Osteoblastic and anti-osteoclastic activities of strontium-substituted silicocarnotite ceramics: In vitro and in vivo studies

Osteoporosis bone defect is a refractory orthopaedic disease which characterized by impaired bone quality and bone regeneration capacity.Current therapies,including antiosteoporosis drugs and artificial bone grafts,are not always satisfactory.Herein,a strontium-substituted calcium phosphate silicate bioactive ceramic(Sr-CPS)was fabricated.In the present study,the extracts of Sr-CPS were prepared for in vitro study and Sr-CPS scaffolds were used for in vivo study.The cytocompatibility,osteogenic and osteoclastogenic properties of Sr-CPS extracts were characterized in comparison to CPS.Molecular mechanisms were also evaluated by Western blot.Sr-CPS extracts were found to promote osteogenesis by upregulating Wnt/β-catenin signal pathways and inhibit osteoclastogenesis through downregulating NF-κB signal pathway.In vivo,micro-CT,histological and histomorphometric observation were conducted after 8 weeks of implantation to evaluate the bone formation using calvarial defects model in ovariectomized rats.Compared with CPS,Sr-CPS significantly promoted critical sized ovariectomy(OVX)calvarial defects healing.Among all the samples,Sr-10 showed the best performance due to a perfect match of bone formation and scaffold degradation rates.Overall,the present study demonstrated that Sr-CPS ceramic can dually modulate both bone formation and resorption,which might be a promising candidate for the reconstruction of osteoporotic bone defect.

Advanced protein adsorption properties of a novel silicate-based bioceramic: A proteomic analysis

Silicate bioceramics have been shown to possess excellent cytocompatibility and osteogenic activity,but the exact mechanism is still unclear.Protein adsorption is the first event taking place at the biomaterial-tissue interface,which is vital to the subsequent cellular behavior and further influence the biomaterial-tissue interaction.In this work,the protein adsorption behavior of a novel CPS bioceramic was evaluated using the proteomics technology.The results showed that CPS adsorbed more amount and types of serum proteins than HA.FN1 and IGF1 proteins selected from proteomics results were validated by Western-blot experiment.Pathway analysis also revealed mechanistic insights how these absorbed proteins by CPS help mediate cell adhesion and promotes osteogenic activity.Firstly,the dramatically enhanced adsorption of FN1 could greatly promote cell adhesion and growth.Secondly,IGF1 was uniquely adsorbed on CPS bioceramic and IGF1 could activate Rap1 signaling pathway to promote cell adhesion.Thirdly,the increased adsorption of FN1,IGF1 and COL1A2 proteins on CPS explains its better ability on bone regeneration than HA.Fourthly,the increased adsorption of IGF1,CHAD,COL2A1 and THBS4 proteins on CPS explains its ability on cartilage formation.Lastly,the increased adsorption of immunological related proteins on CPS may also play a positive role in bone regeneration.In addition,CPS had a much better cell adhesion ability than HA,proving that more adsorbed proteins really had a positive effect on cell behavior.The more adsorbed proteins on CPS than HA might indicated a better bone regeneration rate at early stage of implantation.