Develop synthetic extracellular matrix for engineering defined 3D human neural tissue

Lead supervisor: Prof. Hagan Bayley (Bayley Group) 

Co-supervisor: Dr Linna Zhou

Commercial partner: PeptiMatrix

Extracellular matrix (ECM) constitutes around 20% of the adult brain volume and plays an important role in brain function and disease. Increasing evidence suggests there are significant ECM changes, including degradation, overproduction and composition alteration, during the development of neurodegenerative disease. 3D tissue models including organoids are powerful tools to model human development and diseases. However, organoids are largely heterogenous and rely on the use of mouse-tumour-derived hydrogels, such as Matrigel. Matrigel is not defined, varies from batch to batch, and has limited potential for applications in the clinic.

To engineer defined 3D neural tissues, we will combine 3D bio-printing with chemically defined hydrogels. Previously we have developed a 3D printing technique to fabricate 3D human neural tissues for disease modelling and tissue repair using iPSCs derived neurons. We will collaborate with PeptiMatrix to design and synthesise novel chemical-defined, peptide-based hydrogels. These hydrogels will be tested to tailor the hydrogel properties to match brain tissue, such as mechanical (e.g. stiffness) and structural properties (e.g. pore size). Compatibility with our 3D printing techniques will also be optimised. The protein motifs of key brain ECM components, such as collagen IV and fibronectin, will be incorporated into the synthetic hydrogel. Different combination and ratio of these motifs will used to test their effects on neural cells. The ability of the hydrogels to support the survival, maturation and function of the iPSC-derived 3D neural tissues will be examined and quantified. Further, we will test the hydrogels with neural cells derived from patients with Parkinson’s disease. The changes of the hydrogels during the culture with healthy and diseased neural cells will also be examined. The developed hydrogels will be defined and compatible with neural tissues to maximise the breadth of potential applications in research and in the clinic.

The proposed project is highly multidisciplinary and aligns with MRC’s research priorities in developing new techniques for neuroscience and for tackling brain diseases such as neurodegeneration. Developing new tools to address neurodegenerative disease is of key economic and societal importance in view of our increasingly ageing population and the burden posed from the prevalence of these diseases. The project seeks to make advances in basic science, through the development of new hydrogel materials and study of their role as synthetic ECM. At the same, the application of these materials to generate 3D neural tissues has significant translational potential.

Synergies from the project include access to highly customisable, chemically defined synthetic ECMs that have already been demonstrated to have potential in 3D cultures. In turn, the commercial partner benefits from applying these materials in cutting edge technologies with significant potential for clinical translation, demonstrating the value of their products. Iterative development will mean that findings from the academic partner will be fed back to the commercial partner to continually improve the hydrogel materials.

Apply using course: DPhil in Chemistry