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, η and [Formula: see text], that decline with age. These parameters reflect the biological age of an individual, where η represents fibroblast proliferation and [Formula: see text] 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 [Formula: see text], and this subset is increased to a larger subset by combining Q with HBOT. The two subsets of [Formula: see text] are determined explicitly by simulations of the model. To make these results applicable in clinical setting, one will have to relate the aging parameters η and [Formula: see text] to tangible marks of biological-aging factors.