Performance Evaluation of a non-Degradable Synthetic Device for Chondral and Osteochondral Defects of the Knee

Injury to joints can lead to painful defects in articular cartilage and the underlying bone, which adversely affect the function and biological health of the entire joint. Current solutions for cartilage (chondral) and cartilage-and- bone (osteochondral) defects, are unreliable, are technically challenging, and often require multiple procedures. A surgeon-engineer-biologist team at Hospital for Special Surgery (HSS) dedicated andgt;10 years of research to the design and functional evaluation of a solution to this problem which led to the formation of the first spin-out company from HSS in its 156-year history. AGelity-OCI (OsteoChondral Implant), is a non-cell based, non- degradable synthetic device, consisting of two layers: a poly(vinyl alcohol) hydrogel, PVA, integrated into a porous Titanium base. The PVA layer is designed with a solid core to withstand physiological loads and a patent protected concentric porous sponge that hydrates in situ to produce a snug press-fit against the host articular cartilage, leading to lateral integration. Using in vitro, in silico, and in vivo models we have demonstrated that AGelity-OCI integrates with bone and articular cartilage without causing joint synovitis, inflammation, or damage to the opposing surfaces of the joint, the interface between PVA and porous titanium (which was optimized using Phase I SBIR funds) maintains mechanical integrity, and the device distributes loads similar to the native tissue. The objective of this study is to fully characterize the mechanical, structural, chemical, morphological, biological, and functional characteristics of AGelity-OCI as per regulatory guidelines. Our over-arching hypothesis is that AGelity-OCI is a safe and effective device for the treatment of focal chondral and osteochondral defects. This hypothesis will be tested using two Specific Aims. Specific Aim 1: To characterize the chemical, morphological, and materials performance of our as-manufactured post-sterilized device and its components. Our hypothesis is that the device will meet federal guidelines for safety. Specific Aim 2: To characterize the biological and functional in vivo behavior of AGelity-OCI. Our hypothesis is that AGelity-OCI will be non-inferior to fresh frozen osteochondral allografts. Our efforts to commercialize this device are at a mature translational de-risked stage: (i) a Pre-IDE meeting with the FDA in February 2018 was completed; the minutes from which frame the details of the current proposal (ii) intellectual property is protected by five patents, (iii) AGelity-OCI is currently manufactured, packaged and sterilized by an FDA registered and ISO certified manufacturing facility, and (iv) the core investigative team spans engineering, surgery, manufacture, pre-clinical testing, regulatory and business strategy. Our device-based approach represents a significant shift in the current paradigm for the treatment of osteochondral defects by avoiding the highly variable results from cell-based approaches and the technical and logistical challenges of graft usage. Successful completion of this study will enable our trajectory to conduct first-in-man studies for AGelity-OCI, resulting in a cost-effective functional solution for the management of chondral and osteochondral defects.To address the debilitating clinical problem of articular cartilage damage, we have developed a non-degradable, off-the-shelf implant, AGelity-OCI, that will integrate with the host cartilage and underlying bone, and reliably provide structural integrity to the defect site. The objective of this study is to fully characterize the mechanical, structural, chemical, morphological, biological, and functional characteristics of AGelity-OCI. By generating data to test our over-arching hypothesis that AGelity-OCI is a safe and effective device for the treatment of focal articular cartilage defects, we will seek regulatory approval for the clinical use of our device.