Cyclic strain affects macrophage cytokine secretion and ECM turnover in electrospun scaffolds

Valentina Bonito, Bente de Kort, Carlijn Bouten, A.I.P.M. Smits (Corresponding author)

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Controlling macrophage behaviour has become a high-potential target strategy for regenerative therapies, such as in situ tissue engineering (TE). In situ TE is an approach in which acellular resorbable synthetic scaffolds are employed to induce endogenous tissue regeneration. However, little is known regarding the effect of the biomechanical environment on the macrophage response to a scaffold. Therefore, the aim of this study was to assess the effect of cyclic strains (0%, 8% and 14% strain) on primary human macrophage polarization in electrospun scaffolds with two different fibre diameters in the micrometer range (4 μm or 13 μm). High strains led to a pro-inflammatory profile in terms of gene expression, expression of surface proteins, and cytokine secretion. These results were consistent for scaffolds with small and large fibre diameters, indicating that the effect of cyclic strain was not affected by the different scaffold microstructures. Notably, macrophages were identified as direct contributors of early secretion of extracellular matrix proteins, including elastin, which was deposited in a strain-dependent fashion. These findings are instrumental for the rational design of scaffolds for in situ TE and underline that immunomodulatory scaffolds for biomechanically loaded applications should be mechanically tailored, e.g. in terms of stiffness and compliance, in order to support a desirable pro-regenerative macrophage phenotype.

LanguageEnglish
JournalTissue engineering. Part A
DOIs
StateE-pub ahead of print - 27 Feb 2019

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Military electronic countermeasures
Macrophages
Scaffolds (biology)
Cytokines
Tissue Engineering
Tissue engineering
Scaffolds
Proteins
Elastin
Tissue regeneration
Fibers
Extracellular Matrix Proteins
Gene expression
Compliance
Regeneration
Membrane Proteins
Stiffness
Polarization
Phenotype
Gene Expression

Cite this

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title = "Cyclic strain affects macrophage cytokine secretion and ECM turnover in electrospun scaffolds",
abstract = "Controlling macrophage behaviour has become a high-potential target strategy for regenerative therapies, such as in situ tissue engineering (TE). In situ TE is an approach in which acellular resorbable synthetic scaffolds are employed to induce endogenous tissue regeneration. However, little is known regarding the effect of the biomechanical environment on the macrophage response to a scaffold. Therefore, the aim of this study was to assess the effect of cyclic strains (0{\%}, 8{\%} and 14{\%} strain) on primary human macrophage polarization in electrospun scaffolds with two different fibre diameters in the micrometer range (4 μm or 13 μm). High strains led to a pro-inflammatory profile in terms of gene expression, expression of surface proteins, and cytokine secretion. These results were consistent for scaffolds with small and large fibre diameters, indicating that the effect of cyclic strain was not affected by the different scaffold microstructures. Notably, macrophages were identified as direct contributors of early secretion of extracellular matrix proteins, including elastin, which was deposited in a strain-dependent fashion. These findings are instrumental for the rational design of scaffolds for in situ TE and underline that immunomodulatory scaffolds for biomechanically loaded applications should be mechanically tailored, e.g. in terms of stiffness and compliance, in order to support a desirable pro-regenerative macrophage phenotype.",
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AU - Bonito,Valentina

AU - de Kort,Bente

AU - Bouten,Carlijn

AU - Smits,A.I.P.M.

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N2 - Controlling macrophage behaviour has become a high-potential target strategy for regenerative therapies, such as in situ tissue engineering (TE). In situ TE is an approach in which acellular resorbable synthetic scaffolds are employed to induce endogenous tissue regeneration. However, little is known regarding the effect of the biomechanical environment on the macrophage response to a scaffold. Therefore, the aim of this study was to assess the effect of cyclic strains (0%, 8% and 14% strain) on primary human macrophage polarization in electrospun scaffolds with two different fibre diameters in the micrometer range (4 μm or 13 μm). High strains led to a pro-inflammatory profile in terms of gene expression, expression of surface proteins, and cytokine secretion. These results were consistent for scaffolds with small and large fibre diameters, indicating that the effect of cyclic strain was not affected by the different scaffold microstructures. Notably, macrophages were identified as direct contributors of early secretion of extracellular matrix proteins, including elastin, which was deposited in a strain-dependent fashion. These findings are instrumental for the rational design of scaffolds for in situ TE and underline that immunomodulatory scaffolds for biomechanically loaded applications should be mechanically tailored, e.g. in terms of stiffness and compliance, in order to support a desirable pro-regenerative macrophage phenotype.

AB - Controlling macrophage behaviour has become a high-potential target strategy for regenerative therapies, such as in situ tissue engineering (TE). In situ TE is an approach in which acellular resorbable synthetic scaffolds are employed to induce endogenous tissue regeneration. However, little is known regarding the effect of the biomechanical environment on the macrophage response to a scaffold. Therefore, the aim of this study was to assess the effect of cyclic strains (0%, 8% and 14% strain) on primary human macrophage polarization in electrospun scaffolds with two different fibre diameters in the micrometer range (4 μm or 13 μm). High strains led to a pro-inflammatory profile in terms of gene expression, expression of surface proteins, and cytokine secretion. These results were consistent for scaffolds with small and large fibre diameters, indicating that the effect of cyclic strain was not affected by the different scaffold microstructures. Notably, macrophages were identified as direct contributors of early secretion of extracellular matrix proteins, including elastin, which was deposited in a strain-dependent fashion. These findings are instrumental for the rational design of scaffolds for in situ TE and underline that immunomodulatory scaffolds for biomechanically loaded applications should be mechanically tailored, e.g. in terms of stiffness and compliance, in order to support a desirable pro-regenerative macrophage phenotype.

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