“Cardiac failure is a critical condition that results in life-threatening consequences. Due to a limited number of organ donors, tissue engineering has emerged to generate functional tissue constructs and provide an alternative means to repair and regenerate damaged heart tissues.”
Such is the sentiment from Ali Khademhosseini and a team from Massachusetts. In fact, they reported here, that in 2009 an average of 77 U.S. citizens underwent transplant each day, but 20 died as a result of a lack of organ availability. The aim, then, in the absence of treatment, is to repair the damaged organ in-situ so as to negate the need for transplant at all.
Hydrogels are already used in the regeneration of a variety of tissues, and combined with some of the brightest minds in the field significant advances are being made in regenerative medicine: in May this year a team in Toronto have successfully repaired brain tissue after stroke and partially reversed blindness. These versatile substances are also used in disposable nappies, silica gel and contact lenses, so there’s a high chance you’ve already been exposed to them without even knowing it!
These polymers exhibit many desirable characteristics in regenerative medicine. They are relatively easy to synthesise, they can act as solute transports/drug-delivery systems, exhibit elastic properties as well as preventing thrombosis. Their structure also enables them to create a “scaffolding” for cells.
This last point is crucial when combined with the hydrogel’s other properties, but I’ll return to that shortly.
First, consider what happens to cardiac tissue after an acute myocardial infarction: during infarct, the oxygen supply to myocardial cells is reduced or diminished, causing irreversible cell death and necrosis around the occluded artery/arteries. The scar tissue that takes the place of the once-functioning cardiac muscle has none of its contractility and the heart is far less efficient as it once was. Cardiac output, systolic and diastolic functions are affected and whilst medication, reperfusion techniques a bit of luck regarding preserved left ventricle function all provide a better prognosis, heart failure is a serious risk and figures regarding mortality rates aren’t great: MI, specifically STEMI brings with it a 30% mortality rate, 50% of this figure dying before hospital admittance and 10-15% being re-hospitalised one year after the index event.
So, where do hydrogels come into the picture?
In the case of extreme loss of cardiac function and the inability of conventional treatment to improve the given prognosis, hydrogels provide an environment in which it is possible to introduce stem cells, growth factor, gene injection or therapeutic medication in an ‘artificial’ environment that simultaneously provides mechanical support to the infarcted area and aids in the replacement of necrotic tissue. As well as being a relatively non-invasive procedure when it comes to the injection of the treatment, the hydrogels scaffold itself is naturally degraded by the body when the process is complete.
According to another team in Massachusetts, published here, trials have shown significant success since they began in small animals, but their application isn’t as straightforward in large primates. They commenced in humans in 2008 (in an extremely truncated form), but in order for hydrogels to be viable in widespread clinical treatment, much more research is required. An example of this is that not much is known about the exchange of signals that take part in the movement of stem cells to an injured myocardial tissue post-hydrogel treatment. Optimum degradation time is a further issue in humans.
Despite these, and other setbacks, there remains great promise in hydrogels to lower global mortality rates as a result of MI. In recent years, significant advances in research are making the possibility of myocardial repair in humans an almost visible reality.