Titanium dioxide nanostructures that reduce the infectivity of respiratory syncytial virus.

The spread of respiratory diseases has gained significant attention since the detection and rapid global spread of COVID-19. Respiratory viruses are commonly transmitted when an infected person coughs or sneezes onto a surface, infecting persons who subsequently contact this surface. For this reason, developing surfaces with inherent antipathogenic properties is crucially needed for controlling the spread of deadly pathogens. Recent studies have established the antipathogenic potential of hydrothermally synthesised titanium dioxide (TiO2) nanostructured surfaces against bacteria strains (Gram-positive and negative) and several respiratory viruses, including SARS-CoV-2, HRV-16 and HCoV-NL63. This study investigates the antiviral behaviour of TiO2 nanostructured surfaces against Respiratory Syncytial Virus (RSV), a respiratory virus commonly contracted by children, to reduce viral transmission in high-traffic environments such as hospitals and childcare centers. Mimicking droplets produced when a person coughs or sneezes, RSV droplets were exposed to nanostructured surfaces to investigate their antiviral potential. Results show that nanostructured TiO2 reduced the RSV infectious viral load at all timepoints compared to control surfaces, showing 1.7, 2.6 and 3.2 log reductions after 2-, 5- and 7-hours exposure, respectively. Interestingly, virus exposed to nanostructured surfaces showed little to no infectivity after 5 h exposure while viable virus was still detected on control surfaces after 7 h exposure. These encouraging results establish TiO2 nanostructured surfaces as a potential method for reducing transmission and spread of respiratory viruses and bacterial strains.

TiO2 Nanostructures That Reduce the Infectivity of Human Respiratory Viruses Including SARS-CoV-2.

The rapid emergence and global spread of the COVID-19 causing Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and its subsequent mutated strains has caused unprecedented health, economic, and social devastation. Respiratory viruses such as SARS-CoV-2 can be transmitted through both direct and indirect channels, including aerosol respiratory droplets, contamination of inanimate surfaces (fomites), and direct person-to-person contact. Current methods of virus inactivation on surfaces include chemicals and biocides, and while effective, continuous and repetitive cleaning of all surfaces is not always viable. Recent work in the field of biomaterials engineering has established the antibacterial effects of hydrothermally synthesized TiO2 nanostructured surfaces against both Gram-negative and -positive bacteria. The current study investigates the effectiveness of said TiO2 nanostructured surfaces against two enveloped human coronaviruses, SARS-CoV-2 and HCoV-NL63, and nonenveloped HRV-16 for surface-based inactivation. Results show that structured surfaces reduced infectious viral loads of SARS-CoV-2 (5 log), HCoV-NL63 (3 log), and HRV-16 (4 log) after 5 h, compared to nonstructured and tissue culture plastic control surfaces. Interestingly, infectious virus remained present on control tissue culture plastic after 7 h exposure. These encouraging results establish the potential use of nanostructured surfaces to reduce the transmission and spread of both enveloped and nonenveloped respiratory viruses, by reducing their infectious period on a surface. The dual antiviral and antibacterial properties of these surfaces support their potential application in a wide variety of settings such as hospitals and healthcare environments, public transport and community hubs.

Effects of Nanopillar Size and Spacing on Mechanical Perturbation and Bactericidal Killing Efficiency.

Nanopatterned surfaces administer antibacterial activity through contact-induced mechanical stresses and strains, which can be modulated by changing the nanopattern's radius, spacing and height. However, due to conflicting recommendations throughout the theoretical literature with poor agreement to reported experimental trends, it remains unclear whether these key dimensions-particularly radius and spacing-should be increased or decreased to maximize bactericidal efficiency. It is shown here that a potential failure of biophysical models lies in neglecting any out-of-plane effects of nanopattern contact. To highlight this, stresses induced by a nanopattern were studied via an analytical model based on minimization of strain and adhesion energy. The in-plane (areal) and out-of-plane (contact pressure) stresses at equilibrium were derived, as well as a combined stress (von Mises), which comprises both. Contour plots were produced to illustrate which nanopatterns elicited the highest stresses over all combinations of tip radius between 0 and 100 nm and center spacing between 0 and 200 nm. Considering both the in-plane and out-of-plane stresses drastically transformed the contour plots from those when only in-plane stress was evaluated, clearly favoring small tipped, tightly packed nanopatterns. In addition, the effect of changes to radius and spacing in terms of the combined stress showed the best qualitative agreement with previous reported trends in killing efficiency. Together, the results affirm that the killing efficiency of a nanopattern can be maximized by simultaneous reduction in tip radius and increase in nanopattern packing ratio (i.e., radius/spacing). These findings provide a guide for the design of highly bactericidal nanopatterned surfaces.

Mechanics of Bacterial Interaction and Death on Nanopatterned Surfaces.

Nanopatterned surfaces are believed to kill bacteria through physical deformation, a mechanism that has immense potential against biochemical resistance. Because of its elusive nature, this mechanism is mostly understood through biophysical modeling. Problematically, accurate descriptions of the contact mechanics and various boundary conditions involved in the bacteria-nanopattern interaction remain to be seen. This may underpin conflicting predictions, found throughout the literature, regarding two important aspects of the mechanism-that is, its critical action site and relationship with geometry. Herein, a robust computational analysis of bacteria-nanopattern interaction is performed using a three-dimensional finite element modeling that incorporates relevant continuum mechanical properties, multilayered envelope structure, and adhesion interaction conditions. The model is applied to more accurately study the elusory mechanism and its enhancement via nanopattern geometry. Additionally, micrographs of bacteria adhered on a nanopatterned cicada wing are examined to further inform and verify the major modeling predictions. Together, the results indicate that nanopatterned surfaces do not kill bacteria predominantly by rupture in between protruding pillars as previously thought. Instead, nondevelopable deformation about pillar tips is more likely to create a critical site at the pillar apex, which delivers significant in-plane strains and may locally rupture and penetrate the cell. The computational analysis also demonstrates that envelope deformation is increased by adhesion to nanopatterns with smaller pillar radii and spacing. These results further progress understanding of the mechanism of nanopatterned surfaces and help guide their design for enhanced bactericidal efficiency.

Control of bacterial attachment by fracture topography.

In the biomedical arena, bacterial fouling is a precursor to complications such as implant infection and nosocomial infection. These complications are further compounded by biochemical mechanisms of resistance that threaten the action of traditional antibacterial strategies. Accordingly, antibacterial property by physical, not biochemical, mechanisms of action is becoming increasingly popular and promising. The present work falls in line with this paradigm shift. Here, microtextured Ti-6Al-4V surfaces were manufactured by destructive tension at three different cross-head speeds, probed with scanning electron microscopy (SEM) and multifocus optical microscopy, and treated with Staphylococcus aureus to study bacterial attachment. The fractographic study revealed the presence of dual-mode fracture, typical of Ti-6Al-4V, comprising  regions of both ductile, microvoid coalescence and brittle, cleavage faceting. Based on load-extension curves, quantitative roughness data, and qualitative SEM visualisation, it was evident that cross-head speed modulated fracture behaviour such that increased speed produced more brittle fracture whilst lower speeds produced more ductile fracture. The topography associated with ductile fracture was found to possess notable antibiofouling property due to geometric constrains imposed by the coalesced microvoids. Accordingly, fracture at low cross-head speeds (1 mm/min and 10 mm/min) yielded significant reduction in bacterial attachment, whilst fracture at high cross-head speeds (100 mm/min) did not. The greatest reduction (~72%) was achieved at a cross-head speed of 1 mm/min. These findings suggest that antibiofouling property can be elicited by fracture and further 'tuned' by fracture speed. Discovery of this novel, albeit simple, avenue for topography-mediated antibacterial property calls for further research into alternate techniques for the manufacture of 'physical antibacterial surfaces'.