Effect of Electrospun Fiber Diameter and Alignment on Macrophage Activation and Secretion of Proinflammatory Cytokines and Chemokines

Saino, Enrica; Focarete, Maria Letizia; Gualandi, Chiara; Emanuele, Enzo; Cornaglia, Antonia Icaro; Imbriani, Marcello; Visai, Livia

doi:10.1021/bm200248h

Cited by 249 publications

(240 citation statements)

References 53 publications

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“…11,12 Also, it has been published that the separation between struts as well as the morphology of pores and the angle formed between struts affect macrophages reponse. 13 In fact, we have recently confirmed that the variation of scaffold geometry from an orthogonal configuration (squared pores) to a diagonal configuration (triangular pores) (see Fig. 1) affects both macrophages morphology and cytokine expression (data not shown).…”

Section: Design and Architecture Of 3d Scaffoldsmentioning

confidence: 65%

3D printed PLA-based scaffolds

et al. 2013

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Section: Design and Architecture Of 3d Scaffoldsmentioning

confidence: 65%

3D printed PLA-based scaffolds

et al. 2013

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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.

1,085

970

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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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“…Note that this test was not conducted for 10 Gel as this scaffold proved difficult to fabricate and did not show advantages in early testing. Future work should examine cytokine expression similarly to that demonstrated in a previous study, providing more information on the releaste [41]. …”

Section: Vegf Releasatementioning

confidence: 91%

“…These charge interactions vary dependent upon the polymer; 10 SF was the only scaffold that saw an increase in pore area upon the addition of PRGF and the other materials showed relatively consistent trends between concentrations. It has previously been demonstrated that fiber diameter plays a role in MAC activation and their secretion of proinflammatory molecules, where nanofibers have increased biocompatibility in comparison to microfibers [41]. Thus, the various diameters of these materials nanofibers are expected to have an affect on MAC activation.…”

Section: Statisticsmentioning

confidence: 99%

Using Electrospun Scaffolds to Promote Macrophage Phenotypic Modulation and Support Wound Healing

Hixon¹,

Dunn²,

Flores³

et al. 2017

Electrospinning

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Abstract:The development of pressure ulcers in spinal cord injury patients is extremely common, often requiring extensive surgical procedures. Macrophages (MACs) play a crucial role in the innate immune system, contributing to wound healing and overall regeneration. MACs have been found to possess the potential to be activated by external factors from their M0 inactive state to an M1 proinflammatory or M2 regenerative state. This study conducted a comprehensive evaluation of MAC phenotype in response to electrospun scaffolds of varying material fiber/pore diameter, fiber stiffness, and +/− inclusion of platelet-rich plasma (PRP). Generally, it was found that the addition of PRP resulted in decreased pore size, where 5 silk fibroin (SF) had the stiffest fibers. Furthermore, PRP scaffolds demonstrated an increased production of VEGF and chemotaxis. The polycaprolactone (PCL) and SF scaffolds had the largest cell infiltration and proliferation. Overall, it was found that 5% SF had both ideal fiber and pore structure, allowing for cell infiltration further enhanced by the presence of PRP. Additionally, this scaffold led to a reasonable production of VEGF while still allowing fibroblast proliferation to occur. These results suggest that such a scaffold could provide an off-the-shelf product capable of modifying the local MAC response.

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Effect of Electrospun Fiber Diameter and Alignment on Macrophage Activation and Secretion of Proinflammatory Cytokines and Chemokines

Cited by 249 publications

References 53 publications

3D printed PLA-based scaffolds

3D printed PLA-based scaffolds

Modulation of macrophage phenotype by cell shape

Using Electrospun Scaffolds to Promote Macrophage Phenotypic Modulation and Support Wound Healing

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