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，影响超过3000万成年人 每年给美国带来超过1300亿美元的经济负担。关节置换术是一种公认的 程序，但其有限的寿命使这种治疗不能接受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， 一旦替代品磨损，就可以提供具有成本效益的治疗方案。Cytex以前的工作集中在 开发一种结构，通过使用3D编织织物来创建一个高- 高性能、精确设计的植入物，用于治疗大型软骨病变。这种3D编织支架可以 在植入后立即发挥作用，同时促进细胞向内生长、增殖和随后的生长。 组织发育此外，植入物仅替代关节表面的患病部分， 如果将来有必要进行手术干预，则应保持自体骨量完整。商业化 有效的软骨表面置换植入物对这些中度 严重OA，提供了一个外科修复的选择，目前还没有。我们已经做出了杰出的 临床前大动物研究的进展，并表明我们的方法使用仿生支架迅速 恢复关节功能并减轻疼痛。Cytex的软骨表面置换植入物可以制造成 匹配髋关节和膝关节中的复杂几何形状和自定义曲率， 设计用于目前软骨修复方案无法治疗的大型关节炎病变。因为 我们已经成功地将我们的技术应用于日益复杂的动物模型中， 目前正在寻求投资，以加快这项技术的市场，同时追求后续 通过小企业NIH机制提供资金。为此，本提案的目的是制定和 验证生产设备和工艺是否符合cGMP标准， 我们植入物的商业化生产作为设计和建立新的制造工艺， 技术是赢得第三方投资和监管批准的一个重大障碍，我们的目标是 利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。这项工作的成功完成将使Cytex能够加速其创新技术 走向商业化生产线。

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.