Page 336 - v11i4

International

Journal of Bioprinting

RESEARCH ARTICLE
Three-dimensional bioprinting of gelatin

methacryloyl hydrogel with a tri-layered
vascularized architecture for full-thickness

skin regeneration

Yichen Luo 1 id , Dan Li 2 id , Cai Lin 3 id , Xue Zhou 1 id , Jien Ma * , and Bin Zhang *
4 id
1 id
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
(This article belongs to the Special Issue: Advances in 3D Bioprinting)

Abstract

The skin is the largest organ of the human body and is the primary barrier against
*Corresponding authors: external stressors. However, in cases of severe skin damage or pathological
Bin Zhang
(zbzju@zju.edu.cn) conditions, the body’s natural physiological repair mechanisms are often insufficient
Jien Ma to support effective skin tissue repair and regeneration. Bioprinting, a form of three-
(majien@zju.edu.cn) dimensional (3D) printing technology, utilizes various biomaterials and cells to
construct complex 3D structures, offering the potential to overcome the limitations
Citation: Luo Y, Li D, Lin C, Zhou X,
Ma J, Zhang B. Three-dimensional of conventional tissue-engineered skin and to develop functional skin substitutes.
bioprinting of gelatin methacryloyl In this study, we developed a 3D bioprinter with excellent printing performance to
hydrogel with a tri-layered fabricate vascularized skin substitutes. Through methacrylic anhydride-mediated
vascularized architecture for full-
thickness skin regeneration. modification of gelatin, we synthesized gelatin methacryloyl (GelMA) with varying
Int J Bioprint. 2025;11(4):328-349. degrees of substitution. The resulting GelMA hydrogel exhibited excellent mechanical
doi: 10.36922/IJB025090069 properties, swelling ratio, porosity, and rheological properties. To create a hydrogel-
Received: February 26, 2025 multicellular composite bio-ink, we adjusted the concentration of the GelMA solution
1st revised: March 24, 2025 and co-cultured human immortalized epidermal cells, human foreskin fibroblasts, and
2nd revised: April 14, 2025
Accepted: April 15, 2025 human umbilical vein endothelial cells to optimize biological function. Importantly,
Published online: April 16, 2025 by fine-tuning the printing parameters, the 3D extrusion-printed lines successfully
fused into a continuous membrane, enhancing interlayer bonding and mechanical
Copyright: © 2025 Author(s).
This is an Open Access article integrity. This process enabled the construction of a vascularized skin substitute
distributed under the terms of the with distinct reticular and papillary layers. In addition, the 3D-printed vascularized
Creative Commons Attribution skin was implanted into skin defect models established in BALB/c nude mice and
License, permitting distribution,
and reproduction in any medium, New Zealand rabbits to investigate its regenerative capabilities. These findings
provided the original work is hold significant implications for the utilization of 3D-printed vascularized skin for
properly cited. improving skin injury repair, thereby advancing the field of skin tissue engineering.
Publisher’s Note: AccScience
Publishing remains neutral with
regard to jurisdictional claims in Keywords: Three-dimensional bioprinting; Gelatin methacryloyl; Skin injury;
published maps and institutional Vascularized skin
affiliations.

Volume 11 Issue 4 (2025) 328 doi: 10.36922/IJB025090069