Design of a composite biomaterial system for tissue engineering applications |
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Institution: | 1. Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, USA;2. Research Service, Edward Hines, Jr. V.A. Hospital, Hines, IL, USA;1. Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA;2. Department of Chemical and Biological Engineering, Tufts University, Medford, MA 02155, USA;3. Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA 02111, USA;1. Department of Biomedical Engineering, Columbia University, 622 West 168th Street, New York, NY 10032, USA;2. School of Biomedical Engineering, Science, and Health Systems, Drexel University, 3141 Chestnut St., Philadelphia, PA 19104, USA;3. Department of Pathology, Columbia University, 630 West 168th Street, New York, NY 10032, USA;4. Lincoln Laboratory, Massachusetts Institute of Technology, 244 Wood Street, Lexington, MA 02420, USA;1. Department of Orthopedic Surgery, and Shanghai Institute of Microsurgery on Extremities, Shanghai Sixth People''s Hospital, 600 Yishan Road, Shanghai, 200233, PR China;2. School of Mechanical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, PR China;3. Department of Rehabilitation Medicine, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, PR China;4. North Cross School Shanghai, Building 2, Lane 803, Shuangcheng Road, Baoshan District, Shanghai, PR China |
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Abstract: | Biomaterials that regulate vascularized tissue formation have the potential to contribute to new methods of tissue replacement and reconstruction. The goal of this study was to develop a porous, degradable tissue engineering scaffold that could deliver multiple growth factors and regulate vessel assembly within the porous structure of the material. Porous hydrogels of poly(ethylene glycol)-co-(l-lactic acid) (PEG–PLLA) were prepared via salt leaching. The degradation time of the hydrogels could be controlled between 1 and 7 weeks, based on hydrogel composition. Fibrin was incorporated into the interconnected pores of the hydrogels to promote neovascularization and as a reservoir for rapid (<5 days) growth factor delivery. Poly(lactic-co-glycolic acid) (PLGA) microspheres were incorporated into the degradable polymeric hydrogel scaffold to allow sustained (>30 days) growth factor delivery. Fibroblast growth factor-1 (FGF-1) and platelet-derived growth factor-BB (PDGF-BB) were delivered from the system owing to their roles in the promotion of angiogenesis and vascular stabilization, respectively. Hydrogels tested in vivo with a subcutaneous implantation model were selected based on the results from in vitro degradation and growth factor release kinetics. Dual growth factor delivery promoted significantly more tissue ingrowth in the scaffold compared with blank or single growth factor delivery. The sequential delivery of FGF-1 following PDGF-BB promoted more persistent and mature blood vessels. In conclusion, a biomaterials system was developed to provide structural support for tissue regeneration, as well as delivery of growth factors that stimulate neovascularization within the structure prior to complete degradation. |
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Keywords: | Neovascularization Tissue engineering Fibroblast growth factor Platelet-derived growth factor |
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