Nanogenerator developed to stimulate living cells

A work led by Gonzalo Murillo, scientist at the CSIC's Instituto de Microelectrónica de Barcelona (IMB-CNM), and Carme Nogués, scientist at the Department of Cellular Biology, Physiology and Immunology of the Universitat Autònoma de Barcelona (UAB), shows that the use of piezoelectric nanogenerators to stimulate living cells electrically is possible. The nanogenerator they have developed is extremely small (measuring a few tenths of nanometers in thickness) and does not need any external power source, two characteristics no one had achieved before.

Since the 18th century, electric pulses have been used as a therapy for treating several diseases. Disorders such as epilepsy, schizophrenia, Parkinson, Alzheimer or depressions can be treated by stimulating the nervous system or the vagus nerve. In 2015, the new “Bioelectronics” therapeutic concept was proposed, which uses electric pulses instead of the current drugs based on chemical compounds.

With the progress of nanotechnology, the development and use of small implantable devices has been investigated, in order to apply this treatment locally. However, the size of the devices is still too large to treat single cells and all the systems need an external source of power.

A new alternative is to harvest the biomechanical energy of the patient and use it to charge the devices, but these are still hundreds of times larger than human cells.

Obtaining an autonomous and very small generator is the achievement of the work developed by the scientists at the IMB-CSIC and the UAB, which has been selected for the cover in the June 21st issue of the Advanced Materials journal. Gonzalo Murillo explains that “the results demonstrate that the electrical interaction between a nanogenerator and human cells produces a small electric field, which stimulates and modulates the cellular activity without causing any harm, and without needing to apply any other external physical or chemical stimulus”.
Energy Produced by the Cell-Nanogenerator Interaction

For the study, bone cells (osteoblasts) were cultivated on a substrate covered by nanogenerators. These are composed of a novel planar structure of zinc oxide. The inherent strength cells make when sticking to the material bends the nanostructure, which in turn reacts by generating a slight electric pulse - due to the known piezoelectric properties of the material.

This electric pulse triggers the opening of the membrane ion-channels, which induces the pass of calcium from the culture medium into the cell. It is this increase of calcium which allows the scientists to know that the nanogenerators are capable of producing the electric pulse.

Carme Nogués, from the UAB, explains that “these kinds of channels are present in several excitable cells like neurons, muscle or bone cells, to which this same method could be applied.

It has been demonstrated that electrical stimulus improves, in bones, cell differentiation and, therefore, bone calcification. In neurons, it allows to stimulate a neuronal circuit, and in striated muscle cells, the muscular contraction.”

The scientists also have shown that viability, proliferation and growth of cells is not affected by the nanogenerator. Now they are working to obtain ‘bioelectronic devices’, biocompatible and biodegradable nanogenerators which could be activated wirerelessly. These devices could be implanted in any of the patient’s tissues and activated by remote control.

The study is in its preliminary stage. “We still have a large way to go before these nanogenerators could be applied to accelerate the ossification of a fracture or as a medical treatment”, explains Dr. Jaume Esteve, scientist at the IMB-CSIC who conceived the nanogenerator together with Murillo.

“In the future, this kind of electrical stimulation could be applied to other cells, such as neurons or muscle cells, opening the way for bioelectronic therapies and a change of paradigm, different from the current one based on pharmacological treatments”, Gonzalo Murillo says.

At the beginning of 2017, the nanogenerators and their process of attainment were protected under a European patent by the CSIC.

This work is part of a research line led by Gonzalo Murillo, aimed at developing devices capable of harvesting micro-energy from vibrations, human body movements and any other mechanical energy from the environment.

Article: Bioelectronics: Electromechanical Nanogenerator–Cell Interaction Modulates Cell Activity (Adv. Mater. 24/2017), Gonzalo Murillo, Andreu Blanquer, Carolina Vargas-Estevez, Lleonard Barrios, Elena Ibáñez, Carmen Nogués, Jaume Esteve

Cover picture: http://www.dicat.csic.es/dicat/images/ADMA-29(24)_OFC.PDF