Polydopamine/gelatin layer-by-layer self-assembled polycaprolactone nanofibers loaded with 4-methoxycinnamic acid for wound healing

Wound healing is a dynamic and tightly regulated biological phenomenon involving coordinated cellular and molecular events essential for tissue repair and regeneration. Conventional wound dressings possess limited bioactivity, antibacterial properties, and structural characteristics that facilitate efficient healing, thereby necessitating advanced wound care strategies. Hence, the main objective of this study is to develop a novel nanofiber-based wound dressing by incorporating 4-methoxycinnamic acid (MCA), a natural bioactive compound, into polycaprolactone nanofibers. To further enhance the biocompatibility, interfacial adhesion, and surface bioactivity, the MCA-loaded nanofibers were surface functionalized using a layer-by-layer (LBL) self-assembly of polydopamine and gelatin, forming a bioactive surface coating enriched with MCA. Comprehensive physicochemical and morphological analyses confirmed that MCA incorporation preserved the structural integrity without any significant alterations in the surface wettability, protein adsorption, or degradation profiles. Furthermore, in vitro biocompatibility was assessed using fibroblast cells, which exhibited favorable cell attachment, proliferation, and migration. Additionally, the dual-loaded LBL nanofibers effectively increased antioxidant activity and enhanced the expression of wound healing-related angiogenic, fibrotic, and anti-inflammatory genes. The fabricated nanofibers also exhibited potent antibacterial activity, with enhanced efficacy. Overall, the incorporation of MCA in both the nanofibrous matrix and adhesive-inspired surface coating shows enhanced angiogenic and regenerative potential and antioxidant, anti-inflammatory, and antimicrobial activities, suggesting its potential application as a multifunctional wound dressing for infection-prone and hard-to-heal wounds.