Cellular gatekeepers of infected wounds: the dual role of adipocytes in coordinating immunity and regeneration

Chronically infected wounds continue to pose a major challenge in clinical practice. Their persistence reflects the convergence of sustained microbial colonization, inappropriate or prolonged immune activation, and insufficient tissue regenerative capacity, which together establish a self-reinforcing pathological environment. In routine clinical management, approaches centered on debridement and antimicrobial therapy often fail to achieve durable healing, indicating that key regulatory mechanisms governing wound repair remain insufficiently understood. Accumulating evidence has drawn attention to adipocytes as an integral, yet previously underrecognized, component of the infected wound microenvironment. Beyond their established metabolic role, adipocytes respond rapidly to infectious injury and contribute to early host defense through several coordinated processes. These include migration-associated morphological remodeling that provides transient coverage at the wound margin, local production of antimicrobial peptides that directly restrict microbial growth, and secretion of complement components and chemotactic mediators that shape the recruitment and function of innate immune cells such as neutrophils and macrophages. As infection is brought under control, adipocyte activity shifts toward supporting tissue repair, with paracrine signals influencing fibroblast behavior, angiogenesis, re-epithelialization, and granulation tissue development. On this basis, this review summarizes current knowledge of adipocyte functions across distinct phases of infected wound healing and discusses emerging translational strategies that leverage adipocyte biology, including refinements in autologous fat grafting and the development of adipose-derived biomaterials. A clearer understanding of adipocyte functional plasticity may help guide therapeutic approaches that integrate immune regulation with regenerative processes, thereby improving outcomes in chronic, non-healing wounds.