Chronic skin wounds pose a significant global health challenge, often leading to severe complications, including lower extremity amputations in diabetic foot ulcers. Current products, such as Apligraf and Integra, have limitations in supporting complete skin regeneration and reinnervation, leading to scar tissue formation with reduced functionality. To address these concerns, electrospun fibers using porcine gelatin, fish gelatin and chitosan in different combinations were produced and crosslinked with various agents (citric acid, glutaraldehyde, genipin, etc). Moreover, these fibers were also produced with and without quercetin, a natural pharmaceutical ingredient. To determine the most suitable fiber as a skin substitute a degradation assay was performed over the course of two months and fiber quality and size was evaluated through Scanning Electron Microscopy. The antioxidant activity and cytotoxicity of quercetin was studied using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and resazurin assays, respectively. Furthermore, adhesion and proliferation assays were conducted with human neuroblastoma cells (SH-SY5Y) to evaluate cellular response in the scaffolds. The results demonstrate that electrospun fibers crosslinked with citric acid maintained a higher percentage of their original structure during degradation when compared to other crosslinking agents. Additionally, porcine gelatin fibers crosslinked with citric acid provided an optimal environment for SH-SY5Y cells to adhere and proliferate, indicating the potential to promote skin reinnervation at the wound site. Quercetin-loaded scaffolds exhibited antioxidant properties, enhancing their therapeutic potential. In conclusion, our electrospun fiber scaffolds show promise as a viable option for skin substitutes with the ability to accommodate neuronal cells, potentially promoting skin reinnervation in chronic wounds. Further research is necessary to optimize fiber production conditions and assess proper skin functionality through neuronal differentiation assays.