Huang Xiuhong, Lin Ziling, Ruan Mingshu, Huang Peizhen, Ding Hongmei, Pan Hao, Cao Jiahui, Ma Chunmei, Zhao Qianhao, Guo Wenping, Wu Keke, Fang Chongkai, Liu Aijun, Zheng Liqin
School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
Department of Hand Surgery and Wound Repair, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.
Mater Today Bio. 2025 Aug 14;34:102196. doi: 10.1016/j.mtbio.2025.102196. eCollection 2025 Oct.
Diabetic wound (DW) complications, driven by persistent oxidative stress, unresolved inflammation, and vascular dysfunction, present a critical clinical challenge. Given mitochondria's pivotal role in inflammatory regulation, intercellular mitochondrial transfer emerges as a promising therapeutic target for DW management. In this study, we engineered a ROS/glucose/pH-triple responsive nanoplatform (WOC) via coordination-driven assembly of tungstate anions (WO ) and chitosan oligosaccharide (COS) to synchronize immunomodulation and angiogenesis for adaptive DW regeneration. The WOC platform demonstrated glucose/pH-triggered release of bioactive components with moderate ROS scavenging capacity, enabling real-time monitoring via visible colorimetric transition. By enhancing mitochondrial bioenergetics, WOC polarized macrophages to M2 phenotype and orchestrated vesicles-dependent mitochondrial transfer to injured endothelial cells, restoring vascular function through upregulated angiogenesis genes, enhanced migration, and tube formation. In diabetic rat models, WOC accelerated wound closure evidently, resolving inflammation and promoting scarless regeneration via balanced collagen deposition. This work establishes mitochondrial transfer as a promising strategy, offering a tunable nanotherapeutic approach to recalibrate cellular cross-talk and microenvironment dynamics in DW healing.
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