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dc.contributor.advisorMcDevitt, Todd C.
dc.contributor.authorNguyen, Anh H.
dc.date.accessioned2016-05-27T13:09:18Z
dc.date.available2016-05-27T13:09:18Z
dc.date.created2015-05
dc.date.issued2014-12-12
dc.date.submittedMay 2015
dc.identifier.urihttp://hdl.handle.net/1853/54845
dc.description.abstractDuring embryo development, extracellular matrix (ECM) remodeling by matrix metalloproteinases (MMPs) and promotes downstream cell specifications. Pluripotent stem cell (PSC) aggregates can recapitulate various aspects of embryogenesis in vitro, and incorporation of biomaterial microparticles also provides an ideal platform to study cell-biomaterial interactions. Stem cell interactions with ECM-based biomaterials can impact tissue remodeling and differentiation propensity via modulation of MMP activity. This work investigated the MMP activity and subsequent mesenchymal differentiation of embryonic stem cell (ESC) aggregates with incorporated gelatin methacrylate (GMA) MPs with either low (20%) or high (90%) cross-linking densities, corresponding to faster or slower degradation rate, respectively. GMA MP incorporation increased total MMP and MMP-2 levels within 3D ESC aggregates in a substrate-dependent manner. GMA MP-incorporated aggregates also expressed higher levels of epithelial-to-mesenchymal transition markers and displayed enhanced mesenchymal morphogenesis than aggregates without MPs, and the MP-mediated effects were completely abrogated with MMP inhibitor treatment. This work predicts that control of proteolytic responses via introducing ECM-based MPs may offer a novel avenue to engineer the ECM microenvironment to modulate stem cell differentiation.
dc.format.mimetypeapplication/pdf
dc.language.isoen_US
dc.publisherGeorgia Institute of Technology
dc.subjectGelatin methacrylate
dc.subjectMicroparticles
dc.subjectPluripotent
dc.subjectStem cells
dc.subjectDifferentiation
dc.titleProteolytically degradable microparticles for engineering the extracellular microenvironment of pluripotent stem cell aggregates
dc.typeDissertation
dc.description.degreePh.D.
dc.contributor.departmentBiomedical Engineering (Joint GT/Emory Department)
thesis.degree.levelDoctoral
dc.contributor.committeeMemberGarcía, Andrés J.
dc.contributor.committeeMemberPlatt, Manu
dc.contributor.committeeMemberBarker, Thomas
dc.contributor.committeeMemberXu, Chunhui
dc.date.updated2016-05-27T13:09:18Z


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