SBIR-STTR Award

?Trauma and overuse of joints can lead to painful defects in the articular cartilage and underlying bone, which adversely affect the mechanical and biological function of the entire joint. Over time this early-stage damage can spread, leading to end-stage osteoarthritis (OA). While treatments for osteochondral defects have been developed to relieve pain and delay the spread of damage, current solutions are perceived as unreliable - requiring early surgical revision. To better treat these defects, we have developed an innovative non- degradable, off-the-shelf device that will provide immediate structural integrity to the defec site for the duration of implantation, while also integrating with the host tissue. The device is non-cell based, non-biodegradable, synthetic and porous, and as such represents a significant shift in the current paradigm for the treatment of chondral and osteochondral defects. The implant consists of a solid cylindrical poly(vinyl) alcohol (PVA) core (to resist joint load) concentrically surrounded by a porous PVA outer rim (press-fit with surrounding tissue and designed to integrate with cartilage), with the solid core attached to a porous metal base (for initial fixation and integration with bone). The device is arthroscopically implanted into the defet in a dehydrated form, which then rehydrates in situ to form a strong interface with the host tissue, thus enabling immediate weight bearing. While a series of in vitro and in vivo animal models have demonstrated that the device can integrate with host tissue and mechanically function much in the way of the native tissue, we encountered several instances of mechanical failure of the device when the PVA disassociated from the metal base. The objective of this study is to modify the PVA-metal interface to prevent failures, while maintaining the ability of th device to mechanically function in a loaded joint. To this end we have used finite element models to direct modifications to: (i) the macroscopic geometry of the PVA-metal interface, and (ii) the stiffness of the PVA-metal interface. Our goal is to determine which combination of changes in macroscopic interlock, and PVA stiffness (15 groups in total) are robust enough to withstand sustained weight bearing. First, we will optimize the shear and tensile strengths of the PVA-metal interface to avoid mechanical failure after device rehydration (Specific Aim 1). Secondly, we will subject the device to repetitive axial and shear forces using a custom rolling-sliding device to simulate the forces applied to the device in situ (Specific Aim 2). Optimized design criteria will be based on the maximum shear and tensile stresses at the PVA-metal interface calculated in the FE model (Aim 1), and characterization of the fatigue properties of the device (Aim 2). Through this suite of tests, we will identify the device design with the highest shear and tensile safety factor that is able to restore load distribution across the joint over extended cycles of loading. The optimal design from this study will be subsequently used for re- implantation into our previously established in vivo horse model.

Public Health Relevance Statement:


Public Health Relevance:
Approximately 3.9 million patients worldwide have been diagnosed with articular cartilage damage. Despite this staggering number, there is no reliable method to treat these painful injuries. To address this serious clinical problem, we have developed a non-degradable, off-the-shelf device that will provide immediate reliable structural integrity to the defect site for the duration of implantation, while also integrating with the host cartilage and underlying bone to provide further fixation. Our study will refine the design of this novel device to ensure that it is structurally sound while maintaining its ability to mechanically function much in the same way as the native cartilage, thereby aiding in the transition of this technology into clinical care.

NIH Spending Category:
Arthritis; Bioengineering; Osteoarthritis

Project Terms:
Address; Affect; Alcohols; Animal Model; articular cartilage; base; Biological; Biological Process; bone; Cartilage; Characteristics; Clinical; clinical care; Clinical Research; commercialization; Consensus; Custom; Defect; Degenerative polyarthritis; design; Device Designs; Devices; Diagnosis; Disease; Elements; Engineering; Ensure; Environment; Equipment Malfunction; Equus caballus; Experimental Models; Failure (biologic function); Fatigue; Gait; Geometry; Goals; Human; Implant; implantation; In Situ; In Vitro; in vivo; in vivo Model; Inflammation; Injury; innovation; interfacial; joint loading; Joints; Knee; Knee joint; Lead; Legal patent; Life; Measures; Mechanics; meetings; Metals; Methods; Modeling; Modification; novel; Operative Surgical Procedures; Orthopedics; osteochondral tissue; Pain; Pathway interactions; Patients; Physiological; prevent; Procedures; Process; Property; public health relevance; Rehydrations; Research; Research Design; response; Safety; sample fixation; Scientist; Second Look Surgery; Series; Shear Strength; Site; Slide; Solid; Solutions; sound; Special Hospitals; Staging; Stress; success; Surface; Surgeon; Synovitis; Technology; Tensile Strength; Testing; Time; Tissues; Trauma; United States Food and Drug Administration; Walking; Weight-Bearing state; Work

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 >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.

Public Health Relevance Statement:
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.

NIH Spending Category:
Arthritis; Bioengineering; Osteoarthritis; Transplantation

Project Terms:
Acute; Address; Adverse reactions; Affect; Aging; Alcohols; Allografting; American; analog; Appearance; articular cartilage; Autologous Transplantation; base; Behavior; Biological; Biological Assay; bone; Businesses; carcinogenicity; Cartilage; Cells; Characteristics; Chemicals; Chronic; Clinical; commercialization; Computer Simulation; Consensus; cost effective; cytotoxicity; Data; Defect; Degenerative polyarthritis; design; Devices; Diagnosis; Disease; Distal; Engineering; Ensure; Environment; Evaluation; experience; first-in-human; Freezing; Friction; Funding; Gel; Gel Chromatography; Guidelines; Hardness; Health; Histologic; Hydration status; Hydrogels; Implant; implantable device; In Situ; In Vitro; in vivo; in vivo Model; Industry; Inflammation; Injury; Intellectual Property; International; irritation; Joints; Knee; Laboratories; Lateral; Lead; Legal patent; Literature; Logistics; manufacturing facility; Mass Spectrum Analysis; mechanical properties; Mechanics; Mediating; meetings; Metals; Methods; Modeling; Morbidity - disease rate; Morphology; off-patent; Operative Surgical Procedures; Organ; Orthopedics; osteochondral tissue; Pain; Pain-Free; particle; Patients; Performance; Periodicity; Phase; Physiological; Plasma; Porifera; Preclinical Testing; primary outcome; Procedures; Process; Protocols documentation; Pyrogens; Recording of previous events; Rehabilitation therapy; Research; research and development; Risk; Safety; sample fixation; scaffold; Scanning Electron Microscopy; secondary outcome; Secure; Site; Small Business Innovation Research Grant; Societies; Solid; Special Hospitals; Spectroscopy, Fourier Transform Infrared; Structure; Surface; Surgeon; Surgical Instruments; Synovitis; systemic toxicity; Testing; Tissues; Titanium; Toxic effect; Translating; Trauma; Veterinarians; Work