Macrophage functional polarization (M1/M2) in response to varying fiber and pore dimensions of electrospun scaffolds

Biomaterials. 2013 Jun;34(18):4439-51. doi: 10.1016/j.biomaterials.2013.02.065. Epub 2013 Mar 17.

Abstract

In this study, we investigated the effect of fiber and pore size of an electrospun scaffold on the polarization of mouse bone marrow-derived macrophages (BMMΦs) towards regenerative (M2) or inflammatory (M1) phenotypes. BMMΦs were seeded on Polydioxanone (PDO) scaffolds electrospun from varying polymer concentrations (60, 100, and 140 mg/ml). Higher polymer concentrations yielded larger diameter fibers with larger pore sizes and porosity. BMMΦ cultured on these scaffolds showed a correlation between increasing fiber/pore size and increased expression of the M2 marker Arginase 1 (Arg1), along with decreased expression of the M1 marker inducible nitric oxide synthase (iNOS). Secretion of the angiogenic cytokines VEGF, TGF-β1 and bFGF was higher among cultures employing larger fiber/pore size scaffolds (140 mg/ml). Using a 3D in vitro angiogenesis bead assay, we have demonstrated that the M2-like profile of BMMΦ induced by the 140 mg/ml is functional. Furthermore, our results show that the pore size of a scaffold is a more critical regulator of the BMMΦ polarization compared to the fiber diameter. The study also shows a potential role for MyD88 in regulating M1 BMMΦ signaling on the large vs. small fiber/pore size PDO scaffold. These data are instructive for the rationale design of implantable prosthetics designed to promote in situ regeneration.

Publication types

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

MeSH terms

  • Animals
  • Arginase / metabolism
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / metabolism
  • Cell Polarity / drug effects*
  • Culture Media, Conditioned / pharmacology
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Endotoxins / metabolism
  • Macrophages / cytology*
  • Macrophages / drug effects
  • Macrophages / enzymology
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Electron, Scanning
  • Myeloid Differentiation Factor 88 / metabolism
  • Neovascularization, Physiologic / drug effects
  • Nitric Oxide Synthase Type II / metabolism
  • Phenotype
  • Polydioxanone / chemistry*
  • Polydioxanone / pharmacology*
  • Porosity
  • Signal Transduction / drug effects
  • Tissue Engineering*
  • Tissue Scaffolds / chemistry*

Substances

  • Culture Media, Conditioned
  • Endotoxins
  • Myeloid Differentiation Factor 88
  • Polydioxanone
  • Nitric Oxide Synthase Type II
  • Arginase