Effects of strontium-incorporated micro/nano rough titanium surfaces on osseointegration via modulating polarization of macrophages.

Macrophages perform multiple functions in both inflammation and wound healing, and are one of the fore front cells during implant osseointegration that influence subsequent process. Essential trace element modification may effectively modulate titanium implant surface biological properties. In this work, strontium (Sr) incorporated micro/nano rough titanium surfaces (Sr-SLA) was fabricated by hydrothermal treatment, and immunoreaction of macrophages was further investigated. In vitro results revealed that Sr doping inhibited inflammatory response of macrophages, further attenuated the inhibitory effect on following bone marrow derived cells (BMSCs) osteogenic differentiation. The regulation of macrophages by Sr-SLA likely involved ERK signaling pathway. Consistently, the in vivo study showed that compared with titanium surface sand-blasted with large grit and double acid-etched (SLA) implants, Sr-SLA implants could enhance new bone formation accompanied with more alternatively activated M2 macrophages infiltration and less classically activated M1 macrophages infiltration. These results reveal the immunomodulatory ability of Sr-SLA of adjusting the functional status of macrophages through inhibiting M1 polarization while promoting M2 polarization.

The optimization of sintering treatment on bovine-derived bone grafts for bone regeneration: in vitro and in vivo evaluation.

Modifications of sintering temperature and treatment time of bovine-derived bone grafts affect their physicochemical properties and further influence biological activity. Three different temperature sintered bovine-derived bone grafts: group I (300 °C 3 h), group II (300 °C 3 h plus 530 °C 6 h), and group III (300 °C 3 h plus 1000 °C 2 h) and Bio-Oss® were characterized and then compared in vitro for their effects on bone marrow stromal cells (BMSCs) migration, proliferation, and differentiation as estimated by cell migration assay, Alkaline phosphatase (ALP) activity assay, and Alizarin red staining. Further, the four bone grafts were implanted into the calvarial defects of rabbits to evaluate bone regeneration and graft degradation. The four deproteinized bovine-derived bone grafts displayed different surface topography. Group II displayed the highest potential of attracting cells. Both groups I and II markedly promote BMSCs differentiation. After 6 and 12 weeks, defects grafted with groups I and II displayed a significant higher bone fraction than defects grafted with group III and Bio-Oss®. Bone graft remnants remained in all four groups. Taken together, sintering at 300 °C for 3 h and sintering at 300 °C for 3 h with an addition of 530 °C for 6 h of bovine-dervied bone grafts displayed potential use in bone regeneration. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 108B:272-281, 2020.

Physiochemical characterization and biological effect of anorganic bovine bone matrix and organic-containing bovine bone matrix in comparison with Bio-Oss in rabbits.

Bovine origin matrix has been widely used in clinical applications and investigated by various research institutions. However, the potential factors that influence bone regeneration are still not thoroughly understood and need further investigations. In this study, bone regeneration properties of anorganic bovine bone matrix (ABBM), organic-containing bovine bone matrix (OBBM), and widely acknowledged anorganic bovine bone matrix (Bio-Oss) were compared. Besides, the correlations between physiochemical characterizations and bone regeneration properties of the three xenografts were also investigated. Physiochemical characterizations were measured by special instrumentations. In animal studies, the three xenografts were implanted into 8-mm-diameter cranial defects of 16 New Zealand white rabbits. The biological effects were evaluated by micro-computed tomography and histomorphometric analysis after 6 and 12 weeks of implantation. The physical characterizations showed that anorganic bovine bone matrix and Bio-Oss had more nanostructures, larger surface area, bigger pore volume, and bigger pore size than that of organic-containing bovine bone matrix. The chemical characterizations showed that anorganic bovine bone matrix and Bio-Oss had higher crystallinity than that of organic-containing bovine bone matrix, and organic-containing bovine bone matrix contained organic nitrogen (N) component. In vivo, anorganic bovine bone matrix and Bio-Oss possessed better bone regeneration properties than that of organic-containing bovine bone matrix. Taken together, nanostructures, larger surface area, bigger pore volume, and bigger pore size of xenografts played an active role in new bone formation. Besides, lower crystallinity and organic N element of xenografts produced a positive effect on graft degradation. The abovementioned findings could provide theoretical basis for better choice in clinical applications and better manufacturing hydroxyapatite-derived bone graft in the future.

The effects of Sr-incorporated micro/nano rough titanium surface on rBMSC migration and osteogenic differentiation for rapid osteointegration.

Recruitment of endogenous bone marrow-derived mesenchymal stem cells (BMSCs) has been widely discussed as an alternative strategy for bone regeneration. Strontium (Sr) is known to direct the BMSCs' commitment to the bone lineage and encourage bone formation; however, the underlying mechanisms remain elusive. In this study, an Sr-incorporated micro/nano rough titanium surface (MNT-Sr) was fabricated by hydrothermal treatment in an attempt to facilitate BMSCs' recruitment and their osteogenic differentiation to enhance rapid osseointegration. Micro rough titanium (MT) was set as the control biomaterial. In vitro, MNT-Sr and its extracts promoted the migration and osteogenic differentiation of BMSCs. In animal studies, green fluorescent protein (GFP)-labeled BMSCs were intravenously injected into wild-type rats for tracing before tibial implantation surgery. The GFP+BMSC recruitment to the implantation site was successfully triggered by MNT-Sr implantation. A trend for increased bone area (BA%), bone-implant contact (BIC%) and removal torque values (RTVs) was observed for the MNT-Sr implant compared to that observed for MT at 2 weeks. Advanced mechanism analysis indicated that Sr2+ enhanced the SDF-1α/CXCR4 signaling pathway both in vitro and in vivo. Taken together, these findings suggest that MNT-Sr has promising therapeutic potential for future use in dental implants by homing endogenous stem cells to stimulate bone regeneration.