VR23 and Bisdemethoxycurcumin Enhanced Nanofiber Niche with Durable Bidirectional Functions for Promoting Wound Repair and Inhibiting Scar Formation

Abstract Chronic wounds pose a significant clinical challenge worldwide, which is characterized by impaired tissue regeneration and excessive scar formation due to over‐repair. Most studies have focused on developing wound repair materials that either facilitate the healing process or control hyperplastic scars caused by over‐repair, respectively. However, there are limited reports on wound materials that can both promote wound healing and prevent scar hyperplasia at the same time. In this study, VR23‐loaded dendritic mesoporous bioglass nanoparticles (dMBG) are synthesized and electrospun in poly(ester‐curcumin‐urethane)urea (PECUU) random composite nanofibers (PCVM) through the synergistic effects of physical adsorption, hydrogen bond, and electrospinning. The physicochemical characterization reveals that PCVM presented matched mechanical properties, suitable porosity, and wettability, and enabled sustained and temporal release of VR23 and BDC with the degradation of PCVM. In vitro experiments demonstrated that PCVM can modulate the functions and polarization of macrophages under an inflammatory environment, and possess effective anti‐scarring potential and reliable cytocompatibility. Animal studies further confirmed that PCVM can efficiently promote re‐epithelialization and angiogenesis and reduce excessive inflammation, thereby remarkably accelerating wound healing while preventing potential scarring. These findings suggest that the prepared PCVM holds promise as a bidirectional regulatory dressing for effectively promoting scar‐free healing of chronic wounds.