title: Engineered endothelial cell adhesion via VCAM1 and E-selectin antibody-presenting alginate hydrogels.
abstract: Materials that adhere to the endothelial cell (EC) lining of blood vessels may be useful for treating vascular injury. Cell adhesion molecules (CAMs), such as endothelial leukocyte adhesion molecule-1 (E-selectin) and vascular cell adhesion molecule-1 (VCAM1), modulate EC-leukocyte interactions. In this study, we mimicked cell-cell interactions by seeding cells on alginate hydrogels modified with antibodies against E-selectin and VCAM1, which are upregulated during inflammation. ECs were activated with interleukin-1α to increase CAM expression and subsequently seeded onto hydrogels. The strength of cell adhesion onto gels was assessed via a centrifugation assay. Strong, cooperative EC adhesion was observed on hydrogels presenting a 1:1 ratio of anti-VCAM1:anti-E-selectin. Cell adhesion was stronger on dual functionalized gels than on gels modified with anti-VCAM1, anti-E-selectin or the arginine-glycine-aspartic acid (RGD) peptide alone. Anti-VCAM1:anti-E-selectin-modified hydrogels may be engineered to adhere the endothelium cooperatively.
authors.affiliation: School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Marjan
authors.initials: M
authors.lastname: Rafat
authors.forename: Lisa S
authors.initials: LS
authors.lastname: Rotenstein
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Hu
authors.forename: Debra T
authors.initials: DT
authors.lastname: Auguste
mesh_terms: D000464:Alginates / Q000494:pharmacology*; D000906:Antibodies / Q000276:immunology*; D002448:Cell Adhesion / Q000187:drug effects; D019040:E-Selectin / Q000276:immunology*; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D005453:Fluorescence; D020723:Glucuronic Acid / Q000494:pharmacology; D006603:Hexuronic Acids / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D020100:Hydrogels / Q000737:chemistry / Q000494:pharmacology*; D053582:Interleukin-1alpha / Q000494:pharmacology; D055595:Mechanical Phenomena / Q000187:drug effects; D056951:Photoelectron Spectroscopy; D015203:Reproducibility of Results; D023822:Tissue Engineering / Q000379:methods*; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology*
chemical_list: D000464:Alginates; D000906:Antibodies; D019040:E-Selectin; D006603:Hexuronic Acids; D020100:Hydrogels; D053582:Interleukin-1alpha; D019010:Vascular Cell Adhesion Molecule-1; D020723:Glucuronic Acid; D016650:Fluorescein-5-isothiocyanate