Bioactive Zein–Nondigestible Oligosaccharide Nanofibers Enable Rapid Tissue Regeneration and Antibacterial Defense

Chronic wounds pose a significant clinical challenge due to persistent inflammation, microbial infection, and impaired tissue regeneration. Conventional wound dressings often lack the multifunctionality needed for comprehensive wound management. In this study, we engineered a nanofibrous wound patch composed of zein (ZM) integrated with nondigestible oligosaccharides (ZM-NDOs), such as Chito-oligosaccharides (ZMC), guluronic and mannuronic-rich alginate-oligosaccharides (ZMAGM), and guluronic-rich alginate-oligosaccharides (ZMAG), to address these limitations. Structural and physicochemical analyses (SEM, FTIR, UTM, and water contact angle) confirmed the formation of bead-free, interconnected fibers with enhanced mechanical strength and hydrophilicity. In vitro cytocompatibility assays using HEK 293T cells demonstrated excellent biocompatibility for both ZM and ZM-NDO patches. Notably, ZMC significantly promoted cellular proliferation and migration in wound scratch assays, accelerating wound closure. In vivo evaluation using a Wistar rat excision wound model further substantiated the therapeutic efficacy of the ZM-NDO patches, showing improved collagen deposition, vascularization, and epithelial regeneration, accompanied by upregulated expression of VEGF, TGF-β, and Col-I mRNA. Moreover, the ZMC scaffolds exhibited significant antibacterial activity against Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus. Collectively, these findings highlight ZM-NDO, particularly ZMC, as a promising, multifunctional, and scalable platform for advanced wound-healing applications.