A crosslinked cartilage-derived matrix for cartilage tissue engineering

用于软骨组织工程的交联软骨衍生基质

• 批准号: 9554775
• 负责人: Frank Moutos
• 金额: $ 40万
• 依托单位: CYTEX THERAPEUTICS INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-17 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9554775
• 关键词: 3D Print; Address; Adult; Affect; Age; Animal Model; Animals; Architecture; Area; Arthritis; Automation; Biocompatible Materials; Biomimetics; Businesses; Cartilage; Cartilage Diseases; Cartilage Matrix; Cells; Chondrogenesis; Clinical; Clinical Research; Complex; Custom; Cyclic GMP; Defect; Degenerative polyarthritis; Development; Devices; Differentiation and Growth; Disease; Economic Burden; Engineering; Equipment; FDA approved; Failure; Fiber; Funding; Future; Geometry; Goals; Healthcare Industry; Hip Joint; Hip region structure; Implant; Individual; Investments; Joints; Knee; Knee joint; Lesion; Longevity; Medical; Methods; Microscopic; Morbidity - disease rate; Operative Surgical Procedures; Orthopedics; Pain; Pathology; Patients; Performance; Positioning Attribute; Printing; Procedures; Process; Production; Property; Quality of life; Readiness; Regenerative Medicine; Regulatory Pathway; Replacement Arthroplasty; Research; Safety; Small Business Innovation Research Grant; Small Business Technology Transfer Research; Source; Sterilization; Structure; Surface; Target Populations; Technology; Textiles; Therapeutic; Time; Tissue Engineering; Tissues; Translating; United States; United States National Institutes of Health; Validation; Work; articular cartilage; base; bone; cartilage degradation; cartilage repair; cell growth; commercialization; cost effective; crosslink; design; disability; economic impact; effective therapy; functional restoration; high risk; implantation; in vivo; innovative technologies; joint destruction; manufacturing process; mechanical properties; mortality; new technology; novel; osteochondral tissue; pre-clinical; premature; programs; repaired; research and development; scaffold; scale up; subchondral bone; success; validation studies; verification and validation; viscoelasticity

Abstract Osteoarthritis (OA) remains a significant source of significant pain and disability, affecting over 30 million adults with an economic burden of over $130 billion per year to the US. Joint replacement is a well-established procedure, but its finite life span makes this treatment unacceptable for younger or more active individuals, who often require additional revision surgeries as they age. Both complicated revision surgery and initial joint replacement carry progressively increasing morbidity and mortality as patient age increases, leaving few good cost-effective treatment options once the replacement wears out. Previous work at Cytex has focused on the development of a construct that addresses these concerns by using a 3D woven textile to create a high- performance, precisely engineered implant for treatment of large cartilage lesions. This 3D woven scaffold can function immediately after implantation, all while encouraging cell ingrowth, proliferation, and subsequent tissue development. Moreover, the implant replaces only the diseased portion of the joint surface, leaving native bone stock intact should future surgical interventions prove necessary. Commercialization of an efficacious cartilage resurfacing implant would have significant clinical impact for these patients with moderate to severe OA, providing a surgical repair option where none currently exist. We have made outstanding progress in pre-clinical large animal studies and showed that our approach using biomimetic scaffolds rapidly restores function to the joint and alleviates pain. Cytex’s cartilage resurfacing implants can be manufactured to match complex geometries and custom curvatures found in the hip and knee joints and are specifically designed for large arthritic lesions that are untreatable with current cartilage repair options. Because of the success we have seen when applying our technology in vivo in increasingly complex animal models, we are currently seeking investments to accelerate this technology to market while simultaneously pursuing follow-on funding through small business NIH mechanisms. To this end, the purpose of this proposal is to develop and validate manufacturing equipment and processes in compliance with cGMP standards to prepare for commercial production of our implant. As the design and establishment of manufacturing processes for novel technologies is a significant hurdle to win both third-party investment and regulatory approval, our goal is to use this Commercialization Readiness Pilot Program to address this impediment while completing our preclinical work. Successful completion of this work will position Cytex to accelerate its innovative technology towards a commercially available product line.

抽象的 骨关节炎 (OA) 仍然是严重疼痛和残疾的重要根源，影响超过 3000 万成年人 关节置换术每年给美国带来超过 1300 亿美元的经济负担。 手术，但其有限的寿命使得这种治疗对于年轻或更活跃的个体来说是不可接受的， 随着年龄的增长，他们经常需要进行额外的翻修手术，包括复杂的翻修手术和初始关节。 随着患者年龄的增加，替代治疗的发病率和死亡率逐渐增加，几乎没有什么好的治疗方法 Cytex 之前的工作主要集中在替代品磨损后的经济有效的治疗方案。 通过使用 3D 机织纺织品来开发一种解决这些问题的结构，以创建高 这种 3D 编织支架可以用于治疗大型软骨病变的高性能、精确设计的植入物。 植入后立即发挥作用，同时促进细胞向内生长、增殖和后续 此外，植入物仅替换关节表面的患病部分，留下关节表面的病变部分。 如果未来的手术干预证明有必要进行商业化，则天然骨量完好无损。 有效的软骨表面重修植入物将对这些患有中度疾病的患者产生显着的临床影响 对于严重的骨关​​节炎，我们提供了目前尚不存在的手术修复方案。 临床前大型动物研究的进展，表明我们使用仿生支架的方法可以快速 Cytex 的软骨表面置换植入物可恢复关节功能并减轻疼痛。 匹配髋关节和膝关节中的复杂几何形状和定制曲率，并且是专门的 专为目前的软骨修复方案无法治疗的大关节炎病变而设计。 当我们在日益复杂的动物模型中应用我们的技术时，我们已经看到了成功，我们 目前正在寻求投资以加速这项技术的上市，同时寻求后续技术 通过小型企业 NIH 机制提供资金 为此，本提案的目的是制定和实施。 验证生产设备和工艺是否符合 cGMP 标准，为 我们的植入物的商业化生产是为了设计和建立新颖的制造工艺。 技术是赢得第三方投资和监管批准的重大障碍，我们的目标是 使用此商业化准备试点计划来解决这一障碍，同时完成我们的 临床前工作的成功完成将使 Cytex 加速其创新技术的发展。 走向商业化的产品线。