Opportunities and challenges of engineered exosomes for diabetic wound healing

The treatment of diabetic wounds is a major challenge faced by the medical system, and there is a growing interest in developing innovative therapies to accelerate wound healing. Regenerative medicine with cells has shown promising potential in skin repair, with the regenerative properties primarily attributed to the paracrine effects of secreted products, including exosomes. Compared to cell-based approaches, using exosomes as a cell-free therapy for chronic wounds has several advantages. Exosomes can regulate intercellular communication by releasing their contents, including mRNA, miRNA, lipids, and proteins, which further promote wound healing. Exosomes are well explored in biomedical application owing to their advantages such as their biocompatibility and low immunogenicity. However, the common method of exosome administration is through injection, but due to their rapid clearance rate in the body, maintaining the necessary therapeutic concentration around the wound is challenging. Therefore, it is necessary to develop a new biocompatible scaffold as a carrier for extracellular vesicles, allowing them to sustain the therapeutic concentration at chronic non-healing wound sites and continuously promote wound healing. Engineered exosomes are kinds of exosomes modified with internal treated molecules, surface decoration or delivered through engineered platform. In addition, some researchers have further processed and modified exosomes, known as engineered exosomes, with internal treated molecules, surface decoration, or delivery through engineered platforms. Compared to regular exosomes, engineered exosomes have greater advantages in promoting wound healing. In this review, we summarize the molecular mechanisms of exosomes from different sources with varying modifications in wound healing. Advantages and limitations of different engineered exosomes for chronic wound repair were also discussed. Finally, we highlight the challenges and future development directions for translating our knowledge of engineered exosomes into clinical practice.