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

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.