Step-growth hydrogels crosslinked through grafted polypeptides enable nano- to macroscale synthetic extracellular matrix design

Step-growth hydrogels crosslinked through grafted polypeptides are introduced as a powerful platform for extending the potential of established hydrogel systems, especially for applications in tissue engineering. Gels crosslinked through grafted polypeptides offer the potential to address many limitations of established poly(ethylene glycol)-only hydrogel systems, but most notably, gels crosslinked through synthetic peptides are expected to 1) provide handles to systematically incorporate and modulate biological, mechanical and chemical signaling, and 2) more closely mimic protein secondary structure found in the native extracellular matrix. A specific grafted N-carboxyanhydride polypeptide, poly(y-propargyl-L-glutamate) (PPLG), forms the foundation of this thesis. PPLG is an especially useful polymer for exploring hydrogel crosslinking through grafted polypeptides because it 1) can be grafted with nearly perfect efficiency with a wide variety of functional groups, and 2) maintains a highly stabilized a-helical secondary structure before and after grafting Characterization of solution phase behavior of PPLG fully grafted with various side groups demonstrates the ability to precisely control polymer bulk behavior by systematically tuning the average ratio of complementary grafting groups, with broad application in pH- and thermo-responsive drug delivery. Extending these solution-phase studies to gel systems, foundational characterizations first establish a modular, well-controlled synthetic platform for synthesizing crosslinker-grafted PPLG, easily extended to a wide variety of covalent crosslinking chemistries. Swelling ratios, fraction polymer incorporation, and bulk gel stiffness measurements of hydrogels crosslinked through grafted PPLG strongly support both stochastic substitution of PPLG grafting groups, and significant a-helical secondary structure of grafted- PPLG even when crosslinked into a gel. Preliminary studies identify grafted PPLG as supporting both 2D and 3D cell culture. Future studies look to expand the scope of these findings to other grafted polypeptide hydrogels with other grafting strategies and grafting groups. Together, these findings recommend gels crosslinked through grafted synthetic polypeptides as a platform for investigating and controlling cellular response for in vitro and in vivo applications.

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Chemical Engineering.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2015

Author dc:creator

• Chopko, Caroline Marie

Advisor dc:contributor.advisor

• Linda Griffith and Douglas Lauffenburger.

• Chemical Engineering.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/98154

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/98154