Unicondylar Resurfacing in an Ovine Osteoarthritis Disease Model

绵羊骨关节炎疾病模型中的单髁表面置换

基本信息

批准号：
10707121
负责人：
Bradley T Estes
金额：
$ 40万
依托单位：
CYTEX THERAPEUTICS INC.
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-08 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10707121
关键词：
3-Dimensional Address Adult Affect Age Allogenic Anatomy Animal Model Applications Grants Autologous Automobile Driving Biological Biological Assay Biological Process Biological Products Biomanufacturing Bone Regeneration Cartilage Cartilage Matrix Cell Culture Techniques Cell Separation Cell Survival Cell Therapy Cells Chemicals Clinical Clinical Research Clinical Trials Collaborations Consumption Contracts Cryopreservation Data Degenerative polyarthritis Development Devices Disease Disease model Economic Burden Elderly Ensure Exclusion Extracellular Matrix Face Freezing Funding Generations Goals Good Manufacturing Process Hip region structure Histocompatibility Antigens Class II Implant Joints Lead Legal patent Lesion Life Life Style Longevity Major Histocompatibility Complex Manufacturer Maps Measures Medical Device Mesenchymal Stem Cells Metals Methods Modification Operative Surgical Procedures Orthopedics Pain Free Patients Phase Phase I/II Clinical Trial Preclinical Testing Procedures Process Production Qualifying Quality Control Quality of life Regenerative Medicine Replacement Arthroplasty Second Look Surgery Series Sheep Source Surgeon System Techniques Technology Testing Therapeutic Time Tissue Engineering Validation Work active lifestyle advanced disease bone marrow mesenchymal stem cell cartilage implant cartilage regeneration cartilage repair commercialization design disability economic cost experience first-in-human hip replacement arthroplasty implantable device implantation in vivo joint function joint loading manufacture older patient osteochondral repair osteochondral tissue patient population pre-clinical preclinical study preservation programs repaired research clinical testing scaffold socioeconomics tissue repair

项目摘要

Abstract Osteoarthritis (OA) is a leading cause of disability in the developed world, affecting over 30 million adults in the US with an economic burden of over $486 billion per year. Advanced OA is most commonly treated with total joint replacement, but this is suboptimal for younger patients, especially those under 55 who lead an active lifestyle, because of the high occurrence of multiple revision surgeries. For this growing patient population, Cytex is developing implants pairing a patented 3D weaving technology with additive manufacturing to facilitate cartilage and bone regeneration in the joint. The implant is designed to support joint loading immediately at the time of implantation and to allow integration and development of osteochondral tissue. Both an acellular implant and a tissue engineered implant that combines the acellular scaffold with autologous cells have demonstrated in large animal models of OA the capability of repairing osteochondral lesions and restoring pain-free joint function for extended durations. The tissue engineered implant is particularly desirable for patients without a potent endogenous cell source to repopulate the acellular implant and synthesize a mature extracellular matrix in vivo. Cytex has chosen femoroacetabular impingement (FAI) in the hip as a lead indication for a pilot clinical study with the acellular implant. FAI presents in active, young patients, with no good option to repair the resulting osteochondral lesions, which progress into more severe OA. The tissue engineered implant will follow the acellular product into clinical study. Autologous cells, as used in our pre- clinical studies, require time-consuming cell isolation and expansion steps. Instead, Cytex will use allogeneic mesenchymal stem cells (MSCs) derived from bone marrow, which express very low levels of major histocompatibility complex (MHC) class I and class II antigens. To prepare the allogeneic tissue engineered implants for clinical study, Cytex must further develop the tissue engineered implant to overcome specific commercialization hurdles. The goal of this proposal is to address these hurdles: 1) Cytex must identify and develop potency assays that measure the biological activity of the seeded cells and set acceptance criteria for those assays. 2) Cytex will identify cryopreservation and storage conditions for the implants to be available off- the-shelf because surgeons and patients are unlikely to wait several weeks for an implant to be made-to-order. 3) manufacturing of the tissue engineered implants will be transferred to a contract manufacturer that follows the current good manufacturing practices (cGMPs) required for regulatory approval. 4) Cytex, with an experienced regulatory consulting firm, will engage with the US FDA to discuss requirements for clinical study approval. The culmination of this project will be an off-the-shelf tissue engineered implant for cartilage repair that will enable Cytex to broaden its implant portfolio and enable treatment for patients that currently have no good clinical options either because of their advanced age or disease state.

抽象的骨关节炎 (OA) 是发达国家残疾的主要原因，影响着超过 3000 万成年人美国每年的经济负担超过4860亿美元。晚期 OA 最常采用总关节置换术，但这对于年轻患者来说并不是最理想的，尤其是那些 55 岁以下、进行积极活动的患者生活方式，因为多次翻修手术的发生率很高。对于这个不断增长的患者群体， Cytex 正在开发将专利 3D 编织技术与增材制造相结合的植入物，以促进关节中的软骨和骨再生。植入物旨在立即支持关节负载植入时间并允许骨软骨组织整合和发育。两者都是无细胞的植入物以及将无细胞支架与自体细胞相结合的组织工程植入物在大型骨关节炎动物模型中证明了修复骨软骨损伤和恢复功能的能力长时间无痛关节功能。组织工程植入物特别适用于没有有效的内源细胞来源来重新填充无细胞植入物并合成成熟细胞的患者体内细胞外基质。 Cytex 选择髋关节股骨髋臼撞击 (FAI) 作为主导无细胞植入物试点临床研究的指征。 FAI 出现在活跃的年轻患者中，无症状修复由此产生的骨软骨损伤的良好选择，骨软骨损伤会进展为更严重的骨关节炎。组织工程植入物将跟随非细胞产品进入临床研究。自体细胞，如我们的预临床研究需要耗时的细胞分离和扩增步骤。相反，Cytex 将使用同种异体间充质干细胞 (MSC) 源自骨髓，其主要表达水平非常低组织相容性复合物 (MHC) I 类和 II 类抗原。准备同种异体组织工程对于用于临床研究的植入物，Cytex 必须进一步开发组织工程植入物以克服特定的问题商业化障碍。该提案的目标是解决以下障碍：1) Cytex 必须识别并开发效力测定来测量种子细胞的生物活性并设定接受标准那些化验。 2) Cytex 将确定植入物的冷冻保存和储存条件，以便在外地使用因为外科医生和患者不太可能等待数周才能定制植入物。 3) 组织工程植入物的制造将转移给随后的合同制造商监管部门批准所需的现行良好生产规范 (cGMP)。 4) Cytex，带有经验丰富的监管咨询公司将与美国FDA合作讨论临床研究要求赞同。该项目的顶峰将是一种现成的用于软骨修复的组织工程植入物这将使 Cytex 能够扩大其植入物产品组合，并为目前没有植入物的患者提供治疗由于他们的高龄或疾病状态，良好的临床选择。