Small Scale Robotics for Automated Dental Biofilm Treatment

用于自动化牙科生物膜治疗的小型机器人

• 批准号: 10427076
• 负责人: Hyun Koo
• 金额: $ 65.64万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-21 至 2023-09-21
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10427076
• 关键词: 3-Dimensional; 3D Print; Adhesions; Anatomy; Apical; Area; Bacteria; Biological; Catalysis; Cell Survival; Cells; Clinical; Complex; Data; Dental; Development; Devices; Dextrans; Disinfection; Drug Delivery Systems; Endodontics; Ensure; Excision; Foundations; Future; In Situ; Infection; Lead; Licensing; Location; Magnetism; Mammalian Cell; Manuals; Mechanics; Methods; Microbial Biofilms; Modality; Modeling; Modification; Molds; Morphology; Motion; Movement; Nanotechnology; Oral; Outcome; Particle Size; Performance; Peroxidases; Polymers; Pre-Clinical Model; Procedures; Property; Pulp Canals; Robot; Robotics; Small Business Innovation Research Grant; Structure; Surface; System; Technology; Therapeutic; Tooth structure; antimicrobial; bactericide; base; clinical application; cost; cytotoxicity; dental biofilm; design; efficacy study; efficacy testing; follow-up; improved; in vivo; innovation; iron oxide nanoparticle; magnetic field; mechanical properties; nanoparticle; new technology; novel strategies; oral biofilm; oral infection; particle; physical property; polymicrobial biofilm; response; robotic system; stem cells; tongue papilla

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 limited efficacy in difficult to reach areas such as the endodontic canal systems. New efficacious, automated technologies capable of precisely targeting complex anatomical areas are needed to kill bacteria as well as degrade and remove biofilm structure. We propose a novel approach that combines nanotechnology and robotics to develop the first automated biofilm eradication platform. We have designed small-scale robots using catalytic nanoparticles as building blocks that display tether-free controlled motion with multifunctionality. Our approach exploits 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 target and remove biofilms with high precision and efficacy, including confined endodontic spaces. We hypothesize that, by tuning CARs magneto-catalytic properties to enhance the ‘kill-degrade-and-remove’ mechanism, improved antibiofilm efficacy and maneuverability can be achieved for targeted endodontic disinfection and drug delivery. To achieve this, we propose (Aim 1) to improve the catalytic and magnetic properties of IONP building blocks via physicochemical modifications including particle size and surface functionalization to enhance catalysis, biofilm targeting and controllability. We will assess catalytic efficiency, magnetic field response, and bioactivity to identify key parameters for CAR improvement. Then, optimized IONPs will be incorporated into two CARs platforms. CAR1s, formed from aggregated IONP, will be used for catalytic bacterial killing and biofilm treatment in root canal systems (Aim 2). We will determine the principles governing magnetic field response and antibiofilm activity, and test the efficacy of these robots to remove biofilms in difficult-to-reach areas in a controlled manner. We will assess bioactivity and maneuverability considering key anatomical and biological complexities using mixed-species biofilm and diverse canal morphologies recapitulated in 3D-printed teeth and ex vivo models. In the second platform, CAR2s will be fabricated by 3D micromolding of functional polymers with embedded IONPs for biofilm removal and drug delivery in the interior of tooth canal (Aim 3). We will study and optimize magnetic control, antibiofilm activity and triggered cargo delivery conditions. Thereafter, we will apply information from the mechanistic studies to design and evaluate CAR2s for simultaneous biofilm removal and drug delivery at the apical region using 3D printed and ex vivo tooth models with mixed-species biofilms. Altogether, we expect that the outcomes of the proposed studies will lead to the first robotic systems developed for automated biofilm treatment for dental applications.

口腔生物膜相关的感染仍然是一个持续的和昂贵的临床问题。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， 在难以到达的区域例如牙髓管系统中，其麻烦且功效有限。新 需要能够精确瞄准复杂解剖区域的有效自动化技术来杀死 细菌以及降解和去除生物膜结构。我们提出了一种新颖的方法， 纳米技术和机器人技术开发第一个自动生物膜根除平台。我们设计了 使用催化纳米颗粒作为积木的小型机器人， 多功能性我们的方法利用具有双重催化-磁性特性的氧化铁纳米颗粒（IONP） （i）原位产生杀菌和生物膜降解反应性分子，和（ii）除去被破坏的生物膜 通过被称为催化抗生物膜机器人（汽车）的磁场驱动的机器人组件。初步数据 证明汽车以高精度和有效性局部靶向和去除生物膜，包括限制性的生物膜。 牙髓间隙我们假设，通过调整汽车的磁催化特性来增强 可通过“降解-去除”机理，提高涂膜的功效和可操作性， 实现有针对性的根管消毒和药物输送。为达致这个目的，我们建议（目的1） 通过物理化学修饰改善IONP结构单元的催化和磁性 包括颗粒尺寸和表面功能化以增强催化、生物膜靶向和可控性。我们 将评估催化效率、磁场响应和生物活性，以确定CAR的关键参数 改进.然后，优化的IONP将被纳入两个汽车平台。CAR 1，由 聚合的IONP将用于根管系统中的催化细菌杀灭和生物膜处理（目的2）。 我们将确定磁场响应和磁膜活动的原理，并测试其功效。 这些机器人以可控的方式清除难以到达区域的生物膜。我们将评估生物活性 和可操作性，考虑到关键的解剖学和生物学复杂性，使用混合物种生物膜， 在3D打印牙齿和离体模型中重现了不同的根管形态。在第二个平台中，CAR 2 将通过具有嵌入式IONP的功能聚合物的3D微成型制造，用于生物膜去除和药物 目的3：在根管内给药。我们将研究和优化磁控制，磁膜活性， 触发货物交付条件。此后，我们将应用机理研究中的信息进行设计 并使用3D打印技术评估CAR 2在顶端区域同时去除生物膜和递送药物的能力。 和具有混合物种生物膜的离体牙齿模型。总的来说，我们希望拟议的 研究将导致第一个机器人系统开发的自动生物膜处理牙科应用。