CollaLink: Guided-regenerative Scaffold for Augmentation of Anterior Cruciate Ligament Repair

总结 前交叉韧带（ACL）的撕裂导致膝关节不稳定并降低活动性。估计 美国每年报告225，000例ACL撕裂，相当于约70亿美元的医疗费用。优选的治疗 是用自体移植物或同种异体移植物重建患者的ACL，这可能导致供体部位发病或 免疫反应，并增加慢性膝关节疾病的风险，如骨关节炎。用新 随着手术技术和生物增强技术的进步，ACL一期修复方法已经获得了 重新唤起了人们对保存患者自体组织的兴趣，有助于预防长期的膝关节问题。最近，主要 ACL修复仅适用于近端ACL撕裂，而中间层撕裂不修复 主要是因为失败率高。据我们所知，没有其他生物学上的增强。 中期物质撕裂的初级修复市场。因此，临床上需要能够 使中间物质撕裂的初级修复成为可能。CollaMeetings Inc.开发生物纺织医用植入物， 高强度纯胶原蛋白线通过其专利的高通量电化学压缩工艺生产。 在CollaMeetings生产的线轴线由工业编织机编织，以获得CollaLink， 管状编织物，只需在ACL撕裂处滑动即可展开，并缝合到位，以跨越中间 修复过程中物质撕裂。除了手术适用性外，CollaLink还具有再生作用。 胶原蛋白分子在丝线内单向排列，模仿韧带的天然地形 的筋宿主胶原平行于这些线模板化，导致有序的组织沉积。 广泛的研究表明，胶原蛋白线赋予干细胞的地形tenoinductive效果。的 交联剂京尼平，这是用来稳定线程，极化巨噬细胞的亲再生， 表型通过第一阶段项目，CollaMeetings旨在确定CollaLink的可行性， 一种ACL修复加固，能够对猪的ACL中段撕裂进行一期修复， 模型我们假设CollaLink放置在中间物质ACL撕裂周围将提供大孔 用于成纤维细胞浸润和从头胶原蛋白沉积的支架 并促进有利于再生的环境以改善韧带愈合和机械负荷强度。中 配对设计，猪的胸骨将在中间物质处横断，每条腿将用缝线修复 不管有没有CollaLink植入后12周，将对韧带进行机械测试， 松弛度和强度，并针对生物相容性、组织整合和基质类型进行免疫/组织学处理。 第一阶段的成功实现将证明未来第二阶段的工作是合理的，以测试CollaLink对重建的影响， 其他等同器械，并开发关节镜输送工具和方案。CollaLink服务的商业化 有效的益处，如保留患者自身韧带，消除供体部位发病率， 自体移植，减少膝关节长期骨关节炎的发生。

Summary Tears of the anterior cruciate ligament (ACL) lead to instability of the knee and reduce mobility. An estimated 225,000 ACL tears are reported annually in the US, equating to ~$7B in medical costs. The preferred treatment is reconstruction of the patient’s ACL with an autograft or allograft, which can cause donor site morbidity or immunological response, and have an increased risk of chronic knee conditions, like osteoarthritis. With new advances in surgical techniques and biological augmentations, ACL primary repair methods have gained renewed interest to save a patient’s native tissue, helping prevent long-term knee problems. Lately, primary repair of the ACL is designated for proximal ACL tears only whereas mid-substance tears are not repaired primarily due to high rate of failure. To the best of our knowledge, there is no other biologic augmentation on the market for primary repair of mid-substance tears. Therefore, there is a clinical need for technologies that will enable primary repair of mid-substance tears. CollaMedix Inc. develops biotextile medical implants using high- strength pure-collagen threads produced by its patented high-throughput electrochemical compaction process. Spooled threads manufactured at CollaMedix are braided by industrial braiding machines to obtain CollaLink, a tubular braid that is deployed simply by sliding over the ACL tear and sutured into place to span the mid- substance tear during the repair process. Besides surgical applicability, CollaLink has regenerative effects. Collagen molecules are unidirectionally aligned within threads, mimicking the native topography of ligaments and tendons. Host collagen is templated parallel to these threads, resulting in an ordered tissue deposition. Extensive research has shown collagen threads impart a tenoinductive effect on stem cells topographically. The crosslinking agent genipin, which is used to stabilize threads, polarizes macrophages to the pro-regenerative phenotype. Through this Phase I project, CollaMedix aims to establish the feasibility of the CollaLink as an ACL repair augmentation that will enable primary repair of ACL mid-substance tears in a porcine model. We hypothesize that CollaLink placed around a mid-substance ACL tear will provide a macroporous scaffolding for fibroblast infiltration and de novo collagen deposition throughout the continuum of the scaffold and promote a pro-regenerative environment for improved ligament healing and mechanical load strength. In a paired design, pigs’ ACLs will be transected at the mid-substance, and each leg will be repaired with sutures either with or without a CollaLink. At 12 weeks post-implantation, the ligaments will be mechanically tested for laxity and strength, and processed for immuno/histology for biocompatibility, tissue integration, and matrix type. Successful attainment of Phase I would justify future Phase II work to test CollaLink against reconstruction and other predicates and develop an arthroscopic delivery tool and protocol. Commercialization of CollaLink offers impactful benefits such as preservation of the patient’s own ligament, elimination of donor site morbidity in autografting, and reducing the occurrence of long-term osteoarthritis of the knee.