Accelerated wound healing in diabetes by reprogramming the macrophages with particle-induced clustering of the mannose receptors.

The rate-limiting step in cutaneous wound healing, namely, the transition from inflammation to cell proliferation, depends on the high plasticity of macrophages to prevent inflammation in the wound tissues in a timely manner. Thus, strategies that reprogram inflammatory macrophages may improve the healing of poor wounds, particularly in the aged skin of individuals with diabetes or other chronic diseases. As shown in our previous study, KGM-modified SiO nanoparticles (KSiNPs) effectively activate macrophages to differentiate into the M2-type phenotype by inducing mannose receptor (MR) clustering on the cell surface. Here, we assess whether KSiNPs accelerate wound healing following acute or chronic skin injury. Using a full-thickness excision model in either diabetic mice or healthy mice, the wounds treated with KSiNPs displayed a dramatically increased closure rate and collagen production, along with decreased inflammation and increased angiogenesis in the regenerating tissues. Furthermore, KSiNPs induced the formation of M2-like macrophages by clustering MR on the cells. Accordingly, the cytokines produced by the KSiNP-treated macrophages were capable of inducing fibroblast proliferation and subsequent secretion of extracellular matrix (ECM). Based on these results, KSiNPs display great potential as an effective therapeutic approach for cutaneous wounds by effectively suppressing excessive or persistent inflammation and fibrosis.