Nanoporous titanium implant functionalized with sustained strontium release orchestrates immune microenvironment for enhanced osseointegration

Abstract

Objectives Insufficient osseointegration remains a major limitation of dental and orthopedic implants. This study aimed to develop a strontium-releasing nanoporous titanium surface (TDS) with improved interfacial stability and immunomodulatory capacity to promote implant osseointegration. Methods A nanoporous titanium surface was fabricated by anodization and selected over a nanotube structure because of its greater interfacial stability. Polydopamine-mediated coordination was then used to immobilize strontium on the nanoporous surface. Surface properties and strontium release were characterized. Macrophage polarization and the effects of the TDS-modulated immune microenvironment on osteogenic differentiation of mouse bone marrow mesenchymal stem cells (mBMSCs) and angiogenic activity of human umbilical vein endothelial cells (HUVECs) were evaluated in vitro. Additional experiments were performed to assess the direct effects of TDS on osteogenic and angiogenic responses. Osseointegration was examined in a rat femoral condyle defect model, and macrophage transcriptomic profiling was conducted. Results TDS retained a uniform nanoporous morphology, showed favorable hydrophilicity, and provided sustained strontium release. It promoted macrophage polarization toward the anti-inflammatory M2 phenotype and reduced pro-inflammatory responses. The TDS-modulated immune microenvironment significantly enhanced osteogenic differentiation and angiogenic activity, while direct material effects provided additional support. In vivo experiments further confirmed satisfactory osseointegration in bone defect areas after TDS implantation for 4 and 8 weeks. Transcriptomic analysis identified gene expression changes associated with immune regulation, inflammatory responses, and angiogenesis. Conclusions Overall, this study provides experimental evidence and a practical design strategy for the development of immunomodulatory titanium implants with improved osseointegration.