Biomaterials for Artificial Organs

Michael Lysaght,Thomas J Webster

• Publisher: Woodhead Publishing
• Year: 2010
• ISBN:
  9780857090843
• Topic: Technologie et ingénierie
• Subtopic: Science des matériaux

The worldwide demand for organ transplants far exceeds available donor organs. Consequently some patients die whilst waiting for a transplant. Synthetic alternatives are therefore imperative to improve the quality of, and in some cases, save people's lives. Advances in biomaterials have generated a range of materials and devices for use either outside the body or through implantation to replace or assist functions which may have been lost through disease or injury. Biomaterials for artificial organs reviews the latest developments in biomaterials and investigates how they can be used to improve the quality and efficiency of artificial organs.Part one discusses commodity biomaterials including membranes for oxygenators and plasmafilters, titanium and cobalt chromium alloys for hips and knees, polymeric joint-bearing surfaces for total joint replacements, biomaterials for pacemakers, defibrillators and neurostimulators and mechanical and bioprosthetic heart valves. Part two goes on to investigate advanced and next generation biomaterials including small intestinal submucosa and other decullarized matrix biomaterials for tissue repair, new ceramics and composites for joint replacement surgery, biomaterials for improving the blood and tissue compatibility of total artificial hearts (TAH) and ventricular assist devices (VAD), nanostructured biomaterials for artificial tissues and organs and matrices for tissue engineering and regenerative medicine.With its distinguished editors and international team of contributors Biomaterials for artificial organs is an invaluable resource to researchers, scientists and academics concerned with the advancement of artificial organs.

• Reviews the latest developments in biomaterials and investigates how they can be used to improve the quality and efficiency of artificial organs
• Discusses commodity biomaterials including membranes for oxygenators and cobalt chromium alloys for hips and knees and polymeric joint-bearing surfaces for total joint replacements
• Further biomaterials utilised in pacemakers, defibrillators, neurostimulators and mechanical and bioprosthetic heart valve are also explored

Part I

Commodity biomaterials

1

Membranes for oxygenators and plasma filters

S. Breiter, Membrana GmbH, Germany

Abstract:

Membranes used for blood oxygenation and blood plasma separation represent well-proven applications as artificial organs. Although the absolute consumption is much less compared with dialysis membranes, their relevance for medical devices and healthcare around the world does not hide behind the big brother. This chapter illustrates the cornerstones for production and application of these products. Blood oxygenation membranes produced by different methods, both symmetrical and asymmetrical, are discussed first. The second part describes hydrophobic and hydrophilic synthetic blood plasma separation membranes. For both types of membranes, membrane make-up and medical device implications are considered.

Key words

blood oxygenation

plasma separation

TIPS

SIPS

membrane structure

membrane manufacture

artificial lung

apheresis

1.1 Introduction

Over one million patients per year undergo cardiac surgery with the aid of the heart–lung machine. This life-saving procedure on the organ, which is said to be the centre of life, love and desire, often takes less than an hour, although difficult cases may extend to six or even ten hours. While the cardiac surgeon performs the operation, a pump keeps the blood flowing and membranes inside an oxygenator take over from the lungs in that they add oxygen and remove carbon dioxide from the blood.

In tens of thousands of cases of sepsis or severe lung trauma, the lung needs assistance or rest for a few days. A similar setting as for cardiac surgery may then release the stressed organs for several days. In such cases, membrane lungs have worked in clinics for more than four weeks.

A great number of diseases can be alleviated by removing the harmful substances from blood that cause clogging of arteries, recurring or even persisting inflammation or overshooting immune response. Often the removal of these substances would damage blood cells; therefore cells and blood plasma are separated and the plasma is then cleaned vigorously. The procedure that does this separation with the least stress for the blood cells is plasma separation with membranes.

Over the years, tens of millions of lives have been saved and many more have been eased with the help of membranes for blood oxygenation and plasma separation. While cardiac surgery today is an established procedure, where improvements over generations have built a gold standard, long-term lung assistance and plasma separation and plasma treatment are rather in their infancy. It is still a matter of debate how to achieve the best results, who should perform the procedures, which patients can effectively and efficiently be treated and last, but not least, who will pay for these procedures.

Membranes as biomaterials form the basis for the procedures of lung substitution and plasma separation. These membranes are readily available and look very simple: white capillaries, wound to bundles or finished with rather basic textile technologies. But it is not as simple as that: they represent the highest standards of biomedical technology.

1.2 Membranes for blood oxygenation

1.2.1 History

To perform delicate surgery on the human heart, for many interventions it is essential to stop the heart beating (e.g. for any surgery on the heart valves), and for all procedures the stoppage greatly facilitates the work of the surgeon. The heart with its four chambers pumps the blood through body and brain, which consume oxygen and produce carbon dioxide, and through the lungs simultaneously, where carbon dioxide is exhaled and oxygen taken up. If during a cardiac surgery procedure the heart is still then the lungs are also at rest. This means that the blood not only needs to be pumped through body and brain to continue their supply, but also needs to be oxygenated artificially. Therefore, for any cardiac surgery procedure where the heart is stopped, a device to oxygenate the blood and to remove the carbon dioxide is also needed.

A good overview of the development of the blood oxygenator is given by Leonard.¹ The first heart–lung machines have worked with film or bubble oxygenators.^2,3 In film oxygenators, blood was passed over sieves, plates or discs in pure oxygen or an oxygen-rich atmosphere. Oxygen and carbon dioxide were exchanged on this large surface. The second generation of oxygenators, bubble oxygenators, simply consisted of a bubble chamber where oxygen was dispersed into the patient’s blood and a defoamer which removed the majority of gaseous residuals from the blood. Both procedures were a major insult to the patient and their blood, and therefore a more gentle procedure had to be found.

In the 1940s, Kolff observed that the blood in his rotating drum kidneys turned to a brighter red during treatment. This was simply due to take up of oxygen through the cellophane membrane he used to separate the blood from the dialysis solution, which was exposed not only to the dialysate, but also to the open air. In a way, the first clinical application of an artificial kidney also was the first application of a membrane artificial lung. From this starting point, Kolff et al. developed a membrane oxygenator, the first clinical application of which was described in 1956⁴.

The first membrane oxygenators incorporated various membrane materials, among them cellophane, polyethylene (PE) and Teflon, all of which were comparatively impermeable to oxygen. In the 1960s, the first oxygenators with silicone membranes were developed.⁵ For these, thin films of polysiloxane (silicone) were supported by meshes or sieves, then wrapped to a roll or stacked to a pile to incorporate sufficient surface in a volume that could still be handled. Those oxygenators had large priming volumes and large surfaces and consequently resulted in considerable blood dilution and blood damage.

In the 1980s, the first oxygenators with microporous membrane sheets were produced. The preferred material for microporous membranes in blood oxygenation was and remains polypropylene (PP).⁶ Owing to the presence of pores, the permeability of these membranes to oxygen was much higher than that of any other material before, so that the limiting factor for gas transfer was no longer the membrane, but the gas transport within the blood films directly adjacent to the membrane (see also page 10).

The next breakthrough in oxygenator performance was the introduction of capillary membranes. Those had the same pore size and same polymer (PP) as the flat sheet microporous membranes introduced. Similar to the development with haemodialysers, the introduction of capillary membranes reduced the priming volume of the oxygenator and turned a bulky space consumer into a handy device. The first capillary membrane oxygenators worked with blood flow inside the capillaries, but soon the trend to blood flow outside the capillaries prevailed: blood side pressure drop always used to be a limiting factor for ‘blood inside’ oxygenators, and the ‘blood outside’ models were smaller and more handy, and demanded less priming and thus less haemodilution. Finally, this was also welcomed from the manufacturer’s perspective, as it saves about half the amount of membrane.

These microporous membranes provide excellent performance, but compared with the older silicone membranes are more prone to plasma breakthrough. Around the year 2000, the first oxygenators with a membrane from polymethyl-pentene (PMP) with a very thin dense outer skin on a microporous body were introduced. These provide performance on the same level as the microporous PP membranes, but do not show the phenomenon of plasma breakthrough.

Today, almost all commercially available blood oxygenators incorporate capillary membranes and have the blood flow outside and the gas flow inside the capillaries. Most of the oxygenators have microporous membranes of PP, and a growing share is equipped with the dense PMP membrane type. Only one silicone membrane oxygenator is still commercially available.

1.2.2 Material, polymer and technical requirements

Gas transfer

Membranes for blood oxygenation need to provide sufficient gas exchange and at the same time prevent any mixing of blood and gas (oxygen or oxygen-enriched air). The driving force for the gas transport across the membrane wall is the difference in chemical potential of the gas ...