Exosome-mediated macrophage polarization: Pioneering pathways in diabetic wound healing

Recent studies have identified an essential role of macrophage polarization imbalance in the impaired diabetic wound healing process. Macrophages are key players in wound healing, and their transition from the pro-inflammatory M1 phenotype to the anti-inflammatory and reparative M2 phenotype is crucial for effective wound repair. However, in diabetic conditions, this balance is disrupted, leading to prolonged M1 activation and reduced M2 functionality, which hinders the healing process. Exosomes, known for their role in intercellular communication, have garnered significant interest for their diverse functions in immune modulation, angiogenesis, inflammation regulation, and tissue regeneration. Research has demonstrated the ability of exosomes to modulate macrophage polarization, facilitating the shift from M1 to M2 phenotypes, ameliorating the inflammatory milieu, and thereby promoting tissue repair and regeneration. However, the specific mechanisms underlying exosome-mediated regulation of macrophage phenotypic transitions in diabetic wounds remain inadequately elucidated. Moreover, exosomes, serving as novel drug delivery vehicles, present advantages such as enhanced targeting, reduced immunogenicity, and prolonged drug presence, offering considerable promise for diabetic wound management. This review comprehensively outlines advancements in understanding how exosomes influence macrophage polarization in diabetic wound healing, emphasizing the pathophysiological processes of diabetic wounds, the dysregulation of macrophage polarization, and their interactions with exosomes. It also assesses current research limitations and clinical challenges while proposing future research directions, thereby introducing novel theoretical perspectives and potential strategies for diabetic wound therapy.