Phase II year
2020
(last award dollars: 2021)
Phase II Amount
$1,679,032
Fewer than 1 in 5 young patients suffering from activity limiting hip osteoarthritis (OA) choose to undergo total hip replacement (THR) surgery, opting instead for symptom management. Despite being the standard of care in hip OA, THR is not an ideal procedure for the young patient population because they will require multiple revision surgeries in their lifetime, each iteration posing additional complications, quicker implant failures, and overall decreased satisfaction. While the etiology of disease in this young population is diverse, one clear target for intervention is femoroacetabular impingement (FAI), which directly leads to osteochondral (OC) damage within the joint. Currently, there are no effective treatments for the OC lesions caused by FAI, so these joints continue to degenerate and eventually require a THR. As such, there is a critical need for new interventions that delay or halt the progression of FAI disease and the need for that initial joint replacement. Our technology restores the function of the joint while only replacing the surface-level, diseased tissue. The technological basis of our implant is a 3D woven scaffold, engineered to mimic the mechanical properties of articular cartilage, which is then thermally bonded to a rigid printed substrate, which is engineered for bone ingrowth. In order to function long-term in vivo, the implant must be populated with cells capable of robust tissue synthesis. In this context, preculture with bone marrow derived mesenchymal stem cells (MSCs) may be required for clinical use. However, a clear need exists to prove the chondrogenic potential of highly variable MSC lots prior to their use clinically. The goals of this Direct to Phase II SBIR application are therefore to first devise a method for rapidly screening the chondrogenic potential of allogeneic MSCs using RNA sequencing in Aim 1, and then in Aim 2, to tissue-engineer a MSC-based joint resurfacing implant to repair a large OC acetabular defect in an ovine model of FAI (CAM-type), at a site often implicated in the young patient. All animals will receive an osteochondroplasty procedure to relieve impingement and then be randomized to one of the following groups: 1) Control, debridement only; 2) acellular implant only control; and 3) allogeneic MSC-based, tissue-engineered implant. Outcome measures are selected to longitudinally track lameness, pain, and function during the study. As MRI is the gold standard for clinical assessment, all animals will receive an MRI at the beginning of the study and after sacrifice, and these scans will be correlated to histological and biomechanical properties of joint tissues. Systemic toxicity testing will also be assessed according to ISO 10993-11. We expect that positive outcomes will enable us to move this technology closer to clinical practice, with the ultimate goal of developing strategies to treat FAI and other cartilage-related disease.
Public Health Relevance Statement: Project Narrative The overarching purpose of this project is to develop a treatment for repairing cartilage defects in young patients that arise from extra bone growth in the hip joint (condition known as Femoroacetabular, Impingement), and secondarily, to develop tools for rapidly quantifying the potency of stem cells for use with our technology. Our approach comprises a unique biphasic implant that is engineered to withstand joint loading while supporting the regeneration of diseased joint tissues, thereby offering distinct advantages over current surgical treatments. A successful outcome will help move this technology closer to clinical use, providing solutions for patients who have no good treatment options, and potentially becoming a viable treatment for osteoarthritis and other joint diseases.
Project Terms: 3-Dimensional; 3D Print; acetabulum; active lifestyle; Adult; Affect; Allogenic; American; Anatomy; Animals; arthropathies; articular cartilage; Autologous; Automobile Driving; base; Biocompatible Materials; Biomechanics; Biomimetics; bone; bone engineering; Bone Growth; Bone Marrow; Caring; Cartilage; cartilage repair; Cells; Chondrocytes; Chondrogenesis; Clinical; Clinical assessments; clinical practice; Control Groups; Data; Debridement; Defect; Deformity; Degenerative polyarthritis; design; Development; disability; Disease; Economic Burden; effective therapy; Engineering; Etiology; Face; Failure; FDA approved; functional restoration; Gene Cluster; Genes; genetic signature; Genetic Transcription; Goals; Gold; Growth; Hip Joint; Hip Osteoarthritis; Hip region structure; hip replacement arthroplasty; Histologic; Human; Implant; implant design; implantation; improved; in vivo; Intervention; joint function; joint loading; Joints; Knee; Lesion; Life Style; Longevity; Magnetic Resonance Imaging; Measurement; Measures; mechanical properties; Mesenchymal Differentiation; Mesenchymal Stem Cells; Methods; Modeling; Natural regeneration; novel strategies; Operative Surgical Procedures; osteochondral tissue; Outcome; Outcome Measure; Pain; Pathway Analysis; patient population; Patients; Phase; Population; preservation; Procedures; Property; Randomized; rapid technique; regenerative; repaired; Replacement Arthroplasty; Reporting; Resected; response; risk minimization; satisfaction; scaffold; Scanning; screening; Secondary to; Sheep; Site; Small Business Innovation Research Grant; Source; standard care; standard of care; stem cell therapy; stem cells; Structure; subchondral bone; Surface; Surgeon; symptom management; systemic toxicity; Technology; Textiles; Tissue Engineering; Tissues; tool; Total Hip Replacement; Toxicity Tests; transcriptome sequencing; Translating; uptake; Weight-Bearing state; Work
