A one-two punch of inflammation and oxidative stress promotes revascularization for diabetic foot ulcers

Abstract

Patients with diabetic foot ulcers (DFU) suffering from severe lower limb ischemia face the risk of amputation. Concomitant oxidative stress and hyperinflammation commonly manifest within the tissue affected by DFU, exacerbating the deterioration of DFU wounds. One-two punch strategy of anti-oxidative damage plus anti-inflammatory is anticipated to tackle the challenge of non-healing diabetic wounds. Here, we introduced a dual-approach treatment strategy involving the probiotic Weissella cibaria (WC) modified with desferrioxamine (DFO). This engineered probiotic, known as WC@DPA, aims to ameliorate oxidative stress within the ischemic microenvironment and stimulate the formation and proliferation of endothelial tubular structures. When applied with chronic wounds and ischemic hindlimb injuries in diabetic mice, WC@DPA gel demonstrated an effective performance in modulating oxidative damage, reducing local vascular inflammation, and facilitating muscle tissue repair and vascular reconstruction. We believe that our engineered probiotic represents a promising therapeutic avenue for managing ischemic injuries associated with DFU.