title: Rapid cross-linking of elastin-like polypeptides with (hydroxymethyl)phosphines in aqueous solution.
abstract: In situ gelation of injectable polypeptide-based materials is attractive for minimally invasive in vivo implantation of biomaterials and tissue engineering scaffolds. We demonstrate that chemically cross-linked elastin-like polypeptide (ELP) hydrogels can be rapidly formed in aqueous solution by reacting lysine-containing ELPs with an organophosphorous cross-linker, beta-[tris(hydroxymethyl)phosphino]propionic acid (THPP) under physiological conditions. The mechanical properties of the cross-linked ELP hydrogels were largely modulated by the molar concentration of lysine residues in the ELP and the pH at which the cross-linking reaction was carried out. Fibroblasts embedded in ELP hydrogels survived the cross-linking process and were viable after in vitro culture for 3 days. DNA quantification of ELP hydrogels with encapsulated fibroblasts indicated that there was no significant difference in DNA content between day 0 and day 3 when ELP hydrogels were formed with an equimolar ratio of THPP and lysine residues of the ELPs. These results suggest that THPP cross-linking may be a biocompatible strategy for the in situ formation of cross-linked hydrogels.
authors.affiliation: Department of Biomedical Engineering, Box 90281, Duke University, Durham, North Carolina 27708-0281, USA.
authors.forename: Dong Woo
authors.initials: DW
authors.lastname: Lim
authors.forename: Dana L
authors.initials: DL
authors.lastname: Nettles
authors.forename: Lori A
authors.initials: LA
authors.lastname: Setton
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Chilkoti
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000138:chemical synthesis*; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004247:DNA / Q000032:analysis; D004549:Elastin / Q000737:chemistry* / Q000235:genetics; D005347:Fibroblasts / Q000737:chemistry / Q000166:cytology; D020100:Hydrogels / Q000138:chemical synthesis*; D006863:Hydrogen-Ion Concentration; D008239:Lysine / Q000032:analysis; D051379:Mice; D041681:NIH 3T3 Cells; D009943:Organophosphorus Compounds / Q000737:chemistry*; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry* / Q000235:genetics; D010720:Phosphines / Q000737:chemistry; D011422:Propionates / Q000737:chemistry*; D012996:Solutions; D014867:Water
chemical_list: D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D020100:Hydrogels; D009943:Organophosphorus Compounds; D019151:Peptide Library; D010455:Peptides; D010720:Phosphines; D011422:Propionates; D012996:Solutions; C521879:beta-(tris(hydroxymethyl)phosphino)propionic acid; D014867:Water; D004247:DNA; D004549:Elastin; D008239:Lysine