A NOVEL 3D SKIN DISEASE MODEL TO ASSESS MACROPHAGE FUNCTION IN DIABETES.

A major challenge in the management of patients suffering from diabetes is the risk of developing non-healing foot ulcers. Most in vitro methods to screen drugs for wound healing therapies rely on conventional 2D cell cultures that do not closely mimic the complexity of the diabetic wound environment. In addition, while 3D skin tissue models of human skin exist, they have not previously been adapted to incorporate patient-derived macrophages to model inflammation from these wounds. Here we present a three-dimensional human skin equivalent model incorporating blood derived monocytes and primary fibroblasts isolated from patients with diabetic foot ulcers. We demonstrate that the monocytes differentiate into macrophages when incorporated into human skin equivalents (HSEs) and secrete a cytokine profile indicative of the pro-inflammatory M1 phenotype seen in diabetic foot ulcers. We also show how the interaction between fibroblasts and macrophages in the HSE can guide macrophage polarization. Our findings take us a step closer to creating a human, 3D skin-like tissue model that can be applied to evaluate the response of candidate compounds needed for potential new foot ulcer therapies in a more complex tissue environment that contributes to diabetic wounds.