Abstract: Scarring poses a significant challenge in wound healing, especially for chronic wounds like those linked to diabetes. This study developed a dual drug-loaded core-shell fiber scaffold (PSPC) containing curcumin (Cur) in the shell and salvianolic acid B (SAB) in the core via electrospinning to address this challenging issue through synergistic anti-inflammatory and anti-fibrosis efficacy. The PSPC scaffold presented favorable tensile properties (3.78 ± 0.29 MPa of tensile strength and 337.64 % ± 32.07 % of elongation at break) and suture retention (2.71 ± 0.17 N). In vitro experiments confirmed that this scaffold was biocompatible, supporting cell adhesion and proliferation. Additionally, it also scavenged excessive intracellular reactive oxygen species (ROS) and promoted macrophage polarization towards the regenerative M2 phenotype. In vivo studies using a mouse diabetic wound model showed that the PSPC scaffold effectively mitigated inflammatory responses, promoted neoangiogenesis, and facilitated epidermal formation and re-epithelialization. More importantly, the scaffold also modulated collagen synthesis, decreased the collagen type I/III ratio, supported the functional regeneration of hair follicles, sebaceous glands, and other skin appendages, then ultimately achieved the goal of chronic diabetic wound healing and scar reduction. The developed dual drug-loaded fiber scaffold integrating anti-inflammatory and anti-fibrosis presents a promising strategy for the anti-scarring treatment of chronic wounds.

Key words: Electrospinning, Anti-inflammatory, Anti-scarring, Diabetic wound healing