Establishing a 3D human skin equivalent towards the development of a diabetic foot ulcer in vitro model

Introduction: Diabetes mellitus, a severe health problem, is often associated with complications, such as the development of ulcers, primarily on the feet. Diabetic foot ulcers (DFUs) are characterized by a hyperglycemic and pro-inflammatory environment, a higher risk of infection, and poor wound healing. The functionality of fibroblasts and keratinocytes is compromised, impacting the processes of re- epithelialization, differentiation, and remodeling of the dermal layer.In vitro models are important for testing new therapies and for better understanding the mechanisms of the disease, while avoiding the ethical issues associated with animal models. However, current DFU models still have limitations, particularly the lack of important immune-bacterial interactions. Conclusions and future work: A 3D human skin in vitro model was developed and presents distinct dermal and epidermal layers, as well as viscoelastic behavior. The use of extra high glucose concentrations (50 mM) resulted in reduced metabolic activity in cells of the dermal layer and in a significant reduction in epidermis thickness. Variation in glucose concentrations did not affect the rheological properties of the 3D model. Next steps: Use of primary human keratinocytes for the epidermal layer; Incorporation of pro-inflammatory THP-1 macrophages.