Commercialization of 3D scaffold platforms for neuronal cell culture models

Project Information

SCAFFOLD-NEEDS

Grant agreement ID: 851734

DOI

10.3030/851734

Project closed

EC signature date 30 April 2019

Start date 1 August 2019

End date 31 January 2021

Funded under

• EXCELLENT SCIENCE - Future and Emerging Technologies (FET)

Total cost

€ 100 000,00

EU contribution

€ 100 000,00

Coordinated by

ASTON UNIVERSITY
United Kingdom

Periodic Reporting for period 1 - SCAFFOLD-NEEDS (Commercialization of 3D scaffold platforms for neuronal cell culture models)

Reporting period: 2019-08-01 to 2021-01-31

Summary of the context and overall objectives of the project

The development of methods to isolate and generate human stem cells along with technology to selectively differentiate them into specific cell and tissue types has excited many with the promise of the ability to study human cell function and utilise them for regeneration in disease and trauma. However, many past attempts to develop regenerative brain and central nervous system therapies have been disappointing, with the introduced stem cell derived neurons not integrating nor signalling physiologically with endogenous cells. A major confounding issue has been that derived neurons are grown in two dimensions, which does not mimic the in vivo three dimensional interactions nor the myriad developmental cues they would receive in vivo.
In the Meso Brain project the idea of a functional three dimensional human stem cell derived neural networks of defined and reproducible architecture was investigated, based on that of a brain cortical module that displays in vivo connectivity and activity.
The project Scaffold-Needs analyzed how the research approaches and results obtained can be used to develop products that can represent valuable novel tools in biomedicine. Product concepts, application concepts and market analyses and commercialization concepts were developed.
Scaffold-Needs aims to pave the way for reproducible scaffolds that can be manufactured on a large scale. The development of such a technological platform is fundamental to a new era of biological and medical research based on human neural networks to treat diseases such as Parkinson's, dementia, and trauma.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

3D scaffold demonstrators: production, optimisation, development of a product line
3D polymer scaffold demonstrators with and without electrodes were successfully fabricated by two-photon polymerization (2PP) at Laser nanoFab GmbH. A number of design options for scaffold printing were investigated. Optimization of the fabrication process was carried out and the appropriate parameters were established to produce complex 3D scaffolds of different sizes, shapes and with different pore sizes. Several scaffold prototypes were produced for investigations of neuronal cell growth and network formation. The successful formation of a neural network with hiPSCs neuronal stem cells after 11 days of differentiation on 3D polymer scaffolds was demonstrated. The resulting neuronal networks showed high quality and uniformity.

Market analysis and assessment
A market analysis was conducted with the aim of commercializing these innovative products. Leading biologists, scientific experts and potential customers were contacted to understand the actual needs for customized scaffolds. An overview of the requirements and the existing experiences of the participants with 3D cultures was compiled. Price expectations for customised 3D scaffolds were analyzed.
Current competitors in the scaffold technology market were identified and their role evaluated. The analysis shows that there are several suppliers of commercial scaffolds for tissue engineering. The greater part of them produces sponge-like scaffolds with random structure (hydrogels, nanofiber-based scaffolds, polymeric scaffolds). Some vendors sell 3D printed structures, but due to the technical limitations of the applied technologies, these are relatively rough. The structure and complexity of these scaffolds is not determined by customer needs, but by the limited possibilities of manufacturing technologies.

Business plan development
A business plan was developed to investigate the commercialization potential of the 3D high-resolution scaffolds. Laser nanoFab's strategic and financial plans for the short, medium and long term have been identified. This developed business plan provides an overview of the state of the international scaffold market and the economic potential of our product. It also identifies the company's goals and opportunities in this area, derives operational activities and provides an initial assessment of the profitability of activities in this market.

IP identification
IP assays were identified, patent and literature searches were conducted and the results were summarized and evaluated. The assessment of patentability was based on a thorough patent search and a literature search of scientific publications in the field of biomedical scaffolds for 3D cell culture. The patent search revealed that freedom to operate is given. The basis for drafting up patent applications has been created for our inventions.

Dissemination and Exploitation
The following activities were carried out:

Event Attendances (selected activities)
o Prof. Dr. Boris Chichkov "Laser printing" (LNF), TRR 225 Online Summer School “Technologies for Biofabrication” (online) (Erlangen, Germany), 20th to the 24th July 2020
o Prof. Dr. Boris Chichkov " Laser printing of biomaterials and living cells" (LNF), plenary speaker, VII TROITSK CONFERENCE ON MEDICAL PHYSICS (TCMP-7) (online) (Troitsk, Russia), 19th to the 21th October 2020
o Prof. Dr. Boris Chichkov " Laser printing of biomaterials and living cells" (LNF), plenary speaker, 6th International A.M. Prokhorov Symposium on Lasers in Medicine and Biophotonics (online) (St. Petersburg, Russia), 2nd to the 6th November 2020

Publications
o J. A. Crowe1, A. El-Tamer, D. Nagel, A. Koroleva, J. Madrid-Wolff, O. E. Olarte, S. Sokolovsky, E. Estevez-Priego, A.-A. Ludl, J. Soriano, P. Loza-Alvarez, B. N. Chichkov, E. J. Hill, H. R. Parri, E. U. Rafailov. Development of two-photon polymerised scaffolds for optical interrogation and neurite guidance of human iPSCderived cortical neuronal networks, Lab Chip, 2020, 20, 1792-1806
DOI: https://doi.org/10.1039/C9LC01209E
o A. Koroleva, A.Deiwick A. El Tamer, Y. Shi, A. Ludl, J. Soriano Fradera, D. Guseva, E. Ponimaskin and B.Chichkov. In vitro development of iPSCs derived functional neuronal networks on laser fabricated 3D scaffolds. ACS Applied Materials & Interfaces, 2021 13 (7), 7839-7853
DOI: https://doi.org/10.1021/acsami.0c16616

Project videos
We have recently developed a concept of very short videos (about 1 minute), each focusing on and presenting a core idea of our technology and products.

Direct advertising , Project Flyer
A Scaffold-Needs flyer was designed to inform leading biologists, scientific experts and potential customers and to communicate our products and technologies.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The commercially available scaffold platforms from Laser nanoFab will provide a high throughput tool for screening novel drugs and compounds that may impact upon the disease process and expedite the process of drug development. This will be of benefit to patients/clinicians and pharmaceutical companies as it will speed up the process of drug development for numerous diseases and disorders (such as Alzheimer's disease, Parkinson's disease, Huntington’s disease and other neurodegenerative disorders). High-precision scaffolds with cell-specific dimensions and additional design features can be produced to meet customer requirements.
We will offer an intelligent solution for 3D culture that enables our customers to grow any type of cells in a realistic 3D environment, to build customer own in vitro assays and to analyze complex cell interactions.
We are planning to enter the market via a market niche, in which we are not initially competing with existing products.

3D human iPSC-derived neuronal network developed in a laser fabricated scaffold. Green: neurons