Thou Shall Not Heal: Overcoming the Non-Healing Behaviour of Diabetic Foot Ulcers by Engineering the Inflammatory Microenvironment

The document reviews innovative strategies to treat diabetic foot ulcers (DFUs) by engineering the inflammatory microenvironment, focusing on modulating macrophage behavior to promote healing. Traditional treatments are often inadequate, leading to severe complications. Recent approaches include 'smart dressings' with biologics like growth factors and cytokines, biomaterials, and cell-based therapies to shift macrophages from a pro-inflammatory to a pro-healing state. These strategies aim to enhance tissue repair, reduce chronic inflammation, and improve healing outcomes. Notably, ON101 showed promising results in a clinical trial with 74 patients achieving complete healing. Challenges remain in translating these therapies to clinical practice, but the potential for improved DFU treatment is significant.