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Brain Patch Technology

Applicant Braschler Thomas
Number 163684
Funding scheme SNSF Professorships
Research institution Département de Pathologie et Immunologie Faculté de Médecine / CMU Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Mechanical Engineering
Start/End 01.10.2016 - 30.09.2020
Approved amount 1'570'990.00
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All Disciplines (6)

Discipline
Mechanical Engineering
Material Sciences
Electrical Engineering
Fluid Dynamics
Chemical Engineering
Neurophysiology and Brain Research

Keywords (10)

transplantation; regenerative; stroke; microfluidics; neuron; microelectrodes; perfusion; hydrogel; parkinsons; scaffold

Lay Summary (German)

Lead
Grössere Verluste von Hirngewebe, etwa bei einem Hirnschlag, gelten in heutiger medizinischer Praxis als praktisch irreversibel. Es ist nämlich trotz spektakulärer Fortschritte in der Entwicklung neuronaler Stammzellentechnologie nach wie vor extrem schwierig, grössere Mengen an neuralem Gewebe zu ersetzen. Wir entwickeln eine innovative Technologie - die “Brain Patches” - mit dem Ziel, dem Neurochirurgen minimal invasiv implantierbares künstliches neurales Gewebe zur Vefügung zu stellen.
Lay summary

Inhalt und Ziele des Forschungsprojekts

 

Es ist mittlerweilen eine etablierte Erkenntnis, dass neurale Stammzellen die Fähigkeit haben, Nervenzellen und weitere Komponenten des Hirngewebes auszubilden. Trotzdem gelingt es zur Zeit noch nicht, grössere Verluste an Hirngewebe durch künstlich herangezogene Zellen zu ersetzen. Während die grundlegenden Kultur- und Differenziationsprotokolle laufend verbessert werden, fehlt uns eine geeignete chirurgische Technologie zum Einsatz grösserer, organisierter Implantate. Ziel der Entwicklung der “Brain Patches” ist es, diese Lücke zu schliessen. 

 

Die Brain-Patches sind eine Kombination aus einem innovativen, komprimierbarem Biomaterial, mikrofabrizierte Perfusions- und Stimulationsnadeln und neuronalen Stammzellen. Das Biomaterial schützt das junge Nervengewebe bei der minimal-invasiven Transplantation, während Perfusion und Stimulation dazu verwendet werden, die Stammzellenumgebung auch nach der Implantation zu überwachen und zu beeinflussen. Spezielle Anliegen sind uns gezielte Punkt-zu-Punkt Verbindungen, die kontrollierte Entwicklung und Differenzierung der Stammzellen im Gehirn, aber auch die Kontrolle über die immunologische Umgebung.

 

Wissenschaftlicher und gesellschaftlicher Kontext des Forschungsprojekts

 

Die Grundlegende wissenschaftliche Frage dieses Projektes ist es, welche Grundbedingungen künstliches implantiertes Nervengewebe zum Ueberleben und zum Funktionieren braucht. Die praktische, angewandte Frage ist es, wie man diese Bedingungen im Gehirn, bei und vor allem nach der Implantation zur Verfügung stellen kann. Eine Antworte auf diese beide Fragen ist von enormer Tragweite bei der Therapie von heute schwer zu behandelnden Folgen eines Hirnschlags oder Hirntraumas, neurodegenerativen Erkrankungen wie der Parkinsonschen Krankheit, und möglicherweise in der Immunotherapie von Krebserkrankungen des Zentralnervensystems. 

Direct link to Lay Summary Last update: 02.08.2016

Lay Summary (French)

Lead
Encore aujourd’hui, une perte suffisamment importante de tissus neural, par exemple lors d’un accident vasculaire cérébral, entraîne des conséquences dramatiques et souvent irréversibles. L’utilisation de cellules souches neurales est sur le pas de créer une nouvelle branche à part entière de la neurochirurgie, permettant une véritable régénération neurale. Mais à ce jour, il nous manque notamment un outil de transplantation cellulaire minimalement invasif assurant la survie des cellules transplantés assorti d’un outil permettant de contrôler leur environnement, devenir et fonction in-vivo. En rapprochant biomatériaux et microfabrication, notre groupe vise à fournir ces outils sous forme de “Brain Patch”. La question scientifique sous-jacente est: Quelles sont les conditions indispensables à une bonne survie et intégration fonctionnelle des cellules neurales souches?
Lay summary

Contenu et objectifs du travail de recherche

Le but de ce projet est d’améliorer la survie, mais aussi le contrôle sur le devenir et la fonction de cellules neurales souches transplantées in-vivo. Pour ceci, nous développons un tissus neural compressible pour une implantation minimalement invasive. Nous y associeront des outils microfabriqués pour perfuser et stimuler ce tissus une fois implanté dans une lésion cérébrale suite à un accident vasculaire cérébral ou encore une maladie neurodégénérative telle la maladie de Parkinson.

 

Au-delà d’un simple outil de transplantation, nous visons à gagner un véritable contrôle sur l’implant. Ceci ouvre des perspectives fondamentalement nouvelles. Par exemple, la perfusion peut être utilisée pour favoriser une différentiation voulue, tel qu’une différentation en neurones produisant la dopamine pour pallier à la maladie de Parkinson, au-delà de la transplantation même. Alternativement, en perfusant des immunomodulateurs, nous visons aussi le développement d’une nouvelle stratégie du traitement de certains cancer cérébraux. Finalement, des implants pré-formés et pré-organisés pourront servir de connexions point-à-point pour addresser des paralysies.   

 

Contexte scientifique et social du projet de recherche

 

Notre question fondamentale est la suivante: Comment peut on contrôler l’environnement cellulaire dans le cerveau comme on le fait actuellement en plaque de culture? A la clé sont la solution d’importants problèmes tel la survie de cellules souches transplantés, leur bonne différentation et intégration, et finalement leur fonction. Ceci pourrait amener de nouvelles solutions à des problèmes médicaux aussi graves que fréquentes, telles les conséquences dévastatrices d’un accident vasculaire cérébral, la perte de la voie de la dopamine dans la maladie de Parkinson ou le manque d’une réponse immunitaire approprié dans des cancers cérébraux.  

Direct link to Lay Summary Last update: 02.08.2016

Responsible applicant and co-applicants

Employees

Publications

Publication
Neural priming of adipose-derived stem cells by cell-imprinted substrates
Ghazali Zahra Sadat, Eskandari Mahnaz, Bonakdar Shahin, Renaud Philippe, Mashinchian Omid, Shalileh Shahriar, Bonini Fabien, Uckay Ilker, Preynat-Seauve Olivier, Braschler Thomas (2020), Neural priming of adipose-derived stem cells by cell-imprinted substrates, in Biofabrication.
Injectable, scalable 3D tissue-engineered model of marrow hematopoiesis
Tavakol Daniel Naveed, Tratwal Josefine, Bonini Fabien, Genta Martina, Campos Vasco, Burch Patrick, Hoehnel Sylke, Béduer Amélie, Alessandrini Marco, Naveiras Olaia, Braschler Thomas (2020), Injectable, scalable 3D tissue-engineered model of marrow hematopoiesis, in Biomaterials, 232, 119665-119665.
Additive manufacturing of hierarchical injectable scaffolds for tissue engineering
Béduer A., Piacentini N., Aeberli L., Da Silva A., Verheyen C.A., Bonini F., Rochat A., Filippova A., Serex L., Renaud P., Braschler T. (2018), Additive manufacturing of hierarchical injectable scaffolds for tissue engineering, in Acta Biomaterialia, 76, 71-79.
Pore Size Manipulation in 3D Printed Cryogels Enables Selective Cell Seeding
Serex Ludovic, Braschler Thomas, Filippova Aleksandra, Rochat Ariane, Béduer Amélie, Bertsch Arnaud, Renaud Philippe (2018), Pore Size Manipulation in 3D Printed Cryogels Enables Selective Cell Seeding, in Advanced Materials Technologies, 3(4), 1700340-1700340.

Datasets

Injectable, Scalable 3D Tissue-Engineered Model of Marrow Hematopoiesis

Author Tavakol, Daniel N.; Tratwal, Josefine; Bonini, Fabien; Genta, Martina; Burch, Patrick; Sylke, Hoehnel; Béduer, Amélie; Alessandrini, Marco; Naveiras, Olaia; Braschler, Thomas
Publication date 17.09.2019
Persistent Identifier (PID) https://doi.org/10.5281/zenodo.3437654
Repository Zenodo
Abstract
Raw research dataset for the publication "Injectable, Scalable 3D Tissue-Engineered Model of Marrow Hematopoiesis"

Neural priming of adipose-derived stem cells by cell-imprinted substrates

Author Ghazali, Zahra Sadat; Eskandari, Mahnaz; Bonakdar, Shahin; Renaud, Philippe; Mashinchian, Omid; Bonini, Fabien; Uckay, Ilker; Preynat-Seauve, Olivier; Braschler, Thomas
Publication date 30.05.2020
Persistent Identifier (PID) 10.5281/zenodo.3904173
Repository Zenodo
Abstract
Raw data and figure evaluation scripts for the manuscript Neural Priming of Adipose-Derived Stem Cells by Cell-Imprinted Substrates Ghazali, Zahra Sadat; Eskandari, Mahnaz; Bonakdar, Shahin; Renaud, Philippe; Mashinchian, Omid; Shalileh, Shahriar; Bonini, Fabien; Uckay, Ilker; Preynat-Seauve, Olivier; Braschler, Thomas

Highly efficient cardiac differentiation and maintenance by thrombin-coagulated fibrin hydrogels enriched with decellularized porcine heart extracellular matrix

Author Navaee, Fatemeh; Renaud, Philippe; Braschler, Thomas
Publication date 21.05.2020
Persistent Identifier (PID) 10.5281/zenodo.3838400
Repository Zenodo
Abstract
Dataset on the effect of different hydrogels on the culture of model cell lines and cardiomyocytes

Data: An injectable meta-biomaterial

Author Béduer, Amélie; Bonini, Fabien; Verheyen, Connor; Burch, Patrick; Braschler, Thomas
Publication date 29.04.2019
Persistent Identifier (PID) 10.5281/zenodo.2653804
Repository Zenodo
Abstract
Dataset supporting the manuscript "An injectable meta-biomaterial" by the authors of this dataset.

Neurotubes: Cryogel carriers for differentiation and delivery of mature neurons in the treatment of Parkinson's disease

Author Filippova, Aleksandra; Bonini, Fabien; Efremova, Liudmila; Preynat-Seauve, Olivier; Béduer, Amélie; Krause, Karl-Heinz; Braschler, Thomas
Publication date 14.01.2020
Persistent Identifier (PID) 10.5281/zenodo.3608207
Repository Zenodo
Abstract
Raw data for the publication:Neurothreads: Cryogel carriers for differentiation and delivery of mature neurons in the treatment of Parkinson's disease

An injectable meta-biomaterial

Author Béduer, Amélie; Bonini, Fabien; Verheyen, Connor; Genta, Martina; Martins, Mariana; Brefie-Guth, Joé; Filippova, Aleksandra; Burch, Patrick; Braschler, Thomas
Publication date 12.06.2020
Persistent Identifier (PID) 10.5281/zenodo.3891122
Repository Zenodo
Abstract
This contains the raw images and the content of the Codeocean capsule for the manuscript "An injectable meta-biomaterial".This is a largely updated version of the data set at https://zenodo.org/record/2653804#.X6wjDx17lR0 ("Data: An injectable meta-biomaterial") elaborated in the review process, contains immunological analysis and long-term data.

Codeocean calculation capsule particleShear

Author Béduer, Amélie; Bonini, Fabien; Verheyen, Connor; Genta, Martina; Martins, Mariana; Brefie-Guth, Joé; Filippova, Aleksandra; Burch, Patrick; Braschler, Thomas
Publication date 15.07.2020
Persistent Identifier (PID) 6934377
Repository CodeOcean
Abstract
CodeOcean capsule. Permits to reproduce all evaluations, statistics, and figure plotting for the manuscript "An injectable meta-biomaterial" in an automated fashion.This capsule supports the development of an injectable meta-material. It provides the Python simulation "particleShear", describing the rheological behaviour of variously shaped and crosslinked microparticle suspensions. It additionally contains quantitative simulation and physical and in-vivo measurement data for the manuscript "An injectable meta-biomaterial". The capsule provides reproducible simulation demo, data analysis and replotting of the quantitative figures of the manuscript: Fig. 2 recapitulates a large scale run of the particleShear simulation on a cluster, Fig. 3 corresponding physical characterization, Fig. 4 in-vivo shaping performance and biocompatibility and Fig. 5 meta-material generalization. Data and evaluation on Supplementaries 1-11 is also provided.

Collaboration

Group / person Country
Types of collaboration
EPFL - Volumina Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Exchange of personnel
- Industry/business/other use-inspired collaboration
UNIGE - Group Karl-Heinz Krause Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
EPFL - Naveiras lab Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
HUG - Service Neurochirurgie Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
EPFL - LMIS4 Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Group Philippe Saas / Université de Franche-Comté France (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Exchange of personnel
Group Olivier Preynat-Seauve, UNIGE Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
EPFL - Detox Lens Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Industry/business/other use-inspired collaboration

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Progress report PATIM Individual talk Cryogel carriers for dopaminergic neural cell transplantation 30.09.2020 Genève, Switzerland Fillippova Aleksandra;
PhD retreat 2020 Talk given at a conference Scaffold-supported transplantation of hematopoietic stem and progenitor cells for the treatment of chronic granulomatosis 09.09.2020 Genève, Switzerland Bréfie-Guth Joé;
Progress report PATIM Individual talk Biomaterial development for a chemo-free bone marrow transplantation 17.12.2019 Genève, Switzerland Bréfie-Guth Joé;
Neuroscience 2019 (50th annual meeting of Society for Neuroscience) Poster Cryogel carriers for transplantation of mature dopaminergic neurons in treatment of Parkinson’s disease 19.10.2019 Chicago, Illinois, United States of America Fillippova Aleksandra; Braschler Thomas;
Annual Meeting of the Swiss Society for Biomaterials and Regenerative Medicine Poster A cryogel platform for differentiation and transplantation of dopaminergic neurons in treatment of Parkinson’s disease 23.05.2019 Muttenz, Switzerland Fillippova Aleksandra; Braschler Thomas;
1st Annual Meeting of the NeuroLeman Networks and Doctoral Schools Poster A cryogel platform for differentiation and transplantation of dopaminergic neurons in treatment of Parkinson’s disease 02.05.2019 Les Diablérets, Switzerland Braschler Thomas; Fillippova Aleksandra;
Department Retreat PATIM Talk given at a conference Cryogel-assisted stem cell therapy for infarcted brain tissue repair 10.04.2019 Les Pensières, France Bonini Fabien;
Progress report PATIM Individual talk The use of a self-assembling and porous biomaterial for cell transplantation 12.12.2018 Geneva, Switzerland Bonini Fabien;
Progress report PATIM Individual talk Cryogel carriers for dopaminergic neural cell transplantation 12.12.2018 Genève, Switzerland Fillippova Aleksandra;
Biomaterial Engineering Society 2018 Annual Meeting Poster Recapitulating bone marrow hematopoietic stromal niches with 3D scalable bioscaffolds 17.10.2018 Atlanta, Georgia, United States of America Braschler Thomas; Bonini Fabien; Béduer Amélie;
PhD retreat - Biology-Medicine doctoral school Talk given at a conference Startup and Innovative Project 03.10.2018 Leysin, Switzerland Béduer Amélie;
Annual meeting of the European Society for Biomaterials Poster Cryogel system development for study and treatment of Parkinson's disease 09.09.2018 Maastricht, Netherlands Fillippova Aleksandra; Braschler Thomas;
Lemanic neuroscience annual meeting (LNAM) Poster Cryogel system development for study and treatment of Parkinson's disease 02.09.2018 Les Diablérets, Switzerland Fillippova Aleksandra; Braschler Thomas;
Séminaire LAAS- CNRS Individual talk Scaffold-based tissue engineering with demonstration experiment 27.07.2018 Toulouse, France Béduer Amélie;
Progress report PATIM Talk given at a conference Brain tissue reconstruction using a minimally invasive and self-assembling biomaterial 28.02.2018 Genève, Switzerland Bonini Fabien;
Department retreat PATIM Talk given at a conference Self-organizing scaffolds for neural cell transplantation, Presentation T. Braschler 10.10.2017 Annecy, France Béduer Amélie; Fillippova Aleksandra; Bonini Fabien; Braschler Thomas;
Department retreat PATIM Poster Brain tissue reconstruction using bioengineered polysaccharide-based cryogel, Poster F. Bonini 10.10.2017 Annecy, France Braschler Thomas; Bonini Fabien; Béduer Amélie; Fillippova Aleksandra;
Department retreat PATIM Poster Reconstruction of nigrostriatal pathway using a functionalized hydrogel scaffold, poster by A. Filippova 10.10.2017 Annecy, France Béduer Amélie; Fillippova Aleksandra; Braschler Thomas; Bonini Fabien;
Lemanic neuroscience annual meeting (LNAM) Poster Reconstruction of nigrostriatal pathway using a functionalized hydrogel scaffold, Poster A. Filippova 01.09.2017 Les Diablerets, Switzerland Bonini Fabien; Fillippova Aleksandra; Béduer Amélie; Braschler Thomas;
PhD retreat - Biology-Medicine doctoral school Poster Brain tissue reconstruction using bioengineered polysaccharide-based cryogel, poster F. Bonini 27.04.2017 Champéry, Switzerland Braschler Thomas; Fillippova Aleksandra; Béduer Amélie; Bonini Fabien;


Knowledge transfer events

Active participation

Title Type of contribution Date Place Persons involved
Journée de l'innovation Poster 31.10.2019 Geneva, Switzerland Braschler Thomas;
Seminar at Sanofi on stem cells and scaffolds Talk 27.02.2017 Paris, France Braschler Thomas; Béduer Amélie;


Awards

Title Year
2ème meilleur poster de la journée d'innovation des Hôpitaux universitaires de Genève 2019
Best oral presentation at department retreat 2019

Use-inspired outputs

Associated projects

Number Title Start Funding scheme
154342 Neuronal transplantation using preformed injectable hydrogels 01.08.2015 International short research visits
194813 Cell Patch Technology 01.10.2020 SNSF Professorships
161347 In vivo perfused and stimulated scaffolds for neural cell therapy 01.12.2015 Ambizione

Abstract

The project aim is to develop "brain patches". These living neural scaffolds can be transplanted minimally invasively into the brain for functional recovery in stroke, Parkinson's disease and other conditions with focal neural tissue loss. Compared to existing neural scaffolds, the key innovation to ensure in-situ viability is in-vivo perfusion. We propose electrically active brain patches to favor neural reconnection, directional brain patches to replace lost neural tracts with specific connection, and, in international collaboration, immunologically active patches to address locally metastatic glioma.
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