Enhanced osteointegration of implants in aged rats via a stem cell pool aging reversion strategy

The senescence of mesenchymal stem cells (MSCs) leads to the significant change of their metabolic activity and physiological behaviors. In the context of orthopedic treatment, the osteointegration of titanium implant is largely affected by MSC aging, imposing considerable limitations on its long-term application. In this study, a surface modification on titanium implants was designed to enhance osteointegration by effectively regulating the functions of senescent MSC: A typical micro-nano topological structure was established on the implant surface to improve the osteogenic differentiation of MSCs. Then a functional hydrogel coating was covalently modified to the implant surface through a poly-dopamine layer. For senescent MSCs, firstly, the coating can eliminate the activation of senescence-associated secretory phenotype (SASP) of senescent MSCs by micro-nano topological structure, and it accelerated the proliferation of non-senescent MSCs by the reactive oxygen species (ROS) scavenging. With the degradation of the hydrogel coating, the composition of stem cell pool around the implant interfaces gradually rejuvenated, as the number of non-senescent MSCs increased and senescent MSCs decreased. Meanwhile, the exposed micro-nano topological structure showed significant effect on the osteogenic differentiation of MSCs, and ultimately promoted the osteointegration in aging rats. These results provided promising insights for the design and application of orthopedic titanium implants for aging patients.