title: Co-immobilization of adhesive peptides and VEGF within a dextran-based coating for vascular applications.
abstract: Multifunctional constructs providing a proper environment for adhesion and growth of selected cell types are needed for most tissue engineering and regenerative medicine applications. In this context, vinylsulfone (VS)-modified dextran was proposed as a matrix featuring low-fouling properties as well as multiple versatile moieties. The displayed VS groups could indeed react with thiol, amine or hydroxyl groups, be it for surface grafting, crosslinking or subsequent tethering of biomolecules. In the present study, a library of dextran-VS was produced, grafted to aminated substrates and characterized in terms of degree of VS modification (%VS), cell-repelling properties and potential for the oriented grafting of cysteine-tagged peptides. As a bioactive coating of vascular implants, ECM peptides (e.g. RGD) as well as vascular endothelial growth factor (VEGF) were co-immobilized on one of the most suitable dextran-VS coating (%VS=ca. 50% of saccharides units). Both RGD and VEGF were efficiently tethered at high densities (ca. 1nmol/cm(2) and 50fmol/cm(2), respectively), and were able to promote endothelial cell adhesion as well as proliferation. The latter was enhanced to the same extent as with soluble VEGF and proved selective to endothelial cells over smooth muscle cells. Altogether, multiple biomolecules could be efficiently incorporated into a dextran-VS construct, while maintaining their respective biological activity.
  
  
  
  This work addresses the need for multifunctional coatings and selective cell response inherent to many tissue engineering and regenerative medicine applications, for instance, vascular graft. More specifically, a library of dextrans was first generated through vinylsulfone (VS) modification. Thoroughly selected dextran-VS provided an ideal platform for unbiased study of cell response to covalently grafted biomolecules. Considering that processes such as healing and angiogenesis require multiple factors acting synergistically, vascular endothelial growth factor (VEGF) was then co-immobilized with the cell adhesive RGD peptide within our dextran coating through a relevant strategy featuring orientation and specificity. Altogether, both adhesive and proliferative cues could be incorporated into our construct with additive, if not synergetic, effects.
authors.affiliation: Department of Chemical Engineering, Groupe de Recherche en Sciences et Technologies Biomédicales, Bio-P(2) Research Unit, École Polytechnique de Montréal, P.O. Box 6079, succ. Centre-Ville, Montréal (QC) H3C 3A7, Canada; Institute of Biomedical Engineering, École Polytechnique de Montréal, P.O. Box 6079, succ. Centre-Ville, Montréal (QC) H3C 3A7, Canada.
authors.forename: Samantha
authors.initials: S
authors.lastname: Noel
authors.affiliation: Department of Chemical Engineering, Groupe de Recherche en Sciences et Technologies Biomédicales, Bio-P(2) Research Unit, École Polytechnique de Montréal, P.O. Box 6079, succ. Centre-Ville, Montréal (QC) H3C 3A7, Canada; Institute of Biomedical Engineering, École Polytechnique de Montréal, P.O. Box 6079, succ. Centre-Ville, Montréal (QC) H3C 3A7, Canada.
authors.forename: Charles
authors.initials: C
authors.lastname: Fortier
authors.affiliation: Department of Chemical Engineering, Groupe de Recherche en Sciences et Technologies Biomédicales, Bio-P(2) Research Unit, École Polytechnique de Montréal, P.O. Box 6079, succ. Centre-Ville, Montréal (QC) H3C 3A7, Canada; Institute of Biomedical Engineering, École Polytechnique de Montréal, P.O. Box 6079, succ. Centre-Ville, Montréal (QC) H3C 3A7, Canada.
authors.forename: Frederic
authors.initials: F
authors.lastname: Murschel
authors.affiliation: Institute of Biomedical Engineering, École Polytechnique de Montréal, P.O. Box 6079, succ. Centre-Ville, Montréal (QC) H3C 3A7, Canada.
authors.forename: Antoine
authors.initials: A
authors.lastname: Belzil
authors.affiliation: Institute of Biomedical Engineering, École Polytechnique de Montréal, P.O. Box 6079, succ. Centre-Ville, Montréal (QC) H3C 3A7, Canada.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Gaudet
authors.affiliation: Department of Chemical Engineering, Groupe de Recherche en Sciences et Technologies Biomédicales, Bio-P(2) Research Unit, École Polytechnique de Montréal, P.O. Box 6079, succ. Centre-Ville, Montréal (QC) H3C 3A7, Canada.
authors.forename: Mario
authors.initials: M
authors.lastname: Jolicoeur
authors.affiliation: Department of Chemical Engineering, Groupe de Recherche en Sciences et Technologies Biomédicales, Bio-P(2) Research Unit, École Polytechnique de Montréal, P.O. Box 6079, succ. Centre-Ville, Montréal (QC) H3C 3A7, Canada; Institute of Biomedical Engineering, École Polytechnique de Montréal, P.O. Box 6079, succ. Centre-Ville, Montréal (QC) H3C 3A7, Canada. Electronic address: gregory.decrescenzo@polymtl.ca.
authors.forename: Gregory
authors.initials: G
authors.lastname: De Crescenzo
mesh_terms: D000269:Adhesives / Q000737:chemistry*; D049109:Cell Proliferation; D020099:Coated Materials, Biocompatible / Q000737:chemistry*; D003911:Dextrans / Q000737:chemistry*; D057809:HEK293 Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000145:classification / Q000378:metabolism*; D006801:Humans; D009842:Oligopeptides / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000737:chemistry*
chemical_list: D000269:Adhesives; D020099:Coated Materials, Biocompatible; D003911:Dextrans; D009842:Oligopeptides; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C047981:arginyl-glycyl-aspartic acid
keywords: Cell selectivity; Co-immobilization; Dextran; ECM peptides; VEGF