The Role of Macrophage Phenotype in Vascularization of Tissue Engineering Scaffolds

By Kara L. Spiller, Rachel R Anfang, Krista J. Spiller, Johnathan Ng, Kenneth R. Nakazawa, J. Daulton, G. Vunjak‐Novakovic. Biomaterials, 2014

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Angiogenesis is crucial for the success of most tissue engineering strategies. The natural inflammatory response is a major regulator of vascularization, through the activity of different types of macrophages and the cytokines they secrete. Macrophages exist on a spectrum of diverse phenotypes, from “classically activated” M1 to “alternatively activated” M2 macrophages. M2 macrophages, including the subsets M2a and M2c, are typically considered to promote angiogenesis and tissue regeneration, while M1 macrophages are considered to be anti-angiogenic, although these classifications are controversial. Here we show that in contrast to this traditional paradigm, primary human M1 macrophages secrete the highest levels of potent angiogenic stimulators including VEGF; M2a macrophages secrete the highest levels of PDGF-BB, a chemoattractant stabilizing pericytes, and also promote anastomosis of sprouting endothelial cells in vitro; and M2c macrophages secrete the highest levels of MMP9, an important protease involved in vascular remodeling. In a murine subcutaneous implantation model, porous collagen scaffolds were surrounded by a fibrous capsule, coincident with high expression of M2 macrophage markers, while scaffolds coated with the bacterial lipopolysaccharide were degraded by inflammatory macrophages, and glutaraldehyde-crosslinked scaffolds were infiltrated by substantial numbers of blood vessels accompanied by high levels of M1 and M2 macrophages. These results suggest that coordinated efforts by both M1 and M2 macrophages are required for angiogenesis and scaffold vascularization, which may explain some of the controversy over which phenotype is the angiogenic phenotype.

Subfields: Immunology, Molecular Biology, Surgery

View Paper: https://www.semanticscholar.org/paper/aac49b2a28f0f618710038cf17b9432d25ef4f4a

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Citations in the corpus

Sequential delivery of immunomodulatory cytokines to facilitate the M1-to-M2 transition of macrophages and enhance vascularization of bone scaffolds (2014, neutral): “density gradient centrifugations, as we have previously described [21].”
The Role of Macrophages in Acute and Chronic Wound Healing and Interventions to Promote Pro-wound Healing Phenotypes (2018, background): “They also secrete high levels of PDGF, which is involved in angiogenesis (Spiller et al., 2014).”
Inflammation, Fracture and Bone Repair (2016, background): “In this line, M1 and M2macrophages have been recently described as promoters of scaffold vascularization in vitro by promoting the sprout formation by endothelial cells and the anastomosis of M1-induced sprouting vessels, respectively [183].”