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The Therapeutic Effect on Bone Mineral Formation from Biomimetic Zinc Containing Tricalcium Phosphate (ZnTCP) in Zinc-Deficient Osteoporotic Mice
Authors:Joshua Chou  Jia Hao  Hirokazu Hatoyama  Besim Ben-Nissan  Bruce Milthorpe  Makoto Otsuka
Institution:1. Faculty of Pharmacy, Research Institute of Pharmaceutical Science, Musashino University, Nishi-Tokyo, Japan.; 2. Oral Implantalogy and Regenerative Dental Medicine, Tokyo Medical and Dental University, Tokyo, Japan.; 3. Advanced Tissue Regeneration and Drug Delivery Group, Faculty of Science, University of Technology Sydney, Sydney, New South Wales, Australia.; UC Davis School of Medicine, United States of America,
Abstract:The aim of this study was to evaluate the therapeutic efficacy of biomimetic zinc-containing tricalcium phosphate (ZnTCP) produced by hydrothermally converting calcium carbonate exoskeletons from foraminifera, in the treatment of osteoporotic mice. X-Ray powder diffraction showed crystallographic structures matching JCPDS profile for tricalcium phosphate. Mass spectroscopy used to calculate total composition amount showed similar amount of calcium (5×104 µg/g) and phosphate (4×104 ppm) after conversion and the presence of zinc (5.18×103 µg/g). In vitro zinc release showed no release in PBS buffer and <1% zinc release in 7 days. In vivo evaluation was done in ovariectomized mice by implanting the ZnTCP samples in the soft tissues near the right femur bone for four weeks. Thirty ddY mice (5 weeks old, average weight of 21 g) were divided into six experimental groups (normal, sham, OVX, β-TCP, ZnTCP and direct injection of zinc). CT images were taken every two weeks where the bone mineral density (BMD) and bone mineral content (BMC) were calculated by software based on CT images. The ZnTCP group exhibits cortical and cancellous bone growth of 45% and 20% respectively. While sham, OVX and β-TCP suffered from bone loss. A correlation was made between the significant body weight increase in ZnTCP with the significant increase in plasma zinc level compared with OVX. The presented results indicate that biomimetic ZnTCP were effective in preventing and treating bone loss in osteoporotic mice model.
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