Skin-Inspired Mechanically-Responsive Antimicrobial Hydrogels with Liposome-Based Crosslinkers

Ning Shao; Rui Liu; Jingjing Gan; Yuanjin Zhao

doi:10.1016/j.eng.2026.01.022

Engineering ›› :202601022 DOI: 10.1016/j.eng.2026.01.022

Research

research-article

Skin-Inspired Mechanically-Responsive Antimicrobial Hydrogels with Liposome-Based Crosslinkers

Author information +

History +

PDF

Abstract

Biocompatible hydrogels are highly valuable for wound management; however, improving their mechanical compatibility and achieving controlled drug release for dynamic wound treatment remain challenging. Inspired by skin structure and function, a novel mechanically-responsive hydrogel was developed using drug-loaded liposomes as structural units. The crosslinked hydrogel network was generated via free-radical polymerization of acrylamide, incorporating double-bond-functionalized liposomes as crosslinkers. Deformable liposomes endowed the hydrogel with improved mechanical properties and enabled controlled drug release in response to mechanical deformation. The rifampin-loaded mechanically-responsive hydrogel exhibited strong antimicrobial activity both in vitro and in vivo. In addition, anti-inflammatory effects and enhanced wound-healing properties were observed in dynamic wound environments. These findings indicate that mechanically-responsive skin-mimicking hydrogels offer a promising strategy for dynamic wound management.

Keywords

Skin-inspired / Antimicrobial / Hydrogel / Liposome / Mechanically responsive

Cite this article

Download citation ▾

Ning Shao, Rui Liu, Jingjing Gan, Yuanjin Zhao. Skin-Inspired Mechanically-Responsive Antimicrobial Hydrogels with Liposome-Based Crosslinkers. Engineering 202601022 DOI:10.1016/j.eng.2026.01.022

登录浏览全文

4963

注册一个新账户忘记密码

References

Publishing order | Descend order by publishing year | Descend order by cited within

[1]	Peña OA, Martin P. Cellular and molecular mechanisms of skin wound healing. Nat Rev Mol Cell Biol 2024; 25(8):599-616.

[2]	Uberoi A, McCready-Vangi A, Grice EA. The wound microbiota: microbial mechanisms of impaired wound healing and infection. Nat Rev Microbiol 2024; 22(8):507-21.

[3]	Martin P, Pardo-Pastor C, Jenkins RG, Rosenblatt J. Imperfect wound healing sets the stage for chronic diseases. Science 2024; 386(6726):eadp2974.

[4]	Wang Y, Guo J, Cao X, Zhao Y. Developing conductive hydrogels for biomedical applications. Smart Med 2023; 3(1):e20230023.

[5]	Yu R, Zhang H, Guo B. Conductive biomaterials as bioactive wound dressing for wound healing and skin tissue engineering. Nano-Micro Lett 2021; 14(1):1.

[6]	Pranantyo D, Yeo CK, Wu Y, Fan C, Xu X, Yip YS, et al. Hydrogel dressings with intrinsic antibiofilm and antioxidative dual functionalities accelerate infected diabetic wound healing. Nat Commun 2024; 15(1):954.

[7]	Ouyang J, Ji X, Zhang X, Feng C, Tang Z, Kong N, et al. In situ sprayed NIR-responsive, analgesic black phosphorus-based gel for diabetic ulcer treatment. Proc Natl Acad Sci USA 2020; 117(46):28667-77.

[8]	Liang Y, He J, Guo B. Functional hydrogels as wound dressing to enhance wound healing. ACS Nano 2021; 15(8):12687-722.

[9]	Chen S, Sun L, Zhou X, Guo Y, Song J, Qian S, et al. Mechanically and biologically skin-like elastomers for bio-integrated electronics. Nat Commun 2020; 11(1):1107.

[10]	Zhang F, Zhang H, Wang S, Gao M, Du K, Chen X, et al. A dynamically phase-adaptive regulating hydrogel promotes ultrafast anti-fibrotic wound healing. Nat Commun 2025; 16(1):3738.

[11]	Ma Y, Hua M, Wu S, Du Y, Pei X, Zhu X, et al. Bioinspired high-power-density strong contractile hydrogel by programmable elastic recoil. Sci Adv 2020; 6(47):eabd2520.

[12]	Zhang YS, Khademhosseini A. Advances in engineering hydrogels. Science 2017; 356(6337):eaaf3627.

[13]	Sutherland TE, Dyer DP, Allen JE. The extracellular matrix and the immune system: a mutually dependent relationship. Science 2023; 379(6633):eabp8964.

[14]	Liu W, Gao R, Yang C, Feng Z, Ou-Yang W, Pan X, et al. ECM-mimetic immunomodulatory hydrogel for methicillin-resistant Staphylococcus aureus-infected chronic skin wound healing. Sci Adv 2022; 8(27):eabn7006.

[15]	Wu J, Pan Z, Zhao ZY, Wang MH, Dong L, Gao HL, et al. Anti-swelling, robust, and adhesive extracellular matrix-mimicking hydrogel used as intraoral dressing. Adv Mater 2022; 34(20):e2200115.

[16]	Wu F, Ren Y, Lv W, Liu X, Wang X, Wang C, et al. Generating dual structurally and functionally skin-mimicking hydrogels by crosslinking cell-membrane compartments. Nat Commun 2024; 15(1):802.

[17]	Zhang W, Wu B, Sun S, Wu P. Skin-like mechanoresponsive self-healing ionic elastomer from supramolecular zwitterionic network. Nat Commun 2021; 12(1):4082.

[18]	Lin J, Wang Z, Huang J, Tang S, Saiding Q, Zhu Q, et al. Fertility restoration microenvironment-protected exosome-hydrogel for facilitating endometrial. Small 2021;17:2007235.

[19]	Jiang Y, Wu X, Wang X, Kong B, Wang J, Zhang H. Living hydrogel with blood derived elements for wound healing. Mater Today Bio 2025;33:102002.

[20]	Liang C, Dudko V, Khoruzhenko O, Hong X, Lv ZP, Tunn I, et al. Stiff and self-healing hydrogels by polymer entanglements in co-planar nanoconfinement. Nat Mater 2025; 24(4):599-606.

[21]	Chen G, Wang F, Zhang X, Shang Y, Zhao Y. Living microecological hydrogels for wound healing. Sci Adv 2023; 9(21):eadg3478.

[22]	Lin X, Cai L, Cao X, Zhao Y. Stimuli-responsive silk fibroin for on-demand drug delivery. Smart Med 2023; 2(2):e20220019.

[23]	Roh EJ, Kim DS, Kim JH, Lim CS, Choi H, Kwon SY, et al. Multimodal therapy strategy based on a bioactive hydrogel for repair of spinal cord injury. Biomaterials 2023;299:122160.

[24]	Peng X, Chen J, Gan Y, Yang L, Luo Y, Bu C, et al. Biofunctional lipid nanoparticles for precision treatment and prophylaxis of bacterial infections. Sci Adv 2024; 10(14):eadk9754.

[25]	Rahman MM, Wang J, Wang G, Su Z, Li Y, Chen Y, et al. Chimeric nanobody-decorated liposomes by self-assembly. Nat Nanotechnol 2024; 19(6):818-24.

[26]	Correa S, Grosskopf AK, Klich JH, Hernandez HL, Appel EA. Injectable liposome-based supramolecular hydrogels for the programmable release of multiple protein drugs. Matter 2022; 5(6):1816-38.

[27]	Li G, Liu S, Chen Y, Zhao J, Xu H, Weng J, et al. An injectable liposome-anchored teriparatide incorporated gallic acid-grafted gelatin hydrogel for osteoarthritis treatment. Nat Commun 2023; 14(1):3159.

[28]	Wang X, Shi H, Huang S, Zhang Y, He X, Long Q, et al. Localized delivery of anti-inflammatory agents using extracellular matrix-nanostructured lipid carriers hydrogel promotes cardiac repair post-myocardial infarction. Biomaterials 2023;302:122364.

[29]	Cheng R, Liu L, Xiang Y, Lu Y, Deng L, Zhang H, et al. Advanced liposome-loaded scaffolds for therapeutic and tissue engineering applications. Biomaterials 2020;232:119706.

[30]	Zhi Y, Che J, Zhu H, Liu R, Zhao Y. Glycyrrhetinic acid liposomes encapsulated microcapsules from microfluidic electrospray for inflammatory wound healing. Adv Funct Mater 2023; 33(43):2304353.

[31]	Kong B, Liu R, Cheng Y, Shang Y, Zhang D, Gu H, et al. Structural color medical patch with surface dual-properties of wet bioadhesion and slipperiness. Adv Sci 2022; 9(31):e2203096.

[32]	Eom Y, Kim SM, Lee M, Jeon H, Park J, Lee ES, et al. Mechano-responsive hydrogen-bonding array of thermoplastic polyurethane elastomer captures both strength and self-healing. Nat Commun 2021; 12(1):621.

[33]	Zhang CW, Si M, Chen C, He P, Fei Z, Xu N, et al. Hierarchical engineering for biopolymer-based hydrogels with tailored property and functionality. Adv Mater 2025; 37(22):e2414897.

[34]	Wu F, Pang Y, Liu J. Swelling-strengthening hydrogels by embedding with deformable nanobarriers. Nat Commun 2020; 11(1):4502.

[35]	Grijalvo S, Mayr J, Eritja R, Díaz DD. Biodegradable liposome-encapsulated hydrogels for biomedical applications: a marriage of convenience. Biomater Sci 2016; 4(4):555-74.

[36]	Lyu D, Chen S, Guo W. Liposome crosslinked polyacrylamide/DNA hydrogel: a smart controlled-release system for small molecular payloads. Small 2018; 14(15):e1704039.

[37]	Bao B, Zeng Q, Li K, Wen J, Zhang Y, Zheng Y, et al. Rapid fabrication of physically robust hydrogels. Nat Mater 2023; 22(10):1253-60.

[38]	Liu J, Wu M, Lu J, He Q, Zhang J. Janus intelligent antibacterial hydrogel dressings for chronic wound healing in diabetes. ACS Appl Polym Mater 2023; 5(4):2596-606.

[39]	Fu F, Chen Z, Zhao Z, Wang H, Shang L, Gu Z, et al. Bio-inspired self-healing structural color hydrogel. Proc Natl Acad Sci USA 2017; 114(23):5900-5.

[40]	Fang K, Wang R, Zhang H, Zhou L, Xu T, Xiao Y, et al. Mechano-responsive, tough, and antibacterial zwitterionic hydrogels with controllable drug release for wound healing applications. ACS Appl Mater Interfaces 2020; 12(47):52307-18.

[41]	Zhao P, Zhang Y, Chen X, Xu C, Guo J, Deng M, et al. Versatile hydrogel dressing with skin adaptiveness and mild photothermal antibacterial activity for methicillin-resistant staphylococcus aureus-infected dynamic wound healing. Adv Sci 2023; 10(11):e2206585.

[42]	Aizik G, Ostertag-Hill CA, Chakraborty P, Choi W, Pan M, Mankus DV, et al. Injectable hydrogel based on liposome self-assembly for controlled release of small hydrophilic molecules. Acta Biomater 2024;183:101-10.

[43]	Wu S, Liu G, Shao P, Lin X, Yu J, Chen H, et al. Transdermal sustained release properties and anti-photoaging efficacy of liposome-thermosensitive hydrogel system. Adv Healthc Mater 2024; 13(2):e2301933.

[44]	Shan J, Che J, Song C, Zhao Y. Emerging antibacterial nanozymes for wound healing. Smart Med 2023; 2(3):e20220025.

[45]	Li S, Wang L, Zheng W, Yang G, Jiang X. Rapid fabrication of self-healing, conductive, and injectable gel as dressings for healing wounds in stretchable parts of the body. Adv Funct Mater 2020; 30(31):2002370.

[46]	Moghadamtousi SZ, Rouhollahi E, Hajrezaie M, Karimian H, Abdulla MA, Kadir HA. Annona muricata leaves accelerate wound healing in rats via involvement of Hsp70 and antioxidant defence. Int J Surg 2015;18:110-7.

[47]	She Y, Liu H, Yuan H, Li Y, Liu X, Liu R, et al. Artificial intelligence-assisted conductive hydrogel dressings for refractory wounds monitoring. Nano-Micro Lett 2025; 17(1):319.

[48]	Park J, Kim TY, Kim Y, An S, Kim KS, Kang M, et al. A mechanically resilient and tissue-conformable hydrogel with hemostatic and antibacterial capabilities for wound care. Adv Sci 2023; 10(30):e2303651.

[49]	Zhong Q, Zhang R, Chen Y, Tan S, Huang L, Zhang J, et al. A mechanical contraction-driven hydrogel dressing for Ph visualization and tailored acute/chronic wound healing. Adv Funct Mater 2025; 36(7):e12807.

[50]	Meng X, Qiao Y, Do C, Bras W, He C, Ke Y, et al. Hysteresis-free nanoparticle-reinforced hydrogels. Adv Mater 2022; 34(7):e2108243.

[51]	Fang Y, Nie T, Li G, Wang L, Du J, Wu J. Multifunctional antibiotic hydrogel doped with antioxidative lycopene-based liposome for accelerative diabetic wound healing. Chem Eng J 2024;480:147930.

[52]	Xing D, Xia G, Tang X, Zhuang Z, Shan J, Fang X, et al. A multifunctional nanocomposite hydrogel delivery system based on dual-loaded liposomes for scarless wound healing. Adv Healthc Mater 2024; 13(28):e2401619.

[53]	Wang C, Shirzaei Sani E, Shih CD, Lim CT, Wang J, Armstrong DG, et al. Wound management materials and technologies from bench to bedside and beyond. Nat Rev Mater 2024; 9(8):550-66.

[54]	Liu K, Zhang C, Chang R, He Y, Guan F, Yao M. Ultra-stretchable, tissue-adhesive, shape-adaptive, self-healing, on-demand removable hydrogel dressings with multiple functions for infected wound healing in regions of high mobility. Acta Biomater 2023;166:224-40.