Zein-Coated Zn Metal Particles-Incorporated Nanofibers: A Potent Fibrous Platform for Loading and Release of Zn Ions for Wound Healing Application

• Published in: ACS applied materials & interfaces 2024-09, Vol.16 (37), p.49197-49217
• Main Authors: Shrestha, Sita, Shrestha, Bishnu Kumar, Tettey-Engmann, Felix, Auniq, Reedwan Bin Zafar, Subedi, Kiran, Ghimire, Sanjaya, Desai, Salil, Bhattarai, Narayan
• Format: Article
• Language: English
• Subjects: Animals; Biological and Medical Applications of Materials and Interfaces; Human Umbilical Vein Endothelial Cells; Humans; Metal Nanoparticles - chemistry; Mice; Nanofibers - chemistry; NIH 3T3 Cells; Polyesters - chemistry; Tissue Scaffolds - chemistry; Wound Healing - drug effects; Zein - chemistry; Zinc - chemistry
• ISSN: 1944-8244; 1944-8252; 1944-8252
• DOI: 10.1021/acsami.4c13458

Metal particles incorporated into polymer matrices in various forms and geometries are attractive material platforms for promoting wound healing and preventing infections. However, the fate of these metal particles and their degraded products in the tissue environment are still unknown, as both can produce cytotoxic effects and promote unwanted wound reactions. In this study, we develop biodegradable fibrous biomaterials embedded with metal particles that have an immune activation functions. Initially, biodegradable zinc (Zn) nanoparticles were modified with zein (G), a protein derived from corn. The zein-coated zinc particles (Z–G) were then embedded in polycaprolactone (P) fibers at different weight ratios to create fibrous biomaterials via electrospinning, which were subsequently analyzed for potential wound healing applications. We performed multimodal evaluations of the fibrous scaffolds, examining physicochemical properties such as fiber morphology, mechanical strength, hydrophilicity, degradation, and release of zinc ions (Zn2+), as well as biological properties, including in vitro cell culture studies. We provide evidence that the integration of 2.4 wt % of Z–G particles in polycaprolactone (PCL) nanofibrous scaffolds improved its physicochemical and biological functions. The in vitro cellular response of the scaffolds was evaluated using a series of cytotoxicity assays and immunocytochemistry analyses with three different cell types: mouse-derived fibroblast cell lines (NIH/3T3), human dermal fibroblasts (HDFn), and human umbilical vein endothelial cells (HUVECs). The composite fibrous scaffold exhibited robust activation and proliferation of NIH/3T3 and HDFn cells, along with a significant angiogenic potential in HUVECs. Immunocytochemistry confirmed elevated expression of vimentin and α-smooth muscle actin (α-SMA), suggesting that NIH/3T3 and Haden cells were highly differentiated into myofibroblasts. Additionally, the increased expression of CD31 and VE-cadherin in HUVECs suggests that the scaffold supports tube formation, thereby enhancing neovascularization and promoting an effective immune response. Overall, our findings demonstrate the regenerative potential of the self-enhanced Zn hemostatic bioscaffolds, which deliver both Zn2+ ions and zein proteins to nourish cells. This capability not only modulates cellular activities but also contributes to tissue repair and remodeling, making the scaffolds suitable for wound repair and various bioen