A polydopamine-assisted strontium-substituted apatite coating for titanium promotes osteogenesis and angiogenesis via FAK/MAPK and PI3K/AKT signaling pathways

Early osteointegration is essential for biomedical implants. Surface modifications can significantly compensate for an implant's lack of biocompatibility and osteo-differentiation. They can also be designed to promote angiogenesis in order to assist osteogenesis and ultimately facilitate bone regeneration. In this study, a polydopamine-assisted strontium-substituted apatite coating (Ti@PDA + SrHA) was fabricated on a multifunctional titanium implant to induce both angiogenic and osteogenic abilities for rapid osseointegration. Polydopamine and Sr-substituted hydroxyapatite were coated on the implant through biomineralization. The in vitro results showed that Ti@PDA + SrHA improved cell adhesion and increased the proliferation of rat bone marrow-derived mesenchymal stem cells (rBMSCs) and human umbilical vein endothelial cells (HUVECs). Ti@PDA + SrHA upregulated the expression of ALP activity and osteogenic genes in rBMSCs and elevated angiogenic genes in both rBMSCs and HUVECs. Mechanically, the FAK/MAPK signaling pathway was activated in rBMSCs, and the PI3K/AKT signaling pathway was activated in both rBMSCs and HUVECs. Consistent with these findings, Ti@PDA + SrHA accelerated new bone formation and rapid osseointegration in the femoral condyle implantation study with good stability. Overall, we fabricated a multifunctional biocompatible implant with better angiogenic and osteogenic performance compared to the non-coated implant.