化學固定骨生長因子於磷酸鈣陶瓷作為生物活性骨替代材料之研究

A Study of Immobilization of Bone Growth Factor on Calcium Phosphate Bioceramics as a Viable Bone Substitute

董國忠(Guo-Chung Dong)

指導教授 ： 林峰輝 ； 江彰吉 ； 黃金旺

中原大學/理學院/化學研究所/博士(2002年)

https://doi.org/10.6840/cycu200200100

摘要

骨缺陷的治療與填補，往往需要藉助於人工填充材料的使用。因此很多合成的填充材料被發展。其中，磷酸鈣陶瓷與生醫玻璃已被證實具有良好的生物適應性及生物活性，可以與自然組織刑成良好的骨鍵結，並且於臨床上已被使用於骨缺陷的治療成效良好，並且對骨組織具有再生的能力，於骨修復研究上很被看好，但由於磷酸鈣陶瓷本身僅具有骨誘導生長的功能，而不具有引導骨組織在生的能力，因此，此類材料在全面修復骨缺陷上仍有很大困難。
　　本研究中，我們將利用兩階段的化學程序來改質磷酸氫鈣陶瓷之表面性質。首先，利用二異氰酸為偶合劑將磷酸氫鈣陶瓷表面活化，使陶瓷表面具有反應基，其鍵結關係將藉由FTIR及NMR等化學結構分析儀器獲得證實。其次，將中草藥骨碎補利用醯胺化鍵結於偶合劑的另一端上，如此達成兩階段的陶瓷改質。有關骨碎補的釋放情形及生物適應性將透過釋放測試及細胞培養與兔體植入進行初步評估。
　　結果顯示，二異氫酸己烷與磷酸氫鈣陶瓷異相反應後將以urethane的鍵結結合，其共價情形為CaPO4-CO-NH-(CH2)6-N=C=O，進一步處理後尾端異氰氫酸根將轉變為一級胺根，其結構為CaPO4-CO-NH-(CH2)6- NH2。透過此胺基，骨碎補可在偶合劑EDC的作用下與磷酸氫鈣陶瓷形成醯胺鍵結，穩定地固定骨碎補於陶瓷表面。此外，經細胞培養及兔體植入試驗證實，此材料可增進骨母細胞之活性，並且可有效促進兔體較大的骨缺陷的修復。

關鍵字

二異氰酸己烷 ； 骨碎補 ； 骨誘導性 ； 表面改質 ； 磷酸氫鈣 ； 化學固定

並列摘要

To accelerate the healing of bone defects or to enable to heal at all, it is often necessary to fill them with suitable substance. Among these, calcium phosphates and bioactive glass have been proven to be biocompatible and bioactive materials, and have been successfully used clinically for repair of bone defects and augmentation of osseous tissue. However, those bioceramics have only the property of osteoconduction without any osteoinduction.
　　In our study, two-step of chemical immobilization was performed to surface-modified calcium hydrogenphosphate (MCHP). The first was to modify the surface of calcium hydrogen-phosphate (CHP) with coupling agent of diisocyanate. The linkage between CHP and diisocyanate will be characterized by FTIR and NMR. The second step was to immobilize chemically Gusuibu onto MCHP. Moreover, their mechanism of Gusuibu release and biocompatibility was evaluated and quantitative analyzed by spectrophotometer, cell culture test and implantation to rabbit.
　　The results show me that the linkage between HMDI and the surface of CHP is a urethane linkage as CaPO4-CO-NH-(CH2)6-N=C=O. After further treatment, the terminal group of MCHP will be converted into a primary amine group as the formula of CaPO4-CO-NH-(CH2)6- NH2. The primary amine was then reacted with Gusuibu by the help of cross-linking agent of EDC, and immobilized the Gusuibu on the surface of the MCHP. After immobilization, Gusuibu was remained stably on GI-MCHP. It also was proved to be with stimulation for osteoblasts activity and repairing of rabbit’s large bone defect

並列關鍵字

Gusuibu ； osteoinduction ； HMDI ； surface-modified ； chemical immobilization ； calcium hydrogenphosphate

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