title: Decreasing matrix modulus of PEG hydrogels induces a vascular phenotype in human cord blood stem cells.
abstract: Adult and congenital cardiovascular diseases are significant health problems that are often managed using surgery. Bypass grafting is a principal therapy, but grafts fail at high rates due to hyperplasia, fibrosis, and atherosclerosis. Biocompatible, cellularized materials that attenuate these complications and encourage healthy microvascularization could reduce graft failure, but an improved understanding of biomaterial effects on human stem cells is needed to reach clinical utility. Our group investigates stem-cell-loaded biomaterials for placement along the adventitia of at-risk vessels and grafts. Here, the effects of substrate modulus on human CD34+ stem cells from umbilical cord blood were evaluated. Cells were isolated by immunomagnetic separation and encapsulated in 3, 4, and 6 weight% PEG hydrogels containing 0.032% gelatin and 0.0044% fibronectin. Gels reached moduli of 0.34, 4.5, and 9.1 kPa. Cell viability approached 100%. Cell morphologies appeared similar across gels, but proliferation was significantly lower in 6 wt% gels. Expression profiling using stem cell signaling arrays indicated enhanced self-renewal and differentiation into vascular endothelium among cells in the lower weight percent gels. Thus, modulus was associated with cell proliferation and function. Gels with moduli in the low kilopascal range may be useful in stimulating cell engraftment and microvascularization of graft adventitia.
authors.affiliation: Nemours - Alfred I. duPont Hospital for Children, Department of Biomedical Research, 1600 Rockland Road, Wilmington, DE 19803, United States; Nemours - Alfred I. duPont Hospital for Children, Critical Care Department, 1600 Rockland Road, Wilmington, DE 19803, United States.
authors.forename: Shruthi
authors.initials: S
authors.lastname: Mahadevaiah
authors.affiliation: Nemours - Alfred I. duPont Hospital for Children, Department of Biomedical Research, 1600 Rockland Road, Wilmington, DE 19803, United States.
authors.forename: Karyn G
authors.initials: KG
authors.lastname: Robinson
authors.affiliation: Department of Materials Science and Engineering, University of Delaware, 201 Du Pont Hall, Newark, DE 19716, United States.
authors.forename: Prathamesh M
authors.initials: PM
authors.lastname: Kharkar
authors.affiliation: Department of Materials Science and Engineering, University of Delaware, 201 Du Pont Hall, Newark, DE 19716, United States.
authors.forename: Kristi L
authors.initials: KL
authors.lastname: Kiick
authors.affiliation: Nemours - Alfred I. duPont Hospital for Children, Department of Biomedical Research, 1600 Rockland Road, Wilmington, DE 19803, United States. Electronic address: Robert.Akins@nemours.org.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Akins
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry; D001808:Blood Vessels / Q000166:cytology* / Q000254:growth & development*; D002454:Cell Differentiation; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D055119:Elastic Modulus; D005260:Female; D005312:Fetal Blood / Q000166:cytology* / Q000502:physiology; D006244:Hardness; D006801:Humans; D020100:Hydrogels / Q000737:chemistry; D008422:Materials Testing; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials; D020100:Hydrogels; D011092:Polyethylene Glycols
keywords: Cell encapsulation; Gene expression; Stem cell; Vascular grafts; vWF (von Willibrand factor)