Thousands of people need to have new heart valves fitted every year. When they are available and the body accepts them, human or animal transplants are used. Where this is not the case, synthetic products manufactured by medical engineering companies are chosen instead. Plastics play a major role in the latter case. Scientists have now developed a new kind of artificial heart valve with the help of what is known as the electrospinning process. The new plastic-based heart valve is for the first time capable of growing with the patient.
There is no greater proof of life for us human beings than the heartbeat. Embryos already have a heartbeat when they are four weeks old and only five millimetres long. Driven by electrical impulses, the heart that is about the size of a fist in an adult of average fitness pumps blood through our body incessantly – 70 times a minute, 4,200 times an hour, 100,800 times a day, 36,792,00 times a year. When we are exerting ourselves and sometimes when we are resting too, we feel our heart throbbing and pounding. In many respects, our heartbeat is the most important indication of our vitality and creativity as human beings, while it is confirmation that life has come to an end when it stops beating.
Most frequent cause of death
Cardiovascular diseases are the most frequent causes of death, at least in people living in the industrialised world. Circulatory disorders of the cardiac muscle due to the narrowing of the blood vessels (stenosis) that occurs as a result of arteriosclerosis because of deposits in the arteries play the most important role here. The consequence of narrowed or clogged arteries is that the heart, which is by nature a muscle, does not receive sufficient oxygen, which can lead in the course of time to death of the muscle tissue and thus of the patient.
Second on the list of causes of death due to the heart is the heart attack, which is triggered, for example, by a blood clot that clogs the blood vessel and stops the blood flowing completely. In third place is heart failure, which can be congenital and is associated with insufficient heart pumping capacity.
The heart is a hollow muscle that operates like a pump. It keeps the blood circulation system going with its contractions, as a result of which all body tissues are supplied with oxygen and necessary nutrients. During the pumping process, blood is forced out of the heart into the vascular system. When the heart muscle relaxes, new blood flows in. A septum divides the heart up into a left half and a right half, which consist in turn of a left and right atrium and a left and right ventricle. The atriums and the ventricles are connected by heart valves. The purpose of the heart valves is to make sure that no blood flows in the wrong direction, which can have dramatic consequences. The blood flows into the ventricles from the atriums and then flows on via heart valves into the blood vessels that take it away.
On closer examination, it becomes clear that the four heart valves really do act as valves; they regulate the direction of blood flow. Congenital heart defects, degenerative changes as one gets older or inflammation can, however, have an impact on the heart valves and stop them working properly. It is not unusual for functional disorders to lead to heart failure or other serious heart diseases.
An operation is often the only cure
Heart valve disorders can occur at any age and an operation is frequently the only cure. Whereas it is possible to eliminate the heart valve problem suffered by some patients without replacing the natural heart valve, most patients require the heart valve to be removed and replaced by a different one. Thousands of people all over the world now live with redesigned, implanted human, animal or artificial heart valves.
Children can have heart valve defects too. Due to the growth process that young people go through, several operations are normally needed in order to adapt the size of the implant to the size of the heart. Every operation proves to be a burden on and risk for the patient, however.
Artificial heart valve based on the way nature works
Dr. Svenja Hinderer. (Image: Körber-Stiftung/David Ausserhofer).
Svenja Hinderer, a former member of the staff of the Institute of Interfacial Process Engineering and Plasma Technology at Stuttgart University in Germany, started to search for a synthetic implant that is able to grow with the heart. Her objective was to develop a material that was a suitable replacement for the valve and provided the human body cells with as physiological an environment as possible to grow. In this context, the chemist focussed in particular and primarily on the connective tissue that gives structure and support and, among other things, carries out an important function in the settlement of functional body cells.
The functionality of an implant and its ability to grow depend above all on one fundamental factor: body cells have to be able to accept it as quasi-endogenous body tissue and literally populate it comprehensively in all spatial directions. At least in the case of heart valves, which are in constant motion, it also requires a certain amount of flexibility and strength combined at the same time with a precise, tightly closing fit. Svenja Hinderer found a solution in the course of her doctorate.
Biocompatible polymer blend that is suitable for heart valves
The scientist identified appropriate polymer material in a blend of polyethylene glycol (PEG) and polylactic acid (polylactide, PLA).
Depending on the chain length, polyethylene glycol is a liquid or solid, chemically inert, water-soluble and non-toxic polymer that can be modified and therefore allows itself to be crosslinked under the influence of UV light too. Due to its properties, it is used frequently in medicine, in pharmacy, in industrial applications, in cell biology research and in cosmetic products.
Polylactic acid can be obtained and synthesised from milk and is one of the polyesters from which formable plastics (thermoplastics) can be produced under the influence of heat. PLA is biocompatible, i.e. this polymer is in the broadest sense tolerated well by the living organism.
Spinning in an electrical field
Svenja Hinderer used the electrospinning method to process the polymer blend into a sufficiently permeable synthetic support tissue in the shape of a heart valve.
Electrospinning involves the production of what are generally very thin fibres from polymer solutions via treatment in an electrical field. The polymer solution is applied to an electrode in an electrical field and is stretched and accelerated by the other electrode. In the course of this operation, a complex process is carried out, during which the polymer blend is split up into fine and extremely fine fibres and webs that are deposited on the second electrode as a non-woven fabric. The diameter of the final fibres is less than 1,000 nanometres on average. A human hair is about 80,000 nanometres thick.
Optimisation of the material properties
Svenja Hinderer reports that she included proteoglycanes – which, among other things, determine the water storage capacity of the heart valve tissue – in the spinning process, in order to make the properties of the material even more similar to those of natural heart valves. The scientist explains that it was important to make sure that the sensitive proteins, which settle on the transplant, do not lose their function. At the end of her tests, Svenja Hinderer succeeded in producing a structure that was very similar in its morphology to the natural, extra-cellular matrix of the heart valve.
In a bioreactor, which pumps water through the valves – like the heart pumps blood – the chemist simulated the physiological pressure exerted by the heart – with satisfactory results: the material passed the test. The bioreactor simulation apparently documented in an impressive way how the material took over the opening and closing function as a heart valve substitute.
A next test was carried out in a bioreactor developed by an engineering student in her team, in which she managed to cultivate the electrospun material together with human cells. Svenja Hinderer: “Due to the mechanical stimulation in the reactor – which was modelled on the situation in the human organism – the cells started to form elastic fibres after only six days.” The tissue created in the bioreactor had the same structures as an embryonal heart valve that develops naturally.
Promising results demand further research
Elastic fibres give tissues like skin, blood vessels or – in this case – heart valves their resistance and elasticity. Once they are destroyed, the human organism is not able to regenerate or replace them itself. They are only formed during the embyonal development phase and in the first years after birth. The artificial heart valve based on the way nature works that has been developed by Dr Svenja Hinderer can help to eliminate irreversible damage effectively:
The polymer-based substrate, which is stable and at the same time elastic, is biocompatible and sterilisable – and is therefore eminently suitable for medical applications. The aim is now “to develop a cell-free medical product that is not settled by cells until after it has been implanted in the patient”. To achieve this aim, Hinderer – who has headed the “biomaterials, bioreactors and bioimaging” group at the Fraunhofer Institute for Interfacial Engineering and Biotechnology (IGB) since July 2015 – is researching how the substrates can be modified with further specific proteins, in order to attract stem cells specifically.
Further plan: while the cells settle on the material and form a new heart valve with their own matrix, the basic polymer structure is supposed to degrade later on in the body. As a result, it has the potential to grow as the child’s heart grows. However, until this stage has been reached, the artificial heart valve will have to prove its effectiveness initially at the animal level in pigs.