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

描述（由申请人提供）：标准微骨折术是修复受损关节软骨的一线、广泛使用且具有成本效益的手术技术，但其受到长期疗效降低和较大病变适用性有限的限制。这导致与初级和后续治疗费用相关的经济负担迅速增长，仅在美国每年估计超过400亿美元。因此，任何改善软骨缺损手术结果并降低总治疗成本的疗法都将具有显著的临床和经济影响。因此，本研究的总体目标是评价一种可植入的无细胞增强和软骨诱导支架，用于在用标准微骨折治疗的大型动物模型（绵羊）中增强大型全层软骨病变的修复。该支架基于由聚己内酯制成的三维（3D）编织纤维支架，我们之前已经证明该支架可以促进和支持富含蛋白聚糖和II型胶原蛋白的稳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年后约5%）。我们还证明了这种无细胞植入物能够保持在临界尺寸的缺损中，而不需要额外的锚定。在本研究中，24只成年绵羊将接受右侧内侧股骨髁上的大（~ 80 mm 2）单侧软骨缺损。在12只绵羊中，将使用标准微骨折术治疗缺损，然后使用定制的3D编织PCL植入物覆盖。其余12只绵羊将仅接受标准微骨折治疗。将在术后12周（每组n=6）或24周（每组n=6）处死绵羊。所有手术关节将在术后即刻、1周、2周、6周和12周（活动物）以及12周和24周处死时进行X线片检查。尸检后，将通过CT以及大体和组织学半定量评分评价关节。此外，将通过压痕测试分析修复组织、周围软骨和对侧肢体髁的天然软骨的机械性能。预计数据将有助于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骨软骨缺损中的软骨再生。我们有重要的初步数据来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增强修复和增加微骨折手术患者人群方面的有效性，以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.