Ti₃C₂T_x@PLGA/Icaritin microspheres-modified PLGA/β-TCP scaffolds modulate Icaritin release to enhance bone regeneration through near-infrared response

Porous poly (lactic-co-glycolic acid)/<i>β</i>-tricalcium phosphate/Icaritin (PLGA/<i>β</i>-TCP/ICT, PTI) scaffold is a tissue engineering scaffold based on PLGA/<i>β</i>-TCP (PT) containing Icaritin, the main active ingredient of the Chinese medicine Epimedium. Due to its excellent mechanical properties and osteogenic effect, PTI scaffold has the potential to promote bone defect repair. However, the release of ICT from the scaffolds is difficult to control. In this study, we constructed Ti₃C₂T<i>_x</i>@PLGA/ICT microspheres (TIM) and evaluated their characterization as well as ICT release under near-infrared (NIR) irradiation. We utilized TIM to modify the PT scaffold and performed biological experiments. First, we cultured rat bone marrow mesenchymal stem cells on the scaffold to assess biocompatibility and osteogenic potential under on-demand NIR irradiation. Subsequently, to evaluate the osteogenic properties of TIM-modified scaffold<i>in vivo</i>, the scaffold was implanted into a femoral condyle defect model. TIM have excellent drug-loading capacity and encapsulation efficiency for ICT, and the incorporation of Ti₃C₂T<i>_x</i>endows TIM with photothermal conversion capability. Under 0.90 W cm^-2NIR irradiation, the temperature of TIM maintained at 42.0 ± 0.5 °C and the release of ICT was accelerated. Furthermore, while retaining its original properties, the TIM-modified scaffold was biocompatible and could promote cell proliferation, osteogenic differentiation, and biomineralization<i>in vitro</i>, as well as the osteogenesis and osseointegration<i>in vivo</i>, and its effect was further enhanced through the modulation of ICT release under NIR irradiation. In summary, TIM-modified scaffold has the potential to be applied in bone defects repairing.