Osteochondral tissue repair in an ovine model using a 3D woven poly (e-caprolacto

描述（由申请人提供）：标准微骨折是修复关节软骨损伤的一线、广泛使用且成本低廉的手术技术，但其长期疗效下降，且对较大病变的适用性有限。这导致了与初级和后续治疗费用相关的快速增长的经济负担，据估计，仅在美国每年就超过400亿美元。由此可见，任何能改善软骨缺损的手术效果并降低总体治疗费用的治疗方法都将产生重大的临床和经济影响。因此，本研究的总体目标是在大型动物模型（羊）中评估一种可植入的、无细胞的增强和软骨诱导支架，以增强对标准微骨折治疗的大的、全层软骨病变的修复。该支架基于三维（3D）编织纤维支架，由聚（己内酯）制成，我们之前已经证明，它可以促进和支持富含蛋白聚糖和II型胶原的强健软骨细胞外基质的合成，同时保持适当的仿生机械性能，这主要是由于PCL的缓慢降解（2年后降解约5%）。我们还证明了这种无细胞植入物在不需要额外锚定的情况下保持在临界尺寸缺陷中的能力。在本研究中，24只成年羊将在右侧股骨内侧髁处接受大（~80mm2）单侧软骨缺损。在12只羊中，将用标准的微骨折治疗缺陷，然后用定制的3d编织PCL植入物覆盖。其余12只羊只接受标准微骨折治疗。在手术后12周（每组n=6）或24周（每组n=6）处死羊。所有手术关节将在术后、活体动物1周、2周、6周和12周以及12周和24周献祭时立即进行x线摄影。尸检后，关节将通过CT和大体和组织学半定量评分进行评估。此外，修复组织、周围软骨和对侧肢体髁的天然软骨的力学性能将通过压痕测试进行分析。数据有望在确定我们的产品是否能够在其大体和组织学外观以及与天然透明软骨相关的机械性能方面增强大型骨软骨缺损的软骨再生方面具有指导意义。我们有大量的初步数据来支持我们下一步评估这种方法的商业潜力，我们相信这项研究将使我们能够评估我们的技术在增强修复和增加微骨折手术患者数量方面的功效，从而实现延迟或消除后续手术的目标。

DESCRIPTION (provided by applicant): Standard microfracture is a first-line, widely used and cost-effective surgical technique for repairing damaged articular cartilage, but, it is limited by decreased long-term efficacy and limited applicability in larger lesions. This leads to a burgeoning economic burden associated with primary and follow-up treatment costs, estimated at more than 40 billion dollars annually in the U.S. alone. It follows that any therapy that improves surgical outcomes for cartilage defects and reduces overall treatment costs will have significant clinical and economical impact. Therefore, the overall goal of this study is to evaluat an implantable, cell-free reinforcing and chondroinductive scaffold for enhancing repair of large, full-thickness cartilage lesions in a large animal model (ovine) treated with standard microfracture. This scaffold is based on a three-dimensional (3D) woven fiber scaffold made from poly(caprolactone) that we have previously demonstrated to promote and support the synthesis of a robust cartilaginous extracellular matrix rich in proteoglycans and type II collagen all while maintaining appropriate biomimetic mechanical properties, largely owing to the slow degradation of PCL (~5% after 2 years). We have also demonstrated the ability of this cell-free implant to remain in a critically-sized defect without the need for additional anchoring. In this study, 24 adult sheep will receive, large (~80mm2), unilateral chondral defects on right medial femoral condyles. In 12 sheep, defects will be treated with standard microfracture and then covered with custom-fit 3D-woven PCL implants. The remaining 12 sheep will be treated with standard microfracture only. Sheep will be sacrificed at 12 (n=6 for each group) or 24 (n=6 for each group) weeks post-procedure. All operated joints will be radiographed immediately postoperatively, at 1 week, 2 weeks, 6 weeks, and 12 weeks in the live animals, and at the 12 and 24-week sacrifice dates. Following necropsy joints will be evaluated by CT and gross and histological semi- quantitative scoring. In addition, mechanical properties of repair tissue, the surrounding cartilage, and native cartilage from contralateral limb condyles will be analyzed via indentation testing. Data are expected to be instructive in determining if our product is able to enhance cartilage regeneration in a large osteochondral defect in terms of its gross and histological appearance as well as mechanical properties in relation to native hyaline cartilage. We have significant preliminary data to support our taking this logical next step toward evaluating the commercial potential of this approach, and we believe this study will enable us to assess the efficacy of our technology for enhancing repair and increasing the patient population for microfracture surgery, towards the goal of delaying or eliminating the need for follow-up procedures.