June 2017 | Issue 30


Academia's role in innovations in medicine





By Nicole Lim, Assistant Director, Communications & External Relations

Until the late 1970s, open chest surgery was the only way to treat a blocked coronary artery. Thanks to a series of mind-boggling engineering innovations – from balloon angioplasty to stents – treatment for blocked arteries has improved in leaps and bounds.
The first improvement was to obviate the need for open chest surgery which came with balloon angioplasty, a procedure where doctors guide a deflated balloon from an incision in a peripheral artery into the arterial branch where blood flow is restricted by plaque. The balloon is inflated and crushes the plaque against the arterial walls. Next came stents. These tubes of biocompatible metal mesh are expanded at the blocked site, where they lock into place and hold the artery open.
Yet each of these advances came at a price. Renewed build-up of plaque over time (restenosis) has been a significant issue, and newer drug-eluting stents put patients at risk of life-threatening blood clots (thrombosis).
What was needed was an innovation in material and design for a next-generation solution. This is when NTU Materials Science & Engineering Chair Professor Subbu Venkatraman became interested. Delivering his ‘Innovations in Medicine’ Lecture at the Clinical Sciences Building Learning Studio on 27 April, the serial innovator and entrepreneur gave LKCMedicine Year 1 and 2 students a glimpse into the world of medical innovation, its opportunities and pitfalls from his own wide-ranging experience.
Making stents safer

Following talks with local clinicians about what was needed for the perfect stent, Prof Subbu and his team compiled a list of requirements for this new device. It had to dissolve eventually yet be mechanically strong for six to nine months. And, most importantly for the clinicians, it had to be made of a material that could be crimped, so that the device could be deployed like existing metal stents via an artery, and once in place remain strong and open, said Prof Subbu.
Even with demand for biodegradable stents growing, there was little interest from industry in developing this new device as it was deemed too great a risk.
Finding the right material to create a safe and biodegradable stent was one challenge. The other, Prof Subbu noted, was to translate it into a tested and useable device that would improve patient care.
The material they chose was polylactic acid, a reasonably strong polyester derived from starch which degrades into easily-absorbable lactic acid. But unlike metals, cutting out the intricate meshed pattern on polylactic acid was challenging as the standard carbon-dioxide laser proved too blunt an instrument.
"We had to resort to femtosecond lasers to cut these intricate patterns, which was not trivial,” said Prof Subbu.
Being located next to the SIMTech-NTU Joint Lab proved fortuitous as the lab was one of the few places to have the necessary equipment and skills to support the project and create a prototype.
While academic funding and publications got the team this far, moving from innovation to entrepreneurship meant finding investors who would be willing to take a risk.
However, at the time, Singapore venture capitalists had a conservative outlook, with many looking to reap the rewards of their investments within three years.
It took a US-based venture capitalist to keep the project going. With that company’s interest secured, other organisations including the Economic Development Board stepped forward.
After overcoming all these challenges, the financial crisis of 2008 nearly put an end to the project, but the team managed to see the novel stent start human trials and Boston Scientific has come on board to complete the trials required for US Food & Drug Administration (FDA) licensing.
Concluding his account, Prof Subbu said, “We are now in the age of fully degradable drug-eluting stents. The name of the game nowadays is to reduce the strut thickness that defines the profile of the stent or its resistance to the flow of blood in the arteries.”
Golden opportunity for academic innovation

Far from being a one-off success, Prof Subbu highlighted that there are many areas of real need where academia can play a pivotal role. These are areas where the need is great but there is a dearth of human expertise and where industry has failed to make in-roads, such as biodegradable stents or nanomedicines.
“Industry has tried to develop for years a pill that will deliver insulin and it has not been successful. That is something we should tackle. What I mean by tackling is to develop solutions and try to get efficacy proved in humans as quickly as possible, preferably with academic funding,” said Prof Subbu, who has never been one to confine himself to one problem, material or method, and has also brought an extended-release drug-delivery nanomedicine solution into human trials.
With many university patents sitting idly on shelves, academia is sitting on a potential treasure trove.
Concluding his talk, Prof Subbu said, “I think the university has to step in and address some of these ​problems and take them to the next step.”