UBC Theses and Dissertations
Processing of calcium phosphate nanostructures for the study of osteoclastic resorption Chen, Sijia
Osteoporosis is a metabolic bone disease that is characterized by low bone mass and a high risk of fracture. It is caused by the increased activity of osteoclasts and the reduced activity of osteoblasts. Therapeutic approaches for osteoporosis include antiresorptive and anabolic drugs. The advanced-stage cancer induced-osteolytic lesions are also caused by abnormally high activity of osteoclasts. Since osteoclastic activity plays an important role in these areas, it has been the focus of many in vitro studies. Currently used assays for assessing osteoclastic activities include bone/dentin slices and synthetic calcium phosphate coatings. However, these assays have various limitations, from poor mechanical adhesion to low feasibility of drug delivery. The purpose of this dissertation was to develop a reliable calcium phosphate nanostructure for the in vitro study of osteoclastic resorption. In the first study, an ammonia-induced mineralization method (AiM) was developed to create a robust nano-structured calcium phosphate coating (CaP) with mineral pins on the track-etched porous membrane (AiM-CaP insert). The mineral pins enhance coating integration and provide diffusion channels. The uniform coating could be used for the test of osteoclastic resorption. The second study demonstrated that the AiM-CaP insert was a stable in vitro platform for evaluating osteoclastic resorption. In the third study, the feasibility of drug delivery was demonstrated with alendronate. Alendronate was delivered either directly onto the AiM-CaP inserts or diffused through the lower chamber of the cell culture system to inhibit osteoclastic resorption. Quantitative results also provided direct evidence about the influence of alendronate on osteoclasts’ actin rings. This study proved that AiM-CaP insert could be used for testing anti-osteoporosis drugs. The fourth study demonstrated that the prostate cancer cell-conditioned medium enhanced osteoclastic resorption. The results suggested that AiM-CaP inserts have a high potential for investigating cell interactions of osteoblasts/osteoclasts lineages with other bone homing cancer cells. In summary, the AiM-CaP coating reported in this thesis is a unique and reliable platform to study osteoclasts. This platform also provides wide opportunities for coating modification, material-bone cell interactions, new anti-osteoporosis drug tests, and bone metastasis studies in the future.
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