Analyzing polymeric nanofibrous scaffold performances in diabetic animal models for translational chronic wound healing research

Tissue-engineered scaffolds for skin wound healing have undergone tremendous progress since the advent of autologous skin grafts or autografts. The recognition that a three-dimensional (3D) scaffold more closely mimics the biochemical-mechanical milieu of wounds and advancing knowledge of cell biology has led to the next-generation of engineered biopolymeric nanoscaffolds. These can pave the way towards personalized wound care as they can address multiple requirements of skin physiology. A unifying approach is required for translational success of scaffolds, involving clinicians, biologists, and chemists. Following in vitro testing using cell lines, pre-clinical studies on animal models is the next crucial step towards scaffold clinical translation. Often, success noted in these studies does not replicate in human patients due to the heterogeneous nature of wound conditions and causes that cannot be found in a single animal model. In this review, we give an overview of the status of pre-clinical mice models for types 1 and 2 diabetic wound healing and relate this to studies conducted with polymeric nanoscaffolds. Translational shortcomings of these models are analyzed where they fail to provide a good replica of human conditions. Categorization and use of more sophisticated models, which can closely mimic the diabetic features, are addressed for translational use of nanoscaffolds.