Cell-responsive hydrogel for encapsulation of vascular cells

Thomas P. Kraehenbuehl, Lino S. Ferreira, Prisca Zammaretti, Jeffrey A. Hubbell, Robert Langer

Research output: Contribution to journalArticlepeer-review

111 Scopus citations


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 β4 (Tβ4), was examined. We show that the physical incorporation of Tβ4 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 Tβ4 increased the survival of HUVEC compared to gels without Tβ4, and significantly up-regulated the endothelial genes vascular endothelial-cadherin and angiopoietin-2, whereas von Willebrand factor was significantly down-regulated. Incorporation of Tβ4 significantly increased MMP-2 and MMP-9 secretion of encapsulated HUVEC. The gel acts as a controlled Tβ4-release system, as MMP-2 and MMP-9 enzymes trigger the release. In addition, Tβ4 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.

Original languageEnglish (US)
Pages (from-to)4318-4324
Number of pages7
Issue number26
StatePublished - Sep 2009


  • Biomimetic hydrogel
  • Human umbilical vein endothelial cells (HUVEC)
  • Matrix metalloproteinase (MMP)
  • Thymosin β4
  • Vascular tissue engineering

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics


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