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Polymer-tethered epidermal growth factor as an inductive biomaterial surface for connective tissue progenitors

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dc.contributor.advisor Linda G. Griffith. en_US Fan, Vivian H. (Vivian Hanbing) en_US
dc.contributor.other Massachusetts Institute of Technology. Biological Engineering Division. en_US 2007-07-18T13:16:27Z 2007-07-18T13:16:27Z 2006 en_US
dc.description Thesis (Ph. D.)--Massachusetts Institute of Technology, Biological Engineering Division, September 2006. en_US
dc.description "July 2006." en_US
dc.description Includes bibliographical references (leaves 123-137). en_US
dc.description.abstract Connective tissue progenitors (CTP) can act as a pluripotent source of reparative cells during injury and therefore have great potential in regenerative medicine and tissue engineering. However, the response of CTP to most growth factors and cytokines is unknown. Many envisioned applications of CTP, such as treating large defects in bone, involve in vivo implantation of CTP attached to a scaffold, a process that creates an acute inflammatory environment that may be hostile to CTP survival. This project entails the design of a two-component polymeric implant system to aid in the healing process of bony defects by influencing cell behaviors at the implant site through the covalent modification of the implant surface with selected ligands. We investigate cellular responses of CTP on a biomaterial surface covalently modified with epidermal growth factor (EGF) and find that surface-tethered EGF (tEGF) promotes both cell spreading and survival more strongly than saturating concentrations of soluble EGF. By sustaining MEK-ERK signaling, tEGF increases the contact of CTP with an otherwise moderately adhesive synthetic polymer and confers resistance to apoptosis induced by the proinflammatory cytokine, FasL. en_US
dc.description.abstract (cont.) We confirm that these signaling, spreading, and apoptotic responses are conserved across three sources of CTP: an hTERT-immortalized human mesenchymal stem cell (MSC) line, primary porcine bone-marrow CTP, and primary human bone-marrow-derived CTP. We conclude that tEGF may offer a protective advantage to CTP in vivo during acute inflammatory reactions to tissue engineering scaffolds. The tEGF-modified polymers described here could be used together with structural materials to construct CTP scaffolds for the treatment of hard-tissue lesions, such as large bony defects. en_US
dc.description.statementofresponsibility by Vivian H. Fan. en_US
dc.format.extent 137 leaves en_US
dc.language.iso eng en_US
dc.publisher Massachusetts Institute of Technology en_US
dc.rights MIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission. en_US
dc.subject Biological Engineering Division. en_US
dc.title Polymer-tethered epidermal growth factor as an inductive biomaterial surface for connective tissue progenitors en_US
dc.title.alternative Polymer-tethered EGF as an inductive biomaterial surface for CTP en_US
dc.type Thesis en_US Ph.D. en_US
dc.contributor.department Massachusetts Institute of Technology. Biological Engineering Division. en_US
dc.identifier.oclc 144608564 en_US

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