Immune complement activation is attenuated by surface nanotopography

Abstract

The immune complement (IC) is a cell-free protein cascade system, and the first part of the innate immune system to recognize foreign objects that enter the body. Elevated activation of the system from, for example, biomaterials or medical devices can result in both local and systemic adverse effects and eventually loss of function or rejection of the biomaterial. Here, the researchers have studied the effect of surface nanotopography on the activation of the IC system. By a simple nonlithographic process, gold nanoparticles with an average size of 58 nm were immobilized on a smooth gold substrate, creating surfaces where a nanostructure is introduced without changing the surface chemistry. The activation of the IC on smooth and nanostructured surfaces was viewed with fluorescence microscopy and quantified with quartz crystal microbalance with dissipation monitoring in human serum. Additionally, the ability of pre-adsorbed human immunoglobulin G (IgG) (a potent activator of the IC) to activate the IC after a change in surface hydrophobicity was studied. It was found that the activation of the IC was significantly attenuated on nanostructured surfaces with nearly a 50% reduction, even after pre-adsorption with IgG. An increase in surface hydrophobicity blunted this effect. The possible role of the curvature of the nanoparticles for the orientation of adsorbed IgG molecules, and how this can affect the subsequent activation of the IC, are discussed. The present findings are important for further understanding of how surface nanotopography affects complex protein adsorption, and for the future development of biomaterials and blood-contacting devices.

The role of well-defined nanotopography of titanium implants on osseointegration: cellular and molecular events in vivo

“…38,39 The observation of higher bone formation activities induced by the nanopattern, as judged by the higher early periostin staining and the late detection of Ca and P, supports and extends previous histomorphometric findings at implants with similar chemistry, size, and shape of the nanofeatures. 11 Further, the present observations using 80 nm hemispherical protrusions are in agreement with in vivo findings showing increased osteogenesis induced by implants with 70 nm TiO 2 nanotubes inserted in frontal skull bone of minipigs.…”

“…Interestingly, for example, only two studies have been published in the literature on the effect of nanotopography on complement activation. 38,39 A link between biocompatibility and reduced thrombogenicity, at least partly related …”

The Impact of Nanoparticle Protein Corona on Cytotoxicity, Immunotoxicity and Target Drug Delivery

“…NPs may be designed to avoid such immune toxicity, and so improve their safety. In vitro experiments revealed that the physicochemical surface properties of NPs could mediate PC formation, and thus control the activation of complement pathways [141][142][143]. For example, it was shown that changing the surface chemical modification (e.g., methoxyl, carboxyl and amine groups) on polymeric NPs resulted in modulation of complement activation [141].…”

“…The impact of nanoparticle protein corona on cytotoxicity, immunotoxicity & target drug delivery Review when the NP surface was hydrophilic than when it was hydrophobic [142]. Yu et al instead used different conformational states of glycopolymer chains to induce the formation of a PC, which in turn, works as a 'molecular switch' of complement activation [143].…”

Controlling Protein Adsorption through Nanostructured Polymeric Surfaces

“…[62][63][64] For example, theoretical studies of Gu et al and Raffaini and Ganazzoli have shed light on the effect of the surface curvature on the protein adsorption capacity. [65,66] Through the use of carbon nanotubes with various radii, and thus various local curvatures, they showed that protein adsorption becomes more prominent as the local curvature decreases.…”