A Novel Cell-Hydrogel Technology for the Repair of Fibrillated Articular Cartilag

DESCRIPTION (provided by applicant): Arthritis is a leading cause of morbidity in the US; osteoarthritis (OA) is by far the most common type of arthritis. In many cases cartilage degeneration initiates with asymptomatic cartilage fibrillation, progressing over time to clinically significant OA. Joint replacement represents a successful treatment modality for advanced cartilage degeneration in the older patient; however, treatment options for younger patients are limited. A major goal of new cartilage repair strategies is to prolong articular function, and thus delay the time for necessary invasive surgery, including joint replacement. We propose to develop a novel repair method for fibrillated cartilage that will delay or prevent the onset of later stage osteoarthritis. We have available two significant technological advances which together provide a major opportunity to develop a new, potentially minimally invasive approach to repair fibrillated cartilage. We have a novel adhesive technology to covalently bind hydrogel polymer and matrix proteins of the surrounding cartilage; in addition, we use a novel semi-interpenetrating network (sIPN) hydrogel to provide for excellent cell viability and extracellular matrix deposition by chondrocytes. The adhesive technology and sIPN can be combined to provide an adhesive system to deliver functional cells to an articular cartilage repair site. Our product concept is the use of an adhesive cell-laden hydrogel, polymerized in vivo and delivered arthroscopically, to repair fibrillated articular cartilage. Based on our data, the hypothesis is that an adhesive, cell-laden hydrogel will attach to fibrillated cartilage, deposit an extracellular matrix and generate a functional repair of fibrillated cartilage. The intent of this Phase I project is to determine the feasibility of this product concept. Two Specific Aims are proposed: Specific Aim 1. Optimize the adhesive, compressive and cell-viability and matrix synthesis properties of hydrogel-cell constructs; and Specific Aim 2. Determine in vitro repair of fibrillated cartilage using the optimized cell-hydrogel technology with P3 goat chondrocytes, and goat fibrillated cartilage model. The successful completion of this Phase I project will lead to a Phase II project, where the objective will be to determine safety and effectiveness of the repair method in vivo. If successful, the data generated from these studies will be used in an IDE submission to the FDA to initiate a clinical trial. PUBLIC HEALTH RELEVANCE: Osteoarthritis (OA) is by far the most common type of arthritis and an estimated 12.1 percent of the U.S. population (nearly 21 million Americans) age 25 and older have OA; in many cases cartilage degeneration initiates with asymptomatic cartilage fibrillation, progressing over time to clinically significant OA. We propose to develop a novel repair method for fibrillated cartilage that will delay or prevent the onset of later stage osteoarthritis.