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Biofunctionalised Electroconducting Microfibres for the Treatment of Spinal Cord Injury

Periodic Reporting for period 2 - Neurofibres (Biofunctionalised Electroconducting Microfibres for the Treatment of Spinal Cord Injury)

Reporting period: 2018-01-01 to 2019-06-30

Bio-electronic microsystems hold promise for repairing the damaged central nervous system (CNS). However, this potential has not been developed because their implantation inflicts additional neural injury, and ensuing inflammation and fibrosis compromise device functionality. In Neurofibres we want to achieve a breakthrough in “Neuroregenerative Bio-electronics”, developing dual-function devices that will serve as electroactive scaffolds for CNS regeneration and neural circuit activation. We engineered electroconducting microfibres (MFs) that add negligible tissue insult while promoting guided cell migration and axonal regeneration in rodents with spinal cord injury (SCI). The MFs also meet the challenge of probe miniaturisation and biofunctionalisation for ultrasensitive recording and stimulation of neural activity. An interdisciplinary consortium composed of neuroscientists, medical specialists, researchers in biomaterials, protein engineering, physics, and electrical and mechanical engineering, together with a company specialised in fabrication of microcables and microconnectors, will join efforts to design, develop, and test the MFs and complementary technology (microfibre functionalisation, assembling, and electronic interconnection), in order to produce a biologically safe and effective bio-electronic system for the treatment of SCI.
The work carried out has provided fundamental advances that guarantee the accomplishment of the objectives of the project. From a technical point of view, the project is founded on developing microfibres (MFs) with improved mechanical and electrical properties (WP-1), and electronic interconnection (WP-2). Because mechanical mismatching between the interconnected MFs and the neural tissue, or breaking of the MFs, may lead to complete failure of the proposed therapeutic approach, WP-3 deals with the mechanical features of the MFs and the MF/tissue interplay. Biomolecules at the MF surface strongly influence cell responses to the MFs. Therefore, WP-4 develops controllable electro-responsive affibodies for MF functionalisation. The added effort of WPs 1, 2, 3, and 4 will generate a MF-based bio-electronic system suitable for implantation and electrostimulation of the spinal cord. Cellular responses to the isolated components and the connected system are investigated in transgenic mice in WP-5 and 6; whereas the sensory and motor effects of the active bio-electronic system are assessed in rats and pigs in WP-7.
The general plan of the project is being accomplished, given that the first versions of the new MFs, electronic interconnection system, and electro-responsive affibodies were expected for the first 30 months of the project (January 2017 to June 2019) and are in fact partially developed. Testable versions of graphene / carbon MFs have been produced by UCAM, whereas SESCAM improved the electrochemical properties of the conducting polymer coated MFs. The information provided by UNITN on the mechanical properties of the MFs and microwires, and their interplay with biological tissues, is playing a very important role for the selection of successful materials. Preliminary prototypes of interconnected microwires will be released soon by AXON’ Cable, thus accomplishing a critical milestone that will enable the starting of exciting experiments in which electrostimulation will be applied through microwires to neural cells. The development of new affibodies by KTH also advances quickly. As originally planned for this period, the new tools and technologies have been tested in vitro (electrochemical cells, neural cell culture) and in living rodents to investigate their physical properties and their interactions with neural, inflammatory and connective tissue cells, and also to determine the best electrical parameters for spinal cord microstimulation. No less important is to mention that AMU, USAAR and SESCAM adapted and developed new animal models necessary for testing the advanced tools and have provided comprehensive studies of cell reactions and functional outcomes in control animals. The refinement of the mentioned technologies will enable advanced investigations on the usefulness of electrostimulation for aiding spinal cord repair and functional recovery in transgenic mice, rats and pigs, during the final part of the project (July 2019 to December 2020).
The novel and risky approach followed in Neurofibres faces challenging problems associated to the implant of electrodes in regions of open central nervous system trauma. Therefore, additional strategies, including the combination of MFs with neurotrophic gels, cells, and extracellular matrix, are being explored to guarantee that the new technologies are not only studied in animals, but also promote functional recovery after spinal cord injury and thus provide the basis for a real clinical impact in human beings. The data obtained so far provide further support to the use of electroconducting microfibres for the treatment of spinal cord injury.
Neurofibres combines new technologies from the sectors of bioengineering, biomaterials, biotechnology, and electroactive devices, in an innovative bio-electronic system for the treatment of SCI. The project is contributing solid advances in regenerative bioelectronics, which will make possible the modulation of neural regeneration through electroactive microfibres implanted in the lesion site. Although the implantation of the proposed system will present some surgical risks for the patients, the therapeutic approach faces the complexity and intractability of the targeted pathology. Persons with SCI suffer from a multisystemic condition and presently need numerous and expensive healthcare interventions. The proposal contributes a solid basis for developing devices that may improve the functional status and hence the quality of life of these patients. Neurofibres is a viable approach that will reach clinical application in SCI and likely in other neurological diseases. Besides itsfuture impact on the SCI population, it is opportune to remark that Neurofibres will contribute to boost the growth of the European technology sector in the field of bio-electronic systems, structuring a multidisciplinary community of researchers and stakeholders in this field to provide a functional medical solution to restorative neurology.