Modeling treatment of diabetic wounds with oxygen therapy and senolytic drug

Abstract

Diabetic wounds are common in patients with type 2 diabetes; they are ischemic and inflammatory, and difficult to heal without intervention. Hyperbaric oxygen therapy (HBOT) is a standard treatment, but its effectiveness is limited to a subset of the aging population. Senescent fibroblasts, a hallmark of aging, impair wound healing, and senolytic drugs, like quercetin (Q), which target senescent cells, may improve healing. In this study, we developed a mathematical model that defines biological aging through two parameters, and, that decline with age. These parameters reflect the biological age of an individual, where represents fibroblast proliferation and represents the production of the angiogenetic protein VEGF. Our model predicts that treatment with only HBOT achieves wound closure, within normal expectable time, for patients with a limited subset pairs of, and this subset is increased to a larger subset by combining Q with HBOT. The two subsets of are determined explicitly by simulations of the model. To make these results applicable in clinical setting, one will have to relate the aging parameters and to tangible marks of biological-aging factors.