Enhancing immune modulation and bone regeneration on titanium implants by alleviating the hypoxic microenvironment...

Bone implantation inevitably causes damage to surrounding vasculature, resulting in a hypoxic microenvironment that hinders bone regeneration. Although titanium (Ti)-based devices are widely used as bone implants, their inherent bioinert surface leads to poor osteointegration. Herein, a strontium peroxide (SrO₂)-decorated Ti implant, Ti_P@SrO₂, was constructed through coating with poly-L-lactic acid (PLLA) to alleviate the hypoxic microenvironment and transform the bioinert surface of the implant into a bioactive surface. PLLA degradation resulted in an acidic microenvironment and the release of SrO₂ nanoparticles. The acidic microenvironment then accelerated the decomposition of SrO₂, resulting in the release of O₂ and Sr ions. O₂ released from Ti_P@SrO₂ can alleviate the hypoxic microenvironment, thus enhancing cell proliferation in an O₂-insufficient microenvironment. Furthermore, under hypoxic and normal microenvironments, Ti_P@SrO₂ enhanced alkaline phosphatase activity and bone-related gene expression in C3H10T1/2 cells with the continuous release of Sr ions. Meanwhile, Ti_P@SrO₂ suppressed M1 polarization and promoted M2 polarization of bone marrow-derived monocytes under hypoxic and normal conditions. Furthermore, in a rat implantation model, the implant enhanced new bone formation and improved osteointegration after modification with SrO₂. In summary, the newly designed O₂- and Sr ion-releasing Ti implants are promising for applications in bone defects.