Improved Angiogenesis in Response to Localized Delivery of Macrophage-Recruiting Molecules

PLoS One. 2015 Jul 1;10(7):e0131643. doi: 10.1371/journal.pone.0131643. eCollection 2015.


Successful engineering of complex organs requires improved methods to promote rapid and stable vascularization of artificial tissue scaffolds. Toward this goal, tissue engineering strategies utilize the release of pro-angiogenic growth factors, alone or in combination, from biomaterials to induce angiogenesis. In this study we have used intravital microscopy to define key, dynamic cellular changes induced by the release of pro-angiogenic factors from polyethylene glycol diacrylate hydrogels transplanted in vivo. Our data show robust macrophage recruitment when the potent and synergistic angiogenic factors, PDGFBB and FGF2 were used as compared with VEGF alone and intravital imaging suggested roles for macrophages in endothelial tip cell migration and anastomosis, as well as pericyte-like behavior. Further data from in vivo experiments show that delivery of CSF1 with VEGF can dramatically improve the poor angiogenic response seen with VEGF alone. These studies show that incorporating macrophage-recruiting factors into the design of pro-angiogenic biomaterial scaffolds is a key strategy likely to be necessary for stable vascularization and survival of implanted artificial tissues.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inducing Agents / pharmacology*
  • Animals
  • Becaplermin
  • Cell Movement / drug effects
  • Cell Movement / physiology
  • Cells, Cultured
  • Cornea / blood supply
  • Cornea / drug effects
  • Endothelial Cells / drug effects
  • Endothelial Cells / physiology
  • Fibroblast Growth Factor 2 / pharmacology*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Hydrogels
  • Macrophages / drug effects*
  • Macrophages / physiology
  • Mice
  • Neovascularization, Physiologic / drug effects*
  • Proto-Oncogene Proteins c-sis / pharmacology*
  • Tissue Engineering / methods*
  • Tissue Scaffolds
  • Vascular Endothelial Growth Factor A / pharmacology*


  • Angiogenesis Inducing Agents
  • Hydrogels
  • Proto-Oncogene Proteins c-sis
  • Vascular Endothelial Growth Factor A
  • Fibroblast Growth Factor 2
  • Becaplermin