AccScience Publishing / IJB / Online First / DOI: 10.36922/IJB025090069
RESEARCH ARTICLE

Three-dimensional bioprinting of gelatin methacryloyl hydrogel with a tri-layered vascularized architecture for full-thickness skin regeneration

Yichen Luo1 Dan Li2 Cai Lin3 Xue Zhou1 Jien Ma4* Bin Zhang1*
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1 State Key Laboratory of Fluid Power & Mechatronic Systems, School of Mechanical Engineering, Zhejiang University, Hangzhou, Zhejiang, China
2 Department of Electro-Hydraulic Technology and Equipment Research Center, Binhai Industrial Technology Research Institute of Zhejiang University, Tianjin, China
3 Department of Burn, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
4 Department of Electrical Engineering, College of Electrical Engineering, Zhejiang University, Hangzhou, Zhejiang, China
Received: 26 February 2025 | Accepted: 15 April 2025 | Published online: 16 April 2025
(This article belongs to the Special Issue Advances in 3D Bioprinting)
© 2025 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/ )
Abstract

The skin is the largest organ of the human body and is the primary barrier against external stressors. However, in cases of severe skin damage or pathological conditions, the body’s natural physiological repair mechanisms are often insufficient to support effective skin tissue repair and regeneration. Bioprinting, a form of three-dimensional (3D) printing technology, utilizes various biomaterials and cells to construct complex 3D structures, offering the potential to overcome the limitations of conventional tissue-engineered skin and to develop functional skin substitutes. In this study, we developed a 3D bioprinter with excellent printing performance to fabricate vascularized skin substitutes. Through methacrylic anhydride-mediated modification of gelatin, we synthesized gelatin methacryloyl (GelMA) with varying degrees of substitution. The resulting GelMA hydrogel exhibited excellent mechanical properties, swelling ratio, porosity, and rheological properties. To create a hydrogel-multicellular composite bio-ink, we adjusted the concentration of the GelMA solution and co-cultured human immortalized epidermal cells, human foreskin fibroblasts, and human umbilical vein endothelial cells to optimize biological function. Importantly, by fine-tuning the printing parameters, the 3D extrusion-printed lines successfully fused into a continuous membrane, enhancing interlayer bonding and mechanical integrity. This process enabled the construction of a vascularized skin substitute with distinct reticular and papillary layers. In addition, the 3D-printed vascularized skin was implanted into skin defect models established in BALB/c nude mice and New Zealand rabbits to investigate its regenerative capabilities. These findings hold significant implications for the utilization of 3D-printed vascularized skin for improving skin injury repair, thereby advancing the field of skin tissue engineering.  

Graphical abstract
Keywords
Three-dimensional bioprinting
Gelatin methacryloyl
Skin injury
Vascularized skin
Funding
This work was supported by the National Key Research and Development Program of China (Grant No. 2018YFA0703000) and the Key Science and Technology Program of Zhejiang Province (Grant No. 2023C03170 and 2023C03071).
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