Mechanisms and Therapeutic Advances of M2 Macrophages and Mesenchymal Stem Cell-derived Exosomes in Diabetic Wound Healing.

Abstract

Diabetic wound healing remains one of the most significant clinical challenges for surgeons and endocrinologists, given that impaired immune regulation and blocked local tissue repair universally occur in diabetic wound microenvironments. M2 macrophages and exosomes derived from Mesenchymal Stem Cells (MSC-Exos) have emerged as promising therapeutic candidates, owing to their core functions in immune modulation and tissue regeneration. In this review, we systematically elaborate the immunomodulatory properties and polarization mechanisms of M2 macrophages in diabetic wounds, with an emphasis on their capacity to relieve chronic inflammation and facilitate tissue repair. We further summarize the biological characteristics of MSC-Exos and clarify the molecular mechanisms by which these vesicles accelerate wound healing and Extracellular Matrix (ECM) remodeling. More importantly, we focus on the bidirectional synergistic crosstalk between M2 macrophages and MSC-Exos in diabetic wound microenvironments, and highlight their great therapeutic potential for refractory diabetic wounds. Combined with the latest preclinical progress and translational research, we analyze the practical application value of M2 macrophages and MSCExos in diabetic wound management. This review integrates current basic research and preclinical data, aims to lay a solid theoretical basis for targeted intervention in diabetic wounds, and proposes novel combined therapeutic strategies to improve wound healing efficacy.