Dr Manus Biggs’ current research is focused on applying nanofabrication techniques to novel classes of electrically active and responsive ‘smart’ materials. Electricity is ubiquitous in living things. In humans, it provides the basis for thoughts, senses, movement, cardiac activity and evidence is growing that it may also play a crucial role in the functioning of our musculoskeletal system. Consequently, electrically active and responsive or ‘smart’ biomaterials offer significant possibilities for next-generation medical devices.
Dr Biggs’ laboratory is focused on the developed of tuneable, electrically active biomaterials for musculoskeletal and neural regeneration through piezoelectric and electrically conducting polymers, alloys and nanocomposites. Critically, Dr Biggs’ research integrates material science, electronic engineering, top-down nanofabrication techniques and biological functionalisation strategies in the development of next-generation biomaterials platforms.
A key research focus for Dr Biggs is neural biomaterials and the integration of implanted neuroelectrodes to promote functionality at the brain-machine interface. Rapid growth and development at the intersection of neuroscience, computer science, engineering and medicine has allowed the creation of revolutionary neurotechnologies to evaluate and treat nervous system disorders and to restore lost neural functions.
Neural interfaces (NI) have become a major focus of Dr Biggs’ research in an effort to identify and develop novel approaches to augment human cognitive or sensory-motor functions, to interface with computer systems or to control external devices [1]. There are many reasons to interface a device with the central nervous system (CNS), from regulating mood disorders [2], epilepsy [3] or Parkinson’s symptoms [4] with deep brain stimulation to coupling the brain directly to a computer controlled prosthetic [5].
Neural interfaces and the central nervous system
NI systems that sense neural signals, also called brain-computer interfaces, are early-stage neurotechnologies designed to restore control, communication and independence to persons with paralysis when the motor control structures are disconnected from muscle output. When a device is implanted into the CNS, however, an inflammatory response is initiated by the body. Cell types involved in this injury response including astrocytes and microglia, secrete cytokines inhibitory to axon regeneration[6]. Initial electrode insertion is believed to damage multiple structures, including capillaries and the extracellular matrix [7].
During this acute response to CNS injury, microglia become activated and migrate to the electrode interface. The chronic response is characterised by the encapsulation of the implanted electrode or device in scar tissue [7]. This encapsulation is of concern because it is suspected that this encapsulation increases tissue impedance and diminishes the ability of an intracortical arrays to record neural signals, or deep-brain and is inhibitory to axon regrowth [8].
To address this problem, there is a clinical need to reduce scar-tissue encapsulation in situ and improve long-term neuroelectrode function. Biomaterials approaches provide excellent opportunities for functional modification, by integrating electromechanical functionality with biomechanical functionalisation to promote electrode integration and reduce peri-implant inflammation.
Although advances have been made in implantable electrode technologies, key improvements would be facilitated by making electrodes morphologically ‘neuron-like’. Biomimetic design is a paradigm of biomedical engineering and biomimetic morphology has been shown repeatedly by the Biggs lab to induce differential cell function [9]. Concurrently, the Biggs laboratory has identified that nanoscale biomimetic features increase the electrode surface area and reduces electrical impedance [10], enhancing the signal recording quality.
Furthermore, implantable electrode systems which mimic the physicochemical and mechanical properties of the extracellular matrix and that are also electrically conductive may provide solutions to the limitations inherent with neuroelectrode systems by acting as slow-release anti-inflammatory electrode approaches.
References:
[1] L. R. Hochberg, M. D. Serruya, G. M. Friehs, J. A. Mukand, M. Saleh, A. H. Caplan, A. Branner, D. Chen, R. D. Penn, J. P. Donoghue,
Nature 2006, 442, 164.
[2] H. S. Mayberg, A. M. Lozano, V. Voon, H. E. McNeely, D. Seminowicz, C. Hamani, J. M. Schwalb, S. H. Kennedy,
Neuron 2005, 45, 651.
[3] M. Hodaie, R. A. Wennberg, J. O. Dostrovsky, A. M. Lozano, Epilepsia 2002, 43, 603.
[4] H. Gervais-Bernard, J. Xie-Brustolin, P. Mertens, G. Polo, H. Klinger, D. Adamec, E. Broussolle, S. Thobois, Journal of neurology 2009, 256, 225; G. 'Deep-Brain Stimulation for Parkinson's Disease Study',
The New England Journal of Medicine 2001, 345, 956.
[5] G. Santhanam, S. I. Ryu, B. M. Yu, A. Afshar, K. V. Shenoy,
Nature 2006, 442, 195.
[6] V. Marx, Nat Methods 2014, 11, 1099.
[7] V. S. Polikov, P. A. Tresco, W. M. Reichert,
Journal of Neuroscience Methods 2005, 148, 1.
[8] J. N. Turner, W. Shain, D. H. Szarowski, M. Andersen, S. Martins, M. Isaacson, H. Craighead,
Experimental Neurology 1999, 156, 33.
[9] M. J. P. Biggs, R. G. Richards, N. Gadegaard, C. D. W. Wilkinson, R. O. C. Oreffo, M. J. Dalby, Biomaterials 2009, 30, 5094; M. J. P. Biggs, R. G. Richards, M. J. Dalby,
Nanomed-Nanotechnol 2010, 6, 619; J. W. Cassidy, J. N. Roberts, C. A. Smith, M. Robertson, K. White, M. J. Biggs, R. O. Oreffo, M. J. Dalby,
Acta Biomaterialia 2014, 10, 651.
[10] P. Mokarian-Tabari, C. Vallejo-Giraldo, M. Fernandez-Yague, C. Cummins, M. A. Morris, M. J. P. Biggs,
J Mater Sci-Mater M 2015, 26, 20.
Dr Manus Biggs is a Science Foundation Ireland (SFI) investigator and lecturer within the department of biomedical engineering at NUI Galway. He received a PhD in cell engineering from the University of Glasagow in 2009 through research into nanotopographical modification of orthopaedic implants. This was proceeded by postdoctoral experience at Columbia University, New York, where he worked on the nanofabrication of cell platforms for probing T-cell and stem cell processes.
Dr Biggs has published more than 35 papers in peer-reviewed journals and filed two patent applications. To date, he has received 1.8 million euro in competitive research funding. In 2014, Dr Biggs was awarded the UK Society for Biomaterials Larry Hench prize for outstanding contributions to the field of Biomaterials. Dr Biggs has been an Editorial Board Member for European Cells and Materials since 2011 and has served on the board of two grant review panels. He led a New Foundations Symposium at the World Biomaterials Congress, 2016 in Montreal, Canada on 'Engineering the Brain-Machine Interface'. Dr Biggs is also a member of the European Society for Biomaterials International Advisory Committee.
Currently, he is a funded investigator within the framework of the SFI Centre for Research in Medical Devices CÚRAM, an industry-academic-clinicial consortium which aims to establish a world-leading Irish medical device research and development centre to improve and enhance traditional medical devices and develop the next generation of medical implants, cell and drug device combination products to address unmet clinical needs. Dr Biggs was an Early Stage Researcher Award Winner at the 2016 Research Excellence Awards last month, hosted by NUI Galway.