
Kangning SHEN, Jingyi GU, Ximin YUAN, Nian LIU, Yinglin WANG, Jiabin CAI, Yang SHI, Kaiyang WANG, Xinghua YE, Minghao YANG, Zhiyong MA, Zhijian XIE. 3D printing of wet-bonded multilayer scaffolds for skin wound repair[J]. Journal of Zhejiang University Science A, 2026, 27(6): 625-639.
@article{title="3D printing of wet-bonded multilayer scaffolds for skin wound repair",
author="Kangning SHEN, Jingyi GU, Ximin YUAN, Nian LIU, Yinglin WANG, Jiabin CAI, Yang SHI, Kaiyang WANG, Xinghua YE, Minghao YANG, Zhiyong MA, Zhijian XIE",
journal="Journal of Zhejiang University Science A",
volume="27",
number="6",
pages="625-639",
year="2026",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.A2500653"
}
%0 Journal Article
%T 3D printing of wet-bonded multilayer scaffolds for skin wound repair
%A Kangning SHEN
%A Jingyi GU
%A Ximin YUAN
%A Nian LIU
%A Yinglin WANG
%A Jiabin CAI
%A Yang SHI
%A Kaiyang WANG
%A Xinghua YE
%A Minghao YANG
%A Zhiyong MA
%A Zhijian XIE
%J Journal of Zhejiang University SCIENCE A
%V 27
%N 6
%P 625-639
%@ 1673-565X
%D 2026
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.A2500653
TY - JOUR
T1 - 3D printing of wet-bonded multilayer scaffolds for skin wound repair
A1 - Kangning SHEN
A1 - Jingyi GU
A1 - Ximin YUAN
A1 - Nian LIU
A1 - Yinglin WANG
A1 - Jiabin CAI
A1 - Yang SHI
A1 - Kaiyang WANG
A1 - Xinghua YE
A1 - Minghao YANG
A1 - Zhiyong MA
A1 - Zhijian XIE
J0 - Journal of Zhejiang University Science A
VL - 27
IS - 6
SP - 625
EP - 639
%@ 1673-565X
Y1 - 2026
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.A2500653
Abstract: The skin repair process is significantly influenced by the regulation of a dynamic mechanical microenvironment. However, traditional single-layer scaffolds face limitations, including poor mechanical compatibility and weak interfacial adhesion. These drawbacks stem from their inability to mimic the multilayer heterogeneous structure and functional synergy of natural skin. In this paper, a biomimetic skin extracellular matrix (ECM) scaffold with a layered structure bio-polycaprolactone (PCL) skin (BPS) is proposed, consisting of three layers: a surface layer (SL), a support layer (PL), and a base layer (BL). The SL consists of a 3D-printed microporous PCL structure, which simulates the epidermal barrier’s antibacterial and breathable properties. The PL, a surface-modified multilayer PCL scaffold, mimics the dermal layer and provides essential mechanical support and elasticity. The BL, a hydrogel coated onto the surface of the PL, provides excellent biological properties. genipin serves as a crosslinker, and ethylenediamine is used for amination treatment of the PCL scaffold surface. This chemical crosslinking strengthens interlayer connections, enhancing functional synergy and tripling the anti-swelling properties of the hydrogel. Additionally, it improves the wet adhesion of the scaffold to skin tissue, ensuring stable adherence to the wound surface. Compared to traditional scaffolds, this multilayer structure effectively integrates biological functions with mechanical performance, providing sustained protection and support during wound healing.
[1]AgrawalA, RahbarN, CalvertPD, 2013. Strong fiber-reinforced hydrogel. Acta Biomaterialia, 9(2):5313-5318.
[2]AQSIQ (General Administration of Quality Supervision, Inspection and Quarantine of the People’s Republic of China), 2006. Plastics–Determination of Tensile Properties–Part 3: Test Conditions for Films and Sheets, GB/T 1040.3-2006. National Standards of the People’s Republic of China(in Chinese).
[3]ArifZU, KhalidMY, NorooziR, et al., 2022. Recent advances in 3D-printed polylactide and polycaprolactone-based biomaterials for tissue engineering applications. International Journal of Biological Macromolecules, 218:930-968.
[4]ASTM (American Society for Testing and Materials), 2016. Standard Test Method for in vitro Degradation Testing of Hydrolytically Degradable Polymer Resins and Fabricated Forms for Surgical Implants, ASTM F1635-16. ASTM International, West Conshohocken, USA.
[5]ASTM (American Society for Testing and Materials), 2024. Standard Test Method for Strength Properties of Tissue Adhesives in T-Peel by Tension Loading, ASTM F2256-24. ASTM International, West Conshohocken, USA.
[6]BarbuA, NeamtuB, ZăhanM, et al., 2021. Current trends in advanced alginate-based wound dressings for chronic wounds. Journal of Personalized Medicine, 11(9):890.
[7]Barros AlmeidaI, Garcez Barretto TeixeiraL, Oliveira de CarvalhoF, et al., 2021. Smart dressings for wound healing: a review. Advances in Skin & Wound Care, 34(2):1-8.
[8]BoatengJ, CatanzanoO, 2015. Advanced therapeutic dressings for effective wound healing—a review. Journal of Pharmaceutical Sciences, 104(11):3653-3680.
[9]BrohemCA, da Silva CardealLB, TiagoM, et al., 2011. Artificial skin in perspective: concepts and applications. Pigment Cell & Melanoma Research, 24(1):35-50.
[10]ChenY, MaYZ, FuJZ, et al., 2025. Design and fabrication of biomimetic four-region drug-loaded cartilage scaffolds with porous hollow fibers. Journal of Zhejiang University-SCIENCE A, 26(11):1070-1082.
[11]ChenYW, FuT, ZouZF, et al., 2025. Biological reinforced concrete for cartilage repair with 3D printing. Advanced Science, 12(16):2416734.
[12]DhandayuthapaniB, YoshidaY, MaekawaT, et al., 2011. Polymeric scaffolds in tissue engineering application: a review. International Journal of Polymer, 2011:290602.
[13]DoillonCJ, DunnMG, BenderE, et al., 1985. Collagen fiber formation in repair tissue: development of strength and toughness. Collagen and Related Research, 5(6):481-492.
[14]DrobnikJ, StebelA, 2017. Tangled history of the European uses of Sphagnum moss and sphagnol. Journal of Ethnopharmacology, 209:41-49.
[15]GronbeckC, FengH, 2023. Distribution of intermediate and complex skin repairs performed by dermatologists following updated 2020 coding guidelines. Journal of the American Academy of Dermatology, 88(4):954-956.
[16]GuarinoRD, ChaneyBN, Liebmann-VinsonA, et al., 2007. Peptides for Enhanced Cell Attachment and Growth. US Patent 7157275.
[17]GuoLZ, ZhangL, WangZM, et al., 2023. Direct construction of strong, tough, conductive, and adhesive hydrogel bioelectronics enabled by salt-dissolved cellulose. Materials Today Communications, 37:107002.
[18]HanL, LiuZX, LiM, et al., 2025. 3D bioprinting of a dermal scaffold for full-thickness skin tissue regeneration. Bio-Design and Manufacturing, 8:68-84.
[19]Hunter-FeatherstoneE, YoungN, ChamberlainK, et al., 2021. Culturing keratinocytes on biomimetic substrates facilitates improved epidermal assembly in vitro. Cells, 10(5):1177.
[20]HuoXS, WangJL, CongZH, et al., 2025. Strong and tough eutectogels with broad-range tunable mechanical properties via the hydrogen bond network-specific effect. Advanced Functional Materials, 35(27):2422464.
[21]LiXY, GongJP, 2024. Design principles for strong and tough hydrogels. Nature Reviews Materials, 9(6):380-398.
[22]LiuJ, WangSY, XuK, et al., 2020. Fabrication of double crosslinked chitosan/gelatin membranes with Na+ and pH dual-responsive controlled permeability. Carbohydrate Polymers, 236:115963.
[23]LiuN, ShiY, LiJY, et al., 2025. Morphology-guided cellular behavior modulation with 3D-printed engineered ECM. Cell Biomaterials, 1(6):100090.
[24]Maaz ArifM, KhanSM, GullN, et al., 2021. Polymer-based biomaterials for chronic wound management: promises and challenges. International Journal of Pharmaceutics, 598:120270.
[25]MengQ, ShenC, 2018. Construction of low contracted 3D skin equivalents by genipin cross-linking. Experimental Dermatology, 27(10):1098-1103.
[26]NianGD, KimJ, BaoXY, et al., 2022. Making highly elastic and tough hydrogels from doughs. Advanced Materials, 34(50):2206577.
[27]ObagiZ, DamianiG, GradaA, et al., 2019. Principles of wound dressings: a review. Surgical Technology International, 35:50-57.
[28]O’BrienFJ, 2011. Biomaterials & scaffolds for tissue engineering. Materials Today, 14(3):88-95.
[29]OomensCWJ, van VijvenM, PetersGWM, 2017. Skin mechanics. In: Payan Y, Ohayon J (Eds.), Biomechanics of Living Organs. Academic Press, London, UK, p.347-357.
[30]PanP, HuC, LiangAH, et al., 2023. Preparation and properties of antibacterial silk fibroin scaffolds. Polymers, 15(23):4581.
[31]ParkJ, KimTY, KimY, et al., 2023. A mechanically resilient and tissue-conformable hydrogel with hemostatic and antibacterial capabilities for wound care. Advanced Science, 10(30):2303651.
[32]PatelAK, MichaudP, PetitE, et al., 2013. Development of a chitosan-based adhesive. Application to wood bonding. Journal of Applied Polymer Science, 127(6):5014-5021.
[33]PengW, LiD, DaiKL, et al., 2022. Recent progress of collagen, chitosan, alginate and other hydrogels in skin repair and wound dressing applications. International Journal of Biological Macromolecules, 208:400-408.
[34]RobinsonTM, HutmacherDW, DaltonPD, 2019. The next frontier in melt electrospinning: taming the jet. Advanced Functional Materials, 29(44):1904664.
[35]SingerAJ, ClarkRAF, 1999. Cutaneous wound healing. New England Journal of Medicine, 341(10):738-746.
[36]TangP, SongP, PengZY, et al., 2021. Chondrocyte-laden GelMA hydrogel combined with 3D printed PLA scaffolds for auricle regeneration. Materials Science and Engineering: C, 130:112423.
[37]TrichetL, Le DigabelJ, HawkinsRJ, et al., 2012. Evidence of a large-scale mechanosensing mechanism for cellular adaptation to substrate stiffness. Proceedings of the National Academy of Sciences, 109(18):6933-6938.
[38]van den BoschE, GielensC, 2003. Gelatin degradation at elevated temperature. International Journal of Biological Macromolecules, 32(3-5):129-138.
[39]WuSJ, WuJJ, KaserSJ, et al., 2024. A 3D printable tissue adhesive. Nature Communications, 15(1):1215.
[40]YangYT, LiM, PanGY, et al., 2023. Multiple stimuli-responsive nanozyme-based cryogels with controlled NO release as self-adaptive wound dressing for infected wound healing. Advanced Functional Materials, 33(31):2214089.
[41]YaoK, LvS, ZhangXJ, et al., 2025. 3D printing of multiscale biomimetic scaffold for tendon regeneration. Advanced Functional Materials, 35(4):2413970.
[42]YazdiSJM, BaqersadJ, 2022. Mechanical modeling and characterization of human skin: a review. Journal of Biomechanics, 130:110864.
[43]YuYB, XuS, LiSM, et al., 2021. Genipin-cross-linked hydrogels based on biomaterials for drug delivery: a review. Biomaterials Science, 9(5):1583-1597.
[44]ZhangL, WangSH, WangZM, et al., 2023. A sweat-pH-enabled strongly adhesive hydrogel for self-powered e-skin applications. Materials Horizons, 10(6):2271-2280.
[45]ZhaoWX, HuCX, WangYN, et al., 2025. Optimization-based conformal path planning for in situ bioprinting during complex skin defect repair. Bio-Design and Manufacturing, 8:1-19.
[46]ZhouY, ZhuoRX, LiuZL, 2005. Synthesis and characterization of novel aliphatic poly(carbonate-ester)s with functional pendent groups. Macromolecular Rapid Communications, 26(16):1309-1314.
[47]ZussmanE, ChagantiSR, VenugopalJR, et al., 2018. Fiber-Reinforced Hydrogel Composites and Methods of Forming Fiber-Reinforced Hydrogel Composites. US Patent 9950093.
CLC number:
On-line Access: 2026-06-24
Received: 2025-12-15
Revision Accepted: 2026-01-13
Crosschecked: 2026-06-24
Cited: 0
Clicked: 919
Citations: Bibtex RefMan EndNote GB/T7714
Open peer comments: Debate/Discuss/Question/Opinion
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