OsTend: A load-bearing, bi-phasic collagen scaffold for massive rotator cuff repairs

1摘要： 在美国，每年大约有300,000例肩袖(RC)修复手术，估计费用为 30亿美元。RC的晚期变性会导致疼痛和严重残疾。“消极的”或“无法修复的”(&gt；5厘米)泪水 4骨与肌腱分离，肌腱变性，无法修复。 5关节镜检查。占RC撕裂的40%，它们需要昂贵的侵入性肌肉转移或关节成形术 6个程序。覆盖贴片，真皮或其他，充其量被动地加强底层肌腱，并做到 7不利于肌腱的再生，也不利于末端的再生。有一种尚未得到满足的临床需求，即发展再生能力 8植入产品，适用于遭受无法修复的泪水的患者。 9CollaMedex Inc.开发使用我们的高强度纯胶原线的生物编织医疗植入物 10高通量电化学压实专利工艺。CollaMedex制造的缠绕螺纹 11由工业编织机编织，以获得大孔、高度生物相容性、可吸收的支架。 12个胶原蛋白分子在支架线内单向排列，模拟 13肌腱，并向干细胞传递肌腱诱导效应，肌腱特异的表达证明了这一点 14标记肌腱调节蛋白。主胶原蛋白平行于这些线被模板化，产生有序的组织 15证言。此外，用于稳定线条的交联剂Genipin会使巨噬细胞极化为亲核. 16再生表型。 我们设计了这样一种支架，它的一端注入了羟基磷灰石，使其具有骨诱导性 18在另一边保持Teno感应的情况下。这种双相Ostend支架是承重的， 19可缝合，因此可以在与骨和肌腱结合的同时，桥接大的骨-肌腱缺口。这些 20种材料非常适合修复严重撕裂、退化的肌腱。 基于这一重大承诺，CollaMedex Inc.提议在兔子身上测试Ostend的可行性 22慢性RC变性修复模型。兔冈下肌腱将被横断，允许 23退化，并用OsTends修复或未修复。在植入后4周和12周，肌腱将被 24进行组织学机械测试和加工。我们假设奥斯坦德修理组将拥有 25条更结实、更粗的肌腱和更正常的组织学特征，接近完整对照。

1 Summary: 2 There are ~300,000 rotator cuff (RC) repair procedures performed in the US annually at an estimated cost of 3 $4B. Advanced degeneration of the RC causes pain and major disability. ‘Massive’ or ‘Irreparable’ (> 5 cm) tears 4 of RC consist of detachment between bone & tendon, and degeneration of tendon; thus, they cannot be repaired 5 arthroscopically. Representing 40% of RC tears, they require costly and invasive muscle transfer or arthroplasty 6 procedures. Overlay patches, dermal and otherwise, at best passively reinforce the underlying tendon and do 7 not contribute to regeneration of tendon nor the enthesis. There is an unmet clinical need to develop regenerative 8 implant products for patients suffering from irreparable tears. 9 CollaMedix Inc. develops biotextile medical implants using high-strength pure-collagen threads produced by our 10 patented process of high-throughput electrochemical compaction. Spooled threads manufactured at CollaMedix 11 are braided by industrial braiding machines to obtain macroporous, highly biocompatible, resorbable scaffolds. 12 Collagen molecules are unidirectionally aligned within the scaffold threads, mimicking the native topography of 13 tendon, and imparting a tenoinductive effect on stem cells, as evidenced by the expression of tendon-specific 14 marker tenomodulin. Host collagen is templated parallel to these threads, resulting in an ordered tissue 15 deposition. Also, the crosslinking agent genipin that is used to stabilize threads polarizes macrophages to a pro- 16 regenerative phenotype. 17 We have designed such a scaffold that is infused with hydroxyapatite at one end, making it osteo-inductive on 18 that side while remaining teno-inductive on the other. This bi-phasic OsTend scaffold is load-bearing and 19 suturable, so it can bridge a large bone-tendon gap, while integrating with both bone and tendon. These 20 properties are ideal for repairing massively torn, degenerated tendons. 21 Based on this significant promise, CollaMedix Inc. proposes to test the feasibility of OsTend in a rabbit 22 model of chronic RC degeneration and repair. Rabbit infraspinatus tendons will be transected, allowed to 23 degenerate, and repaired with OsTends or left un-repaired. At 4 and 12 weeks post-implant, the tendons will be 24 mechanically tested and processed for histology. We hypothesize that the OsTend repaired group will have 25 stronger, thicker tendons and more normal histological characteristics, approaching that of intact controls.