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This dissertation, Osteoconduction and Osseointegration of a Strontium-containing Hydroxyapatite Bioactive Bone Cement: in Vitro and in Vivo Investigations by Chi-tak, Wong, 黃志德, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of thesis entitled Osteoconduction and Osseointegration of a Strontium-containing Hydroxyapatite Bioactive Bone Cement: In Vitro and In Vivo Investigations Submitted by Chi Tak WONG for the degree of Doctor of Philosophy at The University of Hong Kong in September 2004 The objectives of this study were to optimize the properties of the strontium- containing hydroxyapatite (Sr-HA) bioactive bone cement, to verify whether incorporating strontium into hydroxyapatite increases the mineralization in vitro, to determine osteoconductivity of the Sr-HA bone cement by investigating the in vivo bone response to the Sr-HA bone cement implanted in cancellous bone of rabbits, and to investigate the change in minerals of Sr-HA on a longitudinal time-scale observation in vivo, thereby explaining the mechanism leading to osseointegration of the Sr-HA bone cement. Osteoporosis is a major global health problem. Vertebral compression fractures (VCFs) are especially common in elderly women as a result of postmenopausal osteoporosis. Patients with VCFs usually present with pain, sometimes incapacitating, and limitation of movement. Osteoporotic VCFs adversely affect quality of life, physical function and mental health, and can be fatal. Percutaneous vertebroplasty is a minimally invasive, radiological-guided procedure which uses a large-bore bone-cutting needle to percutaneously access a vertebral body, inject poly(methyl methacrylate) (PMMA) bone cement, and thereby stabilize and reinforce the remaining bone structure. This technique is increasingly being used to treat painful osteoporotic VCFs because it delivers prompt pain relief to approximately 90% of patients. However, several intraoperative and long-term potential complications are associated with this technique, including thermal damage to the neural elements during polymerization of PMMA and negative effects on bone remodeling. These lead to the need for invention of new bioactive bone cements. Strontium-containing hydroxyapatite (Sr-HA) bioactive bone cement was developed to overcome the disadvantages of PMMA bone cement and has desirable properties applicable in vertebroplasty. The Sr-HA bone cement was composed mainly of strontium-containing hydroxyapatite (Sr-HA) filler and bisphenol A diglycidylether dimethacrylate (BIS-GMA) based resin, which is bioactive. In this study, the properties of the Sr-HA bone cement were optimized by modifying its compositions. Tests demonstrated that modified Sr-HA bone cement had a low setting temperature, good handling properties, and mechanical properties desirable in vertebroplasty. Incorporation of strontium into hydroxyapatite in the Sr- HA bone cement stimulated the adhesion of human osteoblasts (SaOS-2) and promoted in vitro bone mineralization. In vivo study results showed that the Sr-HA bone cement stimulated bone formation and bone remodeling in the cancellous bone. The Sr-HA bone cement was confirmed to be osteoconductive and osseointegrated with bone. We propose that the mechanism leading to osseointegration of the Sr-HA bone cement involves dissolution and precipitation processes. Crystalline Sr-HA forms an amorphous layer on its surface which dissolves into the surrounding solution, resulting in over-saturation and precipitation of apatite crystallites. Over time, the bone becomes mature and stably b

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