Annals of Biomedical Engineering

, Volume 43, Issue 3, pp 616–627 | Cite as

Macrophages Modulate Engineered Human Tissues for Enhanced Vascularization and Healing

  • Kara L. Spiller
  • Donald O. Freytes
  • Gordana Vunjak-Novakovic


Tissue engineering is increasingly based on recapitulating human physiology, through integration of biological principles into engineering designs. In spite of all progress in engineering functional human tissues, we are just beginning to develop effective methods for establishing blood perfusion and controlling the inflammatory factors following implantation into the host. Functional vasculature largely determines tissue survival and function in vivo. The inflammatory response is a major regulator of vascularization and overall functionality of engineered tissues, through the activity of different types of macrophages and the cytokines they secrete. We discuss here the cell–scaffold–bioreactor systems for harnessing the inflammatory response for enhanced tissue vascularization and healing. To this end, inert scaffolds that have been considered for many decades a “gold standard” in regenerative medicine are beginning to be replaced by a new generation of “smart” tissue engineering systems designed to actively mediate tissue survival and function.


Scaffold Vascularization Inflammatory response Tissue engineering Healing 



Mature and non-polarized macrophages


Macrophages polarized to the inflammatory phenotype, either by in vitro stimulation or in the in vivo environment


Macrophages polarized to the anti-inflammatory phenotype, either by in vitro stimulation or in the in vivo environment


Macrophages polarized through the addition of IL-4


Macrophages polarized through the addition of IL-10


Peripheral blood mononuclear cells


Mesenchymal stem cells




Tumor necrosis factor-alpha


Toll-like receptors


Vascular endothelial growth factor


Basic fibroblast growth factor


Platelet-derived growth factor-BB


Matrix metalloprotease-9


Monocyte chemoattractant protein-1






Extracellular matrix


Transforming growth factor-β


Stromal-derived factor 1


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Copyright information

© Biomedical Engineering Society 2014

Authors and Affiliations

  • Kara L. Spiller
    • 1
  • Donald O. Freytes
    • 2
  • Gordana Vunjak-Novakovic
    • 3
  1. 1.Drexel UniversityPhiladelphiaUSA
  2. 2.New York Stem Cell Foundation Research InstituteNew YorkUSA
  3. 3.Mikati Foundation Professor of Biomedical Engineering and Medical SciencesColumbia UniversityNew YorkUSA

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