Extracellular matrix-mimetic poly(ethylene glycol) hydrogels engineered to regulate smooth muscle cell proliferation in 3-D |
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| Affiliation: | 1. Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA;2. Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, 9500 Euclid Avenue, L21, Cleveland, OH 44195, USA;1. Dept. Chemical and Biological Engineering, University of Colorado Boulder, Jennie Smoly Caruthers Biotechnology Building, 3415 Colorado Ave, Boulder, CO 80303, USA;2. The BioFrontiers Institute, University of Colorado Boulder, Jennie Smoly Caruthers Biotechnology Building, 3415 Colorado Ave, Boulder, CO 80303, USA;3. Dept. Orthopedic Surgery, Musculoskeletal Tissue Engineering Labs, Massachusetts General Hospital, Harvard Medical School, 55 Fruit St, WAC 435, Boston, MA 02114, USA;4. Div. Plastic Surgery, Plastic Surgery Research Laboratory, Massachusetts General Hospital, Harvard Medical School, 15 Parkman St, WACC 453, Boston, MA 02114, USA;1. CSIRO Manufacturing Flagship, Bayview Avenue, Clayton, Victoria 3169, Australia;2. MIMR-PHI Institute, 27–31 Wright Street, Clayton, Victoria 3168, Australia;1. Rapid Manufacturing Engineering Center, Shanghai University, Shanghai 200444, China;2. Shanghai Key Laboratory of Intelligent Manufacturing and Robotics, Shanghai University, Shanghai 200072, China;1. Hubei Collaborative Innovation Center for Advanced Organochemical Materials & Ministry-of-Education Key Laboratory for the Synthesis and Application of Organic Functional Molecules, Hubei University, Wuhan 430062, China;2. Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong Science and Technology University, Wuhan 430030, China;1. Oncology Unit (TargetsLab), Department of Medical Sciences - Faculty of Medicine - University of Girona, Emili Grahit 77, 17077 Girona, Spain;2. Department of Mechanical Engineering and Industrial Construction - University of Girona, Maria Aurèlia Capmany 61, 17071 Girona, Spain |
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| Abstract: | The goal of this project is to engineer a defined, synthetic poly(ethylene glycol) (PEG) hydrogel as a model system to investigate smooth muscle cell (SMC) proliferation in three-dimensions (3-D). To mimic the properties of extracellular matrix, both cell-adhesive peptide (GRGDSP) and matrix metalloproteinase (MMP) sensitive peptide (VPMSMRGG or GPQGIAGQ) were incorporated into the PEG macromer chain. Copolymerization of the biomimetic macromers results in the formation of bioactive hydrogels with the dual properties of cell adhesion and proteolytic degradation. Using these biomimetic scaffolds, the authors studied the effect of scaffold properties, including RGD concentration, MMP sensitivity, and network crosslinking density, as well as heparin as an exogenous factor on 3-D SMC proliferation. The results indicated that the incorporation of cell-adhesive ligand significantly enhanced SMC spreading and proliferation, with cell-adhesive ligand concentration mediating 3-D SMC proliferation in a biphasic manner. The faster degrading hydrogels promoted SMC proliferation and spreading. In addition, 3-D SMC proliferation was inhibited by increasing network crosslinking density and exogenous heparin treatment. These constructs are a good model system for studying the effect of hydrogel properties on SMC functions and show promise as a tissue engineering platform for vascular in vivo applications. |
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| Keywords: | Poly(ethylene glycol) hydrogel 3-D scaffold ECM-mimetic Smooth muscle cell Cell proliferation |
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