Cholesterol-driven mitochondrial rejuvenation by quercetin nanotherapeutics restores implant osseointegration in diabetes.

ABSTRACT: Poorly controlled diabetes significantly compromises implant osseointegration, with mitochondrial dysfunction in bone marrow mesenchymal stem cells (BMSCs) emerging as a key pathological regulator. However, effective targeted therapies to achieve mitochondrial rejuvenation are still lacking. Given this, we specifically fabricated Qe@TNS coatings, a nanostructured platform that enables localized quercetin (Qe) delivery. Mechanistically, hyperglycemia-induced oxidative damage disrupts cholesterol metabolism in BMSCs, initiating a pathological transition of lipid rafts (LR) from functional liquid-ordered (Lo) to dysfunctional liquid-disordered (Ld) phases (the "switch-off" state). This impairs the LR-dependent mitochondrial quality control (MQC) networks, leading to the loss of mitochondrial

SUBMITTER: Wei J 

PROVIDER: S-EPMC12925295 | biostudies-literature | 2026 Jul

REPOSITORIES: biostudies-literature