Bone repair in patients with osteoporosis remains a big challenge because their injury sites are often accompanied by an abnormal level of inflammation and reactive oxygen species (ROS). ROS is previously visualized, represented by hydrogen peroxide (H 2 O 2 ), in the bone defects. In this study, the H 2 O 2 in osteoporosis animals is further visualized, and it is found that the expression of H 2 O 2 is markedly higher than that in normal animals. Subsequently, a composite hydrogel containing manganese dioxide (MnO 2 )-coated calcium phosphate microspheres loaded with fibroblast activating protein inhibitor (FAPi) is prepared. Among them, MnO 2 is designed to act as an advanced army to eliminate H 2 O 2 and generate oxygen, and constant release of FAPi is used to regulate the immune response and bone formation. In vitro experiments show that the hydrogels effectively reduce intracellular ROS, guide macrophages toward M2 polarization, and alleviate inflammation. Furthermore, the hydrogels enhance the osteogenesis and inhibit osteoclastogenesis. Animal experiments demonstrate that the hydrogels can eliminate ROS, regulate macrophages, and promote repair of osteoporotic bone defects. Together, the findings from this study imply that the multi-pronged approach holds great promise to promote the repair of osteoporotic bone defects by rescuing the ROS microenvironment and guiding the immune response.

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Introduction Despite great progress made in developing orthopedic implants, the development of titanium (Ti) implants with ideal early osseointegration remains a big challenge. Our pilot study has demonstrated that Si-TiO 2 nanotubes on the surface of Ti substrates could enhance their osteogenic activity. Hence, in this study, we aim to comprehensively evaluate the effects of silicon-doped titania (Si-TiO 2 ) nanotubes on the osseointegration property of Ti implants. Materials and Methods The Ti implants were surface modified with Si-TiO 2 nanotubes through in situ anodization and Si plasma immersion ion implantation (PIII) method. Three groups were divided as Ti implants (Ti), Ti modified with TiO 2 nanotubes (TiO 2 -NTs) and Ti modified with Si-TiO 2 nanotubes (Si-TiO 2 -NTs). The morphology of Si-TiO 2 nanotubes was observed by scanning electron microscope. The growth and osteogenic differentiation of MC3T3-E1 cells on the Ti implants were evaluated. Further, the pull-out tests and in vivo osseointegration ability evaluation were performed after implanting the screws in the femur of Sprague Dawley rats. Results The Si-TiO 2 nanotubes could be seen on the surface of Ti implants. The MC3T3-E1 cells could grow on the surface of Ti, TiO 2 -NTs and Si-TiO 2 -NTs, and showed fast proliferation rate on the Si-TiO 2 -NTs. Moreover, the production of some osteogenesis-related proteins (ALP and Runx2) at one week and calcium deposition at four week was also enhanced in Si-TiO 2 -NTs rather than other groups. In vivo osseointegration results showed that Si-TiO 2 nanotube-modified Ti screws had higher pullout force at two and four weeks as well as enhanced new bone formation at six weeks compared to bare Ti screws and Ti screws modified with TiO 2 nanotubes alone. Discussion The modification of Si-TiO 2 -NTs on the Ti substrate could generate a nanostructured and hydrophilic surface, which can promote cell growth. Moreover, the existence of the TiO 2 nanotubes and Si element also can improve the in vitro osteogenic differentiation of MC3T3-E1 cells and early bone formation around the implanted screws. Together, findings from this study show that surface modification of Ti implants with Si-TiO 2 nanotubes could enhance early osseointegration and therefore has the potential for clinical applications.

Osteoporotic Defect Repair In article number 2201067, Chaoyong Liu, Bin Li, Fengxuan Han, and co‐workers describe a multifunctional composite hydrogel approach, which enables effective repair of osteoporotic bone defects by rescuing the ROS microenvironment and guiding the immune response of the bone injury site. The findings provide a novel platform for repair of osteoporotic bone defects based on integrated bone microenviroment regulation.