Abstract
The inflammatory response elicited by oxidative stress in periodontitis dramatically impairs the osteogenic differentiation potential of periodontal ligament stem cells (PDLSCs). Mitochondria sense oxidative stress and regulate the viability and function of PDLSCs and are considered potential targets for regenerative medicine. Resveratrol (RSV) alleviates mitochondrial dysfunction, yet its unsatisfactory bioavailability greatly limits its effectiveness in mitochondrial therapy. Conventional RSV loading methods involving noncovalent interactions or covalent conjugation are either insufficiently stable or require tedious preparation processes. In this study, an RSV nanocarrier system that targets mitochondria was designed by crosslinking guanidine-grafted glycol chitosan (GGC) with RSV and forming zinc ion-based metal coordination bonds (GGC-Zn2+-RSV). Further analyses verified the low cytotoxicity of the synthesized nanoparticles and the indispensable role of guanidine in realizing lysosomal escape and mitochondrial delivery, which could result in more favorable osteogenic efficacy in the inflammatory environment by preserving mitochondrial function. Moreover, in vivo investigations revealed the pronounced effectiveness of GGC-Zn2+-RSV in periodontal wound healing, possibly because GGC-Zn2+-RSV predominantly promotes antioxidation and the recruitment of endogenous stem cells. This study provides a promising and feasible stem cell-based strategy for wound repair in periodontitis and provides insight into the development of novel RSV drug carriers.
Published Version
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