A Treatment Paradigm for Femoracetabular Impingement (FAI)

股骨髋臼撞击症 (FAI) 的治疗范例

基本信息

批准号：
10176418
负责人：
Bradley T Estes
金额：
$ 84.94万
依托单位：
CYTEX THERAPEUTICS INC.
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-06-01 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10176418
关键词：
3-Dimensional 3D Print Adult Affect Allogenic American Anatomy Animals Autologous Automobile Driving Biocompatible Materials Biomechanics Biomimetics Bone Growth Bone Marrow Caring Cartilage Cells Chondrocytes Chondrogenesis Clinical Clinical assessments Control Groups Data Debridement Defect Deformity Degenerative polyarthritis Development Disease Economic Burden Engineering Etiology FDA approved Face Failure Gene Cluster Genes Genetic Transcription Goals Gold Growth Hip Joint Hip Osteoarthritis Hip region structure Histologic Human Implant Intervention Joints Knee Lesion Life Style Longevity Magnetic Resonance Imaging Measurement Measures Mesenchymal Differentiation Mesenchymal Stem Cells Methods Modeling Natural regeneration Operative Surgical Procedures Outcome Outcome Measure Pain Pathway Analysis Patients Phase Population Procedures Property Randomized Rapid screening Replacement Arthroplasty Reporting Resected Scanning Secondary to Sheep Site Small Business Innovation Research Grant Source Structure Surface Surgeon Technology Textiles Tissue Engineering Tissues Total Hip Replacement Toxicity Tests Translating Weight-Bearing state Work acetabulum active lifestyle arthropathies articular cartilage base bone bone engineering cartilage repair clinical practice design disability donor stem cell effective therapy functional restoration genetic signature hip replacement arthroplasty implant design implantation improved in vivo joint function joint loading mechanical properties novel strategies osteochondral tissue patient population preservation rapid technique regenerative repair strategy repaired response risk minimization satisfaction scaffold sheep model standard care standard of care stem cell therapy stem cells subchondral bone symptom management systemic toxicity tool transcriptome sequencing uptake

项目摘要

Abstract: Fewer than 1 in 5 young patients suffering from activity limiting hip osteoarthritis (OA) choose to undergo total hip replacement (THR) surgery, opting instead for symptom management. Despite being the standard of care in hip OA, THR is not an ideal procedure for the young patient population because they will require multiple revision surgeries in their lifetime, each iteration posing additional complications, quicker implant failures, and overall decreased satisfaction. While the etiology of disease in this young population is diverse, one clear target for intervention is femoroacetabular impingement (FAI), which directly leads to osteochondral (OC) damage within the joint. Currently, there are no effective treatments for the OC lesions caused by FAI, so these joints continue to degenerate and eventually require a THR. As such, there is a critical need for new interventions that delay or halt the progression of FAI disease and the need for that initial joint replacement. Our technology restores the function of the joint while only replacing the surface-level, diseased tissue. The technological basis of our implant is a 3D woven scaffold, engineered to mimic the mechanical properties of articular cartilage, which is then thermally bonded to a rigid printed substrate, which is engineered for bone ingrowth. In order to function long-term in vivo, the implant must be populated with cells capable of robust tissue synthesis. In this context, preculture with bone marrow derived mesenchymal stem cells (MSCs) may be required for clinical use. However, a clear need exists to prove the chondrogenic potential of highly variable MSC lots prior to their use clinically. The goals of this Direct to Phase II SBIR application are therefore to first devise a method for rapidly screening the chondrogenic potential of allogeneic MSCs using RNA sequencing in Aim 1, and then in Aim 2, to tissue-engineer a MSC-based joint resurfacing implant to repair a large OC acetabular defect in an ovine model of FAI (CAM-type), at a site often implicated in the young patient. All animals will receive an osteochondroplasty procedure to relieve impingement and then be randomized to one of the following groups: 1) Control, debridement only; 2) acellular ‘implant only’ control; and 3) allogeneic MSC-based, tissue-engineered implant. Outcome measures are selected to longitudinally track lameness, pain, and function during the study. As MRI is the gold standard for clinical assessment, all animals will receive an MRI at the beginning of the study and after sacrifice, and these scans will be correlated to histological and biomechanical properties of joint tissues. Systemic toxicity testing will also be assessed according to ISO 10993-11. We expect that positive outcomes will enable us to move this technology closer to clinical practice, with the ultimate goal of developing strategies to treat FAI and other cartilage-related disease.

摘要：不到五分之一的患有活动限制性髋关节骨关节炎（OA）的年轻患者选择接受全髋关节置换术（THR），尽管是治疗的选择，但还是选择了症状管理。作为髋关节 OA 的护理标准，THR 对于年轻患者群体来说并不是理想的手术，因为他们会在其一生中需要多次修复手术，每次迭代都会带来额外的并发症，更快种植失败，总体满意度下降，而这一年轻人的疾病病因是。股髋臼撞击症 (FAI) 是一项明确的干预目标，它直接导致关节内骨软骨 (OC) 损伤目前，尚无针对 OC 损伤的有效治疗方法。由 FAI 引起，因此这些关节继续退化并最终需要 THR 因此，存在一个关键问题。需要新的干预措施来延缓或阻止 FAI 疾病的进展，以及初始关节的需要我们的技术可以恢复关节的功能，同时仅替换表面患病的部分。我们的植入物的技术基础是 3D 编织支架，旨在模仿机械结构。关节软骨的特性，然后将其热粘合到经过工程设计的刚性印刷基板上为了使骨长入体内，植入物必须充满能够长期发挥作用的细胞。在这种情况下，用骨髓来源的间充质干细胞（MSC）进行预培养。可能需要临床使用，但是，显然需要证明高度的软骨形成潜力。临床使用前的可变 MSC 批次该 Direct to Phase II SBIR 应用的目标是因此首先设计一种快速筛选同种异体MSCs软骨形成潜力的方法在目标 1 中使用 RNA 测序，然后在目标 2 中使用 RNA 测序来组织工程基于 MSC 的关节表面重修植入物修复绵羊 FAI 模型（CAM 型）中的大 OC 髋臼缺损，修复部位经常所有动物都将接受骨软骨成形术以缓解症状。撞击，然后随机分入以下组之一：1) 对照，仅清创；2) 无细胞； “仅植入”控制；以及 3) 基于同种异体 MSC 的组织工程植入。选择在研究期间纵向跟踪跛行、疼痛和功能，因为 MRI 是金标准。临床评估，所有动物将在研究开始时和处死后接受 MRI 检查，这些扫描将与关节组织的组织学和生物力学特性相关。我们还将根据 ISO 10993-11 进行评估，我们预计积极的成果将使我们能够推动这一进程。技术更接近临床实践，最终目标是制定治疗 FAI 和其他疾病的策略软骨相关疾病。