A crosslinked cartilage-derived matrix for cartilage tissue engineering

摘要 骨关节炎(OA)仍然是严重疼痛和残疾的重要来源，影响着3000多万成年人 每年给美国带来超过1300亿美元的经济负担。关节置换术是一个久负盛名的 程序，但其有限的生命周期使这种治疗无法接受的年轻或更活跃的个人， 随着年龄的增长，他们经常需要额外的翻修手术。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，留下的好消息不多。 一旦更换部件磨损，可选择具有成本效益的治疗方案。Cytex之前的工作重点是 开发一种解决这些问题的构造，通过使用3D机织纺织品来创建高- 性能，用于治疗大型软骨病变的精密工程植入物。这种3D编织脚手架可以 在植入后立即发挥作用，同时鼓励细胞生长、增殖和随后 组织发育。此外，植入物只替换关节表面的病变部分，留下 如果将来的外科干预被证明是必要的，原生骨料完好无损。AN的商业化 有效的软骨表面处理植入物将对这些中度患者产生显著的临床影响。 对于严重的骨性关节炎，提供了一种目前尚不存在的手术修复选择。我们已经做出了杰出的贡献 临床前大型动物研究的进展，并表明我们的方法快速使用仿生支架 恢复关节功能，减轻疼痛。Cytex的软骨表面重塑植入物可以制造成 与髋关节和膝关节中的复杂几何形状和自定义曲率相匹配，并特别 专为目前的软骨修复方案无法治愈的大关节炎病变而设计。因为 当我们在体内将我们的技术应用于日益复杂的动物模型时，我们看到了成功，我们正在 目前正在寻求投资，以加快该技术的上市速度，同时寻求后续行动 通过小企业NIH机制提供资金。为此目的，本提案的目的是发展和 验证符合cGMP标准的制造设备和工艺，以准备 我们的植入物的商业生产。作为新颖的制造工艺的设计和建立 技术是赢得第三方投资和监管批准的重要障碍，我们的目标是 使用此商业化准备试验计划解决此障碍，同时完成我们的 临床前工作。这项工作的成功完成将使Cytex能够加速其创新技术 走向商业上可用的产品线。

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.