雙相多孔生物陶瓷骨替代材之物理及生物特性研究

Physical and Biological Properties of Porous Biphasic Bone Graft Substitutes Made by Calcium Sulfate and Hydroxyapatite

張澔宇(Hao-Yu Chang)

指導教授 ： 段維新

國立臺灣大學/工學院/材料科學與工程學研究所/博士(2020年)

https://doi.org/10.6342/NTU202004421

摘要

硫酸鈣和氫氧基磷灰石因具備高生物相容性，多年來被廣泛應用於生物陶瓷領域中。由於兩種材料降解速率差異顯著，因此可將兩者混合製備出具較平穩降解速率的雙相骨替代材。本研究藉由膠體鑄造法成功製備出具穩定多孔結構的生物陶瓷骨替代材。多孔生物陶瓷樣品之孔隙率約在60-70 %之間，孔洞彼此連通且大於100微米。本研究所使用之氫氧基磷灰石是藉由固態反應法所合成。此外，硫酸鈣添加生物玻璃或氫氧基磷灰石並經過燒結熱處理後，可有效提升生物陶瓷試樣的機械強度，且沒有觀察到二次相的生成。從體外降解試驗的結果可以發現，雙相多孔試樣的降解速率可透過硫酸鈣的含量多寡來調整控制。當雙相試樣中的硫酸鈣比例較高時，初始降解速率會較快且降解行為持續的時間將延長。在降解過程中，含硫酸鈣之試樣會釋放鈣離子並與磷酸根離子進行反應生成磷酸鈣鹽類沉澱於樣品上。將MC3T3-E1細胞培養在試樣的萃取液中可以發現，其吸光值於所有樣品的萃取液中皆會隨著培養時間的增長而上升。另一方面，MC3T3-E1細胞也可以貼附，增殖並在整個多孔試樣內遷移且不具細胞毒性。將雙相多孔試樣植入老鼠大腿骨缺損部位三個月後，可以明顯觀察到新骨及血管組織生成。因此，藉由各項分析結果可以證明本研究所製備之雙相多孔試樣為一具實用性的人工合成骨替代材。

關鍵字

硫酸鈣 ； 氫氧基磷灰石 ； 多孔微結構 ； 生物可降解 ； 燒結

並列摘要

Calcium sulfate and hydroxyapatite have both been used as bioceramics with biocompatibility for several years. Since the degradation rate are divergent, a bone graft substitute with moderated degradation rate could be generated by the combination of calcium sulfate and hydroxyapatite. In the present study, calcium sulfate has been added with 1 wt% of bioglass or mixed with hydroxyapatite prepared by solid-state reaction to produce the synthetic bone graft substitutes. According to the gel-casting method, the bone graft substitutes with stable porosity structure have been prepared after sintering without secondary phase presence. The porous structure shows concave macropores (> 100 μm) with interconnected tunnels; the porosity of specimens is about 60-70%. The mechanical strength could be improved by adding 1 wt% of bioglass or hydroxyapatite in calcium sulfate. The results of degradation experiment show that the degradation rate is controlled by the content of calcium sulfate; the starting degradation rate would be faster with higher calcium sulfate ratio in biphasic specimens, and the degradation behavior would perform longer. Calcium ion would release and react with phosphate ion to produce calcium phosphate precipitate on the specimens during degradation. The optical density value would increase during incubation of MC3T3-E1 cells within extracts of all specimens. MC3T3-E1 cells could also attach, proliferate and migrate through the open structure of the specimens. New bone formation and vascularization could be observed in the bone defect after implanted the biphasic specimens for 3 months. Therefore, a practical porous biphasic bone graft substitutes have been prepared successfully in the present study.

並列關鍵字

calcium sulfate ； hydroxyapatite ； porous structure ； biodegradable ； sintering

參考文獻

[1] V. Campana, G. Milano, E. Pagano, M. Barba, C. Cicione, G. Salonna, W. Lattanzi and G. Logroscino, “Bone substitutes in orthopaedic surgery: from basic science to clinical practice,” J. Mater. Sci.-Mater. Med., 25 2445-2461 (2014).

[2] M. Bohner, “Resorbable biomaterials as bone graft substitutes,” Mater. Today, 13 24-30 (2010).

[3] S. Lee, M. Porter, S. Wasko, G. Lau, P. Y. Chen, E. E. Novitskaya, A. P. Tomsia, A. Almutairi, M. A. Meyers and J. McKittrick, “Potential bone replacement materials prepared by two methods,” Mater. Res. Soc. Symp. Proc., 1418 177-188 (2012).

[4] C. M. Murphy, M. G. Haugh and F. J. O'Brien, “The effect of mean pore size on cell attachment, proliferation and migration in collagen-glycosaminoglycan scaffolds for bone tissue engineering,” Biomaterials, 31 461-466 (2010).

[5] S. V. Dorozhkin and M. Epple, “Biological and medical significance of calcium phosphates,” Angew. Chem. Int. Ed. Engl., 41 3130-3146 (2002).