New heart-on-a-chip to speed drug testing
A fast method for manufacturing a heart-on-a-chip using a UV laser could pave the way for straightforward tests of how heart tissue reacts to new clinical drugs.
The platform, developed by researchers at Harvard University, uses a UV micropatterning method to create features on a gel 60 per cent faster than traditional moulding techniques. The study was published in the journal Biofabrication.
Co-lead author Dr Lisa Scudder said: ‘One of the major challenges in drug discovery and development is failure at the clinical testing stage due to cardiac toxicity. A way to overcome this is to develop new preclinical tests for new drugs using engineered tissues that mimic the native organs of the human body such as the heart.’
The heart-on-a-chip has to have tissue that is as contractile and organised as the human heart, so scientists can measure contractile force – a major determinant of heart pumping performance. The cardiac tissue and muscular thin films beat and contract in response to external stimuli like electrical pacing.
The chip is an extension of previous work, which established a platform using the miniaturised structural formation of cardiac muscle on a cantilever of hydrogel. The hydrogel has mechanical properties that are similar to the extracellular matrix of the heart. This pre-patterned substrate results in an organised growth of cardiac muscle. The end goal is to put these tissue structures into a microfluidic environment where the flow of a drug being tested can be regulated and monitored.
However, for these chips to become a tool for drug development and biomedical research in industry, they need to be manufactured on a large-scale, as opposed to the small batch manufacture used in academic research.
Dr Scudder said: ‘The existing way of engineering cardiac tissues involves using photomasks, stamping, and manually moulding gelatine to create patterns in the hydrogel for tissue alignment, but this was taking too long and was not practical for our chip manufacturing needs.
‘Our new heart-on-a-chip fabrication method uses a UV laser to pattern the hydrogel, employing riboflavin to sensitise the gel for optical ablation. This patterning method then allows the cardiac cells to align into organised laminar tissue structures like in the native heart. The UV micropatterning method creates features on the gel much faster, but with the same resolution and reproducibility, as traditional moulding techniques.’
The process is scalable, gives great uniformity, doesn’t alter the properties of the hydrogel, and is up to 60 per cent faster than the old process.
‘It is another step towards the mass production of organs on a chip, which is essential if large pharmaceutical companies are going to accept and utilise them,’ commented co-lead author Dr Janna Nawroth.
Dr Scudder added: ‘This method could be useful for manufacturing other organs-on-a-chip, such as a brain or skeletal muscle-on-a-chip. In the future, we hope to expand on this fabrication method to mimic disease states like fibrosis, or to create more complex three-dimensional tissue structures that could provide new tools for the preclinical drug development process.’