The impact of surface chemistry modification on macrophage polarisation

Abstract

Macrophages are innate immune cells that have a central role in combating infection and maintaining tissue homeostasis. They exhibit remarkable plasticity in response to environmental cues. At either end of a broad activation spectrum are pro-inflammatory (M1) and anti-inflammatory (M2) macrophages with distinct functional and phenotypical characteristics. Macrophages also play a crucial role in orchestrating immune responses to biomaterials used in the fabrication of implantable devices and drug delivery systems. To assess the impact of different surface chemistries on macrophage polarisation, human monocytes were cultured for 6 days on untreated hydrophobic polystyrene (PS) and hydrophilic O2 plasma-etched polystyrene (O2-PS40) surfaces. Our data clearly show that monocytes cultured on the hydrophilic O2-PS40 surface are polarised towards an M1-like phenotype, as evidenced by significantly higher expression of the pro-inflammatory transcription factors STAT1 and IRF5. By comparison, monocytes cultured on the hydrophobic PS surface exhibited an M2-like phenotype with high expression of mannose receptor (MR) and production of the anti-inflammatory cytokines IL-10 and CCL18. While the molecular basis of such different patterns of cell differentiation is yet to be fully elucidated, we hypothesise that it is due to the adsorption of different biomolecules on these surface chemistries. Indeed our surface characterisation data show quantitative and qualitative differences between the protein layers on the O2-PS40 surface compared to PS surface which could be responsible for the observed differential macrophage polarisation on each surface.

Integrin‐Mediated Interactions Control Macrophage Polarization in 3D Hydrogels

“…S8 A and B). The cells cultured on DGEA-coated plates expressed higher levels of the M2 marker CD206, with no noticeable changes in the level of M1 marker expressions (in this case Calprotectin [5] ), compared to BSA control group (Fig. S7 A) indicating a shift towards M2 phenotype in cells cultured on DGEA coated surfaces.…”

“…Samples were incubated at 37°C, 5% CO 2 for 6 days, with fresh complete medium containing cytokines added on Day 3. On Day 6, samples were stained with 1 μg/mL rabbit anti-human mannose receptor antibody (Abcam) and 2 μg/mL mouse anti-human calprotectin antibody (Thermo Scientific) (M2 and M1 markers respectively [5] ) diluted in 5% goat serum in PBS. Secondary antibody staining was then carried out using 8 μg/mL each of goat anti-rabbit Alexa Fluor® 488-conjugated antibody and goat anti-mouse Rhodamine Red-X-conjugated antibody (both from Thermo Fisher Scientific).…”

“…Specifically, the M1 macrophage phenotype is typically induced through interferon gamma (IFNγ) or lipopolysaccharide (LPS) stimulation, while the M2 macrophage phenotype is typically induced through Interleukin-4 (IL-4) or Interleukin-13 (IL-13) stimulation [5] . However, these approaches are not easily translated into in vivo approaches due to the challenge of delivery, temporal nature of the stimulus and risk of adverse effects.…”

Unbiased Analysis of the Impact of Micropatterned Biomaterials on Macrophage Behavior Provides Insights beyond Predefined Polarization States

“…Although the M1-M2 macrophage activation paradigm is a simplification of possible polarisation states, it can still be useful in determining whether macrophages lie towards the proinflammatory end or the anti-inflammatory/pro-wound healing end of the activation spectrum 3 . In order to distinguish the activation state, macrophages are commonly characterised on the basis of properties such as the expression of cellular markers, cytokine profile and phagocytic ability 4 .…”

Immunomodulatory Biomaterials and Regenerative Immunology

“…Concomitant use of new developments in temporal control of multiple growth factor/cytokine delivery; advanced bottom-up assembly methods of engineered tissues such as robotic assembly [15]; use of bioactive miRNAs within scaffolds; and micro/nanoscale topographical and chemical control of scaffold features [16] for inducing anti- or proinflammatory immune cell phenotypes would provide the tools for engineering multicellular organs and establishing in vitro organoids that faithfully model physiological conditions with immune system components. These efforts would bring forth the aspects of ‘regenerative immunology’ in regenerative medicine.…”