Mitochondria-mediated inflammation and diabetic wound healing: mechanisms and therapeutic strategies

Abstract

Diabetic wound (DW) healing impairment is one of the most common and serious complications of diabetes. DW is characterized by a complex pathogenesis involving hyperglycemia, oxidative stress, persistent inflammation, mitochondrial dysfunction, impaired angiogenesis, and neuropathy. Recent studies have revealed that mitochondria are not only the cellular powerhouses but also key organelles regulating inflammatory responses, redox balance, and cell fate. This review summarizes how mitochondrial dysfunction exacerbates inflammation and impedes the healing process in DW through mechanisms such as excessive reactive oxygen species (ROS) production, mitochondrial DNA (mtDNA) leakage, and aberrant inflammasome activation. Furthermore, it comprehensively outlines innovative therapeutic strategies targeting mitochondria, including mitochondria-specific antioxidants, metabolic reprogramming techniques, nanomaterial-based delivery systems, genetic engineering approaches, and natural product applications. These strategies are discussed from molecular mechanisms to clinical applications, aiming to provide new insights and a theoretical basis for the clinical management of DW. Systematic analysis indicates that therapeutic strategies targeting the mitochondria-inflammation axis hold significant potential and may represent a critical breakthrough in addressing the challenge of DW healing.