Polydopamine-mediated curcumin-functionalized electroactive nanofibrous scaffold accelerates infected wound healing via multifactorial microenvironment remodeling

Abstract

Effective remodeling of the wound microenvironment is critical for achieving rapid and high-quality skin regeneration. However, current therapeutic strategies still struggle to simultaneously address the multiple pathological features present in complex wounds, including persistent inflammation, oxidative stress, bacterial infection, and impaired angiogenesis. In this study, we constructed a multifunctional electroactive nanofibrous scaffold, PCL/CNT-PDA@Cur, by functionalizing the surface of a polycaprolactone/carbon nanotube electrospun matrix with polydopamine (PDA)-mediated curcumin (Cur) loading. This surface functionalization is attributed to the π–π stacking and hydrogen bonding interactions between the catechol groups of PDA and the curcumin molecules. The resulting scaffold mimics the structure of the native extracellular matrix (ECM), exhibits enhanced hydrophilicity, stable electrical conductivity, and sustained curcumin release properties. In vitro experiments demonstrated that the PCL/CNT-PDA@Cur scaffold significantly promoted the proliferation and migration of L929 fibroblasts, upregulated the expression of collagen types I and III, and protected cells against oxidative stress-induced apoptosis. The scaffold also enhanced the tube-forming capacity of HUVECs and the expression of angiogenesis-related genes, while effectively scavenging intracellular reactive oxygen species. Moreover, the scaffold was able to drive macrophage polarization toward the anti-inflammatory M2 phenotype. In addition, it exhibited pronounced antibacterial activity against Staphylococcus aureus and Escherichia coli by disrupting bacterial membrane integrity. In the rat full-thickness skin defect infection model, the PCL/CNT-PDA@Cur scaffold effectively controlled wound infection, significantly accelerated wound closure, promoted granulation tissue formation, collagen deposition, and neovascularization, and facilitated the regeneration of skin appendages such as hair follicles. In summary, the PDA-mediated curcumin-loaded electroactive scaffold constructed in this study integrates multiple functions—including antioxidant, antibacterial, immunomodulatory, and pro-angiogenic activities—into a single platform, and preliminarily reveals a potential mechanism involving interference with the bacterial SOS response network through downregulation of RecA and LexA along with upregulation of SulA gene expression, thereby providing a new strategy and experimental basis for the treatment of complex infected wounds.