CC BY
24
Section BRAIN-COMPUTER INTERFACES, COGNITIVE NAVIGATION WORKSHOP AND NEUROENGINEERING
3D Biodegradable Scaffolds Produced by Microstereolithography Tecnique for Neural Tissue Engineering in Experimental Traumatic BrainInjury
I.V. Mukhina1,23 *, A.V. Baliabin1, O.P. Tikhobrazova3, T.A. Mishchenko3, N.A. Schelchkova3, D. Davidenko1, A. Poniatkovskaya3, P.S. Timashev4, and V.N. Bagratashvili4
1 Volga Federal Medical Research Centre, Nizhny Novgorod, Russia;
2 Lobachevsky State University of Nizhni Novgorod, Nizhny Novgorod, Russia;
3 Nizhny Novgorod State Medical Academy Nizhny Novgorod, Russia;
4 Institute of laser and information technologies, Russian Academy of Sciences, Moscow, Russia. * Presenting e-mail: mukhinaiv@mail.ru
Aims
Traumatic brain injury (TBI) occurs, as a result, of direct mechanical insult to the brain, and induces degeneration and death in the central nervous system (CNS). Unfortunately, TBI causes extensive loss of cerebral parenchyma; however, no strategy for reconstruction has been clinically effective. It has been shown that one of the promising approaches used in regenerative medicine are three-dimensional biocompatible scaffolds capable to induce the growth of nerve cells. Such scaffolds are compatible with nerve tissues and can support its recovery during regeneration. Growth of cells and development of tissues depend not only on the material of the scaffold, but also on its 3D structure [1]. To identify new ways of parenchyma reconstruction we used 3D biodegradable scaffolds produced by microstereolithography technique.
Methods
3D biodegradable scaffolds produced by microstereolihography technique from combination of the modified chitosan and hyaluronic acid of high molecular weight [2], the molecular weight of chitosan was 40-50 kDa, and the degree of acetylation was 0.30. Besides chitosan, we used the modified by a reaction with glycidyl methacrylate hyaluronic acid according to the article of O. Kufelt et al. [3].
Biodegradability of scaffolds determined estimated time of degradation within 1-3 months and a mechanism, such as enzymatic hydrolysis. Modified chitosan - hyaluronic acid scaffolds populated with adult stem cells from mouse (C57BL/6j) nasal olfactory lamina propria were transplanted into the lesion cavity of the injured cortex 7 days after TBI, and the mice were sacrificed 21 days after TBI. Sensorimotor function and spatial learning were measured using an array of function tests, MRI and the brain tissue was processed for immunohistology analysis. Recognition memory was evaluated using the Object Recognition Test (ORT) in mice on 25 day after brain injury. Memory was operationally defined by the discrimination ratio for the novel object (DIR), as the proportion of time the animals spent investigating the novel object minus the proportion spent investigating the familiar one during the testing period. The level of cytokines IL-2, IL-4, IL-6, IFN-y, TNF-a, IL-17A, IL-10 was determined in the serum and dissociated cells of the cerebral cortex mice of the C57BL/6 using flow cytometry (FACSCanto II - BECTON DICKINSO, USA). To study the cytocompatibility of scaffolds with cultured cells we used histochemical live/dead cell viability assay.
Results
The data show that scaffolds populated by neuronal stem cells from mouse nasal olfactory lamina propria improve learning and sensorimotor function, reduce the lesion volume, and provide the migration of stem cells into the lesion boundary zone after TBI in mice, reduce the formation of glial scar. In addition, modified chitosan scaffolds reduces the amount of proinflammatory factors TNF-a, IL-6, IL-2 and normalize the content of anti-inflammatory cytokines IL-4, IL-10 locally in the brain, and on the system level. It is important to note that there was no activation of autoimmune processes, the level of IL-17A did not change after the reconstructive surgery.
Conclusions
Neuronal stem cells populated 3D biodegradable scaffolds produced by microstereolihography technique from combination of the modified chitosan - hyaluronic acid may be a new way to reconstruct injured brain and improve neurological function after TBI. These data show that neuronal stem cells from mouse nasal olfactory lamina propria induce neurogen-esis and contribute to restoration of brain tissue via trophic actions. Our experiments on mice may suggest that human olfactory tissue is a conceivable source of nervous system replacement cells. Treatment with 3D biodegradable scaffolds normalize the content of anti-inflammatory/ proinflammatory cytokines without activation of autoimmune processes.
OM&P
Section BRAIN-COMPUTER INTERFACES, COGNITIVE NAVIGATION WORKSHOP AND NEUROENGINEERING
Acknowledgements
The research was supported by the Russian Foundation for Basic Research (grant 13-04-12067). References
1. T.A. Akopova, P.S. Timashev, T.S. Demina, K.N. Bardakova, N.V. Minaev, V.F. Burdukovskii, G.V. Cherkaev, L.V. Vladimirov, A.V. Istomin, E.A. Svidchenko, N.M. Surin, V.N. Bagratashvili, Solid-state synthesis of unsaturated chi-tosan derivatives to design 3D structures through two-photon-induced polymerization, Mendeleev Communications, 2015, 25, 280-282.
2. P.S. Timashev, T.S. Demina, N.V. Minaev, K.N. Bardakova, A.V. Koroleva, O.A. Kufelt, B.N. Chickov, V.Ya. Panchen-ko, T.A. Akopova, V.N. Bagratashvili Fabrication of microstructured materials based on chitosan and its derivatives using two-photon polymerization, High energy chemistry, 2015, 49 (4), 300-303.
3. O. Kufelt, A. El-Tamer, C. Sehring, S. Schlie-Wolter, and B. N. Chichkov, Hyaluronic Acid Based Materials for Scaffolding via Two-Photon Polymerization, Biomacromolecules, 2014, 15 (2), 650-659.
Development of Tactile Feedback Loop Based on Skin Vibro-Stimulation for Brain-Computer Interface
A. Pimashkin1 *, A. Motailo1, M. Shamshin1, S.Yu. Gordleeva1
Lobachevsky State University of Nizhni Novgorod, Nizhny Novgorod, Russia. * Presenting e-mail: pimaskin@neuro.nnov.ru
About 30% of stroke patients suffer from disorders of motor and somatosensory systems [1]. Methods of target rehabilitation of motor and sensory deficits are very important for recovery of these patients [2]. Conventional rehabilitation methods and approaches require a lot of specialized staff and are not enough effective, and for example, the United States spends $36.5 billion a year on it [3]. In this context the rehabilitation approaches based on BCI seem to be the most promising.
The main innovation of these approaches is that BCI allows you to decode the very intention to motion that occurs as a plan of action in the brain, even in deeply paralyzed people. This intention can be identified by the algorhytms and translated into a command for external executive devices: manipulators, exoskeletons, etc. Thus, human intent can be transformed into a real action even in case of strong damage of pathways between brain and the muscles. This will provide an opportunity for patients to control a training device directly by mental efforts that would make rehabilitation more effective and less demanding to support personnel.
However, despite the high level of modern development of BCI technology, including the latest advances of computer and electronic equipment, software and algorithmic approaches and neurophysiological knowledge, all these BCIs have several common disadvantages. These are low information transfer rate, very slow development and poor automation of the BCI skill. Moreover, it is impossible to control a BCI-operated object proportionally, for instance, smoothly move a cursor along the desired path. A few attempts to build a BCI feedback as a result of produced actions have been taken, some of them were successful, but all this was done either invasively or using animals [4].
Therefore, the aim of this work is to develop a suitable for human non-invasive BCI technology with nonvisual feedback loop. This young technology may help to overcome the existing BCIs restrictions in operation speed and accuracy, but which is more important, to make this technology closer to the real organism with its natural sensorimotor pathways and ability to automate new skills.
The relevance of this work is that the proposed new BCI technology for humans will include feedback by means of multi-unit vibro-tactile skin stimulation. This will help to build a BCI technology that can reproduce natural mechanisms of human motor activity by means of muscles that are initially provided by the feedback with the brain.
In this study we developed a circuit which consisted of 5 independent vibro-stimulators placed on the skin surface of the shoulder girdle. The vibromotors were driven by a microcontroller through serial port of the computer and used as a sensor feedback loop. We developed a software that can be used to translate any BCI command to each motor independently with specific vibrating pattern. Decoded patterns of motor movement in EEG experiments were translated into tactile commands to the skin. Each motor generated high-frequency vibration (9000 rpm) during short period (1 sec) after the movement pattern was obtained. We hypothesize that such approach will enhance classification efficacy of the BCI system.
OM&P
