A Biomimetic NAC-Loaded PCL/Modified Chitosan/dECM Fibrous Scaffold for Accelerating Diabetic Wound Healing and...

The development of innovative wound dressings capable of accelerating diabetic wound healing while simultaneously reducing scar formation is a significant clinical challenge. In this study, we designed and fabricated a multifunctional nanofibrous scaffold PCL/Az-CS/dECM/NAC by incorporating decellularized extracellular matrix (dECM) and N-acetylcysteine (NAC) into a composite backbone of polycaprolactone (PCL) and azidobenzoic acid-modified chitosan (AZCS). The scaffold exhibited ideal hydrophilicity and swelling capacity, and demonstrated excellent biocompatibility. In vitro studies demonstrated that the scaffold effectively scavenged reactive oxygen species (ROS) and promoted the polarization of macrophages from the M1 phenotype to the M2 phenotype; in vivo studies confirmed that the PCL/AZ-CS/dECM/NAC scaffold significantly accelerated wound closure, promoted mature angiogenesis, and facilitated orderly collagen deposition. The PCL/AZ-CS/dECM/NAC scaffold mitigated scar formation by increasing the proportion of regenerative type III collagen, optimizing the collagen I/III ratio. Our findings suggest that the PCL/AZ-CS/dECM/NAC scaffold is a highly promising candidate for a multifunctional dressing designed to treat recalcitrant diabetic wounds and prevent excessive scarring.