SBIR-STTR Award

The development and commercialization of a polymer matrix that supports the regeneration of articular cartilage tissue will have a significant impact on the quality of life and the economics of health care in the United States. The long term objective of this proposal is the development of an injectable matrix material that stimulates and supports the in vivo differentiation of chondroprogenitor cells for the repair of traumatic articular cartilage defects. The specific aims for Phase of this project focus on the evaluation of composite matrices that utilize a type I collagen scaffold to present two potential chondroconductive materials, hyaluronic acid and dextran sulfate. The design criteria for the proposed matrices incorporates the use of cost-effective raw materials with well-documented biocompatibility profiles. Bovine type l collagen scaffold "sponges" that are fabricated by the lyophilization and cross-linking of purified fibrils will be surface coated with soluble hyaluronic acid or dextran sulfate polymers. The binding characteristics of these interactions will be monitored using an affinity coelectrophoresis method that is particularly well-suited for the analysis of glycosaminoglycan-protein interactions. The composite matrices will then be tested in vitro for the ability to support chondroprogenitor and mature chondrocyte cell adhesion, migration, growth, and differentiation. The induction of cartilage-specific markers such as the type IIB form of collagen and the suppression of bone- specific markers such as type I collagen will be monitored at the protein and transcriptional levels to assess the influence of composite matrices on differentiation. Soft tissue implantation of matrices seeded with progenitor cells will serve as an initial evaluation of in vivo performance. The development of an artificial matrix that can support cartilage regeneration in situ, without the need for the ex vivo culturing of cells, represents significant technological innovation and extends the basic understanding of chondrogenesis.Proposed commercial application:There is currently no approved nor efficacious cartilage grafting material on the market. Most approaches to date focus on the in vitro generation of cartilage grafting tissue via the ex vivo culturing of mature chondrocytes on artificial matrices. These methods involve elaborate expense, incur substantial risk at the regulatory level, and require surgical implantation. The matrix proposed here will find wide-spread acceptance in the treatment of traumatic articular cartilage injury based on the ease of use during arthroscopic surgery, the efficacy in stimulating cartilage tissue re-growth without ex vivo culturing, and the cost effectiveness of the production process.National Institute of Arthritis and Muscoloskeletal and Skin Diseases (NIAMS)

DESCRIPTION (Adapted from the applicant's abstract): The development and commercialization of extracellular matrix for use in cartilage repair will be of major benefit to the quality of life and to the economics of health care worldwide. The long term objective of this Phase II proposal is to develop a polymer matrix that supports the in situ migration of chondrogenic progenitor stem cells capable of repairing articular cartilage defects. A method of fabricating collagen-proteoglycan matrices was developed in Phase I of the project and the resulting matrices were reported to support both osteogenesis and chondrogenesis. Based on their earlier success, the investigators plan to optimize and refine their collagen based matrices in the Phase II study. Injectible or arthroscopically implantable matrix or matrix impregnated with chondrogenic growth factor will be tested for its ability to integrate with host tissue in cow and sheep cartilage explant cultures. These matrices will also be evaluated using four in vivo animal models (rat, rabbit, dog and horse). The investigators plan to assess implantation of the matrix by athroscopy and to analyze the mechanical properties of the repair tissue. Availability of biocompatible matrices that would facilitate migration and differentiation of autologous progenitor cells stem cells into functional chondrocytes provides a novel, cost-effective technique for restoration and repair of damaged cartilage tissue.PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE

Thesaurus Terms:
articular cartilage, biomaterial development /preparation, cartilage development, extracellular matrix, polymer biomaterial evaluation, collagen, implant, mucopolysaccharide, orthopedics, osteogenesis, proteoglycan, tissue support frame dog, horse, laboratory rabbit, laboratory ratNAT INST OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES