title: Macrophage functional polarization (M1/M2) in response to varying fiber and pore dimensions of electrospun scaffolds.
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.
authors.affiliation: Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA 23284-3067, USA.
authors.forename: Koyal
authors.initials: K
authors.lastname: Garg
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Pullen
authors.forename: Carole A
authors.initials: CA
authors.lastname: Oskeritzian
authors.forename: John J
authors.initials: JJ
authors.lastname: Ryan
authors.forename: Gary L
authors.initials: GL
authors.lastname: Bowlin
mesh_terms: D000818:Animals; D001119:Arginase / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016764:Cell Polarity / Q000187:drug effects*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004731:Endotoxins / Q000378:metabolism; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010641:Phenotype; D016687:Polydioxanone / Q000737:chemistry* / Q000494:pharmacology*; D016062:Porosity; D015398:Signal Transduction / Q000187:drug effects; D023822:Tissue Engineering; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D017077:Culture Media, Conditioned; D004731:Endotoxins; D053594:Myeloid Differentiation Factor 88; D016687:Polydioxanone; D052247:Nitric Oxide Synthase Type II; D001119:Arginase