Characterization of topographical effects on macrophage behavior in a foreign body response model

Chen, Sulin; Jones, Jacqueline A.; Xu, Yuheng; Low, Hong Yee; Anderson, James M.; Leong, Kam W.

doi:10.1016/j.biomaterials.2010.01.074

Cited by 342 publications

(344 citation statements)

References 68 publications

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“…The immune response to tissue-engineered scaffold materials is critical to their success, and as such, investigators have explored whether physical factors, such as substrate topology, influence macrophage behavior. Interestingly, it has been observed that surface features indeed affect macrophage morphology and cytokine secretion profiles (31)(32)(33), as well as the overall and fibrotic responses (34), although the mechanisms underlying these responses have so far remained elusive. Our data suggest that topological cues might lead to different macrophage responses by influencing their shape and cytoskeleton.…”

Section: Discussionmentioning

confidence: 99%

Modulation of macrophage phenotype by cell shape

McWhorter

Wang

Nguyen

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

1,161

975

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Phenotypic polarization of macrophages is regulated by a milieu of cues in the local tissue microenvironment. Although much is known about how soluble factors influence macrophage polarization, relatively little is known about how physical cues present in the extracellular environment might modulate proinflammatory (M1) vs. prohealing (M2) activation. Specifically, the role of cell shape has not been explored, even though it has been observed that macrophages adopt different geometries in vivo. We and others observed that macrophages polarized toward different phenotypes in vitro exhibit dramatic changes in cell shape: M2 cells exhibit an elongated shape compared with M1 cells. Using a micropatterning approach to control macrophage cell shape directly, we demonstrate here that elongation itself, without exogenous cytokines, leads to the expression of M2 phenotype markers and reduces the secretion of inflammatory cytokines. Moreover, elongation enhances the effects of M2-inducing cytokines IL-4 and IL-13 and protects cells from M1-inducing stimuli LPS and IFN-γ. In addition shape-but not cytokine-induced polarization is abrogated when actin and actin/myosin contractility are inhibited by pharmacological agents, suggesting a role for the cytoskeleton in the control of macrophage polarization by cell geometry. Our studies demonstrate that alterations in cell shape associated with changes in ECM architecture may provide integral cues to modulate macrophage phenotype polarization. Macrophages play an essential role in innate immunity and are involved in a variety of immune functions, including host defense and wound healing. In addition, these cells participate in the progression of many chronic inflammatory diseases. To fulfill their functionally distinct roles, macrophages are capable of polarizing toward a spectrum of phenotypes, which include classical (proinflammatory, M1) and alternative (anti-inflammatory, prohealing, M2) activation states, as well as a regulatory phenotype and subtypes of these broad classifications (1). In the presence of inflammatory stimuli and danger signals, macrophages polarize toward the M1 state and release reactive species and inflammatory cytokines to fight pathogens. In contrast, a wound healing environment promotes polarization toward an M2 phenotype and leads to cellular processes that facilitate tissue repair. Although distinct macrophage subpopulations are clearly observed at different phases of the immune response to infection and injury (2), regulation of phenotypic polarization of these remarkably plastic cells still remains poorly defined.Activated macrophages are derived from circulating monocytes or resident tissue macrophages and migrate through the extracellular space in response to chemotactic agents to reach the target wound or infection site. Although it is thought that cytokines and chemokines are the primary regulators of macrophage behavior (3), some recent studies suggest that tissue structure and physical cues in the extracellular environment also contribute to ...

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Section: Discussionmentioning

confidence: 99%

Modulation of macrophage phenotype by cell shape

McWhorter

Wang

Nguyen

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

1,161

975

View full text Add to dashboard Cite

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“…29,30 The solution was loaded into 10 mL Luer-lock syringe with 25-gauge needle, and the infusion rate was regulated by a syringe pump (Harvard PHD syringe pump, Harvard Apparatus, Holliston, MA, USA). The infusion rate was set to 1 mL/h; the distance between the needle tip and steel mash collector was 18 cm.…”

Section: Pcl Nanofibrous Mesh Preparation and Tensile Testmentioning

confidence: 99%

“…28,29 With the decrease in intracapsular pressure, the neoformed tissue induced by a chamber undergoes further expansion.…”

mentioning

confidence: 99%

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Polycaprolactone nanofibrous mesh reduces foreign body reaction and induces adipose flap expansion in tissue engineering chamber

Luo¹,

He²,

Chang³

et al. 2016

IJN

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“…electrospun polymeric fibres, extruded collagen fibres and isoelectrically focused collagen fibres) have been shown to maintain tenocyte phenotype and to differentiate stem cells towards tenogenic lineage in vitro and to induce acceptable regeneration in preclinical models, none of these technologies offers precise control over the spatial distribution of the fibres. Imprinting technologies, on the other hand, have demonstrated a diverse effect on a range of permanently differentiated and stem cell functions, including adhesion, orientation, secretome expression and lineage commitment [41][42][43][44][45][46][47][48] and offer significantly greater control over feature dimension and spacing. Specifically to tendon repair, such technologies have been shown to maintain tenocyte phenotype [38]; to promote aligned tendon-specific ECM deposition [39]; and to differentiate stem cells towards tenogenic lineage [40].…”

Section: Introductionmentioning

confidence: 99%

Substrate topography: A valuable in vitro tool, but a clinical red herring for in vivo tenogenesis

et al. 2015

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractControlling the cell-substrate interactions at the bio-interface is becoming an inherent element in the design of implantable devices. Modulation of cellular adhesion in vitro, through topographical cues, is a well-documented process that offers control over subsequent cellular functions. However, it is still unclear whether surface topography can be translated into a clinically functional response in vivo at the tissue / device interface. Herein, we demonstrated that anisotropic substrates with a groove depth of ~317 nm and ~1,988 nm promoted human tenocyte alignment parallel to the underlying topography in vitro. However, the rigid poly(lactic-co-glycolic acid) substrates used in this study upregulated the expression of chondrogenic and osteogenic genes, indicating possible tenocyte trans-differentiation. Of significant importance is that none of the topographies assessed (~37 nm, ~317 nm and ~1,988 nm groove depth) induced extracellular matrix orientation parallel to the substrate orientation in a rat patellar tendon model. These data indicate that two-dimensional imprinting technologies are useful tools for in vitro cell phenotype maintenance, rather than for organised neotissue formation in vivo, should multifactorial approaches that consider both surface topography and substrate rigidity be established.

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Characterization of topographical effects on macrophage behavior in a foreign body response model

Cited by 342 publications

References 68 publications

Modulation of macrophage phenotype by cell shape

Modulation of macrophage phenotype by cell shape

Polycaprolactone nanofibrous mesh reduces foreign body reaction and induces adipose flap expansion in tissue engineering chamber

Substrate topography: A valuable in vitro tool, but a clinical red herring for in vivo tenogenesis

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