Bioactive hemostatic materials: a new strategy for promoting wound healing and tissue regeneration

Abstract

Wound healing remains a critical global healthcare challenge, with an annual treatment cost exceeding $50 billion worldwide. Over the past decade, significant advances in wound care have focused on developing sophisticated biomaterials that promote tissue regeneration and prevent complications. Despite these developments, there remains a crucial need for multifunctional wound healing materials that can effectively address the complex, multiphase nature of wound repair while being cost effective and easily applicable in various clinical settings. This review systematically analyzes the latest developments in wound healing materials, examining their chemical composition, structural design, and therapeutic mechanisms. We comprehensively evaluate various bioactive components, including natural polymers, synthetic matrices, and hybrid composites, along with their different forms, such as hydrogels, powders, and smart dressings. Special attention is given to emerging strategies in material design that integrate multiple therapeutic functions, including sustained drug delivery, infection prevention, and tissue regeneration promotion. The insights provided in this review illuminate the path toward next-generation wound healing materials, highlighting opportunities for developing more effective therapeutic solutions that can significantly improve patient outcomes and reduce healthcare burden.

Keywords

biomaterials / multifunctional wound healing materials / smart dressings / wound healing

References

[1] Guo B, Dong R, Liang Y, Li M. Haemostatic materials for wound healing applications. Nat Rev Chem. 2021; 5: 773-791.

[2] Lei X-X, Cheng LH-H, Lin H-Y, et al. The minimal active domain of human salivary histatin 1 is efficacious in promoting acute skin wound healing. Military Med Res. 2022; 9: 41.

[3] Rodrigues M, Kosaric N, Bonham CA, Gurtner GC. Wound healing: a cellular perspective. Physiol Rev. 2019; 99: 665-706.

[4] Smirnova A, Yatsenko E, Baranovskii D, Klabukov I. Mesenchymal stem cell-derived extracellular vesicles in skin wound healing: the risk of senescent drift induction in secretome-based therapeutics. Military Med Res. 2023; 10: 60.

[5] Sun BK, Siprashvili Z, Khavari PA. Advances in skin grafting and treatment of cutaneous wounds. Science. 2014; 346: 941-945.

[6] Nguyen HM, Ngoc Le TT, Nguyen AT, Thien Le HN, Pham TT. Biomedical materials for wound dressing: recent advances and applications. RSC Adv. 2023; 13: 5509-5528.

[7] Yu P, Zhong W. Hemostatic materials in wound care. Burns Trauma. 2021; 9:tkab019.

[8] Zhang S, Lei X, Lv Y, Wang L, Wang L-N. Recent advances of chitosan as a hemostatic material: hemostatic mechanism, material design and prospective application. Carbohydr Polym. 2024; 327:121673.

[9] Harugade A, Sherje AP, Pethe A. Chitosan: a review on properties, biological activities and recent progress in biomedical applications. React Funct Polym. 2023; 191:105634.

[10] Huang J, Wu S, Wang Y, et al. Dual elemental doping activated signaling pathway of angiogenesis and defective heterojunction engineering for effective therapy of MRSA-infected wounds. Bioact. 2024; 37: 14-29.

[11] Chen J, Qiu L, Li Q, Ai J, Liu H, Chen Q. Rapid hemostasis accompanied by antibacterial action of calcium crosslinking tannic acid-coated mesoporous silica/silver Janus nanoparticles. Mater Sci Eng C. 2021; 123:111958.

[12] Witte MB, Barbul A. General principles of wound healing. Surg Clin North Am. 1997; 77: 509-528.

[13] Broos K, Feys HB, De Meyer SF, Vanhoorelbeke K, Deckmyn H. Platelets at work in primary hemostasis. Blood Rev. 2011; 25: 155-167.

[14] Barker TH, Engler AJ. The provisional matrix: setting the stage for tissue repair outcomes. Matrix Biol. 2017; 60-61: 1-4.

[15] Parker TJ, Broadbent JA, McGovern JA, Broszczak DA, Parker CN, Upton Z. Provisional matrix deposition in hemostasis and venous insufficiency: tissue preconditioning for nonhealing venous ulcers. Adv Wound Caref. 2015; 4: 174-191.

[16] Eming SA, Krieg T, Davidson JM. Inflammation in wound repair: molecular and cellular mechanisms. J Invest Dermatol. 2007; 127: 514-525.

[17] Wilgus TA, Roy S, McDaniel JC. Neutrophils and wound repair: positive actions and negative reactions. Adv Wound Caref. 2013; 2: 379-388.

[18] Nolan E, Malanchi I. Connecting the dots: neutrophils at the interface of tissue regeneration and cancer. Semin Immunol. 2021; 57:101598.

[19] Koehler J, Brandl FP, Goepferich AM. Hydrogel wound dressings for bioactive treatment of acute and chronic wounds. Eur Polym J. 2018; 100: 1-11.

[20] Herrero-Cervera A, Soehnlein O, Kenne E. Neutrophils in chronic inflammatory diseases. Cell Mol Immunol. 2022; 19: 177-191.

[21] Chen S, Saeed AFUH, Liu Q, et al. Macrophages in immunoregulation and therapeutics. Sig Transduct Target Ther. 2023; 8: 1-35.

[22] Martin P, Gurevich DB. Macrophage regulation of angiogenesis in health and disease. Semin Cell Dev Biol. 2021; 119: 101-110.

[23] Zhou C, Gao Y, Ding P, Wu T, Ji G. The role of CXCL family members in different diseases. Cell Death Discov. 2023; 9: 1-12.

[24] Xiang Y, Dai J, Li Y, et al. ROS-activated CXCR2+ neutrophils recruited by CXCL1 delay denervated skeletal muscle atrophy and undergo P53-mediated apoptosis. Exp Mol Med. 2022; 54: 1011-1023.

[25] Liu H, Zhao H, Zhou M, Zhao X, Lu Y. Neutrophils in cancer drug resistance: roles and therapeutic opportunities. Cancer Lett. 2025; 611:217417.

[26] Hunt M, Torres M, Bachar-Wikstrom E, Wikstrom JD. Cellular and molecular roles of reactive oxygen species in wound healing. Commun Biol. 2024; 7: 1-13.

[27] Dhandhi S, Yeshna V, Monika GB, et al. The interplay of skin architecture and cellular dynamics in wound healing: insights and innovations in care strategies. Tissue Cell. 2024; 91:102578.

[28] Esser JS, Rahner S, Deckler M, Bode C, Patterson C, Moser M. Fibroblast growth factor signaling pathway in endothelial cells is activated by BMPER to promote angiogenesis. Arterioscler Thromb Vasc Biol. 2015; 35: 358-367.

[29] Presta M, Chiodelli P, Giacomini A, Rusnati M, Ronca R. Fibroblast growth factors (FGFs) in cancer: fGF traps as a new therapeutic approach. Pharmacol Ther. 2017; 179: 171-187.

[30] Huveneers S, Phng L-K. Endothelial cell mechanics and dynamics in angiogenesis. Curr Opin Cell Biol. 2024; 91:102441.

[31] Cross MJ, Claesson-Welsh L. FGF and VEGF function in angiogenesis: signalling pathways, biological responses and therapeutic inhibition. Trends Pharmacol Sci. 2001; 22: 201-207.

[32] Shi N, Mei X, Chen S-Y. Smooth muscle cells in vascular remodeling. Arterioscler Thromb Vasc Biol. 2019; 39: e247-52.

[33] Haginoya S, Thomovsky EJ, Johnson PA, Brooks AC. Clinical assessment of primary hemostasis: a review. Top Companion Anim Med. 2023; 56-57:100818.

[34] Drakeford C, Aguila S, Roche F, et al. von Willebrand factor links primary hemostasis to innate immunity. Nat Commun. 2022; 13: 6320.

[35] Grant MA, Beeler DL, Spokes KC, et al. Identification of extant vertebrate Myxine glutinosa VWF: evolutionary conservation of primary hemostasis. Blood. 2017; 130: 2548-2558.

[36] Azer S, Oshinowo O, Fay ME, et al. Introducing a novel biophysical platelet function panel to investigate disorders of primary hemostasis and bleeding of unknown cause. Blood. 2021; 138: 2072.

[37] Huang Y, Wang J, Guo Y, Shen L, Li Y. Fibrinogen binding to activated platelets and its biomimetic thrombus-targeted thrombolytic strategies. Int J Biol Macromol. 2024; 274:133286.

[38] Kholmukhamedov A, Sakurai Y, Hardy EL, Lam WA, Jobe SM. Mitochondrial uncoupling prevents procoagulant platelet formation resulting in decreased thrombus stability. Blood. 2018; 132: 2421.

[39] Didiasova M, Wujak L, Schaefer L, Wygrecka M. Factor XII in coagulation, inflammation and beyond. Cell Signal. 2018; 51: 257-265.

[40] Gailani D, Renné T. The intrinsic pathway of coagulation: a target for treating thromboembolic disease?. J Thromb Haemost. 2007; 5: 1106-1112.

[41] Wilhelm G, Mertowska P, Mertowski S, et al. The crossroads of the coagulation system and the immune system: interactions and connections. Int J Mol Sci. 2023; 24:12563.

[42] Monroe DM, Key NS. The tissue factor-factor VIIa complex: procoagulant activity, regulation, and multitasking. J Thromb Haemost. 2007; 5: 1097-1105.

[43] Kamikubo Y, Mendolicchio GL, Zampolli A, et al. Selective factor VIII activation by the tissue factor-factor VIIa-factor Xa complex. Blood. 2017; 130: 1661-1670.

[44] Kaith BS, Singh A, Sharma AK, Sud D. Hydrogels: synthesis, classification, properties and potential applications—a brief review. J Polym Environ. 2021; 29: 3827-3841.

[45] Udayakumar GP, Muthusamy S, Selvaganesh B, et al. Biopolymers and composites: properties, characterization and their applications in food, medical and pharmaceutical industries. J Environ Chem Eng. 2021; 9:105322.

[46] Pita-López ML, Fletes-Vargas G, Espinosa-Andrews H, Rodríguez-Rodríguez R. Physically cross-linked chitosan-based hydrogels for tissue engineering applications: a state-of-the-art review. Eur Polym J. 2021; 145:110176.

[47] Yang T, Wang L, Wu W-H, Wei S, Zhang W-B. Orchestrating chemical and physical cross-linking in protein hydrogels to regulate embryonic stem cell growth. ACS Macro Lett. 2023; 12: 269-273.

[48] Rebers L, Reichsöllner R, Regett S, et al. Differentiation of physical and chemical cross-linking in gelatin methacryloyl hydrogels. Sci Rep. 2021; 11: 3256.

[49] Yang J, Chen Y, Zhao L, Zhang J, Luo H. Constructions and properties of physically cross-linked hydrogels based on natural polymers. Polym Rev. 2023; 63: 574-612.

[50] Fu X, Hosta-Rigau L, Chandrawati R, Cui J. Multi-stimuli-responsive polymer particles, films, and hydrogels for drug delivery. Chem. 2018; 4: 2084-2107.

[51] Patel DK, Jung E, Priya S, Won S-Y, Han SS. Recent advances in biopolymer-based hydrogels and their potential biomedical applications. Carbohydr Polym. 2024; 323:121408.

[52] Tudu M, Samanta A. Natural polysaccharides: chemical properties and application in pharmaceutical formulations. Eur Polym. 2023; 184:111801.

[53] Samadian H, Maleki H, Allahyari Z, Jaymand M. Natural polymers-based light-induced hydrogels: promising biomaterials for biomedical applications. Coord Chem Rev. 2020; 420:213432.

[54] Koivunotko E, Koivuniemi R, Monola J, et al. Cellulase-assisted platelet-rich plasma release from nanofibrillated cellulose hydrogel enhances wound healing. J Control Release. 2024; 368: 397-412.

[55] Zhang S, Gatsi B, Yao X, Jin Y, Amhal H. Cellulose nanofiber-reinforced antimicrobial and antioxidant multifunctional hydrogel with self-healing, adhesion for enhanced wound healing. Carbohydr Polym. 2024; 352:123189.

[56] Wang Y, Guo Y, Liu Y, et al. Platelet vesicles synergetic with biosynthetic cellulose aerogels for ultra-fast hemostasis and wound healing. Adv Healthc Mater. 2024; 13(17): 2304523.

[57] Mottaghitalab F, Khodadadi Yazdi M, Reza Saeb M, Bączek T, Farokhi M. Green and sustainable hydrogels based on quaternized chitosan to enhance wound healing. Chem Eng J. 2024; 492:152288.

[58] Chen C, Liu Y, Wang H, et al. Multifunctional chitosan inverse opal particles for wound healing. ACS Nano. 2018; 12: 10493-10500.

[59] Deng P, Chen J, Yao L, Zhang P, Zhou J. Thymine-modified chitosan with broad-spectrum antimicrobial activities for wound healing. Carbohydr Polym. 2021; 257:117630.

[60] Theocharidis G, Rahmani S, Lee S, et al. Murine macrophages or their secretome delivered in alginate dressings enhance impaired wound healing in diabetic mice. Biomaterials. 2022; 288:121692.

[61] Xie Y, Li G, Wu J, et al. Injectable self-healing alginate/PEG hydrogels cross-linked via thiol-Michael addition bonds for hemostasis and wound healing. Carbohydr Polym. 2025; 348:122864.

[62] Zhang X, Li Y, Ma Z, He D, Li H. Modulating degradation of sodium alginate/bioglass hydrogel for improving tissue infiltration and promoting wound healing. Bioact Mater. 2021; 6: 3692-3704.

[63] Ferreres G, Pérez-Rafael S, Palacios Ò, et al. Cobalt-phenolic nanoparticles-driven self-assembly of hyaluronic acid hydrogels providing a multifactorial approach for chronic wound management. Chem Eng J. 2024; 494:153064.

[64] He C, Bi S, Zhang R, et al. A hyaluronic acid hydrogel as a mild photothermal antibacterial, antioxidant, and nitric oxide release platform for diabetic wound healing. J Control Release. 2024; 370: 543-555.

[65] Zhou Y, Jia W, Bi J, et al. Sulfated hyaluronic acid/collagen-based biomimetic hybrid nanofiber skin for diabetic wound healing: development and preliminary evaluation. Carbohydr Polym. 2024; 334:122025.

[66] Huang H, Xie Y, Zhong J, et al. Antimicrobial peptides loaded collagen nanosheets with enhanced antibacterial activity, corneal wound healing and M1 macrophage polarization in bacterial keratitis. Compos B Eng. 2024; 275:111283.

[67] Kong W, Bao Y, Li W, et al. Collaborative enhancement of diabetic wound healing and skin regeneration by recombinant human collagen hydrogel and hADSCs. Adv Healthc Mater. 2024; 13:2401012.

[68] Yang D, Zhao W, Zhang S, et al. Dual self-assembly of puerarin and silk fibroin into supramolecular nanofibrillar hydrogel for infected wound treatment. Adv Healthc Mater. 2024; 13:2400071.

[69] Wang F, Lei H, Tian C, et al. An efficient biosynthetic system for developing functional silk fibroin-based biomaterials. Adv Mater. 2024: 2414878.

[70] Fan R, Zhao J, Yi L, et al. Anti-inflammatory peptide-conjugated silk fibroin/cryogel hybrid dual fiber scaffold with hierarchical structure promotes healing of chronic wounds. Adv Mater. 2024; 36:2307328.

[71] Chen Z, Zhou Z, Zhang X, et al. A carboxymethyl chitosan and dextran hydrogel with slow and rapid photothermal conversion for sequential promoting burn wound healing and inhibiting scar proliferation. Carbohydr Polym. 2025; 350:123045.

[72] Zhang Y, Chen Y, Shao P, Luo Y, Liu X, Xu T. Baicalin derivative dynamically cross-linked natural polysaccharide hydrogel for diabetic wound healing. Chem Eng J. 2024; 497:154803.

[73] Xie J, Huang Y, Hu X, et al. A constant filgotinib delivery adhesive platform based on polyethylene glycol (PEG) hydrogel for accelerating wound healing via restoring macrophage mitochondrial homeostasis. Small. 2024: 2408791.

[74] Firuzeh M, Labbaf S, Enayati MH, Dinari M, Mirhaj M. Enhanced wound healing with a bilayered multifunctional quaternized chitosan-dextran-curcumin construct. Carbohydr Polym. 2025; 352:123195.

[75] Yao W, Song Z, Ma X, et al. Asymmetric adhesive SIS-based wound dressings for therapeutically targeting wound repair. J Nanobiotechnol. 2024; 22: 34.

[76] Cai Y, Lin P, Li Y, et al. Alpha-ketoglutarate supramolecular network accelerates diabetic wound healing through exudates management and neovascularization. Chem Eng J. 2024; 502:157837.

[77] Xu J, Lin S, Chen H, et al. Highly active frozen nanovesicles microneedles for senile wound healing via antibacteria, immunotherapy, and skin regeneration. Adv Healthc Mater. 2024; 13:2304315.

[78] Nematollahi S, Maghsoudian S, Motasadizadeh H, et al. Polyhexamethylene biguanidine coated silver nanoparticles embedded into chitosan thiourea/PVA nanofibers as wound healing mats: in vitro and in vivo studies. Carbohydr Polym. 2025; 347:122704.

[79] Kim J-U, Ko J, Kim Y, et al. Electrical stimulating redox membrane incorporated with PVA/gelatin nanofiber for diabetic wound healing. Adv Healthc Mater. 2024; 13:2400170.

[80] Zou F, Wang Y, Tang T, et al. Synergistic strategy constructed hydrogel-aerogel biphase gel (HAB-gel) with self-negative-pressure exudate absorption, M2 macrophage-polarized and antibacterial for chronic wound treatment. Chem Eng J. 2023; 451:138952.

[81] Guo Z, Zhang Z, Zhang N, et al. A Mg2+/polydopamine composite hydrogel for the acceleration of infected wound healing. Bioact Mater. 2022; 15: 203-213.

[82] Zhang L, Yang Y, Wang J, Zhang H, Zhang Z, Guo B. A portable, sprayable, highly malleable, elastic, and hydrophobic antibacterial fibrous wound dressing for infected wound healing. Adv Fiber Mater [Internet]. 2025. Available from:.

[83] Liu H, Shan P, Lu Y, et al. Heparin mimicking sulfonated polyester synergistically promotes bacterial Infected-Wound healing with ROS responsive cinnamaldehyde based prodrugs. Chem Eng J. 2024; 495:153513.

[84] Xiao J, Song Z, Liu T, et al. Cell membrane engineered polypeptide nanonets mimicking macrophage aggregates for enhanced antibacterial treatment. Small. 2024; 20:2401845.

[85] Xie X-T, Gao C-H, Tan L-F, et al. Gene-engineered polypeptide hydrogels with on-demand oxygenation and ECM-cell interaction mimicry for diabetic wound healing. Biomaterials. 2025; 316:122984.

[86] Yan X, Huang H, Bakry AM, Wu W, Liu X, Liu F. Advances in enhancing the mechanical properties of biopolymer hydrogels via multi-strategic approaches. Int J Biol Macromol. 2024; 272:132583.

[87] Sionkowska A. Current research on the blends of natural and synthetic polymers as new biomaterials: review. Prog Polym Sci. 2011; 36: 1254-1276.

[88] Cheng L, Zhuang Z, Yin M, et al. A microenvironment-modulating dressing with proliferative degradants for the healing of diabetic wounds. Nat Commun. 2024; 15: 9786.

[89] Xu D, Feng Y, Song M, et al. Smart and bioactive electrospun dressing for accelerating wound healing. Chem Eng J. 2024; 496:153748.

[90] Zhang X, Liang Y, Huang S, Guo B. Chitosan-based self-healing hydrogel dressing for wound healing. Adv Colloid Interface Sci. 2024; 332:103267.

[91] Devlin JJ, Kircher S, Kozen BG, Littlejohn LF, Johnson AS. Comparison of ChitoFlex®, CELOX™, and QuikClot® in control of hemorrhage. J Emerg Med. 2011; 41: 237-245.

[92] Budde S, Noll Y, Zieglschmid V, Schroeder C, Koch A, Windhagen H. Determination of the efficacy of EVICEL™ on blood loss in orthopaedic surgery after total knee replacement: study protocol for a randomised controlled trial. Trials. 2015; 16: 299.

[93] Lee K, Kim M, Hahn T, Kim J. Comparison of histologic findings in wound healing of rabbit scleral homografts with fibrin glue (Tisseel®) and suture material. J Refract Surg. 1995; 11: 397-407.

[94] Ferroli P, Broggi M, Franzini A, et al. Surgifoam and mitoxantrone in the glioblastoma multiforme postresection cavity: the first step of locoregional chemotherapy through an ad hoc-placed catheter: technical note. Neurosurgery. 2006; 59: E433-4.

[95] Connell SS, Angeli SI, Water TRVD. R024: safety and durability of sepragel vs gelfoam ear Packing. Otolaryngol Head Neck Sur. 2016; 135: P113-P113.

[96] Yoon HS, Na YC, Choi KH, Huh WH, Kim JM. Wound healing effect of regenerated oxidized cellulose versus fibrin sealant patch: an in vivo study. Arch Craniofac Surg. 2019; 20: 289-296.

[97] Matthew IR, Browne RM, Frame JW, Millar BG. Subperiosteal behaviour of alginate and cellulose wound dressing materials. Biomaterials. 1995; 16: 275-278.

[98] Burkatovskaya M, Castano AP, Demidova-Rice TN, Tegos GP, Hamblin MR. Effect of chitosan acetate bandage on wound healing in infected and noninfected wounds in mice. Wound Repair Regen. 2008; 16: 425-431.

[99] Ménaché D. Le PPSB. Rev fr transfus immuno hématol. 1985; 28: 643-658.

[100] Leal-Noval SR, López-Irizo R, Bautista-Paloma J, et al. Efficacy of the prothrombin complex concentrate prothromplex in patients requiring urgent reversal of vitamin K antagonists or presenting with uncontrolled bleeding: a retrospective, single center study. Blood Coagul Fibrinolysis. 2013; 24: 862.

[101] Tang L, Cai S, Lu X, et al. Platelet-derived growth factor nanocapsules with tunable controlled release for chronic wound healing. Small. 2024; 20:2310743.

[102] Hoffman EP, Koo AH. Cerebral thrombosis associated with amicar therapy. Radiology. 1979; 131: 687-689.

[103] Kohno K, Kimura S, Kashima T, et al. Hemostatic effect of tranexamic acid (transamin) during coronary artery bypass grafting. J Artif Organs. 2001; 4: 241-244.

[104] Bhavi SB, Jaju PB. Intravenous iron sucrose v/s oral ferrous fumarate for treatment of anemia in pregnancy. A randomized controlled trial. BMC Pregnancy Childbirth. 2017; 17: 1-6.

[105] Frost DV, Perdue HS, Spruth HC. Vitamin K activity of menadione sodium bisulfite in chickens. J Nutr. 1956; 59: 181-196.

[106] Csákó G, Gazdy E, Csernyánszky H, Szilágyi T. Specificity of bovine thrombin and reptilase for mammalian plasmas. Blut. 1975; 30: 283-288.

[107] Greening DW, Glenister KM, Sparrow RL, Simpson RJ. International blood collection and storage: clinical use of blood products. J Proteomics. 2010; 73: 386-395.

[108] Wang H, Yang L. Applications of injectable hemostatic materials in wound healing: principles, strategies, performance requirements, and future perspectives. Theranostics. 2023; 13: 4615-4635.

[109] Hickman DA, Pawlowski CL, Sekhon UDS, Marks J, Gupta AS. Biomaterials and advanced technologies for hemostatic management of bleeding. Adv Mater. 2018; 30:1700859.

[110] Chavda VP, Teli D, Balar PC, et al. Self-assembled peptide hydrogels for the treatment of diabetes and associated complications. Colloids Surf B. 2024; 235:113761.

[111] Mei L, Mei Q, Dong W, Wu S. Redox-responsive self-assembled peptide hydrogel for mitochondrial-targeted anticancer drug delivery. Appl Mater Today. 2024; 41:102471.

[112] Das TN, Ramesh A, Ghosh A, Moyra S, Maji TK, Ghosh G. Peptide-based nanomaterials and their diverse applications. Nanoscale Horiz [Internet]. 2025. https://pubs.rsc.org/en/content/articlelanding/2025/nh/d4nh00371c. Available from:

[113] Guan T, Li J, Chen C, Liu Y. Self-assembling peptide-based hydrogels for wound tissue repair. Adv Sci. 2022; 9:2104165.

[114] Miserez A, Yu J, Mohammadi P. Protein-based biological materials: molecular design and artificial production. Chem Rev. 2023; 123: 2049-2111.

[115] Bai Q, Teng L, Zhang X, Dong C-M. Multifunctional single-component polypeptide hydrogels: the gelation mechanism, superior biocompatibility, high performance hemostasis, and scarless wound healing. Adv Healthc Mater. 2022; 11:2101809.

[116] Huang Y, Jing W, Zeng J, et al. Highly tough and biodegradable poly(ethylene glycol)-based bioadhesives for large-scaled liver injury hemostasis and tissue regeneration. Adv Healthc Mater. 2023; 12:2301086.

[117] Wang L, Lei K, Li Z, Wang X, Xiao H, Zheng Z. Tetra-PEG-based nano-enhanced hydrogel with excellent mechanical properties and multi-functions. Macromol Mater Eng. 2018; 303:1800325.

[118] He G, Xian Y, Lin H, et al. An injectable and coagulation-independent Tetra-PEG hydrogel bioadhesive for post-extraction hemostasis and alveolar bone regeneration. Bioact Mater. 2024; 37: 106-118.

[119] Li Y, Wang J, Wang Y, Cui W. Advanced electrospun hydrogel fibers for wound healing. Compos B Eng. 2021; 223:109101.

[120] Cheng J, Wang H, Gao J, et al. First-aid hydrogel wound dressing with reliable hemostatic and antibacterial capability for traumatic injuries. Adv Healthc Mater. 2023; 12:2300312.

[121] Weng H, Jia W, Li M, Chen Z. New injectable chitosan-hyaluronic acid based hydrogels for hemostasis and wound healing. Carbohydr Polym. 2022; 294:119767.

[122] Liang Y, Li Z, Huang Y, Yu R, Guo B. Dual-dynamic-bond cross-linked antibacterial adhesive hydrogel sealants with on-demand removability for post-wound-closure and infected wound healing. ACS Nano. 2021; 15: 7078-7093.

[123] Zhou M, Liao J, Li G, et al. Expandable carboxymethyl chitosan/cellulose nanofiber composite sponge for traumatic hemostasis. Carbohydr Polym. 2022; 294:119805.

[124] Li Y, Chen S, Zhang M, Ma X, Zhao J, Ji Y. Novel injectable, self-Healing, long-Effective bacteriostatic, and healed-promoting hydrogel wound dressing and controlled drug delivery mechanisms. ACS Appl Mater Interfaces. 2024; 16: 2140-2153.

[125] Zhang L, Liu M, Zhang Y, Pei R. Recent progress of highly adhesive hydrogels as wound dressings. Biomacromolecules. 2020; 21: 3966-3983.

[126] Li G, Pu Z, Guo S, et al. Durable and biocompatible low adhesion wound dressing material based on interfacial behaviors for wound management. Colloids Surf B. 2025; 247:114413.

[127] Shao Z, Yin T, Jiang J, He Y, Xiang T, Zhou S. Wound microenvironment self-adaptive hydrogel with efficient angiogenesis for promoting diabetic wound healing. Bioact Mater. 2023; 20: 561-573.

[128] Chen J, He J, Yang Y, et al. Antibacterial adhesive self-healing hydrogels to promote diabetic wound healing. Acta Biomater. 2022; 146: 119-130.

[129] Wang H, Cheng J, Sun F, et al. A super tough, rapidly biodegradable, ultrafast hemostatic bioglue. Adv Mater. 2023; 35:2208622.

[130] Guo B, Liang Y, Dong R. Physical dynamic double-network hydrogels as dressings to facilitate tissue repair. Nat Protoc. 2023; 18: 3322-3354.

[131] Elangwe CN, Morozkina SN, Podshivalov AV, Uspenskaya MV. Evaluation of composition effects on the tissue-adhesive, mechanical and physical properties of physically crosslinked hydrogels based on chitosan and pullulan for wound healing applications. Int J Biol Macromol. 2024; 276:133857.

[132] Fabbrizzi L. Beauty in chemistry: making artistic molecules with Schiff bases. J Org Chem. 2020; 85: 12212-12226.

[133] Sajjadi M, Jamali R, Kiyani T, Mohamadnia Z, Moradi A-R. Characterization of Schiff base self-healing hydrogels by dynamic speckle pattern analysis. Sci Rep. 2024; 14:27950.

[134] Liang Y, Xu H, Li Z, Zhangji A, Guo B. Bioinspired injectable self-healing hydrogel sealant with fault-tolerant and repeated thermo-responsive adhesion for sutureless post-wound-closure and wound healing. Nano-Micro Lett. 2022; 14: 185.

[135] Wang L, Yang K, Li X, et al. A double-crosslinked self-healing antibacterial hydrogel with enhanced mechanical performance for wound treatment. Acta Biomat. 2021; 124: 139-152.

[136] Cherri M, Stergiou PS, Ahmadian Z, et al. Redox-responsive hydrogels loaded with an antibacterial peptide as controlled drug delivery for healing infectious wounds. Adv Healthc Mater. 2024; 13:2401289.

[137] Li N, Zhang G, Liu Y, et al. A natural self-assembled gel-sponge with hierarchical porous structure for rapid hemostasis and antibacterial. Adv Healthc Mater. 2023; 12:2301465.

[138] Wang Y, Zhang Y, Yang Y-P, et al. Versatile dopamine-functionalized hyaluronic acid-recombinant human collagen hydrogel promoting diabetic wound healing via inflammation control and vascularization tissue regeneration. Bioact Mater. 2024; 35: 330-345.

[139] Claro AM, Alves CC, dos Santos KS, et al. Regenerated cellulose sponge as sacrificial template for the synthesis of three-dimensional porous alumina-silica scaffold for tissue engineering. J Sol-Gel Sci Technol. 2023; 107: 83-95.

[140] Liang Y, Li M, Yang Y, Qiao L, Xu H, Guo B. pH/Glucose dual responsive metformin release hydrogel dressings with adhesion and self-healing via dual-dynamic bonding for athletic diabetic foot wound healing. ACS Nano. 2022; 16: 3194-3207.

[141] Qin X, Shi H, Wen Z, et al. Triboelectric-responsive drug delivery hydrogel for accelerating infected wound healing. Adv Healthc Mater. 2024; 13:2303474.

[142] Liu H, Li Y, Sun Q, et al. Triboelectric wearable devices for accelerated wound healing. Chem Eng J. 2024; 497:154628.

[143] Chhillar A, Jaiswal A. Hyaluronic acid-based self-healing hydrogels for diabetic wound healing. Adv Healthc Mater. 2024: 2404255.

[144] Li W, Yu Y, Huang R, et al. Multi-bioinspired functional conductive hydrogel patches for wound healing management. Adv Sci. 2023; 10:2301479.

[145] Kang Y, Liu K, Chen Z, et al. Healing with precision: a multi-functional hydrogel-bioactive glass dressing boosts infected wound recovery and enhances neurogenesis in the wound bed. J Control Release. 2024; 370: 210-229.

[146] Gao W, Chen Y, Zhang Y, Zhang Q, Zhang L. Nanoparticle-based local antimicrobial drug delivery. Adv Drug Deliv Rev. 2018; 127: 46-57.

[147] Andreica B-I, Cheng X, Marin L. Quaternary ammonium salts of chitosan. A critical overview on the synthesis and properties generated by quaternization. Eur Polym J. 2020; 139:110016.

[148] Nasaj M, Chehelgerdi M, Asghari B, et al. Factors influencing the antimicrobial mechanism of chitosan action and its derivatives: a review. Int J Biol Macromol. 2024; 277:134321.

[149] Shariatinia Z. Carboxymethyl chitosan: properties and biomedical applications. Int J Biol Macromol. 2018; 120: 1406-1419.

[150] Li J, Mooney DJ. Designing hydrogels for controlled drug delivery. Nat Rev Mater. 2016; 1: 1-17.

[151] Kwak G, Cheng J, Kim H, et al. Sustained exosome-guided macrophage polarization using hydrolytically degradable PEG hydrogels for cutaneous wound healing: identification of key proteins and MiRNAs, and sustained release formulation. Small. 2022; 18:2200060.

[152] Wang M, Hong Y, Fu X, Sun X. Advances and applications of biomimetic biomaterials for endogenous skin regeneration. Bioact Mater. 2024; 39: 492-520.

[153] Lin J, Lian C, Xu L, et al. Hyperglycemia targeting nanomotors for accelerated healing of diabetic wounds by efficient microenvironment remodeling. Adv Funct Mater. 2024: 2417146.

[154] Zheng X, Deng S, Li Y, et al. Targeting m6A demethylase FTO to heal diabetic wounds with ROS-scavenging nanocolloidal hydrogels. Biomaterials. 2024; 317:123065.

[155] Xiang P, Jiang M, Chen X, et al. Targeting grancalcin accelerates wound healing by improving angiogenesis in diabetes. Adv Sci. 2024; 11:2305856.

[156] Sharifzadeh G, Hosseinkhani H. Biomolecule-responsive hydrogels in medicine. Adv Healthc Mater. 2017; 6:1700801.

[157] Park J, Kim TY, Kim Y, et al. A mechanically resilient and tissue-conformable hydrogel with hemostatic and antibacterial capabilities for wound care. Adv Sci. 2023; 10:2303651.

[158] Pourshahrestani S, Zeimaran E, Kadri NA, Mutlu N, Boccaccini AR. Polymeric hydrogel systems as emerging biomaterial platforms to enable hemostasis and wound healing. Adv Healthc Mater. 2020; 9:2000905.

[159] He H, Zhou W, Gao J, et al. Efficient, biosafe and tissue adhesive hemostatic cotton gauze with controlled balance of hydrophilicity and hydrophobicity. Nat Commun. 2022; 13: 552.

[160] Xu J, Chang L, Xiong Y, Peng Q. Chitosan-based hydrogels as antibacterial/antioxidant/anti-inflammation multifunctional dressings for chronic wound healing. Adv Healthc Mater. 2024; 13:2401490.

[161] Jin Y, Lu Y, Jiang X, et al. Accelerated infected wound healing by probiotic-based living microneedles with long-acting antibacterial effect. Bioact Mater. 2024; 38: 292-304.

[162] Li S, Zhi L, Chen Q, Zhao W, Zhao C. Reversibly adhesive, anti-swelling, and antibacterial hydrogels for tooth-extraction wound healing. Adv Healthc Mater. 2024; 13:2400089.

[163] Pedro AQ, Castro LS, Coutinho JAP, Freire MG. Ionogels as advanced materials for overcoming challenges in wound healing and drug delivery. Nano Mater Sci [Internet]. 2024. Available from:. https://www.sciencedirect.com/science/article/pii/S258996512400103X

[164] Wang Y, Zheng Z, Pathak JL, et al. GHK-Cu/Pionin-loaded in situ electrospun PVB/PVP smart dressing promotes wound healing via anti-oxidant, anti-inflammatory, antimicrobial, and tissue regenerative effects. Chem Eng J. 2024; 492:152154.

[165] Zang H, Jiang H, Huang J, et al. Bilayer micropatterned hydrogel scaffolds loaded with ADSCs improved integration with regenerated tissue and diabetic wound healing. Chem Eng J. 2024; 489:151342.

[166] Zhao M, Kang M, Wang J, et al. Stem cell-derived nanovesicles embedded in dual-layered hydrogel for programmed ROS regulation and comprehensive tissue regeneration in burn wound healing. Adv Mater. 2024; 36:2401369.

[167] Khattak S, Ullah I, Sohail M, et al. Endogenous/exogenous stimuli-responsive smart hydrogels for diabetic wound healing. Aggregate. 2024: e688.

[168] Huang L, Li T, Geng W, et al. Oxygen-bonded amorphous transition metal dichalcogenides with pH-responsive reactive oxygen biocatalysis for combined antibacterial and anti-inflammatory therapies in diabetic wound healing. Small. 2024: 2407046.

[169] Wang W, Zhang S, Yuan Z, et al. pH responsive THPS crosslinked injectable hydrogel with Cu-metformin sustained-release for accelerating wound healing. Chem Eng J. 2024; 492:152373.

[170] Wang G, Wang W, Chen Z, et al. Photothermal microneedle patch loaded with antimicrobial peptide/MnO2 hybrid nanoparticles for chronic wound healing. Chem Eng J. 2024; 482:148938.

[171] Hua S, Zhang Y, Zhu Y, et al. Tunicate cellulose nanocrystals strengthened injectable stretchable hydrogel as multi-responsive enhanced antibacterial wound dressing for promoting diabetic wound healing. Carbohydr Polym. 2024; 343:122426.

[172] Huang Z, An H, Guo H, et al. An asymmetric natural nanofiber with rapid temperature responsive detachability inspired by Andrias davidianus for full-thickness skin wound healing. Adv Fiber Mater. 2024; 6: 473-488.

[173] Jiang W, Hou X, Guo X, et al. A superelastic, biofluid-locking, and degradable dressing for wound healing. Carbohydr Polym. 2025; 347:122774.

[174] Freedman BR, Hwang C, Talbot S, Hibler B, Matoori S, Mooney DJ. Breakthrough treatments for accelerated wound healing. Sci Adv. 2023; 9:eade7007.

[175] Mascharak S, desJardins-Park HE, Longaker MT. Fibroblast heterogeneity in wound healing: hurdles to clinical translation. Trends Mol Med. 2020; 26: 1101-1106.

[176] Frantz VK, Clarke HT, Lattes R. Hemostasis with absorbable gauze: (oxidized cellulose). Ann Surg. 1944; 120: 170.

[177] Ye J, Shi C, Lan J, et al. Tannic acid coating gauze immobilized with thrombin with ultra-high coagulation activity and antimicrobial property for uncontrollable hemorrhage. Sci Rep. 2024; 14:16139.

[178] Jia X, Hua C, Yang F, et al. Hydrophobic aerogel-modified hemostatic gauze with thermal management performance. Bioact Mater. 2023; 26: 142-158.

[179] Yang X, Shi N, Liu J, et al. 3D printed hybrid aerogel gauzes enable highly efficient hemostasis. Adv Healthc Mater. 2023; 12:2201591.

[180] Geng H, Dai Q, Sun H, et al. Injectable and sprayable polyphenol-based hydrogels for controlling hemostasis. ACS Appl Bio Mater. 2020; 3: 1258-1266.

[181] Chen Z, Wu H, Wang H, et al. An injectable anti-microbial and adhesive hydrogel for the effective noncompressible visceral hemostasis and wound repair. Mater Sci Eng C. 2021; 129:112422.

[182] Wei Q, Wang Y, Wang H, et al. Photo-induced adhesive carboxymethyl chitosan-based hydrogels with antibacterial and antioxidant properties for accelerating wound healing. Carbohydr Polym. 2022; 278:119000.

[183] Nelson BR, Kirkpatrick BE, Miksch CE, et al. Photoinduced dithiolane crosslinking for multiresponsive dynamic hydrogels. Adv Mater. 2023: 2211209.

[184] An S, Jeon EJ, Han SY, et al. pH-universal catechol-amine chemistry for versatile hyaluronic acid bioadhesives. Small. 2022; 18:2202729.

[185] Zhang K, Xian Y, Li M, et al. Gelable and adhesive powder for lethal non-compressible hemorrhage control. Adv Funct Mater. 2023; 33:2305222.

[186] Shang L, Yan Y, Li Z, Liu H, Ge S, Ma B. Hydro-sensitive, in situ ultrafast physical self-gelatinizing, and red blood cells strengthened hemostatic adhesive powder with antibiosis and immunoregulation for wound repair. Adv Sci. 2024; 11:2306528.

[187] Li B, Li H, Chen H, et al. Microgel assembly powder improves acute hemostasis, antibacterial, and wound healing via in situ co-assembly of erythrocyte and microgel. Adv Funct Mater. 2023; 33:2302793.

[188] Li P, Poon YF, Li W, et al. A polycationic antimicrobial and biocompatible hydrogel with microbe membrane suctioning ability. Nat Mater. 2011; 10: 149-156.

[189] Zhao X, Luo J, Huang Y, et al. Injectable antiswelling and high-strength bioactive hydrogels with a wet adhesion and rapid gelling process to promote sutureless wound closure and scar-free repair of infectious wounds. ACS Nano. 2023; 17: 22015-22034.

[190] Fan P, Dong Q, Yang J, et al. Flexible dual-functionalized hyaluronic acid hydrogel adhesives formed in situ for rapid hemostasis. Carbohydr Polym. 2023; 313:120854.

[191] Ninan L, Monahan J, Stroshine RL, Wilker JJ, Shi R. Adhesive strength of marine mussel extracts on porcine skin. Biomaterials. 2003; 24: 4091-4099.

[192] Olivieri MP, Baier RE, Loomis RE. Surface properties of mussel adhesive protein component films. Biomaterials. 1992; 13: 1000-1008.

[193] Zhong W, Hu R, Zhou S, et al. Spatiotemporally responsive hydrogel dressing with self-adaptive antibacterial activity and cell compatibility for wound sealing and healing. Adv Healthc Mater. 2023; 12:2203241.

[194] Du X, Bi Y, He P, Wang C, Guo W. Hierarchically structured DNA-based hydrogels exhibiting enhanced enzyme-responsive and mechanical properties. Adv Funct Mater. 2020; 30:2006305.

[195] Brooks WLA, Sumerlin BS. Synthesis and applications of boronic acid-containing polymers: from materials to medicine. Chem Rev. 2016; 116: 1375-1397.

[196] Ball AP, Gray JA, Murdoch JMC. Antibacterial drugs today: I. Drugs. 1975; 10: 1-55.

[197] Zhang H, Wu Z, Zhou J, et al. The antimicrobial, hemostatic, and anti-adhesion effects of a peptide hydrogel constructed by the all-d-enantiomer of antimicrobial peptide jelleine-1. Adv Healthc Mater. 2023; 12:2301612.

[198] Cao S, Bi Z, Li Q, Zhang S, Singh M, Chen J. Shape memory and antibacterial chitosan-based cryogel with hemostasis and skin wound repair. Carbohydr Polym. 2023; 305:120545.

[199] Feng W, Wang Z. Shear-thinning and self-healing chitosan-graphene oxide hydrogel for hemostasis and wound healing. Carbohydr Polym. 2022; 294:119824.

[200] Zhong Y, Zhao X, Li G, Zhang D, Wang D. Mussel-inspired hydrogels as tissue adhesives for hemostasis with fast-forming and self-healing properties. Eur Polym J. 2021; 148:110361.

[201] Sekhar KPC, Zhang X, Geng H, Yu Q, Zhang P, Cui J. Biomimetic hemostatic powder derived from coacervate-immobilized thermogelling copolymers. Biomacromolecules. 2023; 24: 5394-5402.

[202] Dong R, Zhang H, Guo B. Emerging hemostatic materials for non-compressible hemorrhage control. Natl Sci Rev. 2022; 9:nwac162.

[203] Chan LW, Wang X, Wei H, Pozzo LD, White NJ, Pun SH. A synthetic fibrin cross-linking polymer for modulating clot properties and inducing hemostasis. Sci Transl Med. 2015; 7: 277ra29-277ra29.

[204] Girish A, Jolly K, Alsaadi N, et al. Platelet-inspired intravenous nanomedicine for injury-targeted direct delivery of thrombin to augment hemostasis in coagulopathies. ACS Nano. 2022; 16: 16292-16313.

[205] Cui C, Fan C, Wu Y, et al. Water-triggered hyperbranched polymer universal adhesives: from strong underwater adhesion to rapid sealing hemostasis. Adv Mater. 2019; 31:1905761.

[206] Lv S, Cai M, Leng F, Jiang X. Biodegradable carboxymethyl chitin-based hemostatic sponges with high strength and shape memory for non-compressible hemorrhage. Carbohydr Polym. 2022; 288:119369.

[207] Pan G, Li F, He S, et al. Mussel- and barnacle cement proteins-inspired dual-bionic bioadhesive with repeatable wet-tissue adhesion, multimodal self-healing, and antibacterial capability for nonpressing hemostasis and promoted wound healing. Adv Funct Mater. 2022; 32:2200908.

[208] Lu X, Liu Z, Jia Q, et al. Flexible bioactive glass nanofiber-based self-expanding cryogels with superelasticity and bioadhesion enabling hemostasis and wound healing. ACS Nano. 2023; 17: 11507-11520.

[209] Zhang K, Bai X, Yuan Z, et al. Layered nanofiber sponge with an improved capacity for promoting blood coagulation and wound healing. Biomaterials. 2019; 204: 70-79.

[210] Du X, Wu L, Yan H, et al. Microchannelled alkylated chitosan sponge to treat noncompressible hemorrhages and facilitate wound healing. Nat Commun. 2021; 12: 4733.

[211] Drenckhan W, Saint-Jalmes A. The science of foaming. Adv Colloid Interface Sci. 2015; 222: 228-259.

[212] Zhou L, Rada J, Zhang H, et al. Sustainable and inexpensive polydimethylsiloxane sponges for daytime radiative cooling. Adv Sci. 2021; 8:2102502.

[213] Liang Y, He J, Guo B. Functional hydrogels as wound dressing to enhance wound healing. ACS Nano. 2021; 15: 12687-12722.

[214] Zhou L, Hu Z, Liu F, et al. Electrospun self-pumping dressing with gastrodin for immunomodulation and rapid healing of diabetic wounds. Chem Eng J. 2024; 495:153424.

[215] Wu X, Wang C, Wang J, et al. Antiadhesive, antibacterial, and anti-inflammatory sandwich-structured ZIF8-containing gauze for enhanced wound healing. Chem Eng J. 2024; 491:152060.

[216] Correa S, Grosskopf AK, Lopez Hernandez H, et al. Translational applications of hydrogels. Chem Rev. 2021; 121: 11385-11457.

[217] Khan MUA, Stojanović GM, Abdullah MFB, et al. Fundamental properties of smart hydrogels for tissue engineering applications: a review. Int J Biol Macromol. 2024; 254:127882.

[218] Shanthar R, Chen K, Abeykoon C. Powder-based additive manufacturing: a critical review of materials, methods, opportunities, and challenges. Adv Eng Mater. 2023; 25:2300375.

[219] Nepal A, Tran HDN, Nguyen N-T, Ta HT. Advances in haemostatic sponges: characteristics and the underlying mechanisms for rapid haemostasis. Bioact Mater. 2023; 27: 231-256.

[220] Leonhardt EE, Kang N, Hamad MA, Wooley KL, Elsabahy M. Absorbable hemostatic hydrogels comprising composites of sacrificial templates and honeycomb-like nanofibrous mats of chitosan. Nat Commun. 2019; 10: 2307.

[221] Mariani F, Serafini M, Gualandi I, et al. Advanced wound dressing for real-time pH monitoring. ACS Sens. 2021; 6: 2366-2377.

[222] Youssef K, Ullah A, Rezai P, Hasan A, Amirfazli A. Recent advances in biosensors for real time monitoring of pH, temperature, and oxygen in chronic wounds. Mater Today Bio. 2023; 22:100764.

[223] Wei J, Zhang W, Mou X, et al. Bioinspired hemostatic and anti-infective armor for wound healing assisted by metal-phenol-polyamine system. Adv Funct Mater. 2024; 34:2306267.

[224] Freedman BR, Uzun O, Luna NMM, et al. Degradable and removable tough adhesive hydrogels. Adv Mater. 2021; 33:2008553.

[225] Chen Y, Wang X, Tao S, et al. Research advances in smart responsive-hydrogel dressings with potential clinical diabetic wound healing properties. Mil Med Res. 2023; 10: 37.

RIGHTS & PERMISSIONS

2025 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.