title: Protease-sensitive PEG hydrogels regulate vascularization in vitro and in vivo.
abstract: Forming functional blood vessel networks in engineered or ischemic tissues is a significant scientific and clinical hurdle. Poly(ethylene glycol) (PEG)-based hydrogels are adapted to investigate the role of mechanical properties and proteolytic susceptibility on vascularization. Four arm PEG vinyl sulfone is polymerized by Michael-type addition with cysteine groups on a slowly degraded matrix metalloprotease (MMP) susceptible peptide, GPQG↓IWGQ, or a more rapidly cleaved peptide, VPMS↓MRGG. Co-encapsulation of endothelial cells and supportive fibroblasts within the gels lead to vascular morphogenesis in vitro that is robust to changes in crosslinking peptide identity, but is significantly attenuated by increased crosslinking and MMP inhibition. Perfused vasculature forms from transplanted cells in vivo in all gel types; however, in contrast to the in vitro results, vascularization in vivo is not decreased in the more crosslinked gels. Collectively, these findings demonstrate the utility of this platform to support vascularization both in vitro and in vivo.
authors.affiliation: Department of Biomedical Engineering, University of Michigan, 2154 Lurie Biomedical Engineering Building, 1101 Beal Ave, Ann Arbor, MI 48109, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: Vigen
authors.forename: Jacob
authors.initials: J
authors.lastname: Ceccarelli
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Putnam
mesh_terms: D000818:Animals; D001692:Biological Transport; D003911:Dextrans / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D020100:Hydrogels / Q000008:administration & dosage* / Q000138:chemical synthesis; D007279:Injections, Subcutaneous; D008297:Male; D020782:Matrix Metalloproteinases / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010455:Peptides / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D058105:Polymerization; D013450:Sulfones / Q000737:chemistry*; D014966:Xanthenes
chemical_list: D003911:Dextrans; D020100:Hydrogels; D010455:Peptides; D013450:Sulfones; D014966:Xanthenes; D011092:Polyethylene Glycols; C009873:divinyl sulfone; C034657:Texas red; D020782:Matrix Metalloproteinases
keywords: angiogenesis; animal models; matrix metalloproteinase; mechanical properties; poly(ethylene glycol)