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Lin Lin's PhD thesis.pdf (3.31 MB)

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Engineering poly (ethylene glycol) hydrogels to regulate smooth muscle cell migration and proliferation

Lin, Lin
http://rave.ohiolink.edu/etdc/view?acc_num=case1401711613

Abstract Details

2014, Doctor of Philosophy, Case Western Reserve University, Biomedical Engineering.
The key role of smooth muscle cell (SMC) migration and proliferation in vascular physiological and pathological remodeling necessitates the exploration of mechanisms underlying these functions. This work focuses on engineering a poly (ethylene glycol) (PEG) hydrogel as a model system to evaluate SMC migration and proliferation in three dimensions (3D). We hypothesized that 3D SMC migration and proliferation can be regulated by the properties of a cell-instructive scaffold, including cell-matrix adhesion, degradability, and cross-linking density. To accomplish this, bio-inert PEG-based hydrogels were designed as the scaffold substrate. To mimic the properties of the extracellular matrix (ECM), cell-adhesive peptide (GRGDSP) and enzyme-sensitive peptide (VPMSMRGG or GPQGIAGQ) were incorporated into the PEG macromer chain. Copolymerization of the biomimetic macromers by photopolymerization resulted in the formation of bioactive hydrogels with the dual properties of cell adhesion and proteolytic degradation. Studies of mass swelling ratio as a function of gel compositions indicated that this hydrogel can be engineered quantitatively to allow for uncoupled investigation of scaffold properties on cell functions. By utilizing these biomimetic scaffolds, we studied the effect of adhesive ligand concentration, proteolysis, and network cross-linking density on 3D SMC migration and proliferation. Our results indicated that 3D SMC migration and proliferation were critically dependent on cell-matrix adhesiveness, proteolysis, and cross-linking density. The incorporation of cell-adhesive ligand significantly enhanced SMC spreading, migration and proliferation, with cell-adhesive ligand concentration mediating 3D SMC migration and proliferation in a biphasic manner. The faster degrading hydrogels promoted SMC migration and proliferation. In particular, higher cross-linking density could impede 3D SMC migration and proliferation despite the presence of cell-adhesive ligands and proteolytically degradable sites. Furthermore, the exogenous factor, heparin, exerted significant inhibitory effect on 3D SMC proliferation. These cell-instructive constructs serve as a good model system to study the effect of hydrogel properties on 3D SMC functions and show promise as a tissue engineering platform for vascular in vivo applications.
Kandice Kottke-Marchant (Committee Chair)
Anirban Sen Gupta (Committee Member)
Horst von Recum (Committee Member)
Stuart Rowan (Committee Member)
196 p.
Biomedical Engineering; Polymers
Smooth muscle cells; PEG hydrogels; 3D cell migration; 3D cell proliferation; biomimetic

Recommended Citations

Citations

  • Lin, L. (2014). Engineering poly (ethylene glycol) hydrogels to regulate smooth muscle cell migration and proliferation [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1401711613

    APA Style (7th edition)

  • Lin, Lin. Engineering poly (ethylene glycol) hydrogels to regulate smooth muscle cell migration and proliferation. 2014. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1401711613.

    MLA Style (8th edition)

  • Lin, Lin. "Engineering poly (ethylene glycol) hydrogels to regulate smooth muscle cell migration and proliferation." Doctoral dissertation, Case Western Reserve University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=case1401711613

    Chicago Manual of Style (17th edition)

case1401711613
787
© 2014, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.