Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/3392
標題: Preparation and Evaluation of a Novel Composite Combined with Genipin Cross-linked Gelatin and TCP Powder as Bone Substitute
以天然交聯劑綠梔子素交聯明膠結合三鈣磷酸鹽粉末之新骨科替代材料的研製與評估
作者: 劉百栓
Liu, Bai-Shuan
關鍵字: Gelatin;明膠;Genipin;Tricalcium phosphate;Bone substitute.;綠梔子素;三鈣磷酸鹽;骨科替代材料
出版社: 化學工程學系
摘要: 
本研究目的為研製與評估一種新的骨科替代材料的適用性與生物適應性,期望材料不但方便於外科手術操作與具有良好的生物適應性之外,更希望植入材料在生物體內的溶解與析出速率,完全符合自然組織的重建模式,並可迅速參與新生組織的形成,使整個材料在植入一段時間之後,完全地被吸收及取代,而成為自然組織的一部份。
本研究以綠梔子素與明膠進行交聯反應,再添加三鈣磷酸鹽之陶瓷粉末,以完成GGT 複合材料之製備。材料特性分析方面,首先以不同添加量的綠梔子素交聯明膠,進行材料交聯程度之評估;之後以最適化添加量的綠梔子素交聯明膠,進行材料最小交聯反應時間之測定。此外,將GGT 材料浸泡於去離子水中,以進行浸泡液中材料釋出各成份濃度之定量分析;以及浸泡於模擬體液中,進行材料體外降解速率之測定。生物適應性評估方面,首先以骨母細胞培養及新生鼠頭蓋骨器官培養之體外測試,評估GGT 材料對骨母細胞生長的促進性或抑制性及促使缺陷骨組織修復的作用。此外,以老鼠皮下植入及兔體頭蓋骨植入之體內測試,評估GGT 材料在生物體內對免疫系統所產生的反應及實際應用於骨缺陷處的填充效應。
材料特性分析結果顯示,綠梔子素添加量達0.5wt%左右時,材料中明膠的交聯程度幾乎已達飽和,若以此添加量與明膠溶液進行交聯反應時,則至少需要經過一天的交聯反應時間,才可使材料達到完全的交聯反應;且在降解速率的測定結果顯示,若以綠梔子素作為交聯劑,可有效地降低GGT 複合材料的降解速率。由體外生物適應性評估結果顯示,當綠梔子素濃度增加至100ppm以上時,將會對骨母細胞造成明顯的生物毒性現象,而GGT 材料於浸泡期間所釋出的明膠及鈣離子,則具有促進骨母細胞增生與分化的能力;而由頭蓋骨器官培養結果發現,GGT 0.5wt%材料對於缺陷骨組織,具有骨引導與促進骨再生的能力。最後由體內生物適應性評估結果顯示,GGT 複合材料於老鼠皮下具有優異的生物適應性;且由兔體頭蓋骨植入實驗結果證實,此填充材料將不致造成植入部位的發炎等生物毒性現象,而且由X 光片顯示GGT 材料具有促進受傷骨組織的癒合能力。

This study prepares and evaluates the feasibility and biocompatibility of adopting a novel composite used as a bone substitute. This composite will hopefully be clinically effective and have good biocompatibility, and to be completely degradable by regenerated tissue after a suitable recovery time.
The GGT composite, combined with genipin cross-linked gelatin and tricalcium phosphate ceramic powders, was produced. First, the cross-linking ability of genipin at various concentrations on the gelatin was studied. Then, the minimal time for completing the cross-linking reaction between gelatin and genipin at the optimal concentration was determined. The substances released from the composites after they were soaked in de-ionized distilled water were analyzed. After the composites were soaked in simulated body fluid, the in vitro degradable rates were determined. Moreover, osteoblastic cell culture and neonatal rat cranial organ culture were used in an in-vitro test, to elucidate whether the substances released from the composites could facilitate the growth of bone cells and the osteoconductivity of the composite on new bone formation. Subcutaneous implantation in rats and the rabbit cranial defect model were used in an in-vivo test, to evaluate the compatibility of the tissue and the potential for accelerating the reconstruction of defective bone of the composites.
Results indicated that complete cross-linking reaction in the genipin-fixed gelatin occurred when 0.5 wt% of genipin was added. At least one day was required to complete the cross-linking reaction between gelatin and 0.5 wt% genipin. In the degradation study, the genipin used as cross-linking reagent could affect the rate of degradation of the composite. Cytotoxic tests revealed that 100 ppm of the genipin in the culture medium was the turning point, over which cytotoxicity to osteoblasts was exhibited. The gelatin and calcium ions were continuously released from the composites in the soaking solution, promoting proliferation and differentiation of the osteoblasts. Additionally, the composites had excellent biocompatibility and could produce osteoconduction for the regenerating bone tissues. Finally, the composites were shown not to be able to reduce biocompatibility during subcutaneous implantation in rats. In the rabbit cranial defect implant test, the composites demonstrated good tissue biocompatibility and were verified progressive growth of new bone into the calvarium defect, by radiographic evaluation.
URI: http://hdl.handle.net/11455/3392
Appears in Collections:化學工程學系所

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