AccScience Publishing / IJB / Online First / DOI: 10.36922/IJB026150134
ORIGINAL RESEARCH ARTICLE
Early Access

3D-bioprinted skin-mimicking bilayer hydrogel dressing with compartmentalized antibacterial and pro-healing functions for diabetic wounds

Wei Cao1 Danxi Li2 Qilong Yang3,4 Haiyang Qiu1 Qinghua Guo5 Shanshan Fu1* Jing Wang1* Wei Lei1*
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1 Department of Orthopedics, Xijing Hospital, The Fourth Military Medical University, Shaanxi, China
2 Department of Thyroid, Breast and Vascular Surgery, Xijing Hospital, The Fourth Military Medical University, Shaanxi, China
3 School of Public Health, Shaanxi University of Chinese Medicine, Shaanxi, China
4 School of Life Science and Technology, Northwestern Polytechnical University, Shaanxi, China
5 Department of Orthopaedics, The Fourth Medical Centre, Chinese PLA General Hospital, Beijing, China
Received: 9 April 2026 | Revised: 15 May 2026 | Accepted: 18 May 2026 | Published online: 19 May 2026
(This article belongs to the Special Issue 3D Printing in Clinical Application)
© 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/ )
Abstract

Diabetic wound healing remains a significant clinical challenge due to persistent infection and impaired tissue regeneration. This study presents a biomimetic, 3D-bioprinted bilayer hydrogel dressing with spatially compartmentalized functions to address these divergent requirements. The upper layer comprises chitosan hydrogel embedded with silver nanoparticles to provide rapid, broad-spectrum antibacterial activity against surface pathogens, and the lower layer consists of methacrylated silk fibroin (SilMA) hydrogel co-encapsulating epidermal stem cell-derived exosomes and metformin to create a pro-regenerative microenvironment in deeper wound strata. Comprehensive in vitro characterization confirmed distinct physicochemical properties between the antibacterial upper layer and the porous, pro-healing lower layer. The upper layer exhibited synergistic bactericidal effects against S. aureus and E. coli, while the lower layer promoted M2 macrophage polarization, endothelial cell migration, and angiogenesis-related gene expression. In a diabetic mouse model of infected full-thickness wounds, compared to monolayer controls, the bilayer dressing significantly accelerated wound closure by increasing granulation tissue formation and neovascularization, while reducing bacterial burden. This compartmentalized design effectively integrates the complementary demands of infection control and tissue regeneration, offering a promising strategy for managing chronic diabetic ulcers.

Keywords
3D bioprinting
Diabetic wound
Hydrogel
Silver nanoparticles
Exosomes
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing