OsTend: A load-bearing, bi-phasic collagen scaffold for massive rotator cuff repairs

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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.