Synthesis and cell adhesive properties of linear and cyclic RGD functionalized polynorbornene thin films.
Described herein is the efficient synthesis and evaluation of bioactive arginine-glycine-aspartic acid (RGD) functionalized polynorbornene-based materials for cell adhesion and spreading. Polynorbornenes containing either linear or cyclic RGD peptides were synthesized by ring-opening metathesis polymerization (ROMP) using the well-defined ruthenium initiator [(H(2)IMes)(pyr)(2)(Cl)(2)Ru═CHPh]. The random copolymerization of three separate norbornene monomers allowed for the incorporation of water-soluble polyethylene glycol (PEG) moieties, RGD cell recognition motifs, and primary amines for postpolymerization cross-linking. Following polymer synthesis, thin-film hydrogels were formed by cross-linking with bis(sulfosuccinimidyl) suberate (BS(3)), and the ability of these materials to support human umbilical vein endothelial cell (HUVEC) adhesion and spreading was evaluated and quantified. When compared to control polymers containing either no peptide or a scrambled RDG peptide, polymers with linear or cyclic RGD at varying concentrations displayed excellent cell adhesive properties in both serum-supplemented and serum-free media. Polymers with cyclic RGD side chains maintained cell adhesion and exhibited comparable integrin binding at a 100-fold lower concentration than those carrying linear RGD peptides. The precise control of monomer incorporation enabled by ROMP allows for quantification of the impact of RGD structure and concentration on cell adhesion and spreading. The results presented here will serve to guide future efforts for the design of RGD functionalized materials with applications in surgery, tissue engineering, and regenerative medicine.
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, United States.
Paresma R
PR
Patel
Rosemary Conrad
RC
Kiser
Ying Y
YY
Lu
Eileen
E
Fong
Wilson C
WC
Ho
David A
DA
Tirrell
Robert H
RH
Grubbs
D001672:Biocompatible Materials / Q000138:chemical synthesis* / Q000737:chemistry; D002448:Cell Adhesion; D002470:Cell Survival; D002478:Cells, Cultured; D061307:Human Umbilical Vein Endothelial Cells / Q000502:physiology*; D006801:Humans; D020100:Hydrogels / Q000138:chemical synthesis* / Q000737:chemistry; D009842:Oligopeptides / Q000737:chemistry*; D010969:Plastics / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D058105:Polymerization; D011485:Protein Binding; D023822:Tissue Engineering
D001672:Biocompatible Materials; D020100:Hydrogels; D009842:Oligopeptides; D010969:Plastics; C071464:polynorbornen; D011092:Polyethylene Glycols; C047981:arginyl-glycyl-aspartic acid