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Engineering Poly(Ethylene Glycol) Hydrogel Scaffolds to Modulate Smooth Muscle Cell Phenotype

Beamish, Jeffrey Alan
http://rave.ohiolink.edu/etdc/view?acc_num=case1246649015

Abstract Details

2009, Doctor of Philosophy, Case Western Reserve University, Biomedical Engineering.
This work investigated the hypothesis that smooth muscle cell (SMC) phenotype can be modulated by a cell-instructive hydrogel scaffold. By modulating SMCs toward a quiescent contractile phenotype, such a scaffold may facilitate the regeneration of functional vascular tissue as part of a tissue engineered blood vessel (TEBV) and may mitigate SMC intimal hyperplasia, which is one of the common modes of vascular prosthesis failure. A photopolymerizable poly(ethylene glycol) diacrylate (PEGDA) hydrogel system was employed because this scaffold material can be engineered quantitatively to meet a broad range of physical and biological design specifications. PEGDA hydrogel networks were copolymerized with poly(ethylene glycol) monoacrylate (PEGMA), which could tether pendent cell-adhesive peptides to the network. The physical characteristics of a range of copolymer network compositions (5-20% w/w PEGDA, 0-20% PEGMA) were determined and analyzed for the scaffold design. Mass swelling ratio (7.5±0.1 to 27.1±0.7) and shear modulus (4.0±0.6 to 104±4 kPa) data indicated that hydrogel properties were controlled quantitatively and independently of PEGMA concentration. SMCs attached to PEGDA-co-GRGDSP-PEGMA (RGD-gels) in a ligand specific manner. RGD-gels also supported modulation toward a contractile SMC phenotype that was indistinguishable from fibronectin control substrates. In these experiments, low serum medium with heparin induced rapid up-regulation of contractile phenotype marker mRNA (2.7- to 25-fold) and proteins, as well as intracellular organization of these markers. Based on these results, RGD-bearing PEGDA hydrogel scaffolds were engineered to modulate SMC phenotype by providing controlled release of heparin. Using PEGDA molecular weight (1-6 kD) and concentration (10-30% w/w), a broad range of release profiles was achieved with durations from hours to weeks. These cell-instructive scaffolds stimulated up-regulation of contractile phenotype markers (~1.5-fold) that was driven by released heparin. These results suggest that the delivery of soluble signaling factors, such as heparin, from an RGD-gel scaffold is an effective approach to induce rapid changes in SMC phenotype. A cell-instructive scaffold system, such as described here, will facilitate the engineering of functional smooth muscle tissue for a variety of applications and may improve the long-term patency of TEBVs.
Roger E. Marchant, PhD (Committee Chair)
Kandice Kottke-Marchant, MD, PhD (Advisor)
Eben Alsberg, PhD (Committee Member)
George R. Dubyak, PhD (Committee Member)
286 p.
Biomedical Research; Engineering
smooth muscle cell; hydrogel; tissue engineering; poly(ethylene glycol)

Recommended Citations

Citations

  • Beamish, J. A. (2009). Engineering Poly(Ethylene Glycol) Hydrogel Scaffolds to Modulate Smooth Muscle Cell Phenotype [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1246649015

    APA Style (7th edition)

  • Beamish, Jeffrey. Engineering Poly(Ethylene Glycol) Hydrogel Scaffolds to Modulate Smooth Muscle Cell Phenotype. 2009. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1246649015.

    MLA Style (8th edition)

  • Beamish, Jeffrey. "Engineering Poly(Ethylene Glycol) Hydrogel Scaffolds to Modulate Smooth Muscle Cell Phenotype." Doctoral dissertation, Case Western Reserve University, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=case1246649015

    Chicago Manual of Style (17th edition)

case1246649015
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© 2009, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.