Small Scale Robotics for Automated Dental Biofilm Theranostics

项目摘要 口腔生物被膜相关感染仍然是一个持久且代价高昂的临床问题。现有的治疗方法无法 同时杀死和物理破坏生物膜，并需要手动生物膜去除程序， 在难以触及的区域，如根管系统，效率降低，笨重。此外， 在临床过程中，用于诊断的样本检索的选择有限。高效、自动化 需要能够精确定位复杂解剖区域的技术来提取样本、杀死和 清除生物膜，并在现场运送药物。我们提出了一种结合纳米技术和 机器人公司将开发第一个用于根管治疗的靶向消毒、移除和采样的自动化系统 生物膜。我们已经设计了小型机器人，使用催化纳米颗粒作为构建块来展示 多功能无系绳可控运动。我们的方法利用氧化铁纳米颗粒(IONPs) 双重催化-磁性，其(I)在原位产生杀菌和降解活性分子的生物膜， 和(Ii)通过被称为催化抗菌膜的磁场驱动的机器人组件去除破坏的生物膜 机器人(汽车)。初步数据表明，汽车局部清除和收集生物膜的精度很高 以及与常规治疗相比的疗效，包括受限的牙髓间隙。通过调整 对汽车系统的磁催化特性和控制，我们将开发机器人装置 适用于同时进行牙髓生物膜治疗、去除和取样的口腔原型 取回。我们建议进一步改进IONP制造的机器人与临床电磁控制器相结合 开发两个基于CARS的口腔生物装置平台。(目标1)由综合IONP组成的CAR1将是 用于催化杀菌、生物膜处理和从根管中提取样本进行诊断分析。 我们将确定CAR1改进的关键参数，评估磁控制、生物活性和 可视化/跟踪。CAR1将针对难以触及的区域进行评估，例如C形/弧形 运河和地峡，以及治疗和回收生物膜。我们将确定和改进CAR1控制 首先使用具有不同根管形态的3D打印牙齿复制品来改善移动和可控性， 然后使用体外拔出的牙齿/打字机和猪下颌模型测试我们的系统。(目标2)CAR2将 通过嵌入IONPs的3D微模塑功能聚合物来制造，用于生物膜的破坏，回收， 以及在根尖区域的药物输送。我们将优化磁控和跟踪、抗生物膜活性和 触发了货物运送，测试了移除和回收生物膜的效果。我们将使用混合-评估生物活性- 3D打印牙根尖区生物膜的种类和可操作性 体外模型，同时严格评估机器人设备的几何形状适合口腔 与常规治疗进行比较。我们预计拟议研究的结果将导致 第一个机器人生物装置系统开发的自动化生物膜治疗在牙科医学中的应用。

PROJECT ABSTRACT Oral biofilm-related infections remain a persistent and costly clinical problem. Existing treatments are unable to simultaneously kill and physically disrupt biofilms and require manual biofilm removal procedures that are cumbersome with reduced efficacy in difficult to reach areas such as endodontic canal systems. Furthermore, options for sample retrieval for diagnostics during clinical procedures are limited. Efficacious, automated technologies capable of precisely targeting complex anatomical areas are needed to retrieve samples, kill and remove biofilms, and deliver drugs on site. We propose a novel approach combining nanotechnology and robotics to develop the first automated system for targeted disinfection, removal, and sampling of endodontic biofilms. We have designed small-scale robots using catalytic nanoparticles as building blocks that display tether-free controlled motion with multifunctionality. Our approach utilizes iron oxide nanoparticles (IONPs) with dual catalytic-magnetic properties that (i) generate bactericidal and biofilm degrading reactive molecules in situ, and (ii) remove the disrupted biofilm via magnetic-field driven robotic assemblies termed Catalytic Antibiofilm Robots (CARs). Preliminary data demonstrate that CARs locally remove and collect biofilms with high precision and efficacy in comparison to conventional treatment, including confined endodontic spaces. By tuning the magneto-catalytic properties and control of the CARs systems, we will develop robotic device prototypes that fit the oral cavity for simultaneous endodontic biofilm treatment, removal and sample retrieval. We propose to further improve IONP-made robots coupled with a clinical electromagnetic controller to develop two CARs-based oral biodevice platforms. (Aim 1) CAR1s, formed from aggregated IONP, will be used for catalytic bacterial killing, biofilm treatment, and sample retrieval from root canals for diagnostic analysis. We will identify key parameters for CAR1s improvement, assessing magnetic control, bioactivity and visualization/tracking. CAR1s will be evaluated for targeting difficult-to-reach areas, such as C-shaped/curved canals and isthmus, as well as treating and retrieving biofilms. We will characterize and improve CAR1 control first using 3D-printed tooth replicas with diverse canal morphologies to improve movement and controllability, followed by testing our system using ex vivo extracted tooth/typodont and pig jaw models. (Aim 2) CAR2s will be fabricated by 3D micromolding functional polymers with embedded IONPs for biofilm disruption, retrieval, and drug delivery at the apical region. We will optimize magnetic control and tracking, antibiofilm activity and triggered cargo delivery, testing efficacy to remove and retrieve biofilms. We will assess bioactivity using mixed- species biofilms and maneuverability to the apical region of the root canal recapitulated in 3D-printed teeth and ex vivo models, while rigorously evaluating the robotic device in geometries suited to the oral cavity with comparisons against conventional treatment. We expect the outcomes of the proposed studies will lead to the first robotic biodevice system developed for automated biofilm theranostics for applications in dental medicine.