gelatin effects on the physicochemical and hemocompatible properties of gelatin/PAAm/laponite nanocomposite hydrogels. ACS Appl Mater Inter 7:18732–18741. https://doi.org/10.1021/acsami.5b05287
Li HB, Cheng F, Wei XJ, Yi XT, Tang SZ, Wang ZY, Zhang YS, He JM, Huang YD (2021) Injectable, self-healing, antibacterial, and hemostatic N,O-carboxymethyl chitosan/oxidized chondroitin sulfate composite hydrogel for wound dressing. Mat Sci Eng C-Mater 118:111324. https://doi.org/10.1016/j.msec.2020.111324
Liu DG, Ma ZS, Wang ZM, Tian HF, Gu MY (2014) Biodegradable poly(vinyl alcohol) foams supported by cellulose nanofibrils: processing, structure, and properties. Langmuir 30:9544–9550. https://doi.org/10.1021/la502723d
Liu W, Du HS, Zhang MM, Liu K, Liu HY, Xie HX, Zhang XY, Si CL (2020) Bacterial cellulose-based composite scaffolds for biomedical applications: a review. ACS Sustain Chem Eng 8:7536–7562. https://doi.org/10.1021/acssuschemeng.0c00125
Liu YL, Ai KL, Lu LH (2014) Polydopamine and its derivative materials: synthesis and promising applications in energy, environmental, and biomedical fields. Chem Rev 114:5057–5115. https://doi.org/10.1021/cr400407a
Lu SC, Zhang XH, Tang ZW, Xiao H, Zhang M, Liu K, Chen LH, Huang LL, Ni YH, Wu H (2021) Mussel-inspired blue-light-activated cellulose-based adhesive hydrogel with fast gelation, rapid haemostasis and antibacterial property for wound healing. Chem Eng J 417:129329. https://doi.org/10.1016/j.cej.2021.129329
Luo JW, Liu C, Wu JH, Lin LX, Fan HM (2019) In situ injectable hyaluronic acid/gelatin hydrogel for hemorrhage control. Mater Sci Eng C-Mater 98:628–634. https://doi.org/10.1016/j.msec.2019.01.034
Ni Z, Yu H, Wang L, Liu X, Shen D, Chen X, Liu J, Wang N, Huang Y, Sheng Y (2022) Polyphosphazene and non-catechol-based antibacterial injectable hydrogel for adhesion of wet tissues as wound dressing. Adv Healthc Mater 11:2101421. https://doi.org/10.1002/adhm.202101421
Qu J, Zhao X, Liang YP, Zhang TL, Ma PX, Guo BL (2018) Antibacterial adhesive injectable hydrogels with rapid self-healing, extensibility and compressibility as wound dressing for joints skin wound healing. Biomaterials 183:185–199. https://doi.org/10.1016/j.biomaterials.2018.08.044
Shao CY, Meng L, Wang M, Cui C, Wang B, Han CR, Xu F, Yang J (2019) Mimicking dynamic adhesiveness and strain-stiffening behavior of biological tissues in tough and self-healable cellulose nanocomposite hydrogels. ACS Appl Mater Inter 11:5885–5895. https://doi.org/10.1021/acsami.8b21588
Shao CY, Wang M, Meng L, Chang HL, Wang B, Xu F, Yang J, Wan PB (2018) Mussel-inspired cellulose nanocomposite tough hydrogels with synergistic self-healing, adhesive, and strain-sensitive properties. Chem Mater 30:3110–3121. https://doi.org/10.1021/acs.chemmater.8b01172
Slaughter BV, Khurshid SS, Fisher OZ, Khademhosseini A, Peppas NA (2009) Hydrogels in regenerative medicine. Adv Mater 21:3307–3329. https://doi.org/10.1002/adma.200802106
Spoljaric S, Salminen A, Luong ND, Seppala J (2014) Stable, self-healing hydrogels from nanofibrillated cellulose, poly(vinyl alcohol) and borax via reversible crosslinking. Eur Polym J 56:105–117. https://doi.org/10.1016/j.eurpolymj.2014.03.009
Tang W, Ma TH, Zhou LN, Wang GY, Wang XL, Ying HJ, Chen C, Wang P (2019) Polyamine-induced tannic acid co-deposition on magnetic nanoparticles for enzyme immobilization and efficient biodiesel production catalysed by an immobilized enzyme under an alternating magnetic field. Catal Sci Technol 9:6015–6026. https://doi.org/10.1039/C9CY01350D
Tao F, Qin LM, Wang ZK, Pan QM (2017) Self-healable and cold-resistant supercapacitor based on a multifunctional hydrogel electrolyte. ACS Appl Mater Inter 9:15541–15548. https://doi.org/10.1021/acsami.7b03223
Taylor DL, Panhuis MIH (2016) Self-healing hydrogels. Adv Mater 28:9060–9093. https://doi.org/10.1002/adma.201601613
Trovatti E, Oliveira L, Freire CSR, Silvestre AJD, Neto CP, Pinto JJCC, Gandini A (2010) Novel bacterial cellulose-acrylic resin nanocomposites. Compos Sci Technol 70:1148–1153. https://doi.org/10.1016/j.compscitech.2010.02.031
Wang CW, Zhou HY, Niu HY, Ma XY, Yuan Y, Hong H, Liu CS (2018) Tannic acid-loaded mesoporous silica for rapid hemostasis and antibacterial activity. Biomater Sci 6:3318–3331. https://doi.org/10.1039/C8BM00837J
Wang Y, Liu SQ, Wang J, Tang F (2020) Polymer network strengthened filter paper for durable water disinfection. Colloid Surf A 591:124548. https://doi.org/10.1016/j.colsurfa.2020.124548
Wang Y, Wu Y, Long LY, Yang L, Fu DH, Hu C, Kong QQ, Wang YB (2021) Inflammation-responsive drug-loaded hydrogels with sequential hemostasis, antibacterial, and anti-inflammatory behavior for chronically infected diabetic wound treatment. ACS Appl Mater Inter 13:33584–33599. https://doi.org/10.1021/acsami.1c09889
Wu M, Chen JS, Huang WJ, Yan B, Peng QY, Liu JF, Chen LY, Zeng HB (2020) Injectable and self-healing nanocomposite hydrogels with ultrasensitive ph-responsiveness and tunable mechanical properties: implications for controlled drug delivery. Biomacromolecules 21:2409–2420. https://doi.org/10.1021/acs.biomac.0c00347
Yang H, Lan XY, Xiong YZ (2022) In situ growth of zeolitic imidazolate framework-l in macroporous pva/cmc/peg composite hydrogels with synergistic antibacterial and rapid hemostatic functions for wound dressing. Gels 8:279. https://doi.org/10.3390/gels8050279
Yang XB, Yan LL, Ma J, Bai YP, Shao L (2019) Bioadhesion-inspired surface engineering constructing robust, hydrophilic membranes for highly-efficient wastewater remediation. J Membr Sci 591:118353. https://doi.org/10.1016/j.memsci.2019.117353
Yu YR, Zhao XW, Ye L (2021) A new mussel-inspired highly self-adhesive & conductive poly (vinyl alcohol)-based hydrogel for wearable sensors. Appl Surf Sci 562:150162. https://doi.org/10.1016/j.apsusc.2021.150162
Zandraa O, Ngwabebhoh FA, Patwa R, Nguyen HT, Motiei M, Saha N, Saha T, Saha P (2021) Development of dual crosslinked mumio-based hydrogel dressing for wound healing application: Physico-chemistry and antimicrobial activity. Int J Pharmaceut 607:120952. https://doi.org/10.1016/j.ijpharm.2021.120952
Zhang TW, Zhao J, Lv XY, Liu F, Wang XL, Li K, Bai ZY, Chen HY, Tian WQ (2021a) Injectable hydrogel based on short-peptide RG5 combined with halloysite nanotubes for rapid hemostasis. J Nanopart Res 23:240. https://doi.org/10.1007/s11051-021-05345-8
Zhang M, Li SC, Yuan X, Zhao J, Hou X (2021) An in situ catechol functionalized ε-polylysine/polyacrylamide hydrogel formed by hydrogen bonding recombination with high mechanical property for hemostasis. Int J Biol Macromol 191:714–726. https://doi.org/10.1016/j.ijbiomac.2021.09.100
Zhang S, Ding F, Liu Y, Ren X (2022) Glucose-responsive biomimetic nanoreactor in bacterial cellulose hydrogel for antibacterial and hemostatic therapies. Carbohydr Polym 292:119615. https://doi.org/10.1016/j.carbpol.2022.119615
Zhang SH, Dong HB, He RD, Wang N, Zhao Q, Yang LG, Qu ZH, Sun LR, Chen SJ, Ma JW, Li JW (2022) Hydro electroactive Cu/Zn coated cotton fiber nonwovens for antibacterial and antiviral applications. Int J Biol Macromol 207:100–109. https://doi.org/10.1016/j.ijbiomac.2022.02.155
Zhang SH, Zhang Q, Chen JM, Dong HB, Cui AH, Sun LR, Wang N, Li JW, Qu ZH (2022) Cost-effective chitosan thermal bonded nonwovens serving as an anti-viral inhibitor layer in face mask. Mater Lett 318:132203. https://doi.org/10.1016/j.matlet.2022.132203
Zhang XH, Wei JJ, Lu SC, Xiao H, Miao QX, Zhang M, Liu K, Chen LH, Huang LL, Wu H (2021) Mussel-inspired conductive hydrogel with self-healing, adhesive, and antibacterial properties for wearable monitoring. ACS Appl Polym Mater 3:5798–5807. https://doi.org/10.1021/acsapm.1c01026
Zhao X, Li P, Guo BL, Ma PX (2015) Antibacterial and conductive injectable hydrogels based on quaternized chitosan-graft-polyaniline/oxidized dextran for tissue engineering. Acta Biomater 26:236–248. https://doi.org/10.1016/j.actbio.2015.08.006
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
Zhong YJ, Seidi F, Li CC, Wan ZM, Jin YC, Song JL, Xiao HN (2021) Antimicrobial/biocompatible hydrogels dual-reinforced by cellulose as ultrastretchable and rapid self-healing wound dressing. Biomacromolecules 22:1654–1663. https://doi.org/10.1021/acs.biomac.1c00086
Zhou J, Wu YZ, Zhang XH, Lai JH, Li YL, Xing J, Teng LP, Chen JH (2021) Enzyme catalyzed hydrogel as versatile bioadhesive for tissue Wound hemostasis, bonding, and continuous repair. Biomacromolecules 22:1346–1356. https://doi.org/10.1021/acs.biomac.0c01329
Zhu J, Li FX, Wang XL, Yu JY, Wu DQ (2018) Hyaluronic acid and polyethylene glycol hybrid hydrogel encapsulating nanogel with hemostasis and sustainable antibacterial property for wound healing. ACS Appl Mater Inter 10:13304–13316. https://doi.org/10.1021/acsami.7b18927
Zhu SH, Lou CW, Zhang SH, Wang N, Li JW, Feng YJ, He RD, Xu CG, Lin JH (2022) Clean surface additive manufacturing of aramid paper-based electrically heated devices for medical therapy application. Surf Interfaces 29:101689. https://doi.org/10.1016/j.surfin.2021.101689
Funding
This work was financially supported by the National Natural Science Foundation of China (No. 51873048), National Natural Science Foundation of China (No. 22005077), Distinguished Young Scholars of the Natural Science Foundation of Heilongjiang Province （YQ2022B007).
Author information
Authors and Affiliations
Contributions
Xiaotong Yi: Methodology, Investigation, Software, Formal Analysis, Writing-Original Draft; Feng Cheng: Methodology, Software, Data curation, Writing-Review & Editing; Xinjing Wei: Validation, Formal Analysis, Investigation; Hongbin Li: Conceptualization, Resources, Writing-Review & Editing; Jingting Qian: Formal Analysis, Data curation; Jinmei He: Writing-Review & Editing, Resources, Supervision, Funding Acquisition Supervision.
Corresponding authors
Ethics declarations
Conflict of interest
There are no competing financial interest or personal relationships to declare.
Ethical approval
All animal experiments were approved by the ethics committee of Harbin institute of technology. All the procedures were carried out in according with the Chinese National Institutes of Health Guidelines for the Care and Use of Laboratory Animals.
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
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Yi, X., Cheng, F., Wei, X. et al. Bioinspired adhesive and self-healing bacterial cellulose hydrogels formed by a multiple dynamic crosslinking strategy for sealing hemostasis. Cellulose 30, 397–411 (2023). https://doi.org/10.1007/s10570-022-04909-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10570-022-04909-8