TMJ SYMPHONY Systems-integrated model and mechanisms of patient-centered holistic outcomes and network-supported training and therapy

项目总结 在美国，大约有3500万人受到颞下颌关节紊乱病(TMD)的影响， 女性寻求治疗的可能性是男性的3-8倍，这使得它非常普遍和昂贵 医疗保健挑战需要立即关注。确定TMD的特定和可治疗的原因是 困难，因为它是由复杂的、多方面的相互作用引起的，涉及生物力学、生物学和 人们对心理社会因素知之甚少。由于这些重大的知识差距和有限的 对TMD、成功的长期治疗方法和患者特有的综合机制的理解 目前还没有治疗指南。我们的建议，TMJ交响乐：系统集成模型和 以患者为中心的整体结果和网络支持的培训和治疗的机制将战略性地 联合一个多学科和多规模的国家财团，以破译 使用计算、细胞、动物和人体模型研究TMJ的结构-功能-疼痛。 这群才华横溢的调查人员将以现有的MPI U01为基础，专注于健康的TMJ结构- 院内NIDCR临床研究人员与院外基础科学家之间的作用。它将利用现有的 国家资源(例如，Re-Join、OPPERA、DOCTRC)，以加快发现和 直接解决TMJ疾病诊断的技术(例如，多模式深度表型、生物标记物)， 从健康的TMJ到临床前的TMJ疾病到TMJ变性/疼痛，治疗(例如，非侵入性 整体/保守疗法、干细胞疗法、组织工程构建)，并改善结果 通过了解患者的适应能力、身心-TMJ联系和环境进行评估 不同患者的TMJ健康/疾病对行为和认知的影响以及社会决定因素 人口。在这个规划阶段，我们将制定战略，在机械知识和 确定组合病因学，同时扩大护理选择，提供循证治疗决策， 以及未来十年针对患者的治疗方式。我们乐观的理由是我们的新 已在改进的方法和技术(例如，椅子侧TMJ结构-功能-疼痛评估工具包 和深度临床表型、TMJ组学、多模式数据驱动模型)和临床医生的热情 和研究人员一样，利用他们的专业知识来确定预防、治疗或治愈这种疾病的临床可交付成果 令人信服的和复杂的紊乱。成功完成这笔规划拨款的以下目标将 磨练我们应对TMD冲击挑战的愿景：(1)组织、协调和建设一个综合的多部门 学科联盟机械地了解TMJ健康和疾病，(2)适应现有的科学和 临床中心，并建立一个以TMJ健康和疾病为重点的综合管理核心 研究，(3)开发临床方案，多地点临床研究和试验网络，以及(4)开发研究 促进跨学科职业发展的培训和教育计划。

PROJECT SUMMARY Approximately 35 million people in the United States are affected by temporomandibular disorders (TMDs) with women 3-8 times more likely to seek treatment compared to men, making it a highly prevalent and expensive healthcare challenge demanding immediate attention. Identifying a specific and treatable cause for TMD is difficult, as it is caused by complex, multifaceted interactions involving biomechanical, biological, and psychosocial components that are poorly understood. Due to these significant gaps in knowledge and the limited integrated mechanistic understanding of TMD, successful long-term therapeutic approaches and patient-specific guidelines to treatment are not available. Our proposal, TMJ SYMPHONY: Systems-integrated model and mechanisms of patient-centered holistic outcomes and network-supported training and therapy, will strategically coalesce a multidisciplinary and multiscale national consortium to decipher the relationships between temporomandibular joint (TMJ) structure-function-pain using computational, cellular, animal and human models. This collective of talented investigators will build upon an existing MPI U01 focused on healthy TMJ structure- function between intramural NIDCR Clinical Researchers and extramural Basic Scientists. It will leverage existing national resources (e.g. RE-JOIN, OPPERA, DOCTRC) to accelerate the translation of discoveries and technologies to directly address TMJ disease diagnosis (e.g., multimodality deep phenotyping, biomarkers), the spectrum of healthy TMJ to preclinical TMJ disease to TMJ degeneration/pain, treatment (e.g., non-invasive holistic/conservative therapies, stem cell therapy, tissue engineered constructs), and improve outcome assessment by understanding patient adaptive capabilities, mind-body-TMJ connection and environmental impact on behavior and perception, and social determinants of TMJ health/disease in a diverse patient population. In this planning phase, we will strategize to make dramatic progress in mechanistic knowledge and identifying combinatorial etiology, while expanding care options, providing evidence-based treatment decisions, and patient-specific treatment modalities over the next decade. What justifies our optimism are our new approaches and techniques already in progress (e.g. chair-side TMJ structure-function-pain assessment toolkit and deep clinical phenotyping, TMJ omics, multi-modality data driven models) and the enthusiasm of clinicians and researchers alike to harness their expertise to identify clinical deliverables to prevent, treat or cure this compelling and complex disorder. The successful completion of the following aims of this planning grant will hone our vision in tackling the TMD IMPACT challenge: (1) Organize, coordinate, and build an integrated multi- disciplinary consortium to mechanistically understand TMJ health and disease, (2) Adapt existing scientific and clinical centers and establish an administrative core which are integrated and focused on TMJ health and disease research, (3) Develop clinical protocols, multi-site clinical research and trials network, and (4) Develop a research training and education program that fosters interdisciplinary career development.