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  • 學位論文

雙相磷酸鈣人工骨移植材料之體內試驗

指導教授 : 楊正昌
共同指導教授 : 李勝揚 鄧乃嘉
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摘要


在骨科與牙科臨床上針對大範圍骨缺損治療時,常使用骨移植材以促進癒合。在市售合成骨移植材中,由氫氧基磷灰石(hydroxyapatite, HA)與β-三鈣磷酸鹽(β-tricalcium phosphate, β-TCP)組成的雙相磷酸鈣(biphasic calcium phosphate, BCP)生醫陶瓷,為廣泛應用之合成骨移植材,但HA具有在體內吸收時間較長之問題。本研究以低結晶性氫氧基磷灰石(poor crystalline HA, PC-HA)與β-TCP組成雙相磷酸鈣骨移植材,藉由動物實驗評估比較不同比例移植材在骨缺損中新骨生成速率。本實驗室以濕式化學沈澱法分別反應生成PC-HA與β-TCP後,經過濾、混合、乾燥、壓錠、燒結、粉碎後以不同網目篩網控制顆粒大小,備製磷酸鈣骨移植材(PC-HA/β-TCP),藉由掃描式電子顯微鏡、傅氏紅外光譜儀與X光繞射分析儀進行材料之物化性分析。在動物實驗時,首先對四隻米格魯成犬拔除所有之小臼齒,等待16週癒合期後,對齒槽骨製造直徑3 mm,高6 mm之圓柱狀人工骨缺損,同時將三種不同比例之 (PC-HA/β-TCP 70/30, 60/40, and 0/100)材料植入缺損處為實驗組,以市售MBCP®(HA/β-TCP=60/40), Cerasorb®(β-TCP=100%)與未放置材料組別作為空白對照組。手術後8週在各區取出直徑5 mm,高8 mm圓柱狀區域進行組織切片觀察。切片結果顯示實驗室材料與市售商品在牙科骨缺損中,皆具備良好生物相容性,且能促進骨癒合。以one-way ANOVA分析新骨生成率(ratio of new bone formation),結果顯示組別間具有統計上差異(P<0.05),以Duncan multiple range test分析顯示有置放骨移植材料之各組之新骨生成率皆明顯優於空白對照組,另PC-HA/β-TCP= 70/30, 60/40之新骨生長率明顯大於β-TCP(100%)。由各組間之信度值(coefficient of variance, CV),可發現PC-HA/β-TCP= 70/30與60/40之新骨生成率較MBCP® 及Cerasorb®商品及空白對照組之分布均勻,推測較適於新生骨生長。結果顯示poor crystalline HA/β-TCP為適合骨缺損使用之新式雙相磷酸鈣骨移植材。

並列摘要


Bone substitute materials are widely used to accelerate healing process while suffering large bone defects in orthopedic and dental clinics. Commercial biphasic calcium phosphate (BCP), containing hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP), is a widely used synthetic bone graft with the shortcoming of prolonged resorption time. In this study, poor crystalline hydroxyapatite (PC-HA) and β-TCP were mixed in different ratios to investigate which mixing ratio could be adapted to the resorption rate of clinical application for dental bony defect. After preparing PC-HA and β-TCP by wet chemical precipitation method separately , granular type bone grafts were collected by filtrating, freeze drying, tableting, sintering, mixing, and size screening. All the bone graft specimens were analyzed with scanning electric microscope (SEM), Fourier transform infrared spectrometer (FT-IR) and X-ray diffraction (XRD). Prior to the implantation experiments, all premolars of 4 beagles were extracted. After 16 weeks of healing period for stabilizing the wound sites in alveolar bone, 8 cylinder type of artificial bony defect (3 mm diameter, 6 mm length) were produced, and filled with disinfected BCP of (PC-HA/β-TCP= 70/30, 60/40, 0/100) as experimental groups and commercial products of MBCP® (HA/β-TCP= 60/40), Cerasorb®(β-TCP=100%), and empty defect as control groups. The cylinder type bone blocks (5 mm diameter, 8 mm length) were brought out at 8 weeks postoperatively for histological studies. There are significant differences of new bone formation ratio between all experimental and control groups (one-way ANOVA, P < 0.05). The results of Duncan multiple range test also showed significant differences between treatment groups compare to empty control groups, PC-HA/ β-TCP=70/30 to β-TCP, and PC-HA/ β-TCP=60/40 to β-TCP groups. Comparison of the coefficient variation (CV), the distribution in experimental groups of new bone formation show better evenness than groups of MBCP®, Cerasorb®, and empty controls. The results showed that BCP of experimental groups and commercial products are biocompatible and the healing effects are better than unfilled empty control groups, indicating BCP of PC-HA/β-TCP is a new choice for bone defects filling.

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