Bio-scaffold engineered device for brown adipose tissue regeneration

Project Information

SCAFFY

Grant agreement ID: 645640

DOI 10.3030/645640

Closed project

EC signature date 25 November 2014

Start date 1 October 2015

End date 30 September 2019

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost € 864 000,00

EU contribution € 864 000,00

Coordinated by

VRIJE UNIVERSITEIT BRUSSEL
Belgium

Periodic Reporting for period 2 - SCAFFY (Bio-scaffold engineered device for brown adipose tissue regeneration)

Reporting period: 2017-10-01 to 2019-09-30

Summary of the context and overall objectives of the project

Obesity and cardio-metabolic disease represent major health problems with vast impacts on the European healthcare
systems. Recent advances in tissue engineering and regenerative medicine can be used to design novel techniques
aiming to boost human metabolism; thus being promising candidates for human metabolic disease treatment.
However, the development of these techniques requires the creation of new technology and knowledge in chemistry,
biomaterials, toxicology, physiology, molecular biology as well as business management and marketing. SMEs do
not have the technical capabilities or the facilities to conduct R&D activities at the level of excellence required for
such development. Academic institutions have the capacity and facilities to conduct research and design activities
necessary to develop the concept into a market product. However, they do not have a viable supply chain to develop
the prototype post project and to exploit the product in the market. To solve this intersectoral problem, the SCAFFY
project will create an effective intersectoral co-operation between academia institutions and SMEs to advance the
concept of bio-scaffold for brown adipose tissue (BAT) regeneration.
The regeneration of BAT has been largely ignored in tissue engineering thus far.
This is because relevant R&D attempts were led by either the public or the private sector alone but
never by a joint-venture of the two. As a result, academic organizations have faced challenges in
finding the right application for the consumer market, while SMEs have been struggling to find the
resources to conduct the necessary state of the art research.
Therfore, the main objectives of the SCAFFY consortium are: putting together knowledge, research
expertise and resources from two large academic participants with business, market and commercialization experience
from three SMEs to: i) ensure a high degree of collaboration between academic and industrial participants though
Networking Activities, ii) go beyond the current state of the art though Researcher & Training Activities, iii) increase
intersectoral transfer of knowledge though Workshop Activities, iv) ensure high level of innovation capacity though
Innovation Activities, v) ensure communication to the scientific community and to the public though Dissemination
and Outreach Activities.

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

During the first 24 months of the Mari-Curi-RISE European project SCAFFY three main objectives have been achieved:
Firstly, the intersectoral and interdisciplinary transfer of knowledge between the Universities and industrial institutions (small companies) involved in the project has been promoted, through the exchange of a total of 6 experience researches and 5 young researchers. The current cooperation has an impact on the personal career of the researchers that have acquired new skills, experiences on different work environment, and they increased their contact network. On the other hand the organization of several workshops has allowed to maximize the transfer of knowledge between the university community and industrial institution that have attended to the workshops.
Secondly, we designed a novel therapy for treatment of obesity and cardio metabolic diseases based on the activation of the brown fat tissue that is responsible for non-shivering thermogenesis upon cold exposure or high fat diet. To reach this goal, the researches have to acquire a deep understanding about brown fat tissue physiological function along different human ages and especially in overweight patients with associated pathologies. These knowledges were essential to define patient targets and the design of the final product depending on the most appropriate admini stration route and site.
At last, we developed bio-scaffold prototypes and assessed their utility for BAT regeneration. Currently a soft injectable scaffolds prototypes: Alginate in combination with other biomaterial such as histogel, has been developed. Simultaneously, mesenchymal stem cell differentiation towards brown adipocytes protocols has been defined. Finally, in order to assess the ability of the scaffolds to modulate angiogenesis and differentiation of mesenchymal to brown cells, in-vitro and ex-vivo assays were performed.
In vivo assays with injectable scaffold seeded with mesenchymal stem cell differentiated to brown adipocytes was the the main objective for the second period (month 24-48). These experiments were prepared in the animalarium of the VUB. Parralel to these experiments, a market analysis was performed. Based on these results, a business plan was developed, awaiting the results from the invivo experiments. The invivo experiments revealed that our product was not ready to be launched into the market yet and some additional improvements are needed. This result was implemented in an updated version of the business-plan that was developed.

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)

In the first two years we identified a suitable scaffold ( Histogel/alginate) for the differentiation of mesenchymal cell in functional BAT cells supporting the new vessel formation. Differentiated cells induce a pro-angiogenic phenotype in endothelial cells, and well respond in term of mitochondrial activity to external stimuli including Isoproterenol. What we expected for the next two years was to validate the possible use of the identified scaffold containing the mesenchymal cells in vivo mesenchymal animal models. Obviously, in order to use the scaffold for human treatment, we need to think about manufacturing and manipulating scaffolds and cells in GMP mode. This is not far from the consortium's possibilities, as mesenchymal cells are already produced in GMP by Histocell and the same produces the matrix for human use. Additionally, a marketing research and bisness plan was made to launch our potential product into the market. Unfortunately, the results from our experiments are not as promising as hoped and additional research will be necessary before the product can be launched into the market.

Team Members from the Scaffy WorkShop