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

基本信息

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
项目类别：
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

项目摘要

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 总结： 2 美国每年进行约 300,000 次肩袖 (RC) 修复手术，估计费用为 3 $4B. RC 的高级退化会导致疼痛和严重残疾。 4 RC由骨与肌腱分离、肌腱退变组成，无法修复； 5 关节镜手术占 RC 撕裂的 40%，需要昂贵的侵入性肌肉移植或关节成形术。 6 个程序，覆盖皮肤和其他部位，最多只能被动地加固下面的肌腱。 7 对肌腱或附着点的再生没有贡献开发再生能力的临床需求尚未得到满足。 8 种适合遭受无法挽回的眼泪的患者的植入产品。 9 CollaMedix Inc. 使用我们生产的高强度纯胶原线开发生物纺织医疗植入物 CollaMedix 制造的 10 项高通量电化学压实专利工艺。 11由工业编织机编织以获得宏观多孔、高度生物相容性、可吸收的支架。 12 胶原蛋白分子在支架线内单向排列，模仿了天然的地形 13 肌腱，并对干细胞产生肌腱诱导作用，肌腱特异性的表达证明了这一点 14 标记肌腱调节蛋白与这些线平行模板化，从而产生有序的组织。 15 沉积此外，用于稳定线的交联剂京尼平将巨噬细胞极化为亲-。 16 再生表型。 17 我们设计了这样一种支架，其一端注入羟基磷灰石，使其具有骨诱导作用。 18 一侧保持张力，另一侧保持张力。这种双相 OsTend 支架具有承重性和稳定性。 19 可缝合，因此它可以桥接大的骨-肌腱间隙，同时与骨和肌腱融合。 20 种特性非常适合修复严重撕裂、退化的肌腱。 21 基于这一重大承诺，CollaMedix Inc. 提议在兔子身上测试 OsTend 的可行性 22 慢性RC变性和修复模型将兔冈下肌腱横断，让其进行。 23 退化，并用 OsTends 修复或不修复在植入后 4 周和 12 周，肌腱将被修复。 24 经过机械测试和组织学处理，我们勇敢地说 OsTend 修复组将有。 25 条更强、更厚的肌腱和更正常的组织学特征，接近完整对照。