The material science of aortic disease
Biomaterials are improving aortic disease surgery, but current materials still have their limitations. Dr Riaz Akhtar of the School of Engineering, University of Liverpool, UK, discusses progress.
The aorta is the largest conduit for blood flow in the human body, exiting the heart and passing through the chest to the abdomen. It is divided by the diaphragm into the thoracic and abdominal aorta and carries around 200 million litres of blood to the body in a typical lifetime. The aorta not only has a role as a conduit, but also helps to regulate heart rate through a change in aortic pressure.
Structurally, the aorta has a layered, composite structure dominated by two structural proteins – collagen and elastin. These proteins are the primary load-bearing components of the aorta. Collagen has a triple helix, rope-like structure and provides tensile strength to the aorta as well as other tissues in the body. Isolated collagen fibres have an elastic modulus of around 1GPa, maximum strain of 10-20% and maximum strength of 70-150MPa.
In contrast, elastin is a rubber-like protein which forms a 3D amorphous network. Elastin has an elastic modulus of around 1MPa and can undergo over 200% strain. Together these proteins allow the aorta to withstand fluctuations associated with the cardiac cycle and handle high-pressure blood. The elastin provides reversible extensibility during the cyclic loading of the cardiac cycle, while collagen provides tensile strength and enables the vessel to withstand high pressures.
Into the structure
Elastin is organised in the form of fibres, known as elastic fibres which dominate the aorta microstructure and are present as an interconnected network. These elastic fibres in the aorta may undergo billions of loading cycles in a typical human lifetime. Unlike many other proteins in the human body, the turnover rate of elastin is close to zero. Hence, materials failure issues, such as fatigue, damage accumulation and fracture, parallel those seen in engineering materials.
The compliance of the aorta, critical to its normal function, is affected with elastic fibre fragmentation which occurs as part of the natural ageing process. Over time, the compliant and rubber-like elastin is replaced with stiffer material, affecting the performance of the cardiovascular system. In March 2011, my colleagues and I presented on the complex microstructural and mechanical properties of the aorta in the context of the natural ageing process, along with the techniques that can be used to measure the mechanical properties at different length scales.
In vivo, a technique known as aortic pulse wave velocity (PWV) can be used to measure arterial stiffness. PWV is based on the relationship between the wave speed of blood and stiffness of the aorta. In vitro characterisation of the aorta is conducted with a range of techniques including tensile, biaxial and nanoindentation techniques, often utilising biopsy samples.
A decline in the microstructure of the aorta, along with a change in mechanical properties, occurs with advancing age in humans. However, some individuals can be afflicted by other, potentially fatal, aortic diseases that affect the structural integrity of the aorta. One such condition is an aortic aneurysm. An aneurysm occurs when there is a local bulge in the aorta that can potentially rupture due to longitudinal splitting of the aortic wall, resulting in life-threatening bleeding. An aneurysm can essentially be described as tensile instability.
Heart of the matter
The Global Burden of Disease 2015 study reports that there were an estimated 168,200 deaths worldwide due to aortic aneurysms in 2013. Statistics from the British Heart Foundation suggest that ruptured aortic aneurysms cause around 5,000 deaths in the UK each year. If a rupture occurs, it is fatal in 80% of cases. The problem of aortic aneurysms is rising with the increase in the global ageing population.
Aneurysms can be classified according to their location – abdominal aortic aneurysms mostly occur in individuals over 65 years old. In contrast, ascending aortic aneurysms - where the aorta is closer to the heart – typically affect the young and their cause can often be related to underlying genetic conditions. They are much more difficult to detect as compared with abdominal aortic aneurysms and as a result, they are often misdiagnosed.
As a result, ascending aortic aneurysms are sometimes misdiagnosed and statistical data are not as readily available as for other conditions. A related condition that often accompanies these aneurysms is aortic dissection. A dissection is when a tear occurs in the inner lining of the aortic wall which then splits longitudinally resulting in a ‘flap’. This means that the interior space of the blood vessel through which blood flows (the lumen) becomes separated by the flap, resulting in an artificial channel known as the false lumen. In this artificial channel, blood is actually flowing through the layers of the aortic wall.
The flow of blood is, therefore, occurring in two channels, in a true and false lumen. If left untreated, the weakened aortic wall can cause the false lumen to expand and eventually rupture. A challenge for vascular surgeons is that thoracic aortic aneurysms and dissections can often be difficult to diagnose and are sometimes referred to as a silent killer. Both fluid and solid mechanics methods have been used to better understand aortic dissections and thereby improve patient treatment and management. Fracture mechanics approaches, common in materials science, can be applied to quantify the tissue resistance to dissection, by measuring the critical energy release rate following initiation of a tear in the tissue wall.
Biomaterials for aortic root repair
A range of different operations can be conducted by vascular surgeons to repair the diseased segment of the aorta, depending on the anatomical location of the aneurysm or dissection. If the aneurysm is at the aortic root, the first part of the aorta where it exits the heart, surgery is carried out to prevent a dissection. Synthetic grafts, typically fabricated from expanded poly(ethylene terephthalate), are successful and widely used for repair of the aortic root. The diseased portion of the tissue is removed and replaced with the graft material, and this can be incorporated with a mechanical heart valve – total root replacement – or with the use of a graft but without loss of the patient’s natural heart valve – valve sparing root replacement.
These approaches have been successfully and widely used for aortic repair. A newer concept that has emerged over the past decade or so is personalised external aortic root support (PEARS). The PEARS approach utilises MRI or CT images of the patient’s aorta to create a CAD model. Rapid prototyping (3D printing) is then used to make a replica of the patient’s aorta. A customised macroporous fabric sleeve is then fabricated which can be placed around the aorta. The patient’s aortic tissue remains entirely intact and the sleeve provides mechanical support to the diseased segment of the aorta and prevents further expansion or rupture.
The origin of PEARS comes from an inspirational story from a patient, Tal Golesworthy, with an engineering background who himself faced a dangerous expansion of his aortic root, but did not wish to undergo a lengthy surgical procedure which would remove his native tissue. His collaboration with a multi-disciplinary team including surgeons and engineers led on to the invention of the ExoVasc PEARS device. A TEDx talk delivered by Mr Golesworthy in 2011, titled How I repaired my own heart, has had over 1.3 million views and highlights the journey from concept to medical device.
A fundamental challenge with biomaterials is mechanical mismatch with native tissue. Despite synthetic grafts being widely used and with success for repair and replacement of aortic tissue, there still remain challenges. As has been reported in past works, there is a compliance mismatchonce the ascending regions of the aorta are replaced with prosthetic grafts.
Researchers, led by Golden Jubilee National Hospital, Glasgow, Cardiothoracic Surgeon Cristiano Spadaccio concluded that despite the significant benefit for patients worldwide since the introduction of synthetic grafts, there can be detrimental effects on the normal cardiovascular function with loss of the native elastomechanical properties of the aorta. This is because of loss of the unique properties of elastin. They report that native blood vessels have around four times more compliance than that of synthetic grafts.
But the rapid and encouraging growth of tissue engineering and biomaterials should see the development of innovative new materials that address these issues in the near future and therefore improve the quality of life for patients.