Magnesium/gallium-layered nanosheets on titanium implants mediate osteogenic differentiation of MSCs and osseointegration under osteoporotic condition

Abstract Osteoporotic fracture is generally hard to be fixed due to its abnormal microenvironment and cells metabolism, leading to poor osteointegration between the implants and surrounding bone tissue. Under osteoporotic condition, the microenvironmental pH would affect osteoblastic metabolism and bone formation/resorption behavior. Thus, it is reasonable to regulate cell metabolism with implanted biomaterials to adjust the pH at osteoporotic fractures and improve the osteogenic ability. To confirm this hypothesis, we fabricated a series of Mg-Ga layered double oxide (LDO) nanosheets on the surfaces of alkali-heat-treated titanium (AT) implants (denoted as AT-xMg/yGa). We found that AT-Mg/Ga with equal molar ratio of Mg2+ and Ga3+ displayed good stability and formed a suitable alkaline microenvironment (about pH 8.5) over long term. Meanwhile, AT-Mg/Ga layers markedly promoted the autophagic activity and induced osteogenesis differentiation of mesenchymal stem cells (MSCs) while suppressing osteoclast generation. Furthermore, in vivo tests further verified that the AT-Mg/Ga implants suppressed osteoclastic bone resorption and prominently promoted new bone formation. Therefore, the fabricated AT-Mg/Ga implants have potential application in the rescue of osteoporosis by suppressing osteoclastogenesis and enhancing the osteogenesis.