Hybrid Composite Scaffolds for Cartilage Tissue Engineering

DESCRIPTION (provided by applicant): Damage and subsequent degeneration of articular cartilage in the form of osteoarthritis represents a major health issue globally, and current estimates report that by the year 2020, over 59 million Americans will be diagnosed with arthritis. As treatment options for the treatment of cartilage lesions are few in number and success is somewhat limited, advanced disease requires total joint replacement. Though well-established, the finite life span of the procedure makes this treatment unacceptable for younger or more active individuals as revisions involve progressively complicated treatment with each joint replacement. The goal of this study is to develop a tissue engineered joint replacement from adult stem cells, derived via liposuction from subcutaneous fat, in combination with an engineered biomaterial scaffold, and a novel bioinductive matrix to form cartilaginous tissue to replace the entire surface of the hip joint. We will combine a novel three-dimensional (3D) fiber weaving technology with human adipose derived adult stem cells and a novel hybrid biomatrix derived from articular cartilage to create a layer of living cartilage that can be used to completely replace a damaged joint surface. We will use a 3D woven scaffold that nearly replicates the load-bearing mechanical properties of articular cartilage at the time of initial cell seeding, thus allowing rapid implantation without a prolonged in vitro culture period or use of a bioreactor. The primary advance of this technology is the development of a chondrogenic inducing agent derived from physical processing of articular cartilage allograft; this material results in rapid synthesis of cartilage macromolecules by ASCs in vitro. The ultimate goal of this study is to develop technologies that can be applied to functional tissue engineering of a variety of tissues that possess complex biomechanical properties. As a first step, we will show that the 3D scaffold can be combined with the cartilage-derived matrix to form a fiber reinforced composite and that the biological and mechanical properties of the cell- seeded constructs will match the complex mechanical properties of articular cartilage both in early and late culture. Secondly, we will assess the ability of the fiber reinforced scaffold to maintain the molded shape over the in vitro culture period to show that it is possible to customize our implants to match complex in vivo contours and geometries. An improved level of biomechanical function will hopefully increase the level of success in the engineered repair of various tissues of the musculoskeletal system as well as other organ systems of the body. PUBLIC HEALTH RELEVANCE: The goal of this Phase I SBIR project is to develop a novel hybrid technology for bioartificial joint resurfacing as a treatment for hip osteoarthritis. The technologic basis involves a combination of adult stem cells, retrieved from subcutaneous fat via liposuction and the use of reconstituted native tissue extracellular matrix in a fiber-reinforced scaffold to regulate stem cell growth and differentiation. The ultimate goal of this study is to develop tissue engineering technologies that can eventually be used to treat osteoarthritis and other joint diseases.