Small Scale Robotics for Automated Dental Biofilm Theranostics

用于自动化牙科生物膜治疗的小型机器人

• 批准号: 10658028
• 负责人: Hyun Koo
• 金额: $ 63.21万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-22 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10658028
• 关键词: 3-Dimensional; 3D Print; Anatomy; Apical; Area; Biological; Cell Survival; Clinical; Collection; Complex; Coupled; Data; Dental; Detection; Development; Devices; Diagnosis; Diagnostic; Disinfection; Drug Delivery Systems; Electromagnetics; Endodontics; Ensure; Excision; Family suidae; Foundations; Future; Geometry; Human; In Situ; Infection; Irrigation; Jaw; Licensing; Location; Magnetism; Mammalian Cell; Manuals; Mechanics; Medicine; Methods; Microbial Biofilms; Modality; Modeling; Molds; Morphology; Motion; Movement; Nanotechnology; Needles; Oral; Oral cavity; Outcome; Performance; Peroxidases; Pharmaceutical Preparations; Polymers; Pre-Clinical Model; Procedures; Property; Pulp Canals; Retrieval; Robot; Robotics; Sampling; Shapes; Site; Small Business Innovation Research Grant; Structure; System; Technology; Testing; Therapeutic; Tooth structure; Ultrasonics; Visualization; antimicrobial; bactericide; clinical application; commercialization; conventional therapy; cost; cytotoxicity; dental biofilm; design; efficacy study; efficacy testing; follow-up; improved; in vivo; iron oxide nanoparticle; magnetic field; microrobot; nanoparticle; new technology; novel strategies; oral biofilm; particle; periapical; polymicrobial biofilm; prototype; response; robotic device; robotic system; soft tissue; stem cells; theranostics; tongue papilla; treatment optimization; 3-Dimensional; 3D Print; Anatomy; Apical; Area; Biological; Cell Survival; Clinical; Collection; Complex; Coupled; Data; Dental; Detection; Development; Devices; Diagnosis; Diagnostic; Disinfection; Drug Delivery Systems; Electromagnetics; Endodontics; Ensure; Excision; Family suidae; Foundations; Future; Geometry; Human; In Situ; Infection; Irrigation; Jaw; Licensing; Location; Magnetism; Mammalian Cell; Manuals; Mechanics; Medicine; Methods; Microbial Biofilms; Modality; Modeling; Molds; Morphology; Motion; Movement; Nanotechnology; Needles; Oral; Oral cavity; Outcome; Performance; Peroxidases; Pharmaceutical Preparations; Polymers; Pre-Clinical Model; Procedures; Property; Pulp Canals; Retrieval; Robot; Robotics; Sampling; Shapes; Site; Small Business Innovation Research Grant; Structure; System; Technology; Testing; Therapeutic; Tooth structure; Ultrasonics; Visualization; antimicrobial; bactericide; clinical application; commercialization; conventional therapy; cost; cytotoxicity; dental biofilm; design; efficacy study; efficacy testing; follow-up; improved; in vivo; iron oxide nanoparticle; magnetic field; microrobot; nanoparticle; new technology; novel strategies; oral biofilm; particle; periapical; polymicrobial biofilm; prototype; response; robotic device; robotic system; soft tissue; stem cells; theranostics; tongue papilla; treatment optimization

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.

项目摘要 与口腔生物膜相关的感染仍然是一个持久且昂贵的临床问题。现有治疗无法 同时杀死并物理破坏生物膜，需要手动生物膜去除程序 难以到达牙髓管系统等地区的疗效降低。此外， 在临床程序期间进行诊断样品检索的选择是有限的。有效，自动化 需要精确靶向复杂解剖区域的技术来检索样品，杀死和 去除生物膜，并在现场输送药物。我们提出了一种新颖的方法，结合了纳米技术和 机器人技术开发了第一个用于牙髓的靶向消毒，去除和采样的自动化系统 生物膜。我们已经使用催化纳米颗粒设计了小型机器人作为显示的块 具有多功能性的无系带控制运动。我们的方法利用氧化铁纳米颗粒（IONP） （i）产生杀菌和生物膜降解反应性分子的双重催化磁性特性，原位 （ii）通过磁场驱动的机器人组件去除破坏的生物膜，称为催化抗生素 机器人（汽车）。初步数据表明，汽车以高精度去除并收集生物膜 与常规治疗相比，包括受限的牙髓空间和功效。通过调谐 磁催化特性和汽车系统的控制，我们将开发机器人装置 适合口腔的原型用于同时牙髓生物膜处理，去除和样品 检索。我们建议进一步改善与临床电磁控制器相结合的IONP制造机器人 开发两个基于汽车的口服生物电视平台。 （AIM 1）由汇总IONP形成的CAR1将是 用于催化细菌杀伤，生物膜治疗和从根管中检索样品，以进行诊断分析。 我们将确定CAR1S改进的关键参数，评估磁控制，生物活性和 可视化/跟踪。将评估CAR1的目标难以到达的区域，例如C形/弯曲 运河和地峡，以及处理和检索生物膜。我们将表征并改善CAR1控制 首先使用具有不同管道形态的3D打印牙齿复制品来改善运动和可控性， 然后使用离体萃取的牙齿/典型和猪颌模型测试我们的系统。 （AIM 2）CAR2将 由3D微镀官能聚合物与嵌入式IONP进行生物膜破坏，检索， 和顶端地区的药物输送。我们将优化磁控制和跟踪，抗体膜活性和 触发了货物输送，测试功效以去除和检索生物膜。我们将使用混合 物种生物膜和对根管的顶端区域的生物膜和可操作性，在3D打印的牙齿上概括了 离体模型，同时严格评估适合口腔的几何形状的机器人装置 与常规治疗的比较。我们预计拟议研究的结果将导致 为自动化生物膜疗法而开发的第一个机器人生物电视系统用于牙科医学应用。