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

OsTend：一种用于大规模肩袖修复的承重双相胶原支架

• 批准号: 10761321
• 负责人: Subba Shankar
• 金额: $ 30万
• 依托单位: COLLAMEDIX INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10761321
• 关键词: Address; Animal Model; Articular Range of Motion; Biocompatible Materials; Bone Growth; Bone Regeneration; Characteristics; Chronic; Clinical; Collagen; Contralateral; Cytoskeleton; Defect; Deposition; Dermal; Distal; Future; Histologic; Histology; Hydroxyapatites; Implant; Industrialization; Infiltration; Left; Legal patent; Licensing; Limb structure; Macrophage; Mechanics; Mesenchymal Stem Cells; Modeling; Muscle; Natural regeneration; Operative Surgical Procedures; Oryctolagus cuniculus; Osteogenesis; Outcome; Outcome Measure; Pain; Patients; Phase; Phenotype; Procedures; Process; Property; Replacement Arthroplasty; Rotator Cuff; Shapes; Sheep; Shoulder; Side; Site; Surgeon; Surgical Models; Surgical sutures; Technology; Tendon structure; Testing; Time; Tissues; Weight-Bearing state; biomaterial compatibility; bone; clinically relevant; collagen scaffold; cost; cost estimate; crosslink; density; design; disability; effective therapy; feasibility testing; genipin; high reward; high risk; improved; in vivo; infraspinatous muscle; manufacture; medical implant; microCT; mimicry; novel; preclinical study; reconstitution; regenerative; repaired; rotator cuff tear; scaffold; scale up; stem cells

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.

1摘要： 2美国每年进行约300，000例肩袖（RC）修复手术，估计费用为 340亿美元。RC的晚期变性导致疼痛和严重残疾。“大量”或“不可修复”（> 5 cm）撕裂 RC的4例包括骨与肌腱之间的脱离以及肌腱变性;因此，它们无法修复 5关节镜检查。占RC撕裂的40%，它们需要昂贵且侵入性的肌肉转移或关节成形术 6个程序。覆盖补丁，真皮和其他，最好的被动加强下面的肌腱， 7例不促进肌腱的再生和附着点的形成。有一个未满足的临床需要， 8种植入产品，适用于患有不可修复撕裂的患者。 9 CollaMeetings Inc.使用我们生产的高强度纯胶原蛋白线开发生物纺织医用植入物 10专利工艺的高通量电化学压实。在CollaMeetings制造的线轴 11通过工业编织机编织以获得大孔的、高度生物相容的、可再吸收的支架。 图12胶原分子在支架线内单向排列，模拟了胶原蛋白的天然形貌。 13肌腱，并赋予对干细胞的肌腱诱导作用，如肌腱特异性 14标记腱调节蛋白。宿主胶原蛋白以平行于这些线的方式模板化，从而形成有序的组织 15篇作文此外，用于稳定线的交联剂京尼平使巨噬细胞极化为亲- 16个再生表型。 17我们设计了这样一种支架，在一端注入羟基磷灰石，使其具有骨诱导性。 18，而另一侧保持ten-inductive。这种双相奥斯坦德支架是承重的， 19可缝合，因此它可以桥接大的骨-肌腱间隙，同时与骨和肌腱结合。这些 20属性是修复大规模撕裂，退化肌腱的理想选择。 21基于这一重大承诺，CollaMeetings Inc.建议在兔子身上测试奥斯坦德的可行性 22例慢性RC退变及修复模型。将切断兔冈下肌肌腱，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 对24件进行机械测试和组织学处理。我们假设奥斯坦德修复组将有 25更强，更厚的肌腱和更正常的组织学特征，接近完整对照组。