AccScience Publishing / IJB / Volume 12 / Issue 2 / DOI: 10.36922/IJB026120099
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RESEARCH ARTICLE

3D-bioprinted asymmetric bilayer scaffolds with anti-infection and pro-regeneration characteristics for chronic diabetic wound healing

Chenyu Zhang1,2,3† ,  Yuan Fang4† ,  Lei Pan5† ,  Hongyu Chen2,3 ,  Yu Han6 ,  Qiang Wu2,3 ,  Ye Sun7 ,  Quan Hu8* ,  Zuyan Lu2,3* ,  Yongqiang Hao2,3* ,  Yuanyuan Liu1*
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1 School of Medicine, Shanghai University, Shanghai, China
2 Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
3 Clinical and Translational Research Center for 3D Printing Technology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
4 Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
5 Nursing Department, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
6 Department of Orthopaedics, Medical 3D Printing Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
7 Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
8 Department of Burns and Plastic Surgery, The Fourth Medical Center of Chinese PLA General Hospital, Beijing, China
†These authors contributed equally to this work.
IJB 2026, 12(2), 026120099 https://doi.org/10.36922/IJB026120099
Received: 17 March 2026 | Revised: 6 April 2026 | Accepted: 8 April 2026 | Published online: 22 April 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/ )
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Abstract

Chronic diabetic wounds, characterized by persistent infection and impaired tissue regeneration, remain a formidable clinical challenge. In the present study, a 3D-bioprinted asymmetric bilayer scaffold was developed by integrating electrospinning and 3D bioprinting technologies to achieve anti-infective and pro-regenerative functions. The scaffold features a distinctive asymmetric architecture comprising a superficial layer (Layer S) and a basal layer (Layer B). Layer B, consisting of electrospun copper(I) oxide (Cu2O)–poly-ε-caprolactone nanofibers, serves as an effective antibacterial barrier specifically targeting methicillin-resistant Staphylococcus aureus (MRSA), while Layer S employs a 3D-bioprinted decellularized extracellular matrix hydrogel loaded with human bone marrow mesenchymal stem cell-derived extracellular vesicles (hBMSC-EVs) to facilitate tissue repair. Experimental results demonstrated that hBMSC-EVs significantly augmented fibroblast proliferation and migration, and the Cu2O-doped layer exhibited potent bactericidal activity against MRSA. In db/db diabetic mice, this asymmetric composite scaffold significantly accelerated wound closure compared to standalone treatments. Histological analysis further confirmed enhanced neovascularization and accelerated extracellular matrix reconstruction. Overall, this synergistic 3D-bioprinted bilayer system provides a high-performance strategy for the targeted management of MRSA-infected chronic diabetic wounds.

Graphical abstract
Keywords
Diabetic wound healing
3D bioprinting
Extracellular vesicles
Decellularized extracellular matrix
Electrospinning
Antibacterial scaffold
Funding
This work was supported by the grants from the National Key R&D Program of China (No. 2023YFC2411303) and the National Natural Science Foundation of China (Grant No. 82402819, 82402940).
Conflict of interest
Yongqiang Hao serves as the guest editor of the special issue, but did not in any way involve in the editorial and peer-review process conducted for this paper, directly or indirectly. Other authors declare they have no competing interests.
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing
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