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

3D bioprinting of mechanically graded GelMA hydrogels with tri-layered vascularized architecture for full-thickness skin regeneration

Yichen Luo1,2 Dan Li3 Cai Lin4 Xue Zhou1,2 Jien Ma5* Bin Zhang1,2*
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1 State Key Laboratory of Fluid Power & Mechatronic Systems, Zhejiang University, Hangzhou 310058, China
2 Department of Mechanical Engineering, Zhejiang University, Hangzhou 310058, China
3 Binhai Industrial Technology Research Institute of Zhejiang University, Tianjin 300450, China
4 Department of Burn, The First Affiliated Hospital of Wenzhou Medical University, Nan Bai Xiang, Wenzhou 325000, China
5 College of Electrical Engineering, Zhejiang University, Hangzhou 310058, China
Submitted: 26 February 2025 | Accepted: 15 April 2025 | Published: 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

Skin is the largest organ of the human body and serves as the primary barrier against external environmental insults. However, in cases of severe skin damage or pathologic conditions, the body's natural physiological repair mechanisms are often insufficient to meet the requirements for skin tissue repair and regeneration. Bioprinting, a form of 3D printing technology, utilizes a variety of materials and cells to construct complex three-dimensional structures, offering the potential to overcome the limitations of tissue-engineered skin and create functional skin substitutes. In this study, we developed a 3D bioprinter with excellent printing performance to fabricate vascularized skin substitute. Through methacrylic anhydride-mediated modification of gelatin, we synthesized GelMA with varying degrees of substitution, and the results demonstrated that GelMA exhibits excellent mechanical properties, swelling ratio, porosity and rheological properties. The hydrogel-multicellular composite ink was fabricated by adjusting the concentration of the GelMA solution with co-culturing HaCaT cells, HFF cells and HUVECs to achieve optimal biological function. Importantly, through adjustments to the printing process parameters, the 3D extrusion-printed lines fused into a membrane and the interlayer bonding of bioink with mechanical differences was enhanced, thereby constructing a vascularized skin substitute containing reticular and papillary layers. In addition, the 3D-printed vascularized skin was implanted into the skin defect models of BALB/c-nu and New Zealand rabbits to further investigate the repair effect of vascularized skin on the defective tissues. The findings of this study hold significant implications for utilizing 3D-printed vascularized skin to enhance skin injury repair and will provide an effective pathway for the advancement of skin tissue engineering technologies.

Keywords
3D Bioprinting
GelMA
Vascularized skin
Skin injury
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