Studies link mitochondrial mechanisms to improved healing in diabetic chronic wounds
Two studies reported mitochondrial mechanisms linked to diabetic wound repair, including targeted mitochondrial transplantation and the circular RNA circMTRNR2. The findings showed improved healing in experimental models and identified potential targets for chronic wound treatment.
Researchers have reported new findings on mitochondrial mechanisms in diabetic chronic wounds, including a targeted mitochondrial transplantation strategy and a mitochondrial circular RNA linked to repair. In diabetic wounds, impaired mitophagy and the accumulation of damaged mitochondria were described as key drivers of endothelial cell dysfunction, while tissue from patients with long-standing diabetic foot ulcers showed reduced levels of the mitochondrial circular RNA circMTRNR2. Both studies said the mitochondrial findings were associated with improved wound healing in experimental models.
One study said mitochondrial transplantation acts by reactivating mitophagy to selectively eliminate dysfunctional mitochondria, thereby restoring mitochondrial homeostasis and rescuing endothelial cell functionality. The researchers engineered a biomimetic mitochondrial transplantation strategy by coating endothelial cell-derived apoptotic vesicle membrane onto the surface of isolated mitochondria. The resulting Mito-AVM complex leveraged homologous targeting and phosphatidylserine-mediated "eat-me" signaling, achieving a 150% increase in delivery efficiency to endothelial cells in diabetic wounds.
The same study also described a 3-aminophenylboric acid-modified hyaluronic acid/polyvinyl alcohol hydrogel for the diabetic wound microenvironment, enabling reactive oxygen species and glucose-triggered sustained release of encapsulated Mito-AVM at the wound site. Animal experiments demonstrated that the system significantly promoted angiogenesis and collagen deposition, accelerating wound healing in diabetic model mice, with efficacy markedly superior to any single therapy. The findings were published in Research under the title "Apoptotic Vesicle Membrane-Mediated Targeted Endothelial Mitochondrial Transplantation-Clearance Therapy for Diabetic Wound Healing."
A separate study identified circMTRNR2 as a mitochondrial circular RNA that plays an important role in the healing of chronic wounds. The RNA was found to be reduced in tissue from patients with long-standing diabetic foot ulcers. Researchers analyzed skin samples from patients with non-healing wounds as well as from healthy donors, and also used an experimental wound model system in both human skin and mice.
The results showed that when circMTRNR2 decreased, fibroblasts' ability to grow, move, and build new tissue was impaired. The study said the molecule appears to support the skin's reparative capacity by protecting the cells' energy metabolism against harmful stress, and that when circMTRNR2 is absent, cellular stress increases and the mitochondria are damaged, which slows down the healing of the wound. In both models of human wound tissue and animal models, the healing process was slower when the amount of circMTRNR2 was reduced and faster when it was increased.
The circMTRNR2 findings were published in Advanced Science as "Mitochondrial CircRNA CircMT‐RNR2 Safeguards Antioxidant Defense to Support Fibroblast Functions in Wound Repair." Both reports described new mitochondrial targets and delivery approaches for diabetic chronic wounds, while stating that more research is needed on future treatment use.