Vibration enhanced cell growth induced by surface acoustic waves as in vitro wound-healing model

We report on in vitro wound-healing and cell-growth studies under the influence of radio-frequency (rf) cell stimuli. These stimuli are supplied either by piezoactive surface acoustic waves (SAWs) or by microelectrode-generated electric fields, both at frequencies around 100 MHz. Employing live-cell imaging, we studied the time- and power-dependent healing of artificial wounds on a piezoelectric chip for different cell lines. If the cell stimulation is mediated by piezomechanical SAWs, we observe a pronounced, significant maximum of the cell-growth rate at a specific SAW amplitude, resulting in an increase of the wound-healing speed of up to 135 ± 85% as compared to an internal reference. In contrast, cells being stimulated only by electrical fields of the same magnitude as the ones exposed to SAWs exhibit no significant effect. In this study, we investigate this effect for different wavelengths, amplitude modulation of the applied electrical rf signal, and different wave modes. Furthermore, to obtain insight into the biological response to the stimulus, we also determined both the cell-proliferation rate and the cellular stress levels. While the proliferation rate is significantly increased for a wide power range, cell stress remains low and within the normal range. Our findings demonstrate that SAW-based vibrational cell stimulation bears the potential for an alternative method to conventional ultrasound treatment, overcoming some of its limitations.

Currently, improving and acceleration of wound-healing is of highest interest in medical science. Reports of “smart” wound-healing techniques range from on-demand emission of inflammatory-inhibiting materials (1) to increased cell growth by releasing growth factors upon cell-induced traction forces (2). There also have been reports on techniques including active electrical and mechanical cell stimulation, e.g., by using soundwaves. Already in the 1960s, Knoch (3) and Klug and coworkers (4) proposed the use of therapeutic ultrasound (US). Since then, it has been shown that US can in fact improve the regeneration and healing rate of soft and hard tissue up to 40% (5–7) for spatially distributed intensities between I_US = 30 mW/cm² and I_US = 500 mW/cm² (8, 9). Furthermore, the potential of US treatment to stimulate the spleen in order to treat inflammatory diseases has been recently demonstrated (10). Despite the obviously beneficial effects of therapeutic US, the application of the technique is still subject to restrictions. It turns out, for example, that the beneficial effects of US undergo a turnaround, leading to a suppressed fracture-healing if the US intensity applied is higher than I_US = 1 W/cm² (11). In this context, it has been shown that US application may induce a temperature rise in tissue of about 0.86 K/min at a power of 1 W/cm² and a frequency of 1 MHz (12), limiting the US therapy to short pulses and low intensities of about I = 30 mW/cm² (13). Moreover, high costs and the requirement of medical assistance during US exposure impede a long-term treatment and limit the application to single sessions. As an answer to these limitations, we recently proposed an approach employing surface acoustic waves (SAWs) for tissue-healing and -recovery treatment to overcome some disadvantages of the US-based methods (14). In recent years, SAWs can be found as mass products in, e.g., filters and radio frequency (rf)-signal processing devices in mobile phones and high-frequency applications but also for the active acoustic manipulation in microfluidic applications. Based on the effect of acoustic streaming (15), SAWs have recently become a quite unique tool in biomedical applications for cell manipulation (16), deadhesion under flow (17), or on-demand patterning (18). Moreover, first results show that SAW-based biochips can yield tailored standing wave-body force fields, which bear the fascinating potential to create a well-defined neural network on a chip (19). In a recent report on SAW-assisted in vitro wound-healing, we were able to demonstrate positive stimulation of cell growth up to 15.2 ± 1.7%. After carefully excluding parasitic temperature-, ballistic-, or nutrient-induced stimulation effects, we were able to narrow down the beneficial SAW-induced mechanisms to the mechanical and electrical component of the SAW. Our findings were later confirmed and supported by Greco et al., who investigated the impact of SAWs on cell proliferation (20).In this article, we continue on the impact of SAW stimulation on cell growth, narrow down the stimulation mechanism, identify the most relevant adjusting parameters, and provide insights into the intracellular reactions induced by SAWs. Moreover, we also address the question of whether the observed phenomenon is due to cell migration or proliferation.     

Folded Sheets as a Universal Material for Shaping Transformed Shell Roofs

This article provides a novel insight into specific properties of flat folded sheets transformed elastically into building roof shells. Elastic twist transformations of the sheets resulting from the arrangement of the sheets on two skew roof directrices cause changes in the geometric and mechanical sheet properties of the roof shell sheeting composed of these sheets. Regular smooth-ruled surfaces and their characteristic lines are used in the analysis of changes in the geometric properties. In the analysis of the mechanical changes, the constitutive relations and complex state of stresses are considered. The analysis is carried out on the basis of the results of the experimental tests and FEM computer simulations. They have led to the development of such a method of shaping of the effectively transformed folded covers that ensures the initial effort of each shell fold to be the smallest possible.     

External quality assessment programmes for detection of HCV RNA,HIV RNA and HBV DNA in plasma: improved proficiency of the participants observed over a 2‐year period

Background and Objectives Two External Quality Assessment Programmes (EQAPs) were run in 2008 and 2009 to evaluate the proficiency of blood centres in detecting, by nucleic acid amplification techniques (NAT), the possible contamination of plasma with hepatitis C virus (HCV), human immunodeficiency virus (HIV) and hepatitis B virus (HBV). Materials and Methods In the EQAP‐2008, three customized panels were designed; each containing positive samples with a viral nominal concentration for the three viruses of about three times the 95% DL of the respective commercial NAT assay. In the EQAP‐2009, the proficiency of the participants was evaluated with a single panel, independently on the NAT method used. Results While 84% (10 2 /12 2 ) of the participants in the EQAP‐2008 correctly identified the positive and negative samples of the panels, in the EQAP‐2009 the percentage of proficient laboratories increased to 97% (118/122). Most importantly, in this 2‐year experience, we observed a decrease in the number of pre‐/postanalytical errors, from 14 in 2008 to two in 2009. Conclusions The design of these two EQAPs allowed participants to assess the performance of the NAT methods applied in their routine screening of blood donations, not only with respect to analytical errors but also to human errors that, despite the high level of automation reached by NAT methods, can still occur.     

A pilot study of scanning acoustic microscopy as a tool for measuring arterial stiffness in aortic biopsies

This study explores the use of scanning acoustic microscopy (SAM) as a potential tool for characterisation of arterial stiffness using aortic biopsies. SAM data is presented for human tissue collected during aortic bypass graft surgery for multi-vessel coronary artery disease. Acoustic wave speed as determined by SAM was compared to clinical data for the patients namely, pulse wave velocity (PWV), blood pressure, cholesterol and glucose levels. There was no obvious trend relating acoustic wave speed to PWV values, and an inverse relationship was found between systolic and diastolic blood pressure and acoustic wave speed. However, in patients with a higher cholesterol or glucose level, the acoustic wave speed increased. A more detailed investigation is needed to relate SAM data to clinical measurements.