AccScience Publishing / IJB / Volume 12 / Issue 1 / DOI: 10.36922/IJB025490504
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RESEARCH ARTICLE

Construction of gelatin methacryloyl-based artificial skin substitutes with “small-micro” vascular networks via hybrid double-crosslinked coaxial and extrusion bioprinting

Yichen Luo1,2 ,  Dan Li3 ,  Cai Lin4 ,  Bin Zhang1,2* ,  Hao Ding5,6* ,  Xue Zhou1,2*
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1 State Key Laboratory of Fluid Power and Mechatronic Systems, Zhejiang University, Hangzhou, Zhejiang 310058, China
2 School of Mechanical Engineering, Zhejiang University, Hangzhou, Zhejiang 310058, China
3 Department of Electro-Hydraulic Technology and Equipment Research Center, Binhai Industrial Technology Research Institute, Zhejiang University, Tianjin 300457, China
4 Department of Burn, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China
5 Department of Cardiology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, China
6 Cardiovascular Key Laboratory of Zhejiang Province, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, China
IJB 2026, 12(1), 672–688; https://doi.org/10.36922/IJB025490504
Received: 2 December 2025 | Accepted: 12 January 2026 | Published online: 16 January 2026
© 2026 by the Author(s).. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

The repair of deep skin defects involving subcutaneous tissue urgently requires vascularized skin substitutes that can provide immediate blood perfusion. However, existing engineering strategies struggle to construct multi-level vascular networks in vitro. This study aims to develop a multi-layered skin substitute with both biomimetic structure and physiological function, incorporating a perfusable “small-micro” hierarchical vascular system. We employed a composite coaxial–extrusion bioprinting strategy. First, a composite bioink consisting of 2% sodium alginate and 5% gelatin methacryloyl was formulated and evaluated for its printability and biocompatibility. Subsequently, using an ionic-photo dual-crosslinking coaxial printing technique, we fabricated subcutaneous small vessels with controllable dimensions and adequate mechanical properties. Finally, small vessels were integrated with an extrusion bioprinted dermal microvascular network and an epidermal layer to form a complete “small-micro” vascular pathway. This multi-layered construct was designed to mimic the stratified characteristics of natural skin. In vitro functional experiments confirmed that the epidermis possesses an excellent barrier function, and the subcutaneous small vessels demonstrated an effective capability for delivering drug molecules. The dual-crosslinking coaxial printing and composite manufacturing strategy proposed in this proof-of-concept study successfully constructed vascularized skin with a hierarchical tubular structure, offering a new solution with clinical translation potential for treating full-thickness skin defects.

Graphical abstract
Keywords
Artificial skin
Blood vessel
Coaxial printing
Gelatin methacryloyl
Three-dimensional bioprinting
Funding
This work was supported by the National Natural Science Foundation (Grant No. 82300566), the Key Science and Technology Program of Zhejiang Province (Grant No. 2023C03170 and 2023C03071), and the China Postdoctoral Science Foundation (Grant No. 2023M733095 and 2025T180562)
Conflict of interest
The authors declare no conflict of interest.
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing
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