Cell-Membrane-Inspired Silicone Interfaces that Mitigate Proinflammatory Macrophage Activation and Bacterial Adhesion

Abstract

Biofouling on silicone implants causes serious complications such as fibrotic encapsulation, bacterial infection, and implant failure. Here we report the development of antifouling, antibacterial silicones through covalent grafting with a cell-membrane-inspired zwitterionic gel layer composed of 2-methacryolyl phosphorylcholine (MPC). To investigate how substrate properties influence cell adhesion, we cultured human-blood-derived macrophages and Escherichia coli on poly(dimethylsiloxane) (PDMS) and MPC gel surfaces with a range of 0.5-50 kPa in stiffness. Cells attach to glass, tissue culture polystyrene, and PDMS surfaces, but they fail to form stable adhesions on MPC gel surfaces due to their superhydrophilicity and resistance to biofouling. Cytokine secretion assays confirm that MPC gels have a much lower potential to trigger proinflammatory macrophage activation than PDMS. Finally, modification of the PDMS surface with a long-term stable hydrogel layer was achieved by the surface-initiated atom-transfer radical polymerization (SI-ATRP) of MPC and confirmed by the decrease in contact angle from 110 to 20° and the >70% decrease in the attachment of macrophages and bacteria. This study provides new insights into the design of antifouling and antibacterial interfaces to improve the long-term biocompatibility of medical implants.

In Vitro Study of the Interaction of Innate Immune Cells with Liquid Silicone Rubber Coated with Zwitterionic Methyl Methacrylate and Thermoplastic Polyurethanes

“…This is consistent with the findings of Bhaskar et al, who have shown that silicone triggers pro-inflammatory immune response [28]. Regarding PMMA-MPC, our results contrast with those of Quin et al In their study, they observed that PMMA-MPC soft gels have lower cell adhesion, exhibit a lower potential to trigger pro-inflammatory macrophage activation, and promote M2-like polarization [29].…”

Silk based scaffolds with immunomodulatory capacity: anti-inflammatory effects of nicotinic acid

“…The differences in cell response between soluble nicotinic acid in the absence of scaffolds and scaffolds loaded with nicotinic acid points towards an indirect role of the scaffolds in antiinflammatory activity, as macrophages are known to be influenced by substrate properties. 98,99 For example spatial confinement of macrophages, as it occurs on 3D scaffolds when compared to flat 2D surfaces, was recently shown to down-regulate pro-inflammatory responses. 99 Also, due to a slow release of the drug from the scaffold into the medium, the local concentration of nicotinic acid on the surface of the scaffolds can be much higher than the soluble nicotinic acid in the medium in the absence of scaffolds, which can in turn increase the anti-inflammatory effect of the drug on the cells.…”

Size matters—in vitro behaviour of human fibroblasts on textured silicone surfaces with different pore sizes

“…Since fibroblasts play a major role in fibrosis development, we focused on the interaction between this type of cells and the silicone material [45,[53][54][55][56][57][58]. The most important markers related to CC known today were assessed [59].…”