Enhancing immune modulation and bone regeneration on titanium implants by alleviating the hypoxic microenvironment and releasing bioactive ions

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 (SrO 2 )-decorated Ti implant, Ti_P@SrO 2 , 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 SrO 2 nanoparticles. The acidic microenvironment then accelerated the decomposition of SrO 2 , resulting in the release of O 2 and Sr ions. O 2 released from Ti_P@SrO 2 can alleviate the hypoxic microenvironment, thus enhancing cell proliferation in an O 2 -insufficient microenvironment. Furthermore, under hypoxic and normal microenvironments, Ti_P@SrO 2 enhanced alkaline phosphatase activity and bone-related gene expression in C3H10T1/2 cells with the continuous release of Sr ions. Meanwhile, Ti_P@SrO 2 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 SrO 2 . In summary, the newly designed O 2 - and Sr ion-releasing Ti implants are promising for applications in bone defects.