posted on 2024-01-25, 12:04authored byXiaoqi Jiang, Junping Ma, Kaikai Xue, Jinghao Chen, Yu Zhang, Guojian Zhang, Kangyan Wang, Zhe Yao, Qing Hu, Cai Lin, Bo Lei, Cong Mao
The repair of diabetic wounds remains challenging, primarily
due
to the high-glucose-derived immune inhibition which often leads to
the excessive inflammatory response, impaired angiogenesis, and heightened
susceptibility to infection. However, the means to reduce the immunosuppression
and regulate the conversion of M2 phenotype macrophages under a high-glucose
microenvironment using advanced biomaterials for diabetic wounds are
not yet fully understood. Herein, we report two-dimensional carbide
(MXene)-M2 macrophage exosome (Exo) nanohybrids (FM-Exo) for promoting
diabetic wound repair by overcoming the high-glucose-derived immune
inhibition. FM-Exo showed the sustained release of M2 macrophage-derived
exosomes (M2-Exo) up to 7 days and exhibited broad-spectrum antibacterial
activity. In the high-glucose microenvironment, relative to the single
Exo, FM-Exo could significantly induce the optimized M2a/M2c polarization
ratio of macrophages by activating the PI3K/Akt signaling pathway,
promoting the proliferation, migration of fibroblasts, and angiogenic
ability of endothelial cells. In the diabetic full-thickness wound
model, FM-Exo effectively regulated the polarization status of macrophages
and promoted their transition to the M2 phenotype, thereby inhibiting
inflammation, promoting angiogenesis through VEGF secretion, and improving
proper collagen deposition. As a result, the healing process was accelerated,
leading to a better healing outcome with reduced scarring. Therefore,
this study introduced a promising approach to address diabetic wounds
by developing bioactive nanomaterials to regulate immune inhibition
in a high-glucose environment.