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

Dongdong Zhang,Han Liu,Xiaodong Xue,Feihong Liu,Jun Wu,Feng Peng,Donghui Wang,Haobo Pan,Mei Li

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.