Modification of Biomaterials with a Self‐Protein Inhibits the Macrophage Response

Kim, Yoon Kyung; Que, Richard; Wang, Szu‐Wen; Liu, Wendy F.

doi:10.1002/adhm.201300532

Cited by 52 publications

(43 citation statements)

References 32 publications

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“…3334 One such example of enhancing the biocompatibility characteristics of the MEA, would be by applying a CD200 coating on the array which would mitigate the macrophage-mediated foreign body response. 35 Additional work will focus on improving the biocompatibility of the MEA and ensuring that the current delivered to the nerve and surrounding tissue will not result in long-term damage. Furthermore, recapitulating the clinical condition in which the efficacy of chronic MEA implantation following complete FN injury and recovery will be assessed.…”

Section: Discussionmentioning

confidence: 99%

Selective Stimulation of Facial Muscles Following Chronic Intraneural Electrode Array Implantation and Facial Nerve Injury in the Feline Model

Sahyouni

Haidar²,

Moshtaghi³

et al. 2017

Otology &Amp; Neurotology

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Background Our group has previously shown that activation of specific facial nerve (FN) fiber populations and selective contraction of facial musculature can be achieved through acute intraneural multi-channel microelectrode array (MEA) implantation in the feline model. Hypothesis Selective stimulation of facial muscles will be maintained in the setting of (1) chronic and (2) acute MEA implantation following FN injury and subsequent recovery. Methods This study included seven cats. In three cats with normal facial function, 4-channel penetrating MEAs were implanted chronically and tested biweekly for six-months. Electrical current pulses were delivered to each channel individually, and elicited electromyographic (EMG) voltage outputs were recorded for each of several facial muscles. For FN injury experiments, two cats received a standardized hemostat-crush injury, and two cats received a transection-reapproximation injury to the FN main trunk. These four underwent acute implantation of MEA and EMG recording in terminal experiments four months post-injury. Results Stimulation through individual channels selectively activated restricted nerve populations, resulting in contraction of individual muscles in cats with chronic MEA implantation and following nerve injury. Increasing stimulation current levels resulted in increasing EMG voltage responses in all cases. Nerve histology showed only minor neural tissue reaction to the implant. Conclusion We have established in the animal model the ability of a chronically implanted MEA to selectively stimulate restricted FN fiber populations and elicit contractions in specific facial muscles. Likewise, following FN injury, selective stimulation of restricted FN fiber populations and subsequent contraction of discrete facial muscles can be achieved following acute MEA implantation.

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Section: Discussionmentioning

confidence: 99%

Selective Stimulation of Facial Muscles Following Chronic Intraneural Electrode Array Implantation and Facial Nerve Injury in the Feline Model

Sahyouni

Haidar²,

Moshtaghi³

et al. 2017

Otology &Amp; Neurotology

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“…For studies examining the effects of collagen, fibrin, and fibrinogen, cells were seeded at 50,000 cells/cm 2 . For studies examining the effects of cytokines (LPS, IFN-γ, IL-4, IL-13) in conjunction with fibrin and fibrinogen, or cytoskeletal staining, cells were seeded at 100,000 cells/cm 2 , a density that we have previously used to examine the effect of cytokines on macrophages [51]. …”

Section: Methodsmentioning

confidence: 99%

Differential regulation of macrophage inflammatory activation by fibrin and fibrinogen

et al. 2017

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Fibrin is a major component of the provisional extracellular matrix formed during tissue repair following injury, and enables cell infiltration and anchoring at the wound site. Macrophages are dynamic regulators of this process, advancing and resolving inflammation in response to cues in their microenvironment. Although much is known about how soluble factors such as cytokines and chemokines regulate macrophage polarization, less is understood about how insoluble and adhesive cues, specifically the blood coagulation matrix fibrin, influence macrophage behavior. In this study, we observed that fibrin and its precursor fibrinogen elicit distinct macrophage functions. Culturing macrophages on fibrin gels fabricated by combining fibrinogen with thrombin stimulated secretion of the anti-inflammatory cytokine, interleukin-10 (IL-10). In contrast, exposure of macrophages to soluble fibrinogen stimulated high levels of inflammatory cytokine tumor necrosis factor alpha (TNF-α). Macrophages maintained their anti-inflammatory behavior when cultured on fibrin gels in the presence of soluble fibrinogen. In addition, adhesion to fibrin matrices inhibited TNF-α production in response to stimulation with LPS and IFN-γ, cytokines known to promote inflammatory macrophage polarization. Our data demonstrate that fibrin exerts a protective effect on macrophages, preventing inflammatory activation by stimuli including fibrinogen, LPS, and IFN-γ. Together, our study suggests that the presentation of fibrin(ogen) may be a key switch in regulating macrophage phenotype behavior, and this feature may provide a valuable immunomodulatory strategy for tissue healing and regeneration.

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“…We found that CD200 inhibited macrophage inflammatory activation in vitro, and reduced local immune response towards implanted polystyrene beads in a mouse subcutaneous implant model. 28 However, it was unclear whether CD200 only inhibits macrophage inflammatory (also known as M1) activation, or if it in fact could promote an anti-inflammatory (also known as M2) macrophage behavior. Furthermore, it remained unknown whether CD200 could modulate the immune response to a clinically relevant biomaterial.…”

Section: Introductionmentioning

confidence: 99%

CD200 modulates macrophage cytokine secretion and phagocytosis in response to poly(lactic-co-glycolic acid) microparticles and films

et al. 2017

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Biocompatibility is a major concern for developing biomaterials used in medical devices, tissue engineering and drug delivery. Poly(lactic-co-glycolic acid) (PLGA) is one of the most widely used biodegradable materials, yet still triggers a significant foreign body response that impairs healing. Immune cells including macrophages respond to the implanted biomaterial and mediate the host response, which can eventually lead to device failure. Previously in our laboratory, we found that CD200, an immunomodulatory protein, suppressed macrophage inflammatory activation in vitro and reduced local immune cell infiltration around a biomaterial implant. While in our initial study we used polystyrene as a model material, here we investigate the effect of CD200 on PLGA, a commonly used biomaterial with many potential clinical applications. We fabricated PLGA with varied geometries, modified their surfaces with CD200, and examined macrophage cytokine secretion and phagocytosis. We found that CD200 suppressed secretion of the pro-inflammatory cytokine TNF-α and enhanced secretion of the anti-inflammatory cytokine IL-10, suggesting a role for CD200 in promoting wound healing and tissue remodeling. In addition, we found that CD200 increased phagocytosis in both murine macrophages and human monocytes. Together, these data suggest that modification with CD200 leads to a response that simultaneously prevents inflammation and enhances phagocytosis. This immunomodulatory feature may be used as a strategy to mitigate inflammation or deliver drugs or anti-inflammatory agents targeting macrophages.

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Modification of Biomaterials with a Self‐Protein Inhibits the Macrophage Response

Cited by 52 publications

References 32 publications

Selective Stimulation of Facial Muscles Following Chronic Intraneural Electrode Array Implantation and Facial Nerve Injury in the Feline Model

Selective Stimulation of Facial Muscles Following Chronic Intraneural Electrode Array Implantation and Facial Nerve Injury in the Feline Model

Differential regulation of macrophage inflammatory activation by fibrin and fibrinogen

CD200 modulates macrophage cytokine secretion and phagocytosis in response to poly(lactic-co-glycolic acid) microparticles and films

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