Diabetic wounds, particularly foot ulcers, are notorious for their slow and often incomplete healing due to reduced blood flow and endothelial cell dysfunction. One of the major contributors to this issue is thrombospondin-1 (TSP-1), which inhibits the growth of new blood vessels, a process crucial for tissue repair. Despite various existing treatments, the challenge of addressing this barrier to healing remains unmet. With the global rise in diabetes cases, new treatments targeting the underlying causes of delayed wound healing have become a critical area of research. In light of these ongoing challenges, this study explores a new approach to stimulate angiogenesis and speed up the healing process.

In a new study published in Burns & Trauma, a team of researchers from leading Chinese institutions has unveiled a novel therapeutic solution for diabetic wound healing. The study introduces an innovative wound dressing that combines miR-221OE-sEVs -- engineered extracellular vesicles that target and reduce TSP-1 levels -- with a GelMA hydrogel to create a sustained-release system. This cutting-edge approach has shown to significantly enhance wound healing and blood vessel formation in diabetic mice, offering hope for more effective treatments in the future.

In their study, the researchers discovered that high glucose conditions commonly found in diabetic wounds lead to increased levels of TSP-1 in endothelial cells, impairing their ability to proliferate and migrate -- key processes for angiogenesis. By utilizing miR-221-3p, a microRNA that targets and downregulates TSP-1 expression, they restored endothelial cell function. The engineered miR-221OE-sEVs were encapsulated within a GelMA hydrogel, ensuring a controlled release at the wound site, mimicking the extracellular matrix. In animal trials, this composite dressing dramatically accelerated wound healing, with a notable increase in vascularization and a 90% wound closure rate within just 12 days, compared to slower healing in control groups.

Dr. Chuan'an Shen, a key researcher in the study, shared his excitement about the potential impact of this innovation: "Our results demonstrate the power of combining advanced tissue engineering with molecular biology. By targeting TSP-1 with miR-221OE-sEVs encapsulated in GelMA, we've not only improved endothelial cell function but also ensured a sustained and localized therapeutic effect. This breakthrough could revolutionize how we approach diabetic wound care, with the potential to improve patients' quality of life significantly."

The success of this engineered hydrogel in diabetic wound healing opens up several exciting possibilities. Beyond diabetic foot ulcers, the technology could be adapted for use in treating other chronic wounds, such as those caused by vascular diseases, or even in regenerating tissues like bone and cartilage. As further research and clinical trials progress, the promise of combining miRNA-based therapies with biocompatible hydrogels could become a cornerstone in regenerative medicine, offering patients more efficient and lasting wound healing solutions.

The study was supported by Beijing Natural Science Foundation (7244411) and Independent Innovation Science Fund of The Fourth Medical Center of the PLA General Hospital (2024-4ZX-MS-06, 2024-4ZX-MS-07, 2024-4ZX-MS-09).