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：股骨髋臼撞击症（FAI）是影响年轻人的常见疾病。 患者人群高于一般骨关节炎 (OA) 人群。如果不加以治疗，FAI 必然会导致 OA，并且， 最终，全髋关节置换术（THA）。事实上，大多数 FAI 诊断都是在 2 岁以下的患者中进行的 40 岁左右，其中许多人年龄在十几岁和二十几岁，这使得 FAI 的治疗在临床上更具挑战性。由于 目前可用的髋关节植入物的使用寿命有限，年轻患者通常需要进行髋关节置换术 在以后的生活中至少进行一次甚至可能多次修复手术。每次翻修手术都会留下髋关节 原生骨较少，导致关节稳定性大大降低。 FAI 是由骨异常或缺陷引起的 髋部结构，通常表现为股骨头非球面或股骨过度生长 髋臼本身。虽然手术干预去除骨质过度生长可以解决痛苦的问题 两个关节部件（股骨头和髋臼）之间的撞击，它不会修复软骨 由骨畸形引起的缺陷，随着时间的推移，这种缺陷会进展并最终导致需要 泰哈。马赛克成形术或微骨折已被用来刺激受损的再生 软骨，但这些手术尚未被证明是成功的。同样，利用干细胞进行生物干预 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性。显然有 对解决修复受损软骨患者挑战的干预措施的需求尚未得到满足 固定资产投资。为了满足这一需求，Cytex 开发了一种治疗双相装置，由高 高性能 3D 编织纺织品（软骨相）热粘合到 3D 打印支架（骨相）。这 植入物立即执行被替换骨软骨组织的功能，并提供有利的 天然组织整合和再生的环境，通过多个先前和正在进行的研究得到证明 体外和体内研究。该应用程序的目标如下：（1）完成所有制造 (cGMP) 设备流程，(2) 向 FDA 提交研究性设备豁免 (IDE)，以启用 临床研究，以及 (3) 进行单中心可行性（安全性）研究，招募最多 15 名患者 诊断为 FAI。入组的患者将有资格成为接受手术治疗的候选者 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。我们已经聘请了几位 合作伙伴在此应用程序中，以最大限度地提高成功结果的可能性。我们的合作伙伴包括 骨科器械试验方面的监管和临床开发专业知识以及临床顾问委员会 诊断和管理髋关节保留手术以治疗 FAI 的专家。我们期望积极的 通过进行关键试验，结果将使该技术更接近临床实践，但也具有积极意义 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中的作用。