Glycine-Functionalized Polycaprolactone Electrospun Nanofibers as Bioactive Scaffolds for Skin Repair

Chronic cutaneous ulcers pose a major clinical challenge due to persistent inflammation, impaired angiogenesis, and limited regenerative capacity, underscoring the need to develop bioactive scaffolds that mimic the extracellular matrix (ECM) and promote skin repair. In this study, electrospun Poly(ε-caprolactone) (PCL) scaffolds functionalized with 10% (PCLGLI10) and 20% (PCLGLI20) glycine were fabricated, physicochemically and mechanically characterized, and evaluated in combination with human Wharton's jelly mesenchymal stromal cells (hWJ-MSCs). Glycine incorporation reduced fiber diameter to the nanoscale range (140-155 nm) and increased scaffold porosity (~71-72%) while preserving mechanical properties compatible with skin. FTIR and X-ray diffraction analyses confirmed glycine incorporation and a polymorphic transition from α- to γ-glycine during electrospinning. Cell viability remained above 95% in all scaffolds; however, PCLGLI10 significantly enhanced cell proliferation, metabolic activity, and the secretion of VEGF and HGF, mediators associated with angiogenesis and tissue repair. Furthermore, in a guinea pig full-thickness wound model, the PCLGLI10+hWJ-MSCs construct promoted a modulated inflammatory response and more organized collagen deposition. These findings support the potential of glycine-functionalized electrospun scaffolds as a promising strategy for chronic cutaneous ulcer regeneration.