A review of diabetic wound models—Novel insights into diabetic foot ulcer

Diabetic foot ulcer (DFU) is a major debilitating complication of diabetes. Many research investigations have been conducted with the aims to uncover the diabetic wound healing mechanisms, develop novel therapeutics, and screen bioactive wound dressings in order to improve the current management of DFU. These would have not been possible without the utilization of an appropriate wound model, especially in a diabetic wound context. This review focuses on the different in vitro research models used in DFU investigations such as the 2D scratch wound assay, 3D skin model, and 3D angiogenesis model as well as their limitations. The current efforts and challenges to apply the 2D and 3D in vitro models in a hyperglycemic context to provide insights into DFU modeling will be reviewed. Perspectives of utilizing 3D bioprinting and skin-on-the-chip model as a diabetic wound model in the future will also be highlighted. By leveraging knowledge from past experiences and current research, an improved experimental model for DFU is anticipated to be established in near future.