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

描述(申请人提供)：标准微骨折是修复受损关节软骨的一线手术技术，被广泛使用且成本效益高，但其长期疗效较低，在较大病变中的适用性有限。这导致了与初级和后续治疗费用相关的迅速增长的经济负担，仅在美国，估计每年就超过400亿美元。因此，任何改善软骨缺陷手术结果并降低总体治疗成本的治疗方法都将对临床和经济产生重大影响。因此，这项研究的总体目标是评估一种可植入的、无细胞的加固和软骨诱导支架，以促进标准微骨折治疗的大型动物模型(绵羊)大型全层软骨损伤的修复。该支架基于由聚己内酯制成的三维(3D)编织纤维支架，我们先前已经证明，该支架可以促进和支持富含蛋白多糖和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(两年后约5%)。我们还展示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大小的缺陷中的能力。在本研究中，24只成年绵羊将在右侧股骨内侧髁上接受大面积(~80mm2)的单侧软骨缺损。在12只绵羊身上，缺陷将用标准的微骨折处理，然后用定制的3D编织PCL植入物覆盖。剩下的12只羊将只接受标准的微骨折治疗。术后12周(每组6只)或24周(每组6只)处死绵羊。所有手术关节均于术后即刻、活体动物1周、2周、6周、12周、12周、24周处死时拍摄X线片。尸检后的关节将通过CT、大体和组织学半定量评分进行评估。此外，还将通过压痕测试分析修复组织、周围软骨和对侧四肢髁突的天然软骨的力学性能。预计数据将有助于确定我们的产品是否能够从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。我们有重要的初步数据支持我们采取这一合乎逻辑的下一步来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加强修复和增加微骨折手术患者数量方面的有效性，从而达到推迟或消除后续程序的需要的目标。

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.