OBIS - Physics and Astronomy

OBIS - Physics and Astronomy

Project 5: 3D tissue-engineering tumour modelling

Recent advances in three-dimensional (3D) cell and tissue culture emphasise the role of the spatial microenvironment in the development of malignant tumours.  Our knowledge of tumour behaviour and pharmacological screens for anti-tumour drugs verified on 2D substrates could be misleading.  Indeed, the lack of progress in a 5-year survival rate for the most spread types of cancer during the recent 30 years as well as current 95% failure rate in clinical trials of anti-neoplastic medicines calls for biomimetic tumour models.

Tissue engineering, being initially focused on reconstruction of tissues and organs for reconstructive surgery, shows considerable promise for modelling cancer towards investigation of oncogenesis, invasion and metastasis.  Tissue engineering constructs (TECs) of tumours include tumour cells, 3D scaffold and “3rd components” (other cell types, signalling molecules, physical factors etc.), allow simulation of the tumour behaviour versus the microenvironment factors.  3D tumour TECs are scalable: from the miniature microfluidic “tumours-on-a-chip” to tissue- and organ-like structures.  The most advanced models require dynamic perfusion, physical and chemical modulators of the cultural environment, which can be realised in bioreactors.  In order to control the endpoints of the tumour TEC, its monitoring in real time is necessary, including sensing and imaging of TECs.

Possible streams of research in this field:

Development of biomimetic 3D tumour models (for the candidates with biomedical background);

Development of bioreactors for tumour tissue engineering (for the candidates with mathematical, physical and engineering/bioengineering background);

Development of the methods of controlling tumour TEC development (for the candidates with physical, optical, engineering/ bioengineering background or background in biochemistry, molecular biology).

Possible research themes:

Effects on dimensionality of microenvironments on tumour behaviour: changing the rules of play. Are the lessons learned from 2D experiments still working in 3D?

Factors involved into the regulation of tumour cell motility and invasiveness in 3D substrates; effects of the scaffold stiffness and geometry (cell-matrix interactions); effects of metabolic gradients; effect of hypoxia; effect of cell-cell interactions;

Factors involved in the regulation of tumour angiogenesis in 3D microenvironments;

Cancer stroma as a novel target for anti-tumour therapy;

Physical barriers of drug delivery in tumours;

Modelling of nanomaterials/ drugs/ contrast agents transport in 3D tumour TECs; role of perfusion and interstitial flows on tumour growth, progression, invasiveness and metastasis;

Development of bioreactors for 3D tumour modelling.

Contact: andrei.zvyagin@mq.edu.au for more information.

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