Biomedical Ultrasound Group

Ultrasound Stimulation of Some Biological Systems

Ultrasound Augmented Gene Therapy

Gene transfer and gene therapy are new promising methods for treating e.g. cancer and vascular diseases. In viral methods, the DNA transfer inside the cells is induced using virus that penetrates through the cell membrane and transports the desired sequences inside the cells. The nonviral methods utilises another approach: the DNA sequence is forced inside the cells using some external force, stimulation, or nonviral carrier. The most important advantage of nonviral method compared to the viral method is lower health risks involved.

Ultrasound augmented gene transfer is a new promising nonviral gene transfer method. It has been shown that the ultrasound stimulation can transfer genes through the cell membranes (sonoporation) in vivo with high transfer rates. This event is induced by acoustic caviation (interaction between an acoustic field and small gas bubbles). The ultrasound stimulation has several advantages. First of all, the ultrasound sources (transducers) can be fabricated in many different forms, and the transducers acoustical properties can be varied in many different ways. This means that the targets of different sizes and locations can be treated effectively. Ultrasound can be focused into the deep located tissues, it can be steered, and even the distorting layers of media can be compensated. Secondly, ultrasound is used in a diagnostics for decades and it has proven to be very safe diagnostic tool. In a therapeutic use, the good targeting of ultrasound means that only the desired treatment area will be sonicated and the therapeutic results affect only to that specific region.

The effective ultrasound parameters and the whole transfer process are still not very well known, and further work is required to make this method more effective.

Research

Our goal is to explore and find the temporal (duty cycle, frequency etc.) and the acoustical parameters (pressure and intensity) to carry out effective ultrasound induced gene transfers. This is performed through in vivo studies using custom, in house-made transducers. The use of ultrasound contrast agents are also of great interest.

Cell Sonication Study

Osteoarthrosis and bone fractures are common health problems. Surgical or other clinical operations provide a costly way to repair cartilage diseases, therefore, new strategies for prevention and treatment of these diseases are of great interest. Modern tissue engineering of artificial cartilages could be the method to treat these restrictive and expensive diseases.

Previously, low intensity ultrasound treatment increased proteoglycan (PG) expression and accelerated bone fracture healing. It also increased PG synthesis in rat chondrocytes in vitro. The signalling mechanisms and the optimal sonication parameters are still unknown. However, these recent results indicate that ultrasound may be a practical method to increase the synthesis of cartilage matrix in scaffolds, subsequently serving as tissue implants.

Research

Our goal in this study is very similar with the gene transfer study: to find effective and practical ultrasound exposure parameters, and to develope more advanced in vitro sonication systems for this specific study. One of the most important parameter that is to be controlled, is the temperature rise inside the plate or bottle that contains the cells. The acoustical boundaries and the absorption can cause dramatical temperature rise which can be very harmfull for the cells. With the suitable combinations of ultrasound parameters and more stable sonication set-ups this can be prevented. This also means more precise calibration and better repeatibility for the experiments.


Figure: Two different cell sonication set-ups and the corresponding pressure field for the six-well plate system. Operating frequency is 1 MHz.