Functional human neural networks grown on 3D laser printed scaffolds
Lead Research Organisation:
Aston University
Department Name: Sch of Life and Health Sciences
Abstract
Background: The last 10 years has seen a revolution in Biology and in Photonics Engineering. Namely, the development of methods to derive specific types of cells e.g. neurons from human induced pluripotent stem cells (iPSCs), and in photonics, the development of 2 Photon Polymerisation (3D laser printing), which allows microfabrication of substates with submicron resolution. In the brain, neurons function in defined 3D networks where the specific cellular and synaptic relationships are critical for effective function. To emulate human neuronal network function in culture, it is therefore, necessary to grow them in three dimensions.
Project: The aim of the project is to determine how 3D scaffold structure affects neuronal network architecture and function. This will involve 3D printing, growth of iPSC derived neurons and functional electrophysiological and calcium imaging of neuronal networks. The Student will also interact with the wider international membership of the recently awarded European FET Consortium, MESO-Brain, which comprises of Neuroscientists, Stem Cell Biologists, Physicists and Photonics experts.
Project: The aim of the project is to determine how 3D scaffold structure affects neuronal network architecture and function. This will involve 3D printing, growth of iPSC derived neurons and functional electrophysiological and calcium imaging of neuronal networks. The Student will also interact with the wider international membership of the recently awarded European FET Consortium, MESO-Brain, which comprises of Neuroscientists, Stem Cell Biologists, Physicists and Photonics experts.
People |
ORCID iD |
| Harri Parri (Primary Supervisor) | |
| Eleni Farmaki (Student) |
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| EP/N509425/1 | 01/10/2016 | 30/09/2021 | |||
| 1941790 | Studentship | EP/N509425/1 | 01/10/2017 | 31/12/2021 | Eleni Farmaki |
| Description | The functionality of a human brain's neural circuitry is achieved through the formation of 3D networks consisting of neurons and glia cells. Recent advances in the emerging field of tissue engineering and regenerative medicine have led to the successful fabrication of 3D structures that serve as scaffolds for complicated neuronal networks. However, the inability to create a model with micron/sub-micron topography that closely mimics a neuronal network's specificity and with the potential to be easily reproducible remains challenging. The only technique that holds sufficient promise to address the barrier of creating a 3D structure with such delicate features is two-photon polymerization (TPP). For our experiments, two commercially available photocurable resins were employed to produce novel designs of 3D laser printed scaffolds. The aim was firstly to assess the biocompatibility and imaging properties of the materials and secondly to evaluate how different architectures affect the proliferation and guidance of neuronal cells seeded on the scaffolds. Our early results showed that both materials meet the non-cytotoxic and low autofluorescence criteria, however long-term biological experiments are still required to fully determine their biocompatibility. Yet, one of the two materials proved to be inadequate to 3D micro-fabrication as all 3D-printed structures were collapsing and. Since this specific material has not been used before for similar experiments, the reasons for its failure are still under investigation. Finally, the experiments regarding the architectural effects of the scaffolds on cells are currently ongoing. |
| Exploitation Route | Neurodegenerative diseases are one of the most significant current socioeconomic problems, costing nearly $800 billion per year in the USA with Alzheimer's dementia (AD) being the most costly and rapidly increasing issue. In order to provide effective treatment plans for these conditions it is essential to understand the pathological underlying mechanisms that triggers them. Neurodegeneration occurs in the central nervous system, which consists of the brain and the spinal cord. The brain is the most complicated and least understood organ in the human body with limited regenerative ability. Both its complexity and susceptibility to degeneration create severe challenges that we need to overcome. Most of the current treatment options are not able to fully restore the functions of the damaged tissue and several of them are related to invasive procedures that require long periods of recovery. The fabrication of a 3D functional human neural network with a well-defined architecture that can be easily reproducible could be mainly utilised to help researchers and clinicians understanding the complicated physiological and pathological mechanisms of neurons and human brain, but also for drug-screening and personalised applications. Moreover, it is an alternative solution to drastically decrease the animal use in research. |
| Sectors | Pharmaceuticals and Medical Biotechnology |
| Description | University of Birmingham - School of Physics and Astronomy |
| Organisation | University of Birmingham |
| Department | School of Physics and Astronomy |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | This collaboration allow us to use the Nanoscribe Professional Photonic GT equipment in the School of Physics and Astronomy. This equipment is very crucial for our research as we use it to produce scaffolds. |
| Collaborator Contribution | Our partners kindly gave us access to their photonics lab and equipment free of charge. |
| Impact | Two-photon polymerisation laser-printed scaffold production. |
| Start Year | 2019 |
| Description | TERMIS-EU 2020 Abstract publication |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | Abstract submission for poster presentation for the TERMIS-EU 2020 Chapter Conference. Abstract was selected among others for publication. Title: 3D laser-printed scaffolds with micro-scale features as potential candidates for growing functional neural networks. (you can find it on page 3 of the link provided below) |
| Year(s) Of Engagement Activity | 2020 |
| URL | https://www.ecmconferences.org/abstracts/2020/Collection1/collection1_poster.pdf |
| Description | Training visit at Laser Center Hannover e.V. (16/04/2019-18/04/2019) |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Postgraduate students |
| Results and Impact | A 3-day training visit was arranged for me in order to get familiar with two-photon polymerisation technique. I was guided and supervised by a photonic expert and I learned the fundamentals of direct laser writing. |
| Year(s) Of Engagement Activity | 2019 |
| Description | UK Nerve Engineering Network meeting |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Postgraduate students |
| Results and Impact | This meeting brought together the UK community in nervous system engineering to promote interdisciplinary collaboration between academic, clinical and industry researchers. |
| Year(s) Of Engagement Activity | 2018 |
| URL | https://www.ucl.ac.uk/healthcare-engineering/events/2018/nov/uk-nerve-engineering-network-meeting |
| Description | V Summer School ''Photonics meets Biology'' |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | During this 5-day summer school we had the opportunity to attend many presentations from academic experts that came from different European universities. The topics covered were related to the applications of photonics in the medical sector. |
| Year(s) Of Engagement Activity | 2019 |
| URL | http://esperia.iesl.forth.gr/~mfarsari/ |