Enhanced M2 Polarization of Oriented Macrophages on the P(VDF-TrFE) Film by Coupling with Electrical Stimulation

Abstract

Electrical stimulation (ES) has been considered a promising strategy in regulating intracellular communication, membrane depolarization, ion transport, etc. Meanwhile, cell topography, such as the alignment and elongation in anisotropic orientation, also plays a critical role in triggering mechanotransduction as well as the cellular fate. However, coupling of ES and cell orientation to regulate the polarization of macrophages is yet to be explored. In this work, we intended to explore the polarization of macrophages on a poly(vinylidene fluoride-trifluoroethylene [P(VDF-TrFE)] film with intrinsic microstripe roughness, which was covered on indium tin oxide planar microelectrodes. We found that mouse bone marrow-derived macrophages (BMDMs) cultured on a P(VDF-TrFE) film exhibited an elongated morphology aligned with the microstripe crystal whisker, but their polarization behavior was not affected. However, the elongated cells were susceptible to ES and upregulated their M2 polarization, as verified by the related expression of phenotype markers, cytokines, and genes, while not affecting M1 polarization. This is due to the increased expression of the M2 polarization receptor interleukin-4Rα on the surface of elongated BMDMs, while the M1 polarization receptor toll-like receptor 4 was not affected. Thus, M2 polarization was singularly enhanced after activation of polarization by ES. The combination of surface morphology and ES to promote M2 single polarization in this work provides a new perspective for regulating macrophage polarization in the field of immunotherapy.

Electrical Stimulation for Immunomodulation

“…Although the mechanism behind the M2 polarizing ability of piezoelectric materials is not well-defined, a few studies in the recent years have suggested the synergistic roles of electrical stimulation and morphology of piezoelectric materials for driving M2 polarization. Gu et al in 2023 reported that electric fields upregulate the IL-4Rα and TLR4 receptors which activate the ion channels such as TRPM7, triggering both M1 and M2 polarization . Nevertheless, the specific microstripe-like morphology of the piezoelectric material modulated the actin rearrangement and resulted in macrophage elongation, thereby increasing the expression of IL-4Rα receptor which ultimately altered the macrophages toward M2, as shown in Figure A.…”

“…(A) Synergistic effects of electrical stimulation and material morphology for promoting M2 polarization. Reproduced from ref . Copyright 2023 American Chemical Society.…”

“…Gu et al in 2023 reported that electric fields upregulate the IL-4Rα and TLR4 receptors which activate the ion channels such as TRPM7, triggering both M1 and M2 polarization. 87 Nevertheless, the specific microstripelike morphology of the piezoelectric material modulated the actin rearrangement and resulted in macrophage elongation, thereby increasing the expression of IL-4Rα receptor which ultimately altered the macrophages toward M2, as shown in Figure 4A. Piezoelectric based electric fields have been reported to regulate not only M2 but also M1 polarization, which is vital for inhibiting tumor growth.…”

3D-Printed Materials for Wastewater Treatment

“…The flexibility of 3D printing allows for the creation of complex geometries and customized structures, enabling the production of membranes tailored to specific wastewater treatment needs . The conventional methods for membrane fabrication include thermally induced phase separation (TIPS), vapor induced separation, and nonsolvent induced phase separation (NIPS) which require large quantities of solvent, toxic monomer materials, and high carbon footprint and generate large amounts of waste leading to adverse effects on human health and environment. , On the other hand, 3D printing being a sustainable method eliminates the need for solvent discharge, offering a more environmentally friendly approach and allowing the development of innovative membranes with diverse features by choosing from a wide range of materials. , The application of 3D printing technology in wastewater treatment can be traced back to 2016 when researchers from the University of Bath utilized a 3D printer to fabricate a membrane module for ultrafiltration . Since then, various kinds of 3D printing techniques, such as selective laser sintering (SLS), fused deposition modeling (FDM), solvent-based slurry stereolithography (3S), inkjet printing, and digital light processing (DLP), have been utilized for fabricating whole membranes as well as their module parts for water treatment. ,, In a typical 3D printing process, computer models prepare and direct ink to transform into 3D objects.…”

“… 4 The conventional methods for membrane fabrication include thermally induced phase separation (TIPS), vapor induced separation, and nonsolvent induced phase separation (NIPS) which require large quantities of solvent, toxic monomer materials, and high carbon footprint and generate large amounts of waste leading to adverse effects on human health and environment. 5 , 6 On the other hand, 3D printing being a sustainable method eliminates the need for solvent discharge, offering a more environmentally friendly approach and allowing the development of innovative membranes with diverse features by choosing from a wide range of materials. 4 , 7 The application of 3D printing technology in wastewater treatment can be traced back to 2016 when researchers from the University of Bath utilized a 3D printer to fabricate a membrane module for ultrafiltration.…”