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The in vivo tissue response to a newly developed fiber-reinforced calcium phosphate cement (CPC) formulation was assessed using a well-established rabbit calvarial defect model. Bilateral subcritical sized (8-mm diameter) defects were surgically created in the parietal bones of each rabbit (a total of 48 rabbits), and randomized to be filled with either the new fiber-reinforced formulation, a conventional CPC (positive control), or left unfilled (negative control). The implant sites were subsequently retrieved after 12, 24, and 52 weeks postsurgery. Each specimen, including the parietal bone craniotomy and underlying brain, were recovered at necropsy and the tissue responses were assessed by histology. The resulting histological slides indicated that there was no evidence of severe inflammatory responses or osteolysis. The data showed new dural and pericranial bone formation along the implants, as well as excellent bone-to-implant interfaces in all of the CPC-filled defects. These results suggest that the biologic response to the new fiber-reinforced CPC formulations and conventional nonreinforced CPC are very similar, and both demonstrate excellent biocompatibility as well as an overall osteophylic response. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012. [ABSTRACT FROM AUTHOR]

Prior studies have shown that implant surface roughness affects osteoblast proliferation, differentiation, matrix synthesis, and local factor production. Further, cell response is modulated by systemic factors, such as 1,25(OH) 2D3 and estrogen as well as mechanical forces. Based on the fact that peri-implant bone healing occurs in a site containing elevated amounts of prostaglandin E2 (PGE2), the hypothesis of the current study is that PGE2 and arachidonic acid (AA), the substrate used by cyclooxygenase to form PGE2, influence osteoblast response to implant surface roughness. To test this hypothesis, 4 different types of commercially pure titanium (cpTi) disks with surfaces of varying roughness (smooth Ti, Ra 0.30 µm; smooth and acid etched Ti [SAE Ti], Ra 0.40 µm; rough Ti, Ra 4.3 µm; rough and acid etched Ti [RAE Ti], Ra 4.15µm) were prepared. MG63 osteoblasts were seeded onto the surfaces, cultured to confluence, and then treated for the last 24 hours of culture with AA (0, 0.1, 1, and 10 nM), PGE2 (0, 1, 10, 25, and 100 nM), or the general cyclooxygenase inhibitor indomethacin (0 or 100 nM). At harvest, the effect of treatment on cell proliferation was assessed by measuring cell number and [³H]-thymidine incorporation, and the effect on cell differentiation was determined by measuring alkaline phosphatase (ALP) specific activity. The effect of AA and PGE2 on cell number was somewhat variable but showed a general decrease on plastic and smooth surfaces and an increase on rough surfaces. In contrast, [³H]-thymidine incorporation was uniformly decreased with treatment on all surfaces. ALP demonstrated the most prominent effect of treatment. On smooth surfaces, AA and PGE2 dose-dependently increased ALP, while on rough surfaces, treatment dose-dependently decreased enzyme specific activity. Indomethacin treatment had either no effect or a slightly inhibitory effect on [²H]-thymidine incorporation on all surfaces. In contrast, indomethacin inhibited ALP on smooth surfaces and stimulated ALP on rough. Taken together, the results indicate that both AA and PGE2 influence osteoblast response by promoting osteoblast differentiation on smooth surfaces, while inhibiting it on rough surfaces. Because implants with rough surfaces are acknowledged to be superior to those with smooth surfaces, these results suggest that use of nonsterioidal anti-inflammatory drugs to block PGE2 production and reduce inflammation may be beneficial in the postoperative period after implant placement. They also indicate that manipulation of the AA metabolic pathway may offer a new therapeutic approach for modulating bone healing after implant placement. Because periimplant healing takes place in a complex cellular environment quite different from the one used in the present study, additional work will be necessary to substantiate these possibilities. [ABSTRACT FROM AUTHOR]

1α,25(OH)2D3 and 24R,25(OH)2D3 mediate their effects on chondrocytes and osteoblasts in part through increased activity of protein kinase C (PKC). For both cell types, 1α,25(OH)2D3 exerts its effects primarily on more mature cells within the lineage, whereas 24R,25(OH)2D3 exerts its effects primarily on relatively immature cells. Studies using the rat costochondral cartilage growth plate as a model indicate that the two metabolites increase PKC activity by different mechanisms. In growth zone cells (prehypertrophic/upper hypertrophic cell zones), 1α,25(OH)2D3 causes a rapid increase in PKC that does not involve new gene expression. 1α,25(OH)2D3 binds its membrane receptor (1,25-mVDR), resulting in activation of phospholipase A2 and the rapid release of arachidonic acid, as well as activation of phosphatidylinositol-specific phospholipase C, resulting in formation of diacylglycerol and inositol-1,4,5-tris phosphate (IP3). IP3 leads to release of intracellular Ca2+ from the rough endoplasmic reticulum, and together with diacylglycerol, the increased Ca2+ activates PKC. PKC is then translocated to the plasma membrane, where it initiates a phosphorylation cascade, ultimately phosphorylating the extracellular signal-regulated kinase-1 and -2 (ERK1/2) family of MAP kinases (MAPK). PKC increases are maximal at 9 min, and MAPK increases are maximal at 90 min in these cells. By contrast, 24R,25(OH)2D3 increases PKC through activation of phospholipase D in resting zone cells. Peak production of diacylglycerol via phospholipase D2 is at 90 min, as are peak increases in PKC. Some of the effect is direct on existing plasma membrane PKC, but most is due to new PKC expression; translocation is not involved. Arachidonic acid and its metabolites also play differential roles in the mechanisms, stimulating PKC in growth zone cells and inhibiting PKC in resting zone cells. 24R,25(OH)2D3 decreases phospholipase A2 activity and prostaglandin production, thereby overcoming this potential inhibitory component, which may account for the delay in the PKC response. Ultimately, ERK1/2 is phosphorylated. PKC-dependent MAPK activity transduces some, but not all, of the physiological responses of each cell type to its respective vitamin D metabolite, suggesting that the membrane receptor(s) and nuclear receptor(s) may function interdependently to regulate proliferation and differentiation of musculoskeletal cells, but different pathways are involved at different stages of phenotypic maturation. [Copyright &y& Elsevier]