Interleukin-10 conjugated electrospun polycaprolactone (PCL) nanofibre scaffolds for promoting alternatively activated (M2) macrophages around the peripheral nerve in vivo

Potas, Jason R.; Haque, Farhia; Maclean, Francesca L; Nisbet, David R.

doi:10.1016/j.jim.2015.03.013

Cited by 59 publications

(41 citation statements)

References 40 publications

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“…Compared with these drug‐delivery scaffolds in the nerve repair, we found that MLT/PCL scaffold could significantly improve SFI and the myelinated axon number. The SFI value of MLT/PCL scaffold was around −10, much better than −40 of NECL1‐loaded PLGA nerve guide conduit at 12 weeks postoperatively . The myelinated axon number of our MLT‐based conduit was over 1.2 × 10 4 at 12 weeks postoperatively, much more than 385 from the salicylic acid‐based conduit result, reported by Lee and even higher than an autograft result, approximately 10 4 in Boer's research .…”

Section: Discussionmentioning

confidence: 49%

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3D melatonin nerve scaffold reduces oxidative stress and inflammation and increases autophagy in peripheral nerve regeneration

Qian

Han

Zhao

et al. 2018

Journal of Pineal Research

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Peripheral nerve defect is a common and severe kind of injury in traumatic accidents. Melatonin can improve peripheral nerve recovery by inhibiting oxidative stress and inflammation after traumatic insults. In addition, it triggers autophagy pathways to increase regenerated nerve proliferation and to reduce apoptosis. In this study, we fabricated a melatonin-controlled-release scaffold to cure long-range nerve defects for the first time. 3D manufacture of melatonin/polycaprolactone nerve guide conduit increased Schwann cell proliferation and neural expression in vitro and promoted functional, electrophysiological and morphological nerve regeneration in vivo. Melatonin nerve guide conduit ameliorated immune milieu by reducing oxidative stress, inflammation and mitochondrial dysfunction. In addition, it activated autophagy to restore ideal microenvironment, to provide energy for nerves and to reduce nerve cell apoptosis, thus facilitating nerve debris clearance and neural proliferation. This innovative scaffold will have huge significance in the nerve engineering.

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Section: Discussionmentioning

confidence: 49%

“…IL‐10, a kind of anti‐inflammatory cytokine, loaded PCL nanofiber conduit, was fabricated using electrospinning. It could improve M2 macrophage phenotype and reduce connective tissue adhesion . Salicylic acid, a type of anti‐inflammatory drug, was loaded on the collagen hydrogel scaffold.…”

Section: Discussionmentioning

confidence: 99%

3D melatonin nerve scaffold reduces oxidative stress and inflammation and increases autophagy in peripheral nerve regeneration

Qian

Han

Zhao

et al. 2018

Journal of Pineal Research

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“…However, the therapeutic application of IL-10 has been limited, CCL2-CCR2 Sciatic nerve ligation injury upregulates the expression of CCL2-CCR2 signal, which in turn polarizes macrophage to M2 phenotype [52,103,112,117,120] GPR84 Ablation of GPR84 induces macrophage M2 polarization after sciatic nerve ligation injury [82] due to the fact that the in vivo bioactive half-life of IL-10 or its peptide fragments only remains for minutes to hours [98]. Interestingly, Potas et al recently found that implantation of IL-10 conjugated electrospun poly(ε-caprolactone) (PCL) nanofibrous scaffolds in sciatic nerve effectively promotes macrophage M2 polarization up to 14 days [90]. These findings shed light for the potential application of IL-10 conjugated PCL nanofibrous scaffolds in promoting peripheral nerve regeneration by stimulating macrophage M2 polarization.…”

Section: Role Of Macrophages In Peripheral Nerve Regenerationmentioning

confidence: 99%

Role of macrophages in Wallerian degeneration and axonal regeneration after peripheral nerve injury

2015

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The peripheral nervous system (PNS) has remarkable regenerative abilities after injury. Successful PNS regeneration relies on both injured axons and non-neuronal cells, including Schwann cells and immune cells. Macrophages are the most notable immune cells that play key roles in PNS injury and repair. Upon peripheral nerve injury, a large number of macrophages are accumulated at the injury sites, where they not only contribute to Wallerian degeneration, but also are educated by the local microenvironment and polarized to an anti-inflammatory phenotype (M2), thus contributing to axonal regeneration. Significant progress has been made in understanding how macrophages are educated and polarized in the injured microenvironment as well as how they contribute to axonal regeneration. Following the discussion on the main properties of macrophages and their phenotypes, in this review, we will summarize the current knowledge regarding the mechanisms of macrophage infiltration after PNS injury. Moreover, we will discuss the recent findings elucidating how macrophages are polarized to M2 phenotype in the injured PNS microenvironment, as well as the role and underlying mechanisms of macrophages in peripheral nerve injury, Wallerian degeneration and regeneration. Furthermore, we will highlight the potential application by targeting macrophages in treating peripheral nerve injury and peripheral neuropathies.

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“…11 The advantage to electrospun fibers is its flexibility to incorporate molecules and simultaneously tailor fiber morphology to regulate M1 and M2 phenotypes. Studies have incorporated immunosuppressive proteins into electrospun fibers using IL-10, 33 nuclear factor kappa-light-chainenhancer of activated B-cell inhibitors, 34 and cyclosporine A 35 and successfully altered immune cell phenotype. We opted to use immunosuppressive galectin-1 as opposed to another M2 inducing biologic because of its direct involvement in muscle regeneration, 15,36 a focus of our group.…”

Section: Discussionmentioning

confidence: 99%

Galectin‐1 promotes an M2 macrophage response to polydioxanone scaffolds

Abebayehu

Spence

Boyan

et al. 2017

J Biomedical Materials Res

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Regulating soft tissue repair to prevent fibrosis and promote regeneration is central to creating a microenvironment conducive to soft tissue development. Macrophages play an important role in this process. Their response can be modulated using biomaterials, altering cytokine and growth factor secretion to promote regeneration. Electrospun polydioxanone (PDO) fiber scaffolds promoted an M2 phenotype when macrophages were cultured on large diameter, highly porous scaffolds, but an M1 phenotype on smaller diameter fibers. Here we investigated whether incorporation of galectin-1, an immunosuppressive protein that enhances muscle regeneration, could promote the M2 response. Galectin-1 was incorporated into large and small fiber PDO scaffolds during electrospinning. Galectin-1 incorporation increased arginase-1 and reduced iNOS and IL-6 production in mouse bone-marrow derived macrophages compared to PDO alone for both scaffold types. Inhibition of ERK mitogen activated protein kinase did not alter galectin-1 effects on arginase-1 and iNOS expression, but reversed IL-6 suppression, indicating that IL-6 is mediated by a different mechanism. Our results suggest that galectin-1 can be used to modulate macrophage commitment to a pro-regenerative M2 phenotype, which may positively impact tissue regeneration when using small diameter PDO scaffolds.

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Interleukin-10 conjugated electrospun polycaprolactone (PCL) nanofibre scaffolds for promoting alternatively activated (M2) macrophages around the peripheral nerve in vivo

Cited by 59 publications

References 40 publications

3D melatonin nerve scaffold reduces oxidative stress and inflammation and increases autophagy in peripheral nerve regeneration

3D melatonin nerve scaffold reduces oxidative stress and inflammation and increases autophagy in peripheral nerve regeneration

Role of macrophages in Wallerian degeneration and axonal regeneration after peripheral nerve injury

Galectin‐1 promotes an M2 macrophage response to polydioxanone scaffolds

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