Zein-Coated Zn Metal\nParticles-Incorporated Nanofibers:\nA Potent Fibrous Platform for Loading and Release of Zn Ions for Wound\nHealing Application

Metal particles incorporated into polymer matrices in\nvarious forms\nand geometries are attractive material platforms for promoting wound\nhealing and preventing infections. However, the fate of these metal\nparticles and their degraded products in the tissue environment are\nstill unknown, as both can produce cytotoxic effects and promote unwanted\nwound reactions. In this study, we develop biodegradable fibrous biomaterials\nembedded with metal particles that have an immune activation functions.\nInitially, biodegradable zinc (Zn) nanoparticles were modified with\nzein (G), a protein derived from corn. The zein-coated zinc particles\n(Z–G) were then embedded in polycaprolactone (P) fibers at\ndifferent weight ratios to create fibrous biomaterials via electrospinning,\nwhich were subsequently analyzed for potential wound healing applications.\nWe performed multimodal evaluations of the fibrous scaffolds, examining\nphysicochemical properties such as fiber morphology, mechanical strength,\nhydrophilicity, degradation, and release of zinc ions (Zn<sup>2+</sup>), as well as biological properties, including in vitro cell culture\nstudies. We provide evidence that the integration of 2.4 wt % of Z–G\nparticles in polycaprolactone (PCL) nanofibrous scaffolds improved\nits physicochemical and biological functions. The in vitro cellular\nresponse of the scaffolds was evaluated using a series of cytotoxicity\nassays and immunocytochemistry analyses with three different cell\ntypes: mouse-derived fibroblast cell lines (NIH/3T3), human dermal\nfibroblasts (HDFn), and human umbilical vein endothelial cells (HUVECs).\nThe composite fibrous scaffold exhibited robust activation and proliferation\nof NIH/3T3 and HDFn cells, along with a significant angiogenic potential\nin HUVECs. Immunocytochemistry confirmed elevated expression of vimentin\nand α-smooth muscle actin (α-SMA), suggesting that NIH/3T3\nand Haden cells were highly differentiated into myofibroblasts. Additionally,\nthe increased expression of CD31 and VE-cadherin in HUVECs suggests\nthat the scaffold supports tube formation, thereby enhancing neovascularization\nand promoting an effective immune response. Overall, our findings\ndemonstrate the regenerative potential of the self-enhanced Zn hemostatic\nbioscaffolds, which deliver both Zn<sup>2+</sup> ions and zein proteins\nto nourish cells. This capability not only modulates cellular activities\nbut also contributes to tissue repair and remodeling, making the scaffolds\nsuitable for wound repair and various bioengineering applications.