The first phase of the programme Create2Solve can start with the three proposals that ZonMw selected to develop animal-free innovations for industry and research. The research groups will develop proof-of-concept projects for two Challenges, formulated by companies in the chemical, pharmaceutical and food industries. The project groups will receive a maximum of 7 months to realise their project. In the autumn of 2020, ZonMw will assess these projects and decide which can be elaborated in phase 2.

Projects selected

In July this year, ZonMw published the two selected Challenges from consortia of companies. ZonMw subsequently selected three of the proposals submitted. These research groups will each receive a maximum of 100,000 euros; that excludes the in-kind contributions from industry and/or the own institution. The research groups will work on proof-of-concept projects for these Challenges. These are the projects:

Challenge 1: Better in-vitro Dosing (BID):

  • Better In-Vitro Dosing (BID): Framework and technology development for improving the quality of in-vitro data
    Project leader Dr Nynke (N.I.) Kramer (Utrecht University, Institute for Risk Assessment Sciences)

Challenge 2: Need for human mini -brains as screening tools to assess efficacy of pharmacological or nutritional agents for neurological disorders characterised by white matter issues:

  • 3D Screening Platform for White Matter defects
    Project leader Dr Vivi (V.M.) Heine (Amsterdam UMC - location VUmc)
  • An animal-free human 3D cortical network platform for screening myelination and inflammation phenotypes. 3D Myelination & Inflammation Cortical network platform (3D MICro-brains)
    Project leader Dr Femke (F.M.S.) de Vrij (Erasmus MC)

Progress of the projects

The project groups will receive support from the companies involved to ensure that the questions from industry and the proof-of-concept project to be developed are well aligned. The Create2Solve committee will also play an active role in supervising the projects. They will visit the projects in the spring of 2020.

Next phase

In the autumn of 2020, ZonMw will select a maximum of one project per Challenge. In the second phase of Create2Solve, the selected proof-of-concept projects will further develop, validate or expand their animal-free innovation into a prototype. The maximum duration of these research projects is 5 years.

Create2Solve: demand-driven animal-free innovations

With Create2Solve, ZonMw supports the development of animal-free innovations with an impact that must lead to commercial methods, models and/or services. The funding for Create2Solve is being provided by the Ministry of Agriculture, Nature and Food Quality and the Dutch Society for the Replacement of Animal Testing. Create2Solve is an initiative of the ZonMw programme More Knowledge with Fewer Animals.

Project summaries

Better In-Vitro Dosing (BID): Framework and technology development for improving the quality of in- vitro data
Project leader Dr Nynke (N.I.) Kramer (Utrecht University, Institute for Risk Assessment Sciences)

The nominal concentration, i.e. the theoretical concentration based on amount of test chemical added to culture medium, is generally used to express concentration-effect relationships in in-vitro toxicity tests. However, for instable, volatile, lipophilic and highly plasma protein bound chemicals, the nominal concentration does not represent the concentration responsible for the observed effect at the target site in cells. In this project, we are further developing tools that control for the degradation, evaporation and binding of chemicals to the in-vitro system setup of these chemicals. These tools include exposing cells in sealed glass vials and microtiter plates dosed through polymers loaded with test chemicals (i.e. partition-controlled dosing). A decision tree will be evaluated to allow researchers to determine whether the use of each of these tools is necessary and applicable for the chemical and in vitro biomarker they wish to test.

3D Screening Platform for White Matter defects
Project leader Dr Vivi (V.M.) Heine (Amsterdam UMC - location VUmc)

White matter abnormalities are present in many neurological disorders, including multiple sclerosis, schizophrenia and Huntington’s disease. White matter is characterised by the presence of myelin and many other cellular structures, including oligodendrocytes, astrocytes, microglia and neurons, contributing to the development and maintenance of proper white matter. While much research is being done on laboratory animals, they do not represent cellular diversity and the large amount of white matter in the human brain. Hence, we need a human model system that is quantitative and represents different neuronal and glial structures. Recent developments in the stem cell field, such as induced pluripotent stem cell (iPSC) technology and mini brain cultures, provide new tools. Here, we aim to develop a high throughput organ-on-a-chip platform, involving different cellular structures in a physiological microenvironment. If successful, these platforms could provide powerful preclinical tools to study disease mechanisms, to identify drug targets or molecules critical to the repair of the white matter.

An animal-free human 3D cortical network platform for screening myelination and inflammation phenotypes. 3D Myelination & Inflammation Cortical network platform (3D MICro-brains),
Project leader Dr Femke (F.M.S.) de Vrij (Erasmus MC)

Recent developments in induced pluripotent stem cell (iPSC) technology offer the unique opportunity to implement lineage-specific human cellular models suitable for drug development applications. In this project, researchers will expand their established platform for 3D neural networks of human brain cells that resemble the human frontal cortex in early development. An industry partner will contribute innovative synthetic extracellular matrix technology to support 3D structure formation. The resulting 3D MICrobrains model will be the essence of cortical structure formation in a miniature format that is literally about 1 millionth the size of a normal human brain. The platform will contain all relevant cell types: functional neurons and glial cell types in layered radial structures, including astrocytes, myelinating white matter cells (oligodendrocytes) and cells that are crucial for immune responses in the brain (microglia). Moreover, this advanced 3D MICro-brain platform is amenable to high throughput analyses for screening purposes.

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