The purpose of this study was to develop a rat model predictive of bisphosphonate-related osteonecrosis of the jaw (BRONJ) after exodontias. Thirty female rats were randomized into 2 groups, control and experimental. The experimental group received 2 intravenous injections of zoledronate (20 μg/kg). The mesial root of the right mandibular first molar was extracted. Rats were euthanized at 0, 4, and 8 weeks. Bone mineral density (BMD), collagen breakdown (pyridinium [PYD]), vascular regeneration (VEGF), and histology were examined. A trend toward higher PYD values was suggested in control vs experimental groups after wounding. Serum VEGF increased significantly after wounding for both control and experimental groups. After 8 weeks, VEGF continued to rise for the experimental group only. In the extraction socket area, BMD was significantly lower after wounding in control vs. zoledronate-treated rats. Histology sections from experimental groups showed bacteria and bone necrosis. Consistent findings of BRONJ features similar to those in humans were observed after zoledronate treatment.
Titanates are inorganic compounds with high affinity for specific metal ions or metal compounds, including gold. We have previously demonstrated that both monosodium titanate (MST) and amorphous peroxo-titanate (APT) alone do not suppress cellular metabolism of several cell types, and we have shown that MST and APT adsorb and release gold compounds in biological salt solutions. In the current study, we extend this work and show that MST and APT loaded with two gold compounds deliver sufficient levels of these compounds to alter the metabolism of mammalian cells. Fibroblasts (L929) or monocytes (THP1) were exposed to MST and APT loaded with either Au(III) or Auranofin(R), a Au(I)-organic compound, for 24-72 h, after which succinate dehydrogenase (SDH) activity of the cells was measured using the MTT method. MST or APT alone did not suppress SDH activity of either cell type. AF and Au(III) alone suppressed SDH activity completely above 2 muM or 300 muM, respectively. APT and MST loaded with either gold compound suppressed L929 fibroblast SDH activity by 30-80% after 72 h, but Au(III)-loaded APT was more potent than AF-loaded APT. Monocyte SDH activity was not affected by any loaded titanate. Our results suggest that titanates could be used for solid phase delivery of metal compounds to affect mammalian cell function of some types of cells.
New polymeric calcium phosphate cement composites (CPCs) were developed. Cement powder consisting of 60 wt% tetracalcium phosphate, 30 wt% dicalcium phosphate dihydrate, and 10 wt% tricalcium phosphate was combined with either 35% w/w poly methyl vinyl ether maleic acid or polyacrylic acid to obtain CPC-1 and CPC-2. The setting time and compressive and diametral tensile strength of the CPCs were evaluated and compared with that of a commercial hydroxyapatite cement. In vitro cytotoxicity and in vivo biocompatibility of the two CPCs and hydroxyapatite cement were assessed. The setting time of the cements was 5–15 min. CPC-1 and CPC-2 showed significantly higher compressive and diametral strength values compared to hydroxyapatite cement. CPC-1 and CPC-2 were equivalent to Teflon controls after 1 week. CPC-1, CPC-2, and hydroxyapatite cement elicited a moderate to intense inflammatory reaction at 7 days which decreased over time. CPC-1 and CPC-2 show promise for orthopedic applications.
Advanced glycation endproducts (AGEs) are a diverse group of molecular adducts formed in environments high in reducing sugars that accumulate with aging and in diabetes. This study tests the hypothesis that AGEs inhibit the stabile osseointegration of dental implants through tissue interactions that interfere with bone turnover and compromise the biomechanical properties at the bone-implant interface. Maxillary first molars were extracted from 32 rats and allowed to heal for 4 weeks. Titanium implants (1 mm x 3 mm) were placed in the healed sockets of 2 groups of 16 rats consisting of 8 rats injected 3 times/wk for 1 month with AGE (prepared from glucose and lysine) and 8 rats injected with vehicle as a control. AGE injections continued for an additional 14 or 28 days before sacrifice. X-ray images, blood, and tissues were collected to examine bone/implant contact ratio, serum pyridinoline ([PYD] a collagen breakdown marker), osteocalcin ([OSC] a bone formation marker), and for immunohistochemistry with antibodies to AGE and the bone turnover-marker protein matrix metalloproteinase1. Compared with the AGE-treated groups, the controls showed significantly higher bone/implant contact at both 14- and 28-day time points. PYD (P < .05) and OSC (trend) levels from controls showed decreases at 28 days when compared with AGE-treated groups. Immunohistochemistry with AGE-specific and bone turnover marker antibodies showed stronger staining associated with the implant/tissue interface in AGE-treated rats. Our studies indicate an association between AGE and inhibition of bone turnover, suggesting that the formation of AGE in high glycemic conditions, such as diabetes, may contribute to a slower rate of osseointegration that negatively affects implant stability.
Few published studies describe the biological properties of calcium phosphate cements (CPCs) for dental applications. We measured several biologically relevant properties of 3 CPCs over an extended (8 wk) interval. Monocalcium phosphate, calcium oxide, and synthetic hydroxyapatite were combined with either modified polyacrylic acid, light-activated modified polyalkenoic acid, or 35% w/w polymethyl vinyl ether maleic acid to obtain Types I, II, and III CPCs, respectively. Set cements were placed in direct contact with L929 fibroblasts for up to 8 weeks. Media Ca(+2) and pH were determined by atomic absorption spectroscopy and pH electrode respectively. Cell mitochondrial function was measured by MTT assay. Type I cements suppressed mitochondrial activity > 90% (vs. Teflon controls), but significantly (p < 0.05) improved to control levels over 8 weeks. Type II cements suppressed mitochondrial activity > 90% at all times. Type III cements elevated mitochondrial activity significantly after 7 wks. The pH profiles approached neutrality by 24 h, and all cements released calcium into the storage medium at all periods (24 h - 8 wk). We concluded that several types of cements had long-term biological profiles that show promise for dental applications.
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