骨修補及再生應用的矽酸鈣基生醫材料之特性分析

Characterization of calcium silicate-based biomaterials for applications of bone repair and regeneration

黃淑卿(Shu-Ching Huang)

指導教授 ： 丁信智

中山醫學大學/口腔醫學院/牙醫學系博士班/博士(2018年)

摘要

生醫陶瓷因與骨組織具相似特性，被認為是適合用於骨修復及再生之生醫材料，其中，磷酸鈣基底陶瓷材料廣受臨床用使用。近年來，矽酸鈣基底材料具有相當好的骨生成性而引起注意。為了評估矽酸鈣基底材料是否具有取代磷酸鈣基底材料做為臨床骨移植物之潛力，自製矽酸鈣骨水泥(CSC)與BoneSource 磷酸鈣骨水泥(CPC) 商品進行體外骨形成性及抑菌活性比較分析。此外，亦研究多孔明膠－矽酸鈣複合支架作為承載負荷應用時的特性評估。結果顯示矽酸鈣骨水泥比磷酸鈣骨水泥更有效提升人類間葉幹細胞之細胞增生、分化、與礦化能力。更重要的是，即使於無添加細胞分化劑的情況下，矽酸鈣骨水泥也可有效誘導間葉幹細胞進行分化。顯而易見地，矽酸鈣骨水泥之抑菌活性顯著高於磷酸鈣骨水泥。關於多孔支架，結果顯示含有明膠之矽酸鈣多孔支架之徑向拉伸強度與孔隙率分別為2 MPa與60%，相似於人體海綿骨，且具優異血管新生活性。交聯劑genepin可穩定複合支架之力學性質。本研究總結矽酸鈣具備誘導幹細胞分化能力及具抑菌活性，可作為磷酸鈣陶瓷之替代品。尤有甚者，結合明膠與矽酸鈣優點之多孔複合材料，改善了矽酸鈣陶瓷材料之降解性、提升力學性質、與血管新生活性，符合組織工程臨床使用需要。

關鍵字

矽酸鈣 ； 骨水泥 ； 骨生成 ； 支架 ； 組織工程 ； 血管新生

並列摘要

Bioceramics share similar properties with nature bone and thus have been considered attractive materials for bone repair and regeneration. Calcium phosphate-based ceramic is one of most promising bioceramics, which is successfully commercialized for clinical uses. Calcium silicate-based materials have attracted a great deal of interest due to their osteogenecity. To evaluate the feasibility of calcium silicate-based materials as an alternative to calcium phosphate, the in vitro osteogenesis and bacteriostatic activity of BoneSource calcium phosphate cement (CPC) with calcium silicate cement (CSC) were compared. In addition, the porous gelatin-calcium silicate composite scaffolds for load-bearing application were characterized. The results indicated that CSC could promote greater proliferation, osteogenic differentiation, and mineralization of human Mesenchymal Stem Cells (hMSCs) compared to CPC. More importantly, CSC effectively induced osteogenic differentiation of hMSCs in the absence of osteogenetic differentiation agents. Of note, CSC showed significantly greater bacteriostatic activity than CPC. Regarding the porous scaffold, the gelatin-containing scaffolds showed a diametral tensile strength of about 2 MPa and a porosity of about 60% which was similar to the cancellous bone, as well as the superior angiogenesis activity of hMSCs. The crosslinker, genipin, could significantly improve the mechanical stability of the scaffold. Our findings suggest that calcium silicate may be considered an alternative to CPCs in terms of inducing cell differentiation and antibacterial activity. Moreover, the combination of calcium silicate and gelatin may satisfy the clinical requirements for tissue engineering applications through controlled degradation, improved mechanical properties, and enhanced angiogenesis.

並列關鍵字

Calcium silicate ； bone cement ； osteogenesis ； scaffolds ； tissue engineering ； angiogenesis

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