Multifunctional Janus Membrane Promotes Neurovascular Network Regeneration for Diabetic Wound Healing.
The complex microenvironment of diabetic wounds poses a formidable challenge to tissue repair, particularly due to the absence of a functional neurovascular network. In this study, we developed a multifunctional Janus-structured scaffold (PLGA-PCL+CS+Cu-TA NS+P2, PCTP) by integrating chitosan (CS) electrospun fibers with PLGA-PCL coaxial electrospun fibers loaded with tannic acid (TA)-copper nanosheets (NSs). The NSs were loaded with PTHrP-2 to enhance bioactivity. The unique "core-shell" design protects the drug and ensures efficient release. The Janus architecture rationally manages wound exudate while maintaining a moist microenvironment conducive to healing. Moreover, PCTP exhibits excellent mechanical properties and sustained release kinetics. Its potent antioxidant and antibacterial activities effectively scavenge reactive oxygen species, protect mitochondrial integrity, and delay cellular senescence. Crucially, PCTP accelerates the regeneration of dermal fibers and epidermis structures while promoting concurrent neurogenesis and angiogenesis, thereby restoring both structural integrity and functional competence. In diabetic rat models, PCTP significantly enhanced vascularization, collagen deposition, and inflammation modulation. Collectively, this multifunctional scaffold represents a promising therapeutic strategy for achieving integrated structural and functional skin regeneration in the challenging diabetic milieu.