Research advances in enhancing wound healing through exosome-induced macrophage reprogramming

Wound healing is a dynamic and complex process that involves the regulation of inflammation, tissue regeneration, and angiogenesis. Macrophage polarization, particularly the transition between M1 and M2 phenotypes, plays a central role in modulating these biological processes. In recent years, exosomes (Exos), as critical mediators of intercellular communication, have gained significant attention for their capacity to modulate macrophage phenotypes and enhance the wound microenvironment. This capability is largely attributed to their natural ability to transport bioactive molecules, including microRNAs (miRNAs), proteins, and lipids. This review systematically summarizes the molecular mechanisms by which Exos reprogram macrophage polarization through the delivery of specific signaling molecules, thereby facilitating the resolution of inflammation, promoting angiogenesis, and accelerating tissue repair. Furthermore, the current progress in applying exosome-based therapies to diabetic wounds, infectious wounds, and chronic refractory wounds is discussed. Finally, this review explores emerging strategies integrating Exos with novel delivery platforms, such as microneedle patches and hydrogels, as well as advances in engineered Exos technologies, and outlines the challenges and future perspectives in this rapidly evolving field.