牙根分岔再生探討: 現行臨床治療策略功效評估與快速列印三維羥基磷灰石生物支架設計

Furcation Defect Regeneration: The Outcome of Current Treatment Strategies and the Development of a Rapidly Prototyped Hydroxyapatite Scaffold

黃湘翎(Hsiang-Ling Huang)

指導教授 ： 張博鈞

國立臺灣大學/醫學院/臨床牙醫學研究所/碩士(2021年)

https://doi.org/10.6342/NTU202103882

摘要

研究目的
在下顎大臼齒牙周分叉缺損的牙周再生手術成功率仍是牙周再生一大挑戰，本研究旨在製作客製化三維組織支架用以有效率促進齒槽骨再生。
研究材料與方法
本實驗第一部分是收集臺大醫院牙周病科在2017年2月到2020年12月所進行的下顎大臼齒牙根分岔處牙周再生手術的病例，牙周再生手術材料骨粉包含自體骨骨粉、異體骨骨粉及異種牛骨粉(DBBM, Deproteinized bovine bone mineral)搭配再生凝膠或牙周再生膜的應用。牙根分叉處骨缺損分為單純牙根分岔處缺損與合併牙根分岔與牙周齒槽骨周圍缺損兩大類，並比對手術前與手術後六個月的臨床根尖放射線影像上牙根分岔處，齒頸部到牙根分岔處齒槽骨線性高度的變化，以牙根分岔到新生成齒槽骨線性高度變化所占牙根分岔點到牙根分岔骨缺損的距離作為線性再生骨高度的比例，另外以牙根分岔到新生成齒槽骨線性高度變化所占患齒近心側與遠心側齒槽骨高度的中心點的比例做為校正骨再生比例。我們以齒槽骨高度的變化、骨再生比例、校正再生比例，三種評估方式作為牙周骨再生效果的評估。
實驗第二部分是評估三維快速成型生物支架在實驗豬下顎骨模型貼合度，利用實驗豬模擬下顎大臼齒牙根分叉的臨床破壞，並利用錐狀電腦斷層掃描實驗豬下顎骨模型後搭配三維影像編輯軟體設計骨缺損模型後，我們利用此模型進行模擬臨床客製化牙根分岔骨支架列印，用三維光固化列印技術列印樹脂模型作為對照組，同時羥基磷灰石彈性骨墨水採用生物列印方式印出三維骨支架。將樹脂骨塊與骨支架分別放回下顎豬骨缺損後，使用微米電腦斷層掃描後，利用影像軟體檢驗此骨生物支架與實驗豬下顎骨缺損到三維骨支架外緣的線性貼合度與比對我們電腦設計的骨塊形狀與三維骨支架相比的體積差異性。
結果
從臨床根尖片可以看出，我們利用手術前後牙根分岔處齒槽骨再生影像的變化，作為評估牙根分岔牙周再生手術的成功指標。在單純的牙根分岔處缺損，在影像上線性再生骨高度為1.45±1.15毫米，骨再生比例為50±40%與校正骨再生比例為39±30%。三種骨粉的使用當中，使用異種牛骨粉(DBBM, Deproteinized bovine bone mineral)達64±38%的骨再生效果，相較自體骨骨粉(Autogenous bone)的16±25%與異體骨骨粉(FDBA) 52±34%有較顯著的成果。女性病患相比於男性病患有顯著更好的牙周再生的成果。
在合併角狀骨缺損和牙根分岔處缺損，在影像上線性再生骨高度為1.35±1.25毫米，骨再生比例為50±34%與校正骨再生比例為38±32%。使用再生凝膠(EMD)較引導骨再生手術牙周再生膜有更顯著性的牙周再生效果。
在實驗豬下顎骨實驗之中，利用電腦斷層分析掃描後的羥基磷灰石生物支架對比電腦設計生物支架線性邊緣貼合度為 82.99±21.12% 和體積密合度85.58±5.48%。
結論
目前臨床牙根分岔再生大約有1.4mm 或40%的再生效果。在三維列印骨支架貼合實驗中，骨生物支架相比樹脂生物支架線性邊緣貼合度為82.99% 和體積密合度85.58%。

關鍵字

牙根分岔骨缺損 ； 組織支架 ； 骨再生 ； 三維列印

並列摘要

Objective
Regeneration of periodontal furcation remains a challenging type of surgery. The aim of this study was to develop a customized 3D tissue scaffold for effective regeneration of periodontal furcation defects.
Materials Methods
The first part of the study was a retrospective analysis of the regeneration outcomes of furcation defects based on radiography data from patients at National Taiwan University Hospital from February 2017 to December 2020. The regeneration bone materials include three kinds of bone substitutes with either membrane or EMD. Both pure furcation defects and combined furcation-angular defects were analyzed, and linear measurement on radiographic X-ray film was taken in the furcation area between the initial period and 6 months after surgery. Linear regeneration improvement, the ratio of linear regeneration improvement and the adjusted ratio of linear regeneration improvement were evaluated as parameters.
The second part of the study was an investigation of the fitness of a rapidly prototyped hydroxyapatite (HA) scaffold for furcation defects. The scaffolds were designed based on cone-beam computed tomography (CBCT) images of experimental furcation defects in pig jaws and printed using a HA-based bioink and an extrusion-based bioprinter. Resin blocks printed using stereolithography 3D printers served as controls. The resultant scaffolds were then placed in the defects, and micro-CT images were taken to measure the linear and volumetric fitness of the scaffolds. The linear adaptation rate was defined as the ratio of HA scaffold length to CAD scaffold length. The fitness rate was defined as the ratio of HA scaffold volume to CAD scaffold volume.
Results
In the pure furcation defects, linear regeneration improvement was 1.45±1.15 mm, the ratio of linear regeneration improvement was 50±40%, and the adjusted ratio of linear regeneration improvement was 39±30%. Among the bone substitutes, deproteinized bovine bone matrix showed the greatest regeneration capability, and females showed a greater improvement in linear furcation regeneration and a higher ratio of linear furcation improvement compared with males.
In the regeneration outcomes of combined furcation-angular defects, linear regeneration improvement was 1.35±1.25 mm, the ratio of linear regeneration improvement was 50±34%, and the adjusted ratio of linear regeneration improvement was 38±32%. Additionally, enamel matrix derivatives led to vastly superior regeneration outcomes relative to barrier membranes.
The HA scaffolds were rapidly prototyped based on CBCT images and were fabricated successfully. Compared with the designed area of regeneration and the resin block controls, the HA scaffold exhibited a linear adaptation rate of 82.99±21.12% and a fitness rate of 85.58±5.48%. The 3D-printed HA scaffold could be a potential strategy for promoting furcation defect regeneration.
Conclusion Current clinical regeneration strategies achieve approximately 1.4-mm or 40% improvement of furcation defects. CBCT-based 3D-printed HA scaffolds with 82.99% linear adaptation and 85.58% fitness could be a potential strategy for furcation defect regeneration.

並列關鍵字

furcation defects ； tissue scaffold ； bone regeneration ； three dimensional printing

參考文獻

Al-Shammari, K. F., C. E. Kazor, and H. L. Wang. 2001. 'Molar root anatomy and management of furcation defects', J Clin Periodontol, 28: 730-40.

Artzi, Z., H. Tal, O. Platner, N. Wasersprung, E. Weinberg, S. Slutzkey, N. Gozali, G. Carmeli, R. Herzberg, and A. Kozlovsky. 2015. 'Deproteinized bovine bone in association with guided tissue regeneration or enamel matrix derivatives procedures in aggressive periodontitis patients: a 1-year retrospective study', J Clin Periodontol, 42: 547-56.

Asa'ad, F., G. Pagni, S. P. Pilipchuk, A. B. Gianni, W. V. Giannobile, and G. Rasperini. 2016. '3D-Printed Scaffolds and Biomaterials: Review of Alveolar Bone Augmentation and Periodontal Regeneration Applications', Int J Dent, 2016: 1239842.

Association, World Medical. 2013. 'World Medical Association Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects', JAMA, 310: 2191-94.

Avila-Ortiz, Gustavo, Juan G. De Buitrago, and Michael S. Reddy. 2015. 'Periodontal Regeneration – Furcation Defects: A Systematic Review From the AAP Regeneration Workshop', Journal of Periodontology, 86: S108-S30.