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

CollaLink：用于增强前十字韧带修复的引导再生支架

• 批准号: 10760639
• 负责人: Christian T. Denny
• 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 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10760639
• 关键词: Accounting; Acute; Allografting; Animal Model; Annual Reports; Anterior; Anterior Cruciate Ligament; Autologous; Autologous Transplantation; Benchmarking; Bilateral; Biological; Biological Products; Blood; Chronic; Clinical; Collagen; Cytoskeleton; Degenerative polyarthritis; Deposition; Development; Devices; Environment; Equation; Excision; Failure; Family suidae; Female; Femur; Fibroblasts; Future; Grant; Health; Histologic; Histology; Immune response; Impairment; Implant; In Vitro; Industrialization; Infiltration; Joints; Knee; Knee Injuries; Knee Osteoarthritis; Lead; Leg; Legal patent; Ligaments; Macrophage; Marketing; Measures; Mechanics; Medical Care Costs; Methods; Morbidity - disease rate; Natural regeneration; Ohio; Operative Surgical Procedures; Outcome; Patient Care; Patients; Phase; Phenotype; Porifera; Porosity; Process; Proprioception; Protocols documentation; Reporting; Research; Research Design; Risk; Rotator Cuff; Site; Slide; Surgical sutures; Techniques; Technology; Tendon structure; Tensile Strength; Testing; Tissues; Treatment Cost; Tube; Tubular formation; United States National Institutes of Health; Urinary Incontinence; Work; achilles tendon; anterior cruciate ligament reconstruction; anterior cruciate ligament rupture; biomaterial compatibility; bone; clinically relevant; commercialization; crosslink; design; experimental study; fabrication; functional loss; genipin; healing; implantation; improved; in vivo; innovation; interest; manufacture; manufacturing scale-up; mechanical load; medical implant; novel; porcine model; premature; preservation; prevent; reconstitution; reconstruction; regenerative; repaired; scaffold; scale up; soft tissue; stem cells; tissue repair; tool; wound healing

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.

摘要 前十字韧带(ACL)撕裂导致膝关节不稳定，降低活动度。据估计 据报道，美国每年有22.5万人前交叉韧带撕裂，相当于约70亿美元的医疗费用。首选治疗方法 是使用自体或同种异体移植物重建患者的前交叉韧带，这可能会导致供区并发症或 免疫反应，并增加患慢性膝关节疾病的风险，如骨关节炎。使用新的 在手术技术和生物强化方面的进展，前交叉韧带的一期修复方法已经获得 重新引起人们的兴趣，挽救患者的自然组织，帮助预防长期的膝盖问题。最近，初选 修复前交叉韧带仅适用于近侧前交叉韧带撕裂，而中层撕裂则不能修复 主要是因为失败率很高。据我们所知，在地球上没有其他的生物增强 一次修复中间物质撕裂的市场。因此，临床上需要一种能够 能够对中间物质撕裂进行一次修复。CollaMedex Inc.开发生物织物医用植入物 由其专利高通量电化学压实工艺生产的强度纯胶原线。 在CollaMedex制造的缠绕线由工业编织机编织，以获得CollaLink，一种 管状编织物，只需滑过前交叉韧带撕裂处并缝合到位，即可展开 修复过程中的物质撕裂。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，模拟韧带的自然形态 还有肌腱。主体胶原蛋白被平行于这些线作为模板，导致有序的组织沉积。 广泛的研究表明，胶原线对干细胞具有局部的肌腱诱导作用。这个 交联剂京尼平用于稳定线条，使巨噬细胞极化为促再生 表型。通过这个第一阶段项目，CollaMedex旨在确定CollaLink的可行性为 一种前交叉韧带修复增强器，将使猪前交叉韧带中间物质撕裂的一期修复成为可能 模特。我们假设，放置在ACL撕裂中间物质周围的CollaLink将提供一个大孔 支架在整个支架连续体中的成纤维细胞渗透和从头开始的胶原沉积 并促进促进再生的环境，以改善韧带愈合和机械负荷强度。在一个 配对设计，猪的前交叉韧带将在中间物质处被横切，每条腿都将用缝线修复 无论有没有CollaLink。在植入后12周，将对韧带进行机械测试 松弛和强度，并进行免疫/组织学生物相容性、组织整合和基质类型的处理。 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针对重建和 其他谓词，并开发关节镜给药工具和方案。CollaLink产品的商业化 有影响的好处，如保留患者自己的韧带，消除供区并发症 自体移植，减少长期膝骨性关节炎的发生。