骨形成蛋白二與人工骨塊應用於牙科植體周圍齒槽骨再生試驗

Evaluation of rhBMP-2 based artificial bone composite in peri-implant alveolar bone regeneration : Radiographic analysis

蔡明訓(Ming-Hsun Tsai)

指導教授 ： 林立德

國立臺灣大學/牙醫專業學院/臨床牙醫學研究所/碩士(2013年)

https://doi.org/10.6342/NTU.2013.10914

摘要

在牙科的臨床工作上，經常會面對到病人因缺乏足夠的骨量而無法成功地置放人工牙根，因此文獻上對於這樣的情形提出很多種在進行植牙之前的手術治療方式，包刮牽引成骨術、引導式骨再生術、自體骨移植和使用生長因子和選擇適合的載體。但是現在對於垂直齒槽骨再生及和植體周圍骨缺損的骨再生，在現代牙科植體學中還是一項困難的挑戰。本研究的目的即是研究骨形成蛋白二在一種人工合成骨塊為載體，來修復植體周圍骨缺損的潛力和效益性。
本實驗中使用了十隻健康的米格魯雄性成犬，六十個表面經多孔鈦金屬氧化處理的人工植體（TiUnite, 4.0 x 8.5 mm; Nobel Biocare, Sweden）植入到六十個下顎骨的齒槽骨缺損（高度為四毫米、長度為十毫米），人工牙根植入的深度為四毫米，留下四點五毫米的齒槽骨上植體周圍的骨缺損。這六十個骨缺損為隨機分布到五個組別（負控制組、人工骨塊組、其他三組分別為每毫升五、二十、五十微克骨形成蛋白二於人工骨塊）和兩個時間點（四周與八週）。為了觀察即量化新生骨的形成，實驗動物的螢光骨染色標定分別於手術當天注射四環黴素、三週後注射鈣黃綠素、六週後注射茜草素紅。牙科根尖放射線照射在術後當下、四週及八週進行。微電腦斷層照射則是於動物犧牲後取下標本後進行並且以軟體分析骨量。
在大部分骨缺損區的癒合情形都相當良好，除了某些區域有軟組織的併發症，而最後有螺絲帽露出的情形，但並沒有其他的發炎反應。放射線學檢查和微電腦斷層在都顯示在八週後，含有骨形成蛋白二的組別在人工植體周圍的垂直高度的骨再生都有不錯的效果。其中每毫升五十微克骨形成蛋白二於人工骨塊的這組在四週擁有最高的佳的骨再生結果（但未達統計顯著差異）、而在八週則是其中每毫升二十微克骨形成蛋白二於人工骨塊的這組的骨再生能力會好。
本研究建立的實驗動物模型是為了評估在人工植體周圍的垂直高度骨再生能力，人工骨塊於本實驗中扮演的角色是當做一個骨引導作用的支架和骨形成蛋白二的載體，且能對骨再生有效的影響，而骨形成蛋白二的濃度和時間點對於骨再生的質量及範圍有顯著的影響。

關鍵字

骨形成蛋白二 ； 人工植體 ； 人工骨塊 ； 垂直高度齒槽骨再生 ； 臨界性骨缺損 ； 動物活體試驗

並列摘要

In daily practice, the clinician is often confronted with bony situations that do not allow placing a dental implant because of a lack of sufficient bone volume. Various treatment options have been described in the literature to augment bone before implant placement including distraction osteogenesis, guided bone regeneration, grafting with autogenous bone, use of growth factors with appropriate carriers. However, vertical ridge augmentation and bone regeneration in peri-implant bone defect still remain a major challenge in current implant dentistry. The purpose of this study is to evaluate the potential and efficacy of an artificial bone composite as a carrier of rhBMP-2 in repairing peri-implant critical size defect.
Ten healthy male adult beagle dogs were used. Sixty titanium porous-oxide surface-modified implants (TiUnite, 4.0 x 8.5 mm; Nobel Biocare, Sweden) were inserted into 60 critical size mandibular alveolar defects (10 mm in width, 4 mm in height). Four millimeters of the implants were placed within the surgically reduced alveolar ridge, creating 4.5 mm, supra-alveolar, peri-implant defects. The 60 defects with dental implants were randomly distributed to 5 groups (empty, artificial bone composite only, bone composite with 5, 20 and 50 μg rhBMP-2) and 2 healing times (4 and 8 weeks). The animals were administered fluorescent bone labels (Tetracycline at first day of operation, calcein at 3 weeks, and alizarin red at 6 weeks) for a qualitative evaluation of bone formation. Periapical x-ray were taken immediately post-surgery (baseline), and at weeks 4 and 8. Micro-CT data were obtained after euthanasia and analyzed using CTan software.
Healing processes of most of the bone defect sites areas were uneventful except some went through soft tissue complications and ended up with cover screw exposure without other signs of inflammation. Both x-ray and micro-CT data showed significantly improved vertical bone regeneration around dental implants at week 8 in groups containing rhBMP-2. Bone composites containing 50μg rhBMP-2 revealed the best bone regeneration at week 4. However, the performance of composites with 20μg rhBMP-2 exceeded any other groups at week 8.
An animal model was established to evaluate vertical bone regeneration around dental implants. The artificial bone composite used in our study may act as an osteoconductive scaffold and a carrier of rhBMP-2, which effectively contributed to bone regeneration. The dosage of rhBMP-2 exerted a great influence on the timing and extent of bone regeneration

並列關鍵字

bone morphogenetic protein-2（BMP-2) ； dental implatns ； artificial bone block ； vertical ridge augmentation ； critical size defect ； in vivo animal study

參考文獻

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