title: Cell-responsive hydrogel for encapsulation of vascular cells.
abstract: The in vitro potential of a synthetic matrix metalloproteinase (MMP)-responsive poly(ethylene glycol) (PEG)-based hydrogel as a bioactive co-encapsulation system for vascular cells and a small bioactive peptide, thymosin beta4 (Tbeta4), was examined. We show that the physical incorporation of Tbeta4 in this bioactive matrix creates a three-dimensional (3D) environment conducive for human umbilical vein endothelial cell (HUVEC) adhesion, survival, migration and organization. Gels with entrapped Tbeta4 increased the survival of HUVEC compared to gels without Tbeta4, and significantly up-regulated the endothelial genes vascular endothelial-cadherin and angiopoietin-2, whereas von Willebrand factor was significantly down-regulated. Incorporation of Tbeta4 significantly increased MMP-2 and MMP-9 secretion of encapsulated HUVEC. The gel acts as a controlled Tbeta4-release system, as MMP-2 and MMP-9 enzymes trigger the release. In addition, Tbeta4 facilitated HUVEC attachment and induced vascular-like network formation upon the PEG-hydrogels. These MMP-responsive PEG-hydrogels may thus serve as controlled co-encapsulation system of vascular cells and bioactive factors for in situ regeneration of ischemic tissues.
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Kraehenbuehl
authors.forename: Lino S
authors.initials: LS
authors.lastname: Ferreira
authors.forename: Prisca
authors.initials: P
authors.lastname: Zammaretti
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Hubbell
authors.forename: Robert
authors.initials: R
authors.lastname: Langer
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D011092:Polyethylene Glycols / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013947:Thymosin / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology; D000099201:Thymosin beta(4)
chemical_list: D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D011092:Polyethylene Glycols; D013947:Thymosin; D000099201:Thymosin beta(4)