Electronic Tissue Technologies for Repair of the Nervous System
Previous and Current Research
Bioelectronic implants, as prostheses or diagnostic devices, have already demonstrated their potential to improve the lives of patients. Beyond the success of the cochlear implant or the deep brain pacemaker, systems to restore vision, tactile sensation or locomotion are at various stages of clinical trials. In addition to providing prosthetic replacement of functions lost through injury or disease, soon it may be possible to employ implants to coordinate and boost regeneration in the damaged organ. A specialist surgeon will place a device inside the patient’s body, where it will blend with host tissues and execute a therapeutic program. The implant may deliver physical and biochemical stimuli and replacement cells to assist the endogenous ability of the body for repair. This strategy could have high impact in the injured central nervous system, where failure of self-repair following stroke, trauma or neurodegeneration can have profound and permanent consequences on the patient’s quality of life.
Making the most out of the functionality of the implant will depend on its seamless integration in the body. Challenges stem from the kinetic nature and mechanical softness of brain tissue, tissue responses to implanted foreign bodies as well as our limited ability to control neural circuits and regenerative processes in situ.
In my previous work, in the laboratory of Stéphanie Lacour at EPFL, we pioneered an electronic device chronically integrated on the surface of the spinal cord (and brain) in rodents (Minev at al, Science 2015). This was enabled by engineering the implant to have elastic properties similar to those of dura mater, the protective membrane of the central nervous system. We integrated nano-structured metallic thin films and nano-composites with silicone elastomers to enable electrical functionality in the device. Through the implant, we applied electrical and chemical neuromodulation to spinal circuits in contact with the implant. This was used to restore locomotion in rats sustaining paralyzing spinal cord injury. This type of neuroprosthesis works by engaging healthy spinal circuits downstream from the injury site, producing step-like locomotion in the hind limbs when stimulation is applied.
The long term vision of our newly established lab at the Biotechnology center of TU Dresden is to develop implantable technologies that deliver a permanent therapeutic effect by orchestrating repair in the nervous system. We like to call these electronic tissues. This is because they will mimic physical and biochemical aspects of host tissues and at the same time be able to deliver pulses of electricity, drugs, cells or light with precise spatial and temporal selectivity. As illustrated in figure 1, the fist target structure for testing our approach will be the spinal cord.
Future Projects and Goals
We are looking for an interdisciplinary-minded pre-doc scientist who will explore 3D printing (and other microfabrication techniques) with soft biomaterials to build implants for the nervous system. A “toolbox” of functional inks will be developed and may include hydrogels, silicones, conductive polymers, nano-composite materials among others. In a second stage of the project, we will evaluate the functionality, longevity and biointegration of our implants in vivo.
Methodological and Technical Expertise
- 3D printing with biomaterials
- micro-fabrication of implantable electrode arrays
- development and testing of soft conductive materials
Ivan R. Minev, Pavel Musienko, Arthur Hirsch, Quentin Barraud, Nikolaus Wenger, Eduardo Martin Moraud, Tomislav Milekovic, Jérôme Gandar, Marco Capogrosso, Rafael Fajardo Torres, Nicolas Vachicouras, Qihan Liu, Natalia Pavlova, Simone Duis, Léonie Asboth, Alexandre Larmagnac, Janos Vörös, Silvestro Micera, Zhigang Suo, Grégoire Courtine, Stéphanie P. Lacour
Electronic dura mater for long-term multimodal neural interfaces
Science 347(6218): 159–163 (2015)
Daniel J. Chew, Lan Zhu, Evangelos Delivopoulos, Ivan R. Minev, Katherine M. Musick, Charles A. Mosse, Michael Craggs, Nicholas Donaldson, Stéphanie P. Lacour, Stephen B. McMahon, James W. Fawcett
A Microchannel Neuroprosthesis for Bladder Control After Spinal Cord Injury in Rat
Science Translational Medicine 5, 210ra155 (2013)
Ivan R. Minev, Pouria Moshayedi, James W. Fawcett, and Stéphanie P. Lacour
Interaction of Glia with a Compliant, Microstructured Silicone Surface
Acta Biomaterialia, no. 6: 6936–42 (2013)
Ivan R. Minev, Daniel J Chew, Evangelos Delivopoulos, James W Fawcett, and Stéphanie P Lacour
High Sensitivity Recording of Afferent Nerve Activity Using Ultra-Compliant Microchannel Electrodes: An Acute in Vivo Validation
Journal of Neural Engineering 9, no. 2: 026005 (2012)