Effect of metformin on periimplant wound healing in a rat model of type 2 diabetes.

PURPOSE: To investigate the effects of hyperglycemia and metformin (a popular biguanide antidiabetic) on periimplant healing. METHODS: Thirty-six male rats were assigned to 3 groups: (1) nondiabetic Wistar-Kyoto rats (controls), (2) Goto-Kakizaki (GK) spontaneously diabetic rats (GK group), and (3) GK rats were fed metformin (100 mg/kg body weight per day) in their water for 4 weeks (GK + Met group). The right maxillary first molars were extracted and sites were allowed 1 month to heal. Titanium implants (1 × 3 mm) were placed in healed extraction sites. Six rats from each group were analyzed at weeks 1 and 4 by micro computed tomography for bone/implant contact ratio, percent bone volume, trabecular number, and bone mineral density. Blood was also analyzed for glucose, HbA1c, and pyridinoline (PYD). RESULTS: At week 1, glucose levels in the GK-Met rats were high, and all bone parameters were similar to GK rats (lower bone parameters and higher PYD than controls). At week 4, glucose levels in the GK-Met rats and all parameters were similar to controls. CONCLUSIONS: Hyperglycemic GK type 2 diabetic rats showed improved blood glucose and wound healing around oral implants after metformin administration.

Development of a rat model of bisphosphonate-related osteonecrosis of the jaw (BRONJ).

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.

Preparation, physical-chemical characterization, and cytocompatibility of polymeric calcium phosphate cements.

Aim. Physicochemical mechanical and in vitro biological properties of novel formulations of polymeric calcium phosphate cements (CPCs) were investigated. Methods. Monocalcium phosphate, calcium oxide, and synthetic hydroxyapatite were combined with either modified polyacrylic acid, light activated polyalkenoic acid, or polymethyl vinyl ether maleic acid to obtain Types I, II, and III CPCs. Setting time, compressive and diametral strength of CPCs was compared with zinc polycarboxylate cement (control). Specimens were characterized using X-ray diffraction, scanning electron microscopy, and infrared spectroscopy. In vitro cytotoxicity of CPCs and control was assessed. Results. X-ray diffraction analysis showed hydroxyapatite, monetite, and brushite. Acid-base reaction was confirmed by the appearance of stretching peaks in IR spectra of set cements. SEM revealed rod-like crystals and platy crystals. Setting time of cements was 5-12 min. Type III showed significantly higher strength values compared to control. Type III yielded high biocompatibility. Conclusions. Type III CPCs show promise for dental applications.

Polymeric-calcium phosphate cement composites-material properties: in vitro and in vivo investigations.

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.

Cytotoxicity, calcium release, and pH changes generated by novel calcium phosphate cement formulations.

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.