AlloBrace: Pure Collagen Augment to Improve Performance and Integration of Allografts

Summary An estimated 225,000 anterior cruciate ligament (ACL) tears are reported annually in the US, equating to ~$7B in medical costs. Tears of the ACL lead to instability of the knee and reduce mobility, if left untreated, it can lead to chronic knee issues. Tears are typically treated by ACL reconstruction (ACLR) using either an autograft or an allograft. Allografts only account for 22-44% of ACLR in the U.S. because autografts have a low failure rate (5%). Harvesting an autograft causes donor-site morbidity (DSM) which leads to muscle weakness of the ipsilateral leg, risk of infection, longer recovery time (9-12 months), chronic knee pain, and higher risk of contralateral ACL tears. Use of allografts prevents DSM. Unfortunately, allografts have an ~14% failure rate and are usually recommended for older and less active patients. Specifically, soft tissue allografts (STA) have poor ligamentization and fail to form a true boney junction between the bone-graft interface. There is a need to improve the biological integration of STAs to increase graft biomechanics, which will lead to lower failure rates. Therefore, CollaMedix Inc. has developed AlloBrace to increase the biological integration of the allograft by stimulating and guiding ligamentization throughout the STA and inducing true bony growth at the bone-graft interface. CollaMedix is in the business of developing medical grade biotextiles using high-strength pure-collagen type I threads produced by its patented high-throughput electrochemical compaction process. The collagen molecules in the thread are unidirectionally aligned within threads, mimicking the native topography of ligaments and tendons, which we have found makes the implant regenerative. Extensive in vivo research has found that new host collagen is templated parallel to these threads, resulting in an ordered tissue deposition. Collagen threads also 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. A hydroxyapatite (HA) coating can be added to impregnant the threads to be osteoconductive. Therefore, we have braided spooled collagen thread with industrial braiding machines and coated each end with HA to create AlloBrace, a pure collagen sheath with tenoinductive and osteoinductive potential. AlloBrace is simply deployed by sliding over the allograft and prepared with traditional ACLR techniques and equipment. To validate AlloBrace, CollaMedix aims to confirm the feasibility of AlloBrace as an enhancement for STA used in ACLR using a porcine model. We hypothesize that AlloBrace will 1) guide cellular infiltration and tissue production throughout the allograft, and 2) stimulate bone growth at the bone-graft interface within the bone tunnels. Specific Aim 1. Refine AlloBrace design to improve graft conformity and to ease surgical deployment. Fabricate AlloBrace with varying diameters (6, 8, 10mm) and layer amounts (2, 3, 4) and determine which configuration conforms best to the STA. Specific Aim 2. Show AlloBrace improves allograft healing biology and knee biomechanics. Compare AlloBrace+STA vs. STA in an 8-week ACLR porcine study. Study assessment will be done by quantitative histology analyzing immune response, wound healing, and tissue integration within the graft and bone-graft interface, as well as biomechanical knee laxity tests. Phase I data will be used to justify future Phase II work to test AlloBrace’s load sharing capacity and compare our device to predicate devices in a larger and longer in vivo study (6 & 9 months). AlloBrace is poised to reduce allograft failure rates which would increase potential use in ACLR and prevent autograft DSM.