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

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.