UltraSOuNd-controlled drug release from Antimicrobial particles for denTAl tissues

龋齿是指口腔中细菌产生的酸性物质破坏了坚硬的牙齿组织。人们认识到，由于牙齿的破坏和牙髓(神经)的感染，许多儿童和成人遭受不必要的疼痛。如果不进行治疗，那么最终需要拔掉牙齿。这种非传染性疾病是完全可以预防的。然而，消除启动这一破坏性过程的细菌所在的已建立的口腔生物膜是一个挑战。一旦细菌穿透牙齿的釉质，它们进入牙髓的途径就得益于牙本质的结构。这种坚硬的牙齿组织包含许多微通道(牙本质小管)，它们从牙齿的外表面传递到内部的牙髓。这种生物膜可以通过饮食和使用含氟牙膏来防止，但一旦形成，就很难根除。抗生素不是很有效，因为没有血液供应使它们能够到达感染区域，因此在治疗牙齿感染时被滥用。在这个研究计划中，我们的目标是用一种基于一种新的颗粒平台的跨学科方法来快速应对生物被膜感染，这种局部给药平台使用超声波作为外部物理刺激，触发包裹的抗菌剂从颗粒内部释放。我们组建了一个拥有化学、牙科和流体力学专业知识的多学科团队，研究超声波引发的二氧化硅颗粒在牙髓模型结构、生物膜和外植牙中的激活和传递。为此，我们将使用现有的牙科仪器，如牙科诊所常用的千赫频率的超声波定标器。我们将使用独特的流动表征方法来阐明超声波对颗粒运动的影响，将颗粒引导到生物膜中，并对药剂释放产生影响。我们选择使用二氧化硅颗粒，因为它们的生物兼容性和二氧化硅材料在牙科中的广泛适用性。我们将使用颗粒设计来控制抗菌剂的包裹，只有在使用超声波触发器时才能释放抗菌剂。这些颗粒将被开发出具有发光特性，以允许光学检测它们在流动中的运动，并监测抗菌剂在溶液中的释放。我们的目标是解决牙科保健中的问题，并通过我们的IMPACT活动加快牙科实践中基于颗粒的治疗。这项拟议的研究还将为在感染的本地化治疗具有挑战性的其他医疗保健领域(假肢、导管)提供抗生素的革命性方法。

Dental caries is the breakdown of the hard dental tissues by the acid produced by bacteria in the mouth. It is recognised that many children and adults suffer unnecessary pain due to the destruction of the tooth and infection of the pulp (nerve). If not treated, then the tooth needs to ultimately be extracted. This non-communicable disease is entirely preventable. Eliminating the established oral biofilm that houses the bacteria that start this destructive process is however a challenge. Once bacteria break through the enamel of the tooth their passage to the pulp of the tooth is helped by the structure of dentine. This hard, dental tissue contains numerous microchannels (dentine tubules), which communicate from the external surface of the tooth to the internal pulp. The biofilm may be prevented by diet and use of fluoride toothpastes but once established is difficult to eradicate. Antibiotics are not very effective as there is no blood supply that enables them to reach the infected area and are therefore misused in the treatment of dental infections. A local treatment is proposed that allows for the rapid release of antibacterial agents at the site of infection.In this research programme we aim to rapidly tackle biofilm infections with an interdisciplinary approach based on a novel particle platform for localised drug-delivery using ultrasound as an external-physical stimulus to trigger the release of an encapsulated antibacterial agent from inside the particles. We have assembled a multidisciplinary team with expertise in chemistry, dentistry and fluid mechanics to study the ultrasound triggered activation and delivery of the silica particles in endodontic model structures, biofilms and explanted teeth. To this end we will use existing dental instruments such as ultrasonic scalers in kHz frequencies which are commonly used in dental clinics. We will employ unique flow characterisation approaches to clarify the effects of ultrasound on particle motion, directing the particles to the biofilm, and on agent release. We have chosen to work with silica particles due to their biocompatibility and the wide applicability of silica materials in dentistry. We will use particle designs to control the entrapment of the antibacterial agent which can only be released upon application of the ultrasound trigger. The particles will be developed with luminescent properties to allow optical detection of their motion in flow and to monitor the antibacterial agent release in solution. We aim to tackle problems in dental healthcare and to accelerate particle based therapies in dental practice through our impact activities. The proposed research will also provide revolutionary ways for antibiotic delivery in other areas of healthcare where localized treatment of infection is challenging (prosthetics, catheters).