Cartilage Regeneration with Tunable Inflammation Resistance

具有可调抗炎能力的软骨再生

• 批准号: 10266157
• 负责人: Bradley T Estes
• 金额: $ 128.37万
• 依托单位: CYTEX THERAPEUTICS INC.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10266157
• 关键词: 3-Dimensional; 3D Print; Address; Adult; Affect; Age; Anatomy; Animal Model; Arthritis; Autologous; Automobile Driving; Biological; Blood Platelets; Bone Regeneration; Cartilage; Chondrocytes; Clinical; Clinical Research; Clinical Trials; Conduct Clinical Trials; Contracts; Cyclic GMP; Data; Defect; Deformity; Degenerative polyarthritis; Devices; Diagnosis; Disease; Economic Burden; Engineering; Enrollment; Ensure; Environment; Exclusion Criteria; Face; Feasibility Studies; Funding; General Population; Goals; Growth; Head; Hip Joint; Hip region structure; Implant; In Vitro; Inflammation; Injections; Intervention; Investigation; Joints; Label; Lead; Legal patent; Lesion; Life; Life Style; Longevity; Magnetic Resonance Imaging; Mechanics; Medical; Metals; Natural regeneration; Operative Surgical Procedures; Orthopedics; Outcome; Pain; Pain-Free; Pathology; Patients; Performance; Phase; Pilot Projects; Plasma; Population; Preparation; Procedures; Process; Quality of life; Replacement Arthroplasty; Resected; Resistance; Risk; Role; Safety; Site; Sterilization; Structure; Technology; Teenagers; Textiles; Therapeutic; Time; Tissues; Validation; acetabulum; active lifestyle; arthropathies; base; bone; cartilage regeneration; cartilage repair; clinical development; clinical practice; clinical research site; cost; design; disability; effective intervention; feasibility trial; first-in-human; functional outcomes; hip replacement arthroplasty; human study; implantation; in vivo; innovation; joint function; joint loading; malformation; manufacturing process; meetings; osteochondral repair; osteochondral tissue; patient population; preservation; repair strategy; repaired; response; restoration; safety study; scaffold; socioeconomics; stem cells; success; treatment strategy

Abstract: Femoroacetabular impingement or FAI is a commonly diagnosed condition affecting a younger patient population than the general osteoarthritis (OA) population. Untreated, FAI invariably leads to OA and, ultimately, total hip arthroplasty (THA). The fact that most FAI diagnoses are made in patients under the age of 40, with many in their late teens and twenties, makes FAI all the more clinically challenging to treat. Due to the limited life span of currently available hip implants, hip replacement in younger patients most often will require at least one and possibly several revision surgeries later in life. Each revision surgery leaves the hip joint with less native bone, resulting in a far less stable joint. FAI arises from abnormalities or defects in the bony structure of the hip, typically taking the form of either asphericity of the femoral head or bony overgrowth of the acetabulum itself. While a surgical intervention to remove the bony overgrowth addresses the painful impingement between the two joint components (femoral head and acetabulum), it does not repair the chondral defect caused by the bony malformation, which, over time, will progress and eventually lead to the need for THA. Mosaicplasty or microfracture have been used in an effort to stimulate the re-growth of damaged cartilage, but these procedures have not proven successful. Similarly, biological interventions utilizing stem cells or platelet rich plasma preparations have not proven to have reliable clinical utility. It is clear that there is an unmet need for an intervention that addresses the challenge of repairing damaged cartilage in patients with FAI. In response to this need, Cytex has developed a therapeutic biphasic device consisting of a high- performance 3D woven textile (cartilage phase) thermally bonded to an 3D printed scaffold (bone phase). This implant immediately performs the functions of the replaced osteochondral tissues and provides a conducive environment for native tissue integration and regeneration, demonstrated through multiple prior and ongoing in vitro and in vivo studies. The goals of this application are as follows: (1) finalize all of the manufacturing (cGMP) processes for the device, (2) file an investigational Device Exemption (IDE) with FDA to enable a clinical study, and (3) conduct a single site feasibility (safety) study enrolling up to 15 patients diagnosed with FAI. The patients to be enrolled will be qualified as surgical candidates for treatment of their FAI and must meet a stringent set of inclusion/exclusion criteria in order to ensure participation in the study at the lowest possible risk, while maximizing the possibility of a successful outcome. We have engaged several partners in this application in order to maximize the possibility of a successful outcome. Our partners include both regulatory and clinical development expertise in orthopaedic device trials and a Clinical Advisory Board of experts in the diagnosis and management of hip preservation surgeries to treat FAI. We expect that positive outcomes will move this technology closer to clinical practice by enabling a pivotal trial, but, also, positive results will establish the role of our implants for other disease states requiring joint restoration surgery.

摘要：髋臼撞击或FAI是一种常见的诊断疾病，影响年轻患者。 患者群体比普通骨关节炎(OA)人群更多。如果不治疗，FAI总是会导致OA， 最终，全髋关节置换术(THA)。事实上，大多数FAI诊断都是在以下年龄的患者中做出的 40岁，其中许多人十几岁或二十多岁，这使得FAI在临床上更具挑战性。由于 目前可用的髋关节植入物的寿命有限，年轻患者的髋关节置换术通常需要 在以后的生活中至少做一次，也可能是几次翻修手术。每一次翻修手术都会让髋关节 天然骨骼较少，导致关节更不稳定。FAI由骨骼的异常或缺陷引起 髋关节的结构，典型的形式为股骨头的非球形或股骨头的骨质增生。 髋臼本身。而通过外科手术移除骨质疏松症可以缓解疼痛。 撞击两个关节部件(股骨头和髋臼)，不会修复软骨 由骨质畸形引起的缺陷，随着时间的推移，这种缺陷会发展并最终导致需要 太好了。马赛克成形术或微骨折已经被用来努力刺激损伤的再生长 但这些手术并未被证明是成功的。同样，利用茎进行生物干预 细胞或富含血小板的血浆制剂尚未被证明具有可靠的临床实用价值。很明显，有 一种未得到满足的需要，即需要一种干预措施，以应对修复慢性阻塞性肺疾病患者受损软骨的挑战 阿辉。为了回应这一需求，Cytex开发了一种治疗性双相设备，由高- Performance 3D机织纺织品(软骨相)热粘合到3D打印支架(骨相)。这 植入物立即发挥被替换的骨软骨组织的功能，并提供有利于 原生组织整合和再生的环境，通过多个先前和正在进行的 体外和体内研究。此应用程序的目标如下：(1)完成所有制造 设备(CGMP)流程，(2)向FDA提交调查设备豁免(IDE)以启用 临床研究，以及(3)进行单点可行性(安全性)研究，纳入最多15名患者 被诊断为FAI。入选的患者将有资格作为外科候选人治疗他们的 FAI，必须满足一套严格的纳入/排除标准，以确保参与研究 尽可能降低风险，同时最大限度地提高成功结果的可能性。我们已经聘请了几个 为了最大限度地提高成功结果的可能性，我们将继续与这一应用程序的合作伙伴合作。我们的合作伙伴包括 在整形外科设备试验方面的监管和临床开发专业知识，以及 髋关节保存手术治疗FAI的诊断和管理专家。我们预计这是积极的 结果将使这项技术更接近临床实践，实现一项关键的试验，但也是积极的 结果将确定我们的植入物在其他需要关节修复手术的疾病状态下的作用。