Functional Tissue Engineering for Cartilage Repair

DESCRIPTION (provided by applicant): Degenerative joint diseases such as osteoarthritis remain the source of significant pain and disability, affecting 20 million adults with an economic burden of over 40 billion per year to the United States. While joint replacement is a well-established procedure, its finite life span makes this treatment unacceptable for younger or more active individuals, often requiring additional surgeries that 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 to form a cartilage-bone composite 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 to create a layer of living cartilage and bone that can be used to completely replace a damaged joint surface. The primary advance of the current technology is the use of 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. A defined combination of growth factors will be used initially to promote the differentiation of both bone and cartilage, followed by novel encapsulation and immobilization technologies to deliver these growth factors from the matrix in a local and sustained manner in vivo. 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 proof- of-principal that composite, cell-seeded constructs can be fabricated with many of the complex mechanical properties of articular cartilage. The development of a 3-D weaving technology will hopefully provide a novel means of developing tissue engineered constructs that are biomechanically functional at the time of creation, through surgical implantation, and integration into host tissues in the body. 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 STTR project is to develop a 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 a novel three-dimensional woven scaffold that is designed to withstand joint loading. The ultimate goal of this study is to develop tissue engineering technologies that can eventually be used to treat osteoarthritis and other joint diseases.