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

使用 3D 编织聚（己内酯）修复绵羊模型中的骨软骨组织

• 批准号: 8455444
• 负责人: Bradley T Estes
• 金额: $ 29.97万
• 依托单位: CYTEX THERAPEUTICS INC.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8455444
• 关键词: Address; Adipose tissue; Adoption; Adult; Affect; Age; Allografting; American; Animal Model; Animals; Apoptosis; Appearance; Arthralgia; Arthritis; Arthroplasty; Autologous; Autologous Transplantation; Autopsy; Biomimetics; Bone Marrow; Cartilage; Cells; Chondrocytes; Clinical; Coagulation Process; Collagen Type II; Communities; Contralateral; Custom; Data; Defect; Development; Disease; Economic Burden; Extracellular Matrix; Fiber; Fibrocartilages; Functional disorder; Goals; Hand; Harvest; Hyaline Cartilage; Implant; In Vitro; Injury; Irrigation; Joints; Lead; Lesion; Life; Limb structure; Longevity; Mechanics; Medial; Medical; Mesenchymal Stem Cells; Methods; Minor; Modeling; Modification; Morbidity - disease rate; Operative Surgical Procedures; Outcome; Pathology; Patients; Phase; Procedures; Property; Proteoglycan; Quality of life; Replacement Arthroplasty; Reporting; Right-On; Risk; Shapes; Sheep; Site; Small Business Technology Transfer Research; Surgeon; Symptoms; Techniques; Technology; Testing; Thick; Time; Tissues; Treatment Cost; United States; Weight-Bearing state; Work; articular cartilage; base; bone; caprolactone; cartilage regeneration; cost; cost effective; disability; follow-up; implantation; improved; osteochondral tissue; patient population; prevent; product development; public health relevance; repaired; restoration; scaffold; three dimensional structure; tissue repair

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.

描述（由申请人提供）：标准微骨折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，但其因长期疗效下降且在较大病变中的适用性有限而受到限制。这导致与初级和后续治疗费用相关的经济负担日益沉重，估计仅在美国每年就超过 400 亿美元。因此，任何改善软骨缺损手术效果并降低总体治疗成本的疗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评估一种可植入的、无细胞的增强和软骨诱导支架，用于增强经标准微骨折治疗的大型动物模型（绵羊）中大的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，我们之前已证明该支架可以促进和支持富含蛋白聚糖和 II 型胶原的坚固软骨细胞外基质的合成，同时保持适当的仿生性机械性能，很大程度上是由于 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留在临界尺寸的缺损中，而无需额外的锚定。在这项研究中，24 只成年羊将在右侧股骨内侧髁上接受大面积（~80mm2）单侧软骨缺损。 12 只羊的缺陷将通过标准微骨折进行治疗，然后用定制的 3D 编织 PCL 植入物覆盖。其余 12 只羊将仅接受标准微骨折治疗。手术后第 12 周（每组 n = 6 只）或 24 周（每组 n = 6 只）处死羊。所有手术关节将在活体动物术后 1 周、2 周、6 周和 12 周以及 12 和 24 周处死日期立即进行射线照相。尸检后的关节将通过 CT 以及肉眼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突的天然软骨的机械性能将通过压痕测试进行分析。数据预计将有助于确定我们的产品是否能够增强大骨软骨缺损的软骨再生，包括其总体和组织学外观以及与天然透明软骨相关的机械性能。我们有重要的初步数据支持我们采取合理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数方面的功效，以实现延迟或消除后续程序需要的目标。