Modified implant with dual functions of antioxidant and extracellular matrix reconstruction for regulating MSCs senescence

Abstract

Bone repair in elderly patients is significantly weaker compared to normal bone repair, and one of the main reasons for this is the senescence of bone marrow mesenchymal stem cells (MSCs), which play a key role in the bone repair process. Therefore, we considered the corresponding surface modification of orthopedic implants to cope with the practical problem of bone defects in elderly patients. In this thesis, we prepared TiO nanotubes loaded with metformin (Glucophage) on Ti substrates, followed by self-assembly layer by layer using chitosan-catechol and gelatin on the surface, to delay MSCs senescence by eliminating excessive reactive oxygen species (ROS) and reconstructing extracellular matrix (ECM), thereby achieving osteogenesis. The results showed a significant reduction in senescence-associated secretory phenotype (SASP) generation, an enhancement of PINK1/Parkin-mediated mitochondrial autophagy, and a decrease in intracellular and extracellular ROS levels in MSCs under the dual effects of antioxidants and ECM reconstruction, suggesting that the degree of senescence in MSCs was significantly reduced. Osteogenesis was also demonstrated by expression of osteogenesis-related genes and staining of animal sections. In conclusion, our material can indeed promote the proliferation and osteogenic differentiation of MSCs by delaying cellular senescence, which is expected to provide a novel approach for clinical solutions to tissue repair problems in elderly patients with bone defects.