The SBIR Phase I proposal aims to investigate the feasibility of developing a unique class of directed chondrocyte/poly(glycolide-co-caprolactone) (PGA-co-PCL) nanofibrous scaffold constructs for articular cartilage repair. Our hypothesis for the design and evaluation of this unique tissue regeneration system is based on several recent findings made in this and other laboratories. (1) Electrospun nanofibrous polycaprolactone (PCL)-based biodegradable scaffolds are suitable for maintenance of chondrocytes. (2) The unique nanofiber fabrication methods, i.e., multiple-jet electrospinning and electroblowing processes, developed by Stonybrook Technology and Applied Research (STAR), Inc., is ideal to fabricate highly porous 3D non-woven scaffolds on an industrial scale suitable for biomedical applications. (3) The multiple-jet electrospinning/electroblowing format in combination with coaxial spinning capability can allow the processing of delicate bioactive materials at low temperatures and in an aqueous environment, where growth factors can be incorporated without fear of thermal decomposition. (4) Post-processing approaches by mechanical stretching can be used to control the mechanical stability, anisotropy and the porosity of electrospun scaffolds. We propose that a judicious combination of the above technologies, i.e., 3D nanofibrous biodegradable scaffolds with prescribed degradation rate, mechanical stability, porosity, anisotropy and controlled-release capability of growth factors (i.e., fibroblast growth factor (FGF-2) and transforming growth factor-a1 (TGF-a1)) will offer a powerful pathway to prepare a new class of chondrocyte delivery scaffolds for repair of articular cartilage. PUBLIC HEALTH RELEVENCE: A unique class of chondrocyte/poly(glycolide-co-caprolactone) (PGA-co-PCL) nanofibrous scaffold constructs for articular cartilage repair is proposed. These constructs consist of three-dimensional biodegradable nanofibrous scaffolds with prescribed degradation rate, mechanical stability, porosity, anisotropy and controlled release capability of growth factors (i.e., fibroblast growth factor (FGF-2) and transforming growth factor-a1 (TGF-a1)).
Project Terms: Abscission; Accounting; Address; Adoption; Affect; Affinity; After Care; After-Treatment; Aftercare; Air; Animal growth regulators, transforming growth factors; Anisotropy; Applied Research; Applied Science; Architecture; Arthritis, Degenerative; Biocompatible Materials; Biologic Products; Biological; Biological Agent; Biological Products; Biomaterials; Biomedical Engineering; Blood Coagulation Factor I; Blood Coagulation Factor One; Blood Factor One; Caliber; Cartilage; Cartilage, Articular; Cartilagenous Tissue; Cell-Extracellular Matrix; Cells; Cellular Morphology; Chemicals; Chondrocytes; Clinical Trials, Phase II; Coagulation Factor I; Coagulation Factor One; Complex; Cytoskeletal Modeling; Cytoskeletal Organization; Cytoskeletal Organization Process; Cytoskeletal Reorganization; DNA Synthesis Factor; Degenerative polyarthritis; Diameter; Drugs; ECGF; ECM; Endothelial Cell Growth Factor; Engineering; Engineering / Architecture; Engineerings; Environment; Evaluation; Excision; Experimental Designs; Extirpation; Extracellular Matrix; FGF; Factor I; Factor One; Fear; Fiber; Fibrinogen; Fibroblast Growth Factor; Fibroblast Growth Regulatory Factor; Fright; GFAC; Genes; Goals; Growth Agents; Growth Factor; Growth Factors, Proteins; Growth Substances; Guidelines; HBGF; Humulin R; In Vitro; Individual; Insulin; Insulin (ox), 8A-L-threonine-10A-L-isoleucine-30B-L-threonine-; Insulin, Regular; Kinetic; Kinetics; Knowledge; Laboratories; Lead; Maintenance; Maintenances; Mammals, Rabbits; Mechanics; Medical; Medication; Membrane; Methods; Methods and Techniques; Methods, Other; Molecular; Monitor; Morphology; NIH; Nanoscale Science; Nanotechnology; National Institutes of Health; National Institutes of Health (U.S.); Novolin R; Organic Solvents; Organic solvent product; Oryctolagus cuniculus; Osteoarthritis; Osteoarthrosis; Pathway interactions; Pattern Formation; Pb element; Performance; Pharmaceutic Preparations; Pharmaceutical Preparations; Phase; Phase 2 Clinical Trials; Phase II Clinical Trials; Polymers; Porosity; Process; Production; Programs (PT); Programs [Publication Type]; Property; Property, LOINC Axis 2; Proteins; Public Health; Rabbit, Domestic; Rabbits; Removal; Research; Retrieval; SBIR; SBIRS (R43/44); Small Business Innovation Research; Small Business Innovation Research Grant; Solutions; Solvents; Specialist; Speed; Speed (motion); Stretching; Structure; Structure of articular cartilage; Surgical Removal; Suspension substance; Suspensions; System; System, LOINC Axis 4; Techniques; Technology; Testing; Texture; Thick; Thickness; Time; Tissue Engineering; Transforming Growth Factors; Tumor Growth Factors; United States National Institutes of Health; aqueous; base; bioengineering; bioengineering/biomedical engineering; biopharmaceutical; biotherapeutic agent; caprolactone; cartilage regeneration; cell morphology; cold temperature; controlled release; degenerative joint disease; design; designing; dosage; drug/agent; engineered tissue; epsilon-caprolactone; experience; gene product; heavy metal Pb; heavy metal lead; hypertrophic arthritis; in vivo; low temperature; mRNA Expression; membrane structure; nano fiber; nano filament; nano scale Science; nano tech; nano technology; nanofiber; nanofibrous; nanofilament; nanotech; pathway; phase 2 study; phase 2 trial; phase II trial; polycaprolactone; programs; protocol, phase II; public health medicine (field); regenerate new tissue; regenerating damaged tissue; repair; repaired; resection; scaffold; scaffolding; study, phase II; suspension; tissue regeneration