Uncharged Helical Modular Polypeptide Hydrogels for Cellular Scaffolds

• Main Authors: Ahrens, Caroline C. (Contributor), Welch, M. Elizabeth (Contributor), Griffith, Linda G (Contributor), Hammond, Paula T (Contributor)
• Other Authors: Massachusetts Institute of Technology. Center for Gynepathology Research (Contributor), Massachusetts Institute of Technology. Department of Biological Engineering (Contributor), Massachusetts Institute of Technology. Department of Chemical Engineering (Contributor), Koch Institute for Integrative Cancer Research at MIT (Contributor), Hammond, Paula T. (Contributor)
• Format: Article
• Language: English
• Published: American Chemical Society (ACS), 2017-02-15T15:33:04Z.
• Subjects: Article
• Online Access: Get fulltext

Grafted synthetic polypeptides hold appeal for extending the range of biophysical properties achievable in synthetic extracellular matrix (ECM) hydrogels. Here, N-carboxyanhydride polypeptide, poly(γ-propargyl-l-glutamate) (PPLG) macromers were generated by fully grafting the "clickable" side chains with mixtures of short polyethylene glycol (PEG) chains terminated with inert (−OH) or reactive (maleimide and/or norbornene) groups, then reacting a fraction of these groups with an RGD cell attachment motif. A panel of synthetic hydrogels was then created by cross-linking the PPLG macromers with a 4-arm PEG star molecule. Compared to well-established PEG-only hydrogels, gels containing PPLG exhibited dramatically less dependence on swelling as a function of cross-link density. Further, PPLG-containing gels, which retain an α-helical chain conformation, were more effective than standard PEG gels in fostering attachment of a human mesenchymal stem cell (hMSC) line for a given concentration of RGD in the gel. These favorable properties of PPLG-containing PEG hydrogels suggest they may find broad use in synthetic ECM.
National Institutes of Health (U.S.) (Grant R01 EB010246-03 and U54-CA112967)
National Institutes of Health (U.S.) (Biomechanics Training Grant)