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Accepted (AM)Open Access (License Unspecified), Open
Journal article
The role of macrophage phenotype in vascularization of tissue engineering scaffolds
Biomaterials, v 35(15), pp 4477-4488
May 2014
PMID: 24589361
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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 for 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.
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Details
- Title
- The role of macrophage phenotype in vascularization of tissue engineering scaffolds
- Creators
- Kara L. Spiller - Drexel UniversityRachel R. Anfang - Columbia UniversityKrista J. Spiller - Columbia UniversityJohnathan Ng - Columbia UniversityKenneth R. Nakazawa - Columbia UniversityJeffrey W. Daulton - MIT Lincoln LaboratoryGordana Vunjak-Novakovic - Columbia University
- Publication Details
- Biomaterials, v 35(15), pp 4477-4488
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000334819800007
- Scopus ID
- 2-s2.0-84896055839
- Other Identifier
- 991019169586704721
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InCites Highlights
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Engineering, Biomedical
- Materials Science, Biomaterials