從工程資訊學到實驗來探討提高植牙可靠性、穩定性與存活率的技術創新

Abstract

簡介： 從Branemark教授發現”骨整合” (osseointegration) 以來，使用牙科人工植體(dental implant)來修補口腔內的缺牙區已經有四十多年的歷史, 並在最近二十年間有突飛猛進的發展。由於高齡人口增加與生活水準的提升，使得牙科人工植體的需求日益提高。舉凡植體材質、形狀、表面處理、連接處設計、支台的設計與材質、以及相關的手術步驟、輔助工具、影像分析軟體、補骨所用的材料、併發症的處理… 等等，都有許多學者與廠商投入其中的研發與改良。在這塊競爭性很高的領域中，有兩個重要的問題被提出並且尋求解答： 1. 如何用有效率的方法來研究並分析近年快速發表出來的論文與專利，以獲得完整的專業知識、預測植體製造業未來的發展趨勢、並且結合臨床與研發上的發現以期解決更多問題。 2. 目前對於改良牙科人工植體成功率方面的評估方式仍有爭議。一直以來植牙區的骨質(bone quality) 被認為是影響植體成功率的重要因子，因此有許多植體設計與手術流程的改良，希望能改善不良骨質區的植體成功率。然而文獻中這些改良未必有效，我們發現其癥結點有二： 首先是對於要被改善的對象欠缺一個通用且可靠的分類法則。若無法客觀篩選想改善的對象的話，就無法確認其效果是否有效。臨床上鑑定骨質不良的方式有四種：使用放射線影像、取下骨塊以組織切片觀察、手術醫師鑽骨時的手感、以及用特定廠牌植牙手機感應回饋輸出鑽骨時的扭力值。其中最常被使用的是”手術醫師鑽骨的手感”。然而手術醫師彼此之間並無明確的標準來界定手感所代表的骨質，使得骨質分類的客觀性與可信度存疑，進而可能影響相關研究結果。 其二就是不確定哪一種評估改善結果的方式最具代表性。植體植入時的初始穩定度(initial stability) 被認為是預測植體是否成功的重要指標。臨床上被認為可代表植體穩定度而且屬於非侵入性的評估方法有兩種：植體植入時的扭力(insertion torque, IT) 以及使用自然頻率分析所得出的植體穩定商值(implant stability quotient, ISQ)。但是由於影響這兩項數值的因子除了手術程序之外，還包含了植體的設計與之前所提到”欠缺客觀評估標準”的骨質。使得這兩種評估方法孰優孰劣以及是否能真正代表植體穩定度尚有爭議。 目的、材料與方法： 本論文將分為三個部份來探討以上所述之兩個重要問題。 1. 採用工程資訊學的方法來建構一個快速統整牙科植體專利以獲得專業資訊的程序，並結合臨床統合分析結果來預測牙科人工植體發展的未來趨勢。本論文中利用建構牙科人工植體本體論(ontology)的方式，先收集註冊於美國國家專利與商標局(United State Patent and Trademark Office)的牙科人工植體專利，然後由牙科植體專家(implant specialist)篩選出有關人工植體連接處設計 (implant connection design)的專利，進行文字探勘(text mining)，篩選出關鍵詞並以此來分群(clustering)，以分析與連接處設計有關的專利發展趨勢。並且也搜尋有關人工植體連接處的臨床試驗(clinical trial)文獻，來探討連接處設計與植體成功率的相關性。 2. 以客觀的測試塊來測試手術醫師鑽骨時的手感，探討不同醫師骨質評估的差異性以及是否能由經驗來累積手感的準確度。論文中以不同密度的聚氨酯(polyurethane)所做的生物力學測試塊 (biomechanical test block)來模擬不同硬度的齒槽骨，邀請有經驗的植牙手術醫師與一般開業牙醫師以直徑2mm 的前導鑚針 (pilot drill) 在不同測試塊上鑽洞，並依照鑽骨時的手感來判定該測試塊的硬度與骨質類別。然後分別看這兩群醫師是否能夠準確的判定出測試塊的硬度順序。 3. 以客觀的測試塊來評估植體形狀、手術程序、以及測試塊硬度對於植體植入扭力(IT)與植體穩定商值(ISQ) 產生何種影響。採用如上述第二部分所使用的聚氨酯生物力學測試塊共四種骨質，將四種不同形狀或直徑的牙科人工植體分別依照廠商建議的手術步驟植入測試塊，在植入過程中每隔0.5mm植入深度連續測量IT、最大植入扭力(peak insertion torque, PIT) 與ISQ，並且依IT隨時間的變化計算出該植入過程的植入能量(insertion energy, IE)。 結果、討論與結論： 1. 搜尋出20篇有提到牙科人工植體連接處設計的專利，使用Normalized Term Frequency-Inverse Document Frequency (NTF-IDF)的分法擷取出關鍵詞(key phrases)，並據此將專利分為四群。以便找出值得分析比較的設計。並且將這些關鍵詞用來搜尋臨床試驗。找到六篇與植體連接處相關的臨床試驗，並發現支台內縮(platform switching) 這個詞為最常被提及的關鍵詞。因此以這個設計與其他設計來做統合分析相比較，探討支台內縮是否影響植體成功率(implant survival rate)與邊緣骨吸收量(marginal bone loss)。發現到植體成功率方面，支台內縮與一般的連接設計無明顯差異；而在邊緣骨吸收量方面，支台內縮似乎比其他連接設計要少，雖然減少量在臨床是否能達到顯著的影響還有待商榷。 2. 不同的牙醫師在診斷測試塊的硬度時有不同的標準。受試者當中六位較有經驗的口腔外科醫師能夠正確的排列出測試塊硬度的順序，而五十九位一般牙醫師中只有二十四位能夠正確診斷。顯示在進行這類與分類骨質有關的研究或臨床試驗時，必須能夠教育手術醫師正確診斷出骨質。此外，或許必須發展一套更客觀的評估骨質方式。 3. 當植體能夠完全植入測試塊時，邊緣皮質骨的有無與植體形狀比較容易影響連續紀錄植入扭力的數據圖(insertion torque profile)，而ISQ 數值受到的影響較小。鑽孔步驟在某些測試塊中會影響到植體是否能在適當扭力下完全被植入。因此依此方法可以在未來繼續探討如何使牙科人工植體能在適當的扭力下植入並且得到高ISQ值，以提高有意義的植體穩定度。而研究中也發現植體的設計會影響植入時植入扭力的變化。不同植體可在相同測試塊上得到相近的最終ISQ值卻有完全不同的最終扭力值(final insertion torque)。未來應進一步探討不同植體在不同骨質的ISQ與IT值與植體受力時微移動(micromotion)之間的關係，以釐清ISQ與IT是否真能代表植體初始穩定度。

Introduction: Dental implants have been used to replace missing teeth and many developments have been introduced over the last two decades. Both academic and industry researchers have invested substantial amounts in research and development to improve the implant materials, designs, surface treatments, implant-abutment connections, and related surgical procedures. In this highly competitive field, there are two important issues to be analyzed and evaluated: 1. More efficient methods are needed to analyze the fast increasing publications and patents in order to predict the R&D trends of the implant industry and promote more advanced clinical solutions including methods, materials, and devices. 2. Many implant designs and surgical protocols claimed to improve implant survival rate or implant stability at the implant site without adequate evaluation of bone quality. Effectiveness of these claims are questionable due to controversies in defining the bone quality and implant stability. Many clinicians evaluate bone quality by using tactile feedback while drilling the bone. Evaluation discrepancy between clinicians has become a confounding factor across clinical trials. Implant initial stability is an important predictor of implant survival. Two non-invasive clinical methods are frequently used to evaluate implant stability: insertion torque (IT) during implant placement and natural frequency analysis or “implant stability quotient” (ISQ) after implant placement. There is no research demonstration which method best represents “true implant initial stability.” Purposes, Materials and Methods 1. Using a cooperative study including researchers of engineering informatics and dental implant specialist (domain experts), a knowledge centric methodology for dental implant technology assessment was introduced to speed the process of patent analysis. This study included a domain specific ontology-based patent analysis of dental implant connections and a meta‐analysis of the related clinical trials. Text mining, extracting key phrases, creating the domain ontology, and analyzing clusters of patents related to implant connection were reviewed. Relations between implant connections and survival rate and marginal bone loss were evaluated using a meta-analysis of related clinical trials retrieved using the patent key phrases. 2. Six oral surgeons and 59 general dentists were invited to evaluate the bone quality of artificial bone blocks fabricated from polyurethane foam blocks (SawbonesR) consisting of different densities. The bone density and quality was evaluated using the tactile feedback obtained by drilling with a 2mm twist drill. A visual analog scale value of bone density and bone quality classification were recorded for each test block. 3. The effects of implant design and bone quality on insertion torque, implant stability quotient, and insertion energy (IE) were studied. Test blocks were used to simulate low or low-to-medium density cancellous bone with and without a thin cortical layer. Four different implants were placed in accordance with the manufacturer’s instructions. The IT and ISQ were recorded for every 0.5-mm of inserted length during implant insertion, and the IE was calculated. Results, Discussions and Conclusions 1. Twenty patents related to implant connection were collected from USPTO and divided into four technology clusters. The key phrases from the patents were used for clustering and to search for related clinical trials and research publications. Platform switching was the key phrase with the highest frequency in related clinical trials. Six trials were included for meta-analysis to evaluate the effect of platform switching on implant survival rate and marginal bone loss. This methodology can be applied to a wide variety of medical and dental devices to link successful clinical trials and their effectiveness to patent designs and innovations in order to provide a new means to qualify patent value. 2. Discrepancy in evaluating bone quality exists among clinicians. Experienced oral surgeons evaluate bone quality more accurately than general dentists. Therefore, it is necessary to develop a calibration system to decrease the measurement discrepancy between dental professionals. 3. The presence of cortical bone and implant designs significantly affect dynamic IT profiles during implant insertion, while not similarly affecting ISQ. Future studies are needed to explore parameters representing implant stability and to modify surgical protocols to improve the ISQ and IT.