Stem cell-derived exosomes in wound healing: mechanistic insights and delivery strategies

Mesenchymal stem cells (MSCs) contribute significantly to wound healing due to their ability to self-renew, modulate immune responses, and differentiate into various cell types. However, challenges such as unpredictable growth, limited vascular transport efficiency, stringent storage and maintenance requirements that limit the widespread clinical use of MSC-based therapy, highlighting the need for developing effective cell-free alternatives. The regenerative effects of MSCs are mediated through paracrine signaling, primarily via their secretome, which includes extracellular vesicles and soluble factors, especially exosomes. Compared to MSC therapy, exosomes provide superior benefits in terms of storage, safety, and efficiency in targeting the wound sites due to their enhanced tissue penetration capabilities. However, a specific aspect that remains underexplored in exosome-based therapy for wound healing is the development of optimized delivery systems, to ensure controlled, sustained release and precise localization of the exosomes at the wound sites. This review uniquely focuses on this critical and emerging area, providing a detailed overview of the current advancements and limitations in exosomes-based wound healing therapies, with a focus on their delivery strategies. The insights presented in this review are expected to accelerate the development of innovative, effective treatments, revolutionizing wound care management and advancing regenerative medicine in clinical practice.