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Silk scaffolds simulate live tumour model

15 Aug 2013

The team (from left): Assoc Prof Nathan, Prof Goh, Dr Tan and Assoc Prof Toh

The realistic 3-D tumour is constructed using silk scaffolds in a pressurised bioreactor
Current drug testing methods for cancer in the laboratory traditionally use two-dimensional (2-D) cell culture systems which cannot replicate the three-dimensional (3-D) properties of the tumour tissue. Results can differ greatly from animal testing, thus the approach is not ideal for drug development.

NUS researchers from the Departments of Bioengineering and Orthopaedic Surgery have created a highly realistic 3-D tumour model that simulates the conditions in the body, to track the effectiveness and progress of drug therapy. The model holds promise for a better approach to study tumours than laboratory methods or experimentation with live animals.

Professor James Goh, Associate Professor Toh Siew Lok and Dr Pamela Tan from the Department of Bioengineering, together with Associate Professor Saminathan Suresh Nathan from the Department of Orthopaedic, conducted their investigation using osteosarcoma, the most common form of bone cancer in children.

Dr Tan noted that little progress has been made in cancer drug therapeutics due to the lack of good pre-clinical drug testing models. The team’s 3-D tumour model gives results closer to those obtained from studies in living tissue, as compared to 2-D studies in the laboratory. When chemotherapeutic drugs were tested on the 3-D tumour construct, their effectiveness in killing cancer cells was greatly reduced, compared to testing the same drugs using the standard 2-D system.

Moreover, the therapeutic doses found using the 3-D tumour framework was within those measured in mice, suggesting that the construct can help bridge the gap between laboratory and animal testing to improve the yield and quality of chemotherapeutic drug screening.

“Our model also makes it possible to study how tumour cells interact with cells of the surrounding tissue, which results in more aggressive tumour behaviour,” Dr Tan added.

The realistic 3-D tumour constructed using 5 mm-wide silk scaffolds in a pressurised bioreactor is the first of its kind. It is able to express markers that indicate the ability of a tumour to initiate blood vessel growth at levels almost identical to that of the mouse model. It also responded to drugs that prevent blood vessel formation in cancer, in a way similar to that observed clinically.

Prof Goh said that the team tapped on tissue engineering techniques to fabricate the 3-D tumour model and reconstructed the tumour tissue into factors and cell types to form a clinically relevant tumour. Silk was chosen to build the scaffolds onto which the osteosarcoma cells were grown because the material has shown ideal properties for cell attachment and growth.

The concept of the tumour microenvironment has been developed over the last 10 years. The group is planning to file a patent for the innovation.

Assoc Prof Nathan revealed that the work will be extended to other cancers and various aspects of the tumour microenvironment such as oxygen levels within the system to create a platform for testing. This could save time and efforts in the application of experimental drugs.