In Vitro Wound Healing Evaluation of Zinc Particle-Embedded Nanofibrous Scaffolds through Protein Expression Profiling

Understanding how the components of bioactive scaffolds regulate coordinated inflammatory and regenerative signaling is critical for the development of advanced wound healing materials. Here, zinc metal particle-embedded polycaprolactone (PZ) electrospun nanofiber scaffolds were evaluated as an immunomodulatory platform that directs protein expression to influence the wound healing process. Scaffolds containing 0, 0.5, and 1 wt % Zn were assessed during fibroblast monoculture, macrophage monoculture, and fibroblast-macrophage coculture models under sustained inflammatory stimulation. Zn incorporation enhanced cell viability and metabolic activity while maintaining low cytotoxicity across all culture systems. Fibroblasts cultured on Zn-containing scaffolds exhibited reduced inflammatory signaling, suppressed COX-2 expression, and increased secretion of proangiogenic and pro-proliferative factors such as EGF, bFGF, and VEGF. Macrophages displayed restrained inflammatory activation, accompanied by elevated growth factor output, consistent with a pro-healing phenotype. Coculture studies revealed that Zn scaffolds selectively dampened inflammatory amplification while preserving cooperative angiogenic signaling, evidenced by reduced IL-6 and COX-2 expression. Altogether, these results establish Zn-embedded PCL scaffolds as a tunable platform for directing inflammatory and regenerative signaling relevant to wound healing applications.