SBIR-STTR Award

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.

Public Health Relevance Statement:
Project Narrative 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.

Project Terms:
21+ years old; 3-D; 3-Dimensional; Adipose tissue; Adult; Affect; Arthritis, Degenerative; Arthropathies NOS; Arthroplasty, Replacement; Articulation; Aspiration Lipolysis; BMP-2; BMP-2A; BMP-6; BMP2; BMP6; Biocompatible Materials; Biomaterials; Biomechanics; Bioreactors; Body Tissues; Bone; Bone Formation; Bone Surface; Bone and Bones; Bones and Bone Tissue; Cartilage; Cartilage, Articular; Cartilagenous Tissue; Cell Differentiation; Cell Differentiation process; Cells; Chondrogenesis; Clinical; Complex; Coxa; Coxarthrosis; Custom; Defect; Degenerative polyarthritis; Development; Economic Burden; Engineering; Engineerings; FDA approved; Fats; Fatty Tissue; Fatty acid glycerol esters; Fiber; Fibrin; GFAC; Gametes; Gel; Germ Cells; Germ-Line Cells; Goals; Growth Agents; Growth Factor; Growth Factors, Proteins; Growth Substances; Head; Hip; Hip Joint; Hip Osteoarthritis; Hip region structure; Human; Human, Adult; Human, General; Immobilization; Implant; In Vitro; Individual; Joint Diseases; Joint Prosthesis Implantation; Joints; Length of Life; Life; Lipectomy, Aspiration; Lipolysis, Suction; Liposuction; Load-Bearing; Loadbearing; Longevity; Man (Taxonomy); Man, Modern; Mechanics; Methods; Methods and Techniques; Methods, Other; Molecular; Musculoskeletal System; Operation; Operative Procedures; Operative Surgical Procedures; Organ System; Osteoarthritis; Osteoarthritis, Hip; Osteoarthrosis; Osteogenesis; Pain; Painful; Phase; Porosity; Procedures; Property; Property, LOINC Axis 2; Relative; Relative (related person); Replacement Arthroplasty; Reproductive Cells; STTR; Sex Cell; Shapes; Site; Small Business Technology Transfer Research; Source; Structure; Structure of articular cartilage; Suction Lipectomy; Surface; Surgical; Surgical Interventions; Surgical Procedure; Techniques; Technology; Testing; Time; Tissue Differentiation; Tissue Engineering; Tissues; United States; Weight-Bearing; Weight-Bearing state; Weightbearing; Work; adipose; adult human (21+); adult stem cell; arthropathic; arthropathies; base; body system; bone; bone morphogenetic protein 2; bone morphogenetic protein 6; degenerative joint disease; design; design and construction; designing; disability; economic impact; engineered tissue; hypertrophic arthritis; immobilization of body part; implantation; improved; in vivo; initial cell; joint disorder; joint injury; joint replacement; life span; lifespan; novel; orthopedic freezing; osteochondral; osteochondral tissue; osteogenic; public health relevance; repair; repaired; scaffold; scaffolding; sexual cell; stem cell population; subcutaneous; success; surgery; vgr-1 protein; white adipose tissue; yellow adipose tissue

The overall goal of this study is to develop a tissue-engineered total joint replacement from an engineered biomaterial scaffold combined with adult bone marrow-derived mesenchymal stem cells (MSCs) for regeneration of the entire femoral surface of the hip joint. We have developed a novel three-dimensionally (3D) woven scaffold that mimics the biomechanical properties of native articular cartilage at the initial time of cell seeding. This anatomically formed scaffold is seeded with MSCs and pre-cultured ex vivo to create a hemispherical layer of living cartilage that can be used to completely replace a damaged joint surface. In the present study, we propose to perform in vivo studies in our canine osteoarthritis model to examine the potential of completely replacing the cartilage surface of the femoral head of the hip. The following two groups will be tested: 1) cartilage denuded from femoral head with implantation of fixation devices (i.e., anchors and suture) only (positive osteoarthritis control group), and 2) preformed 3D woven scaffold precultured with autologous MSCs (2 week ex vivo culture). All groups will be tested in vivo for 6 months. Primary outcomes will be based on joint function and comfort as measured by static and dynamic kinetic analysis, and validated semi-quantitative pain scales. Sequential radiographs of the hip (baseline and every month) will also be taken to monitor any joint morphological changes. At sacrifice, the histological and biomechanical properties of the joint tissues will be compared to radiograph-based measurements. Serum, synovial fluid, synovium, and lymph nodes will be analyzed for biomarkers of osteoarthritis, as well as for adverse inflammatory reactions and to test for wear debris in the joint. Acetabular wear and labral damage will also be assessed histologically.

Public Health Relevance Statement:


Public Health Relevance:
The goal of this study is to develop a technology for total bioartificial joint resurfacing as a treatment for hip osteoarthritis. The technologic basis involvs a combination of adult stem cells, retrieved from bone marrow, and a novel three-dimensionally woven scaffold that is designed to withstand joint loading and induce differentiation of the stem cells. The ultimate goal of this study is to develop tissue-engineering technologies that can eventually be used to treat osteoarthritis and other joint diseases.

Project Terms:
Adult; adult stem cell; Affect; Age; Aging; Animals; Architecture; arthropathies; Arthroplasty; articular cartilage; Autologous; base; Biocompatible Materials; Biological Markers; Biomechanics; bone; Bone Marrow; Canis familiaris; Cartilage; cartilage repair; Cell Differentiation process; cell growth; Cells; Clinical; Control Groups; cost effective; Data; Defect; Degenerative polyarthritis; design; Development; Devices; disability; Disease; Economic Burden; economic impact; effective therapy; Elderly; Engineering; FDA approved; Fiber; functional outcomes; Funding; gait examination; Goals; Grant; Head; Healthcare Industry; Hip Joint; Hip Osteoarthritis; Hip region structure; Histologic; Human; human adult stem cell; Hyaline Cartilage; Image; Implant; implantation; In Vitro; in vivo; Individual; Inflammatory; insight; joint function; joint injury; joint loading; Joints; kinematics; Kinetics; Left; Life; Longevity; lymph nodes; Measurement; Measures; Mechanics; Mesenchymal Stem Cells; Modeling; Monitor; Morbidity - disease rate; Mortality Vital Statistics; Natural regeneration; novel; Operative Surgical Procedures; Pain; Patients; Performance; Phase; preclinical study; primary outcome; Procedures; Property; public health relevance; Quality of life; Reaction; Replacement Arthroplasty; Risk; sample fixation; scaffold; Serum; Shapes; Small Business Technology Transfer Research; Source; stem; stem cell differentiation; Structure; success; Surface; Surgical sutures; Synovial Fluid; Synovial Membrane; Technology; Testing; Time; Tissue Engineering; Tissues; Total Hip Replacement; United States; Veterinarians; Weight-Bearing state; Work