研發有殼層微氣泡沖洗液與探討超音波沖洗器械於改善根管治療效用之研究

Abstract

根管治療的主要目標為移除根管內發炎的牙髓組織及細菌，以防止牙根尖周圍炎。因此，根管清潔的程度是影響根管治療成功率最重要的因素。許多研究指出，超音波沖洗法較其他沖洗方式有較好的根管清潔效果。然而，根管系統是一個極複雜的結構，研究顯示，現今任何根管沖洗方式都無法達到理想的清潔效果，尤其牙根尖區域為最容易有感染源殘留的區域。超音波沖洗法是一種臨床被廣泛使用的根管沖洗法，而其產生的穴蝕效應為其清潔效用的主要來源之一。然而，研究發現超音波沖洗器械需在高功率的驅動下才能有效誘發穴蝕效應產生，但於此同時亦會增加器械斷裂的臨床風險。因此，在本研究中會藉由探討超音波沖洗器械影響誘發穴蝕效應產生的參數，以進一步了解穴蝕效應的發生機制，進而優化現今根管治療的治療策略。 微氣泡在醫療領域中因具有產生聲穿孔效應、藥物傳遞以及增加超音波影像對比度的特色，在醫療領域中已被廣為應用，但在根管治療中卻仍鮮少有微氣泡相關之應用及研究。由於微氣泡能夠於沖洗液中提供穴蝕核，輔助穴蝕效應的發生，具有降低誘發穴蝕效應閾值及增加根管清潔效率的潛力。因此，本研究亦研發含有殼層微氣泡之沖洗液，以期能於根管治療時降低誘發穴蝕效應閾值進而增加根管清潔效率。最後，以口外牙模型進行所研發之治療策略的驗證。 在評估超音波沖洗器械之穴蝕效應產生能力的方法上，長期欠缺具一定解析度且能的同步定量的評估法，過去僅對產生之穴蝕效應進行定性評估而無法提供量化的數據。高頻超音波影像系統能夠提供高解析度之即時影像，在本研究中，我們首次使用高頻超音波影像系統成功即時觀察並定量超音波沖洗器械在根管中引發之穴蝕效應，並且在空間、時間及強度上更細微的量化超音波器械產生的穴蝕效應。此外，藉由超音波沖洗器械之振盪模式，發現穴蝕效應受到諸多參數交互影響。 本研究中亦製作含無殼層及有殼層微氣泡之沖洗液用於超音波沖洗法中，結果證明使用含無殼層微氣泡及有殼層微氣泡調製出之沖洗液，皆可成功降低超音波沖洗器械誘發穴蝕效應的閾值。最後於口外牙實驗中，證明穴蝕效應對於根管清潔效用之正向關係，同時驗證有殼層之微氣泡沖洗液之根管清潔效用，尤其對於最容易殘留感染源的根尖處有顯著提升。 總結來說，本研究中首次使用高頻超音波影像系統驗證超音波沖洗器械誘發之穴蝕效應，同時證明穴蝕效應對根管清潔效用的正向影響。我們亦研發了可用於根管治療之新式有殼層微氣泡沖洗液，並驗證此一具創新性之根管清潔策略可顯著改善根管清潔效用。而超音波沖洗機能量的降低可助於在降低臨床器械斷裂風險的同時，達到更安全且優化的根管清潔效果，進而增加根管治療成功率。而根據本研究對於穴蝕效應機制的探討基礎上，可於未來研發新式超音波能量傳導設備以更有效率的於根管中誘發穴蝕效應。並且，透過於微氣泡殼層上搭載抗菌藥物，以研發新一代具抗菌效果之有殼層微氣泡沖洗液。

The primary objective of root canal treatment is to remove inflamed pulp tissue and bacteria within the root canal to prevent apical periodontitis. Therefore, cleaning efficacy of root canal is the most critical factor affecting the success rate of root canal treatment. Several studies have shown that ultrasonic irrigation provides better root canal cleaning efficacy than other irrigation methods. However, the complex structure of the root canal system poses a challenge to achieving ideal cleaning efficacy, particularly in the apical region. Ultrasonic irrigation is a widely used clinical method for root canal cleaning, and the cavitation effect is one of the physical mechanisms expected to achieve cleaning ability. However, studies have found that the power of ultrasonic irrigation instruments used to trigger the cavitation effect is high and thus increases the risk of instrumental fracture during clinical treatment. Accordingly, in this study, we first investigated the mechanisms of the induction of cavitation effect by ultrasonic irrigation instruments to optimize the current root canal treatment strategy. Microbubbles have been widely used in the medical field due to their ability to produce sonoporation, drug delivery, and the enhancement of ultrasound image contrast. However, there have been limited studies on the applications of microbubbles in root canal treatment. Since microbubbles have the potential to serve as cavitation nuclei in the irrigants, the reduction of the threshold for inducing cavitation effect followed by the improvement of root canal cleaning efficiency may be achieved. Therefore, we developed a novel shelled microbubble-based irrigants aiming to reduce the threshold for inducing the cavitation effect and improve the root canal cleaning efficiency during root canal treatment. Finally, we validated the effectiveness of the designed strategies using an ex vivo tooth model. Currently, there is no appropriate method that allows us to real-time image and quantify the cavitation events in root canal models. Hence, cavitation effects have always been qualitatively evaluated without direct evidence of their occurrence. Since the high-frequency ultrasonic imaging system has high image resolution and can be used for real-time observation, for the first time, we used it to successfully observe and quantify the cavitation effects induced by ultrasonic irrigation instruments within the root canal, enabling a more refined quantification of the cavitation effects in terms of space, time, and intensity. Furthermore, by examining the oscillation mode of the ultrasonic irrigation instruments, we found that many parameters crossly affect the cavitation effect. We also developed irrigants containing non-shelled or shelled microbubbles and applied them during ultrasonic irrigation. It was found that the reduced threshold for inducing cavitation effect could be successfully achieved by using non-shelled or shelled microbubble-based irrigants. Finally, we proved the positive correlation between the cavitation effect and root canal cleaning efficacy in the ex vivo tooth model. The root canal cleaning efficacy, especially for the apical region where infection sources are more likely to remain, was also significantly improved when applying the developed shelled microbubble-based irrigants. In summary, we have successfully demonstrated the occurrence of the cavitation events and proved the positive correlation between the cavitation effect and root canal cleaning efficacy by utilizing the high-frequency ultrasound imaging system. Additionally, we have developed an innovative strategy for root canal treatment that involves using shelled microbubble-based irrigants, which has led to a significant improvement in root canal cleaning efficacy. This approach reduces the utilization of ultrasonic power, thereby lowering the risk of clinical instrumental fracture and ensuring safer and optimized root canal cleaning, thus increasing the success rate of root canal treatment. Future research can focus on developing novel ultrasonic devices that can efficiently transmit energy to induce the cavitation effect. In addition, the use of next-generation irrigants with antibacterial effects by loading antibacterial drugs on the shell layer of microbubbles could also be explored.