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International Journal of Bioprinting
RESEARCH ARTICLE
Application of 3D-printed tissue-engineered
skin substitute using innovative biomaterial
loaded with human adipose-derived stem cells
in wound healing
1
1,2
Huijuan Fu , Dequan Zhang , Jinshi Zeng , Qiang Fu , Zhaoyang Chen ,
1
4
3
Xuer Sun , Yi Yang , Shiyi Li , Minliang Chen *
1
1,2
1,2
1,2
1 Department of Burn and Plastic Surgery, the Fourth Medical Centre, Chinese People’s Liberation
Army General Hospital, Beijing, China
2 Chinese People’s Liberation Army General Hospital, Beijing, China
3 Central Medical Branch of PLA General Hospital, Beijing, China
4 Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking
Union Medical College, Beijing, China
Abstract
Large-scale skin injuries are usually accompanied by impaired wound healing,
resulting in scar formation, or significant morbidity and mortality. The aim of this
study is to explore the in vivo application of 3D-printed tissue-engineered skin
substitute using innovative biomaterial loaded with human adipose-derived stem
*Corresponding author: cells (hADSCs) in wound healing. Adipose tissue was decellularized, and extracellular
Minliang Chen matrix components were lyophilized and solubilized to obtain adipose tissue
(chenml@sohu.com)
decellularized extracellular matrix (dECM) pre-gel. The newly designed biomaterial
Citation: Fu H, Zhang D, Zeng J, is composed of adipose tissue dECM pre-gel, methacrylated gelatin (GelMA), and
2023, Application of 3D-printed methacrylated hyaluronic acid (HAMA). Rheological measurement was performed to
tissue-engineered skin substitute
using innovative biomaterial loaded evaluate the phase-transition temperature and the storage and loss modulus at this
with human adipose-derived temperature. Tissue-engineered skin substitute loaded with hADSCs was fabricated by
stem cells in wound healing. Int J 3D printing. We used nude mice to establish full-thickness skin wound healing model
Bioprint, 9(2): 674.
https://doi.org/10.18063/ijb.v9i2.674 and divided them into four groups randomly: (A) Full-thickness skin graft treatment
group, (B) 3D-bioprinted skin substitute treatment group as the experimental
Received: October 18, 2022
group, (C) microskin graft treatment group, and (D) control group. The amount of
Accepted: November 13, 2022 DNA in each milligram of dECM was 24.5 ± 7.1 ng, fulfilling the currently accepted
Published Online: January 31, 2023 decellularization criteria. The solubilized adipose tissue dECM was thermo-sensitive
biomaterial and underwent a sol-gel phase transition when temperature rises. The
Copyright: © 2023 Author(s).
This is an Open Access article dECM-GelMA-HAMA precursor undergoes a gel-sol phase transition at 17.5°C, where
distributed under the terms of the the storage and loss modulus of the precursor is about 8 Pa. The scanning electron
Creative Commons Attribution microscope showed that the interior of crosslinked dECM-GelMA-HAMA hydrogel
License, permitting distribution,
and reproduction in any medium, is 3D porous network structure with suitable porosity and pore size. The shape of
provided the original work is the skin substitute is stable with regular grid-like scaffold structure. Wound healing
properly cited. in the experimented animals was accelerated after being treated with 3D-printed
Publisher’s Note: Whioce skin substitute, which attenuate inflammatory response, increase blood perfusion
Publishing remains neutral with around the wound, as well as promote re-epithelialization, collagen deposition and
regard to jurisdictional claims in
published maps and institutional alignment, and angiogenesis. In summary, 3D-printed dECM-GelMA-HAMA tissue-
affiliations. engineered skin substitute loaded with hADSCs, which can be fabricated by 3D
Volume 9 Issue 2 (2023) 394 https://doi.org/10.18063/ijb.v9i2.674

