title: Uncharged Helical Modular Polypeptide Hydrogels for Cellular Scaffolds.
abstract: 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.
authors.affiliation: Department of Chemical Engineering, ‡Koch Institute for Integrative Cancer Research, §Department of Biological Engineering, and ∥Center for Gynepathology Research, Massachusetts Institute of Technology , Cambridge, Massachusetts United States.
authors.forename: Caroline C
authors.initials: CC
authors.lastname: Ahrens
authors.affiliation: Department of Chemical Engineering, ‡Koch Institute for Integrative Cancer Research, §Department of Biological Engineering, and ∥Center for Gynepathology Research, Massachusetts Institute of Technology , Cambridge, Massachusetts United States.
authors.forename: M Elizabeth
authors.initials: ME
authors.lastname: Welch
authors.affiliation: Department of Chemical Engineering, ‡Koch Institute for Integrative Cancer Research, §Department of Biological Engineering, and ∥Center for Gynepathology Research, Massachusetts Institute of Technology , Cambridge, Massachusetts United States.
authors.forename: Linda G
authors.initials: LG
authors.lastname: Griffith
authors.affiliation: Department of Chemical Engineering, ‡Koch Institute for Integrative Cancer Research, §Department of Biological Engineering, and ∥Center for Gynepathology Research, Massachusetts Institute of Technology , Cambridge, Massachusetts United States.
authors.forename: Paula T
authors.initials: PT
authors.lastname: Hammond
mesh_terms: D020816:Amino Acid Motifs; D001672:Biocompatible Materials / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects; D005109:Extracellular Matrix / Q000737:chemistry; D006801:Humans; D020100:Hydrogels / Q000737:chemistry* / Q000494:pharmacology; D008301:Maleimides / Q000737:chemistry; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects; D008969:Molecular Sequence Data; D009636:Norbornanes / Q000737:chemistry; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry; D011099:Polyglutamic Acid / Q000031:analogs & derivatives*; D017433:Protein Structure, Secondary; D023822:Tissue Engineering; D054457:Tissue Scaffolds
chemical_list: D001672:Biocompatible Materials; D020100:Hydrogels; D008301:Maleimides; D009636:Norbornanes; D010455:Peptides; D011099:Polyglutamic Acid; D011092:Polyethylene Glycols