分类号学号*************** 学校代码10487 密级
学位申请人：李君
指导教师：张胜民教授
药用复合膜答辩日期：2008年5月23日
A Thesis Submitted in Partial Fulfillment of the Requirements
for the Degree of Master of Engineering
Novel injectable calcium silicate/calcium phosphate composites for bone substitution: Experimental Study
Candidate :Li Jun
Major :Biomaterials and Tissue Engineering
Supervisor :Prof. Zhang Shengmin
Huazhong University of Science & Technology
Wuhan 430074, P. R. China
May，2008
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华中科技大学硕士学位论文
摘要
磷酸钙骨水泥以其良好的生物相容性和骨传导性已经应用于临床。但是也有其不足之处，钙磷酸盐胶凝材料由于其结晶程度和结构稳定性较高，植入生物体内后长期不易降解，从而作为一种异物残留于骨缺损区。 双相磷酸钙（羟基磷灰石/磷酸三钙）骨水泥，它充分利用羟基磷灰石更趋于骨性而磷酸三钙降解快的特点，但其存在的最大缺陷是由于固化时间过长而使初始机械性能不好。
硅酸钙具有良好的生物活性和生物相容性，在模拟体液中能够快速诱导沉积羟基磷灰石。硅酸钙在降解过程中释放出的硅离子还可以促进细胞增殖，并刺激骨形成的基因表达作用。硅酸钙具有良好的自固化性能。
本文将硅酸钙作为骨水泥的主体材料，制备新型硅酸钙/磷酸钙复合骨水泥，具有良好的操作性和可注射性，弥补了双相磷酸钙（羟基磷灰石/磷酸三钙）骨水泥的固化时间过长，钙磷酸盐胶凝材料降解很慢的缺陷。
新型骨水泥的初凝时间在9～17min，具有良好的可操作性。通过流变性能实验检测，骨水泥浆体是一种剪切变稀的浓悬浮体，并且在水化初期快速反应，热分析结果表明水化过程微放热，伴随着失水。凝固后骨水泥支架孔径范围在100～300μm，孔隙率在60.3%~70.7%，有利于骨组织及其他有机组织的长入，加速材料的降解，促进骨的快速愈合。
选用模拟体液（SBF）体系研究了硅酸钙/磷酸钙复合骨水泥的体外降解行为。分别从降解支架的XRD、IR、XRF检测，及降解液的pH, ICP-AES检测对降解实验结果进行了表征。实验结果表明，骨水泥具有较好的生物降解性，并能诱导沉积羟基磷灰石。降解液的pH维持在7.3 ~ 7.8，所设计的骨水泥的pH值变化在生理条件下处于安全变化范围，对人体的刺激小，在接近人体条件下具有一定的稳定性，符合植入材料的性能要求。
通过成骨细胞在骨水泥支架上细胞增殖实验研究骨水泥的生物相容性。MTT法测定结果表明，硅酸钙/磷酸钙复合骨水泥表现出促成骨细胞增殖作用，具有良好的生物相容性。
自动排焊机
关键词：硅酸钙；磷酸钙；骨水泥；降解
华中科技大学硕士学位论文
八角钢Abstract
Novel bone substitute materials were developed by using calcium silicate and calcium phosphate powder as the solid phase, and chitosan solution, solution of sodium phosphate and methylcellulose as the liquid phase. Water-soluble mannitol was used as porogen and mixed with the powder at mass fraction of 20%.It makes up for the deficiency of long setting time of biphasic calcium phosphate ceramic and low degradation of calcium phosphate gelatin materials.
Calcium silicate is bioactive and biodegradable. Calcium silicate can self-set in vivo to form hydroxyapatite with excellent osteoconductivity. The Si released by CS can promote the proliferation of cell and the expression of bone forming gene.
The setting time of the samples was 9~17minutes, which made them easy to operate. In the rheological characteristics measurement, the slurry presented viscoplasticity and thixotropy. The setting reaction was slightly exothermal. And the loss of weight was the result of the loss of water in the setting process of the slurry. Those resulting scaffolds with the porosity of 60.3%~70.7％and the pore size of 100～300 μm were fit for cell infiltration and tissue ingrowth.
Calcium silicate/calcium phosphate composites were soaked in simulated body fluid to investigate in vitro degradation. The scaffolds were characterized by XRD, IR and XRF, while the SBF were charac
terized by pH test paper and ICP-AES. When incubated in simulated body fluid, they were degradable and could form hydroxyapatite with excellent osteoconductivity. The pH of SBF sustained in the range of 7.3 ~ 7.8, which is safe for in vivo experiment.
The biocompatibility of the composite scaffolds was assessed on cell proliferation which was examined with MTT assay. It is proved that novel calcium silicate/calcium phosphate composites promote the proliferation of osteoblast-like cells and have good biocompatiability. Cell culture experiments suggested that these new developed bone substitute materials could have good prospects in bone defect repair.
Keywords:calcium silicate; calcium phosphate; bone cement; degradation
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