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

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.

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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