Abstract
Wound healing is a major clinical challenge and regenerative medicine and tissue engineering suggest new ways to overcome such problems. The cell imprinting method can provide cues that regulate cell function or modulate stem cell differentiation into different lineages. In this study, the rabbit keratinocyte-imprinted polydimethylsiloxane (PDMS) substrate (KiPDMS) was made and associated with adipose-derived stem cells (ADSCs), keratinocytes, and collagen scaffold, provided various treatments. After evaluating ADSCs' differentiation into keratinocytes by qPCR and immunocytochemistry techniques, different treatments were implanted in a rabbit ear, histopathological analysis was performed on measuring the epidermal thickness and neovascularization. The histopathological analysis revealed that treated groups increased epidermal thickness (~ 139% up to ~ 998%) and neovascularization (vessel count /mm2, ~ 111% to ~ 301%) compared to the control group. Collagen scaffolds stimulated re-epithelialization, and implanting ADSCs with or without other factors enhanced its effect. Adding KiPDMS significantly improved re-epithelialization and neovascularization, especially in combination with differentiated keratinocytes. The complete treatment, consisting of all cellular and non-cellular stimulating factors, associated with a significant improvements in re-epithelialization and neovascularization compared with other treatments, including collagen scaffold and some other factors alone or together. These findings suggest that each treatment may have potential applications depending on the medical conditions, particularly in situations where cellular factors are limited.