title: Human microvascular endothelial cell growth and migration on biomimetic surfactant polymers.
abstract: Successful engineering of a tissue-incorporated vascular prosthesis requires cells to proliferate and migrate on the scaffold. Here, we report on a series of "ECM-like" biomimetic surfactant polymers that exhibit quantitative control over the proliferation and migrational properties of human microvascular endothelial cells (HMVEC). The biomimetic polymers consist of a poly(vinyl amine) (PVAm) backbone with hexanal branches and varying ratios of cell binding peptide (RGD) to carbohydrate (maltose). Proliferation and migration behavior of HMVEC was investigated using polymers containing RGD: maltose ratios of 100:0, 75:25 and 50:50, and compared with fibronectin (FN) coated glass (1 microg/cm2). A radial Teflon fence migration assay was used to examine HMVEC migration at 12 h intervals over a 48 h period. Migration was quantified using an inverted optical microscope, and HMVEC were examined by confocal microscopy for actin and focal adhesion organization/ arrangement. Over the range of RGD ligand density studied (approximately 0.19-0.6 peptides/nm2), our results show HMVEC migration decreases with increasing RGD density in the polymer. HMVEC were least motile on the 100% RGD polymer (approximately 0.38-0.6 peptides/nm2) with an average migration of 0.20 mm2/h in area covered, whereas HMVEC showed the fastest migration of 0.48+/-0.06 mm2/h on the 50% RGD surface ( approximately 0.19-0.30 peptides/nm2). In contrast, cell proliferation increased with increasing surface peptide density; proliferation on the 50% RGD surface was 1.5%+/-0.06/h compared with 2.2%+/-0.07/h on the 100% RGD surface. Our results show that surface peptide density affects cellular functions such as growth and migration, with the highest peptide density supporting the most proliferation but the slowest migration.
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve Univeristy, Cleveland, OH 44106, USA.
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Sagnella
authors.forename: Faina
authors.initials: F
authors.lastname: Kligman
authors.forename: Eric H
authors.initials: EH
authors.lastname: Anderson
authors.forename: Jacqueline E
authors.initials: JE
authors.lastname: King
authors.forename: Gurunathan
authors.initials: G
authors.lastname: Murugesan
authors.forename: Roger E
authors.initials: RE
authors.lastname: Marchant
authors.forename: Kandice
authors.initials: K
authors.lastname: Kottke-Marchant
mesh_terms: D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000737:chemistry; D002448:Cell Adhesion / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible / Q000138:chemical synthesis / Q000737:chemistry; D004730:Endothelium, Vascular / Q000166:cytology* / Q000254:growth & development*; D005109:Extracellular Matrix / Q000502:physiology / Q000648:ultrastructure; D006801:Humans; D008320:Maltose / Q000737:chemistry*; D008422:Materials Testing; D008833:Microcirculation / Q000166:cytology / Q000502:physiology; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism*; D011108:Polymers / Q000737:chemistry; D011145:Polyvinyls / Q000737:chemistry*; D013501:Surface-Active Agents / Q000737:chemistry; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D020099:Coated Materials, Biocompatible; D009842:Oligopeptides; D011108:Polymers; D011145:Polyvinyls; D013501:Surface-Active Agents; D008320:Maltose; C047981:arginyl-glycyl-aspartic acid