Phase II year
2020
(last award dollars: 2022)
Phase II Amount
$1,784,887
The temporomandibular joint (TMJ) is a complex joint system critical for dental occlusion, mastication, respiration and speech. The TMJ is comprised of a network of muscles, ligaments, and a fibrocartilaginous disc and condyle. Temporomandibular disorders (TMDs) afflict over 10 million Americans at an annual cost of ~$4 billion, per the NIDCR. Degenerative types of TMDs, including TMJ osteoarthritis (OA), are debilitating, compromise quality of life, and causes permanent tissue loss. Current TMJ OA treatments are typically two-fold, involving either pain management or invasive surgeries, such as total joint replacements with high failure rates. There is a paucity of minimally invasive TMJ therapies that promote tissue regeneration. Regenerative medicine promises the recreation functional tissue that is loss from disease. Thus exploiting the regenerative capabilities of resident stem cells to repair TMJ may represent a minimally invasive stem cell-based treatment for TMJ OA. We have identified fibrocartilage stem cells (FCSCs) that reside in the TMJ condyle superficial zone. Transplanted FCSCs self-organize and regenerate cartilage. Wnt/ï¢Catenin signaling promotes proliferation and inhibits chondrogenic differentiation of FCSCs. However, over-active Wnt/ï¢Catenin deplete FCSCs and cause TMJ OA in mice, rabbits and humans. These data suggest that inhibiting Wnt/ï¢Catenin in FCSCs may serve as a stem cell-based therapeutic strategy for the treatment of TMJ OA. In fact, we showed that blocking Wnt via weekly TMJ intra-articular injections of the Wnt inhibitor sclerostin ameliorated TMJ OA in a rabbit TMJ injury model. However, a pharmacological drug delivery system for chairside, sustained release sclerostin administration to human TMJ OA patients has not been defined. Based on our preliminary data, we hypothesize that delivery of an injectable, sustained release hyaluronic acid-sclerostin hydrogel will target resident TMJ fibrocartilage stem cells to regenerate TMJ.
Public Health Relevance Statement: PROJECT NARRATIVE An innovative targeting treatment for TMJ osteoarthritis is being developed by collective effort between Wnt Scientific LLC and TMJ Biology and Regenerative Medicine Laboratory at Columbia University. The innovative treatment is to deliver recombinant sclerostin, a potent Wnt signal inhibitor, in hyaluronic acid.
Project Terms: Pain management, Pain Control, Pain Therapy, pain treatment, inhibitor/antagonist, inhibitor, Anti-Inflammatory Agents, Anti-Inflammatories, Anti-inflammatory, Antiinflammatories, Antiinflammatory Agents, antiinflammatory, Biology, Cartilage, Cartilaginous Tissue, Cells, Cell Body, Communication, Connective Tissue, Dental Occlusion, Disease, Disorder, Pharmaceutical Preparations, Drugs, Medication, Pharmaceutic Preparations, drug/agent, Extracellular Matrix, Cell-Extracellular Matrix, ECM, Goals, Health, Human, Modern Man, Hyaluronic Acid, Intra-Articular Injections, Intraarticular Injections, Joints, Laboratories, Ligaments, Lubrication, Mastication, Chewing, chewed, chews, Molecular Weight, Mus, Mice, Mice Mammals, Murine, Muscle, Muscle Tissue, muscular, Degenerative polyarthritis, Degenerative Arthritis, Osteoarthritis, Osteoarthrosis, degenerative joint disease, hypertrophic arthritis, osteoarthritic, Legal patent, Patents, Pathology, Patients, Peer Review, Pharmacology, Play, Proteoglycan, Quality of life, QOL, Oryctolagus cuniculus, Domestic Rabbit, Rabbits, Rabbits Mammals, Recreation, Natural regeneration, Regeneration, regenerate, research and development, Development and Research, R & D, R&D, Respiration, respiratory mechanism, Signal Transduction, Cell Communication and Signaling, Cell Signaling, Intracellular Communication and Signaling, Signal Transduction Systems, Signaling, biological signal transduction, Speech, stem cells, Progenitor Cells, Family suidae, Pigs, Suidae, Swine, porcine, suid, Synovial Fluid, Synovia, Temporomandibular Joint, Jaw Joint, Mandibular joint, TMJ, Temporomandibular Joint Disorders, TMJ Diseases, TMJ Disorders, TMJD, Temporomandibular Disorders, Temporomandibular Joint Diseases, Temporomandibular Joint and Muscle Disorder, Testing, Time, Tissues, Body Tissues, Transplantation, transplant, Universities, Drug Delivery Systems, Drug Delivery, Injectable, Mediating, lubricating glycoprotein-I, lubricin, base, Arthroplasty, Joint Prosthesis Implantation, joint arthroplasty, joint replacement, Replacement Arthroplasty, Encapsulated, repair, repaired, Phase, Biological, Link, Diarthrosis, Synovial joint, Chondrocytes, Failure, Fostering, Technology Transfer, Collaborations, Therapeutic, Nature, Life, joint damage, joint trauma, joint injury, knee OA, knee joint OA, knee joint osteoarthritis, Knee Osteoarthritis, Complex, System, Operative Procedures, Surgical, Surgical Interventions, Surgical Procedure, surgery, Operative Surgical Procedures, American, Animal Models and Related Studies, model of animal, model organism, Animal Model, Hydrogels, Structure, novel, fibrocartilaginous, Fibrocartilages, Modeling, drug development, stem cell therapeutics, stem cell treatment, stem cell-based treatment, stem cell therapy, cartilage repair, Regenerative Medicine, Data, NIDCR, NIDR, National Institute of Dental Research, National Institute of Dental and Craniofacial Research, Recombinants, STTR, Small Business Technology Transfer Research, WNT signaling, WNT Signaling Pathway, regenerate new tissue, regenerating damaged tissue, tissue renewal, tissue regeneration, preclinical, pre-clinical, cost, injured, TMJ osteoarthritis, TMJ-OA, Temporomandibular Osteoarthritis, Temporomandibular joint (TMJ) osteoarthritis, Temporomandibular joint osteoarthritis, innovate, innovative, innovation, stem cell technology, regeneration therapy, regenerative therapeutics, regenerative therapy, FDA approved, minimally invasive, treatment strategy, regenerative, Growth Agents, Growth Substances, Proteins Growth Factors, Growth Factor
