Cartilage Regeneration with Tunable Inflammation Resistance

翻译后摘要：股骨髋臼撞击或FAI是一种常见的诊断条件，影响年轻人 患者人群比一般骨关节炎（OA）人群。未经治疗，FAI总是导致OA， 最终，全髋关节置换术（THA）。事实上，大多数FAI诊断是在年龄小于 40岁，其中许多人在青少年后期和二十多岁，使FAI在临床上更具挑战性。 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 至少一次甚至可能多次的翻修手术。每次翻修手术都会使髋关节 更少的原生骨，导致关节更不稳定。FAI是由骨骼的异常或缺陷引起的， 髋关节的结构，通常表现为股骨头的非球面或股骨的骨过度生长。 髋臼本身。虽然手术干预，以消除骨过度生长解决了痛苦的 两个关节部件（股骨头和髋臼）之间的撞击，不能修复软骨 骨畸形引起的缺陷，随着时间的推移，将进展并最终导致需要 THA。镶嵌成形术或微骨折术已被用于刺激受损组织的再生长。 软骨，但这些程序并没有被证明是成功的。同样，利用干细胞的生物干预 细胞或富含血小板的血浆制剂尚未证明具有可靠的临床用途。显然有 一种未满足的干预需求，解决了修复患者受损软骨的挑战， 阿辉为了满足这一需求，Cytex开发了一种治疗性双相装置， 高性能3D编织纺织品（软骨相）热粘合到3D打印支架（骨相）。这 植入物立即执行替代的骨软骨组织的功能，并提供有益的 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证明， 体外和体内研究。本申请的目标如下：（1）完成所有的制造 （2）向FDA提交试验用器械豁免（IDE）， 临床研究，和（3）进行单中心可行性（安全性）研究，最多招募15例患者 诊断为FAI。入组的患者将有资格作为手术候选人治疗其 FAI，并且必须符合一组严格的入选/排除标准，以确保参与研究， 最大限度地降低风险，同时最大限度地提高成功的可能性。我们雇佣了几个 合作伙伴在此应用程序，以最大限度地提高成功的可能性。我们的合作伙伴包括 骨科器械试验的监管和临床开发专业知识， 专家在诊断和管理髋关节保留手术治疗FAI。我们希望积极的 结果将使这项技术更接近临床实践，使一个关键的试验，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中的作用。

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.