Biomaterials for heart repair

13.7 Biomaterials for heart repair

13.7.1 Heart valves

Heart disease is one of the major killers in the devel-

(a)

oped world. Many of the serious conditions arise from the strain imposed on the heart by obstructions to the flow of blood either in the main passages of the cir- culatory system or as a result of valvular disease. The heart acts as a blood pump with four valves which open in response to a unidirectional flow of blood. Two of the valves allow the blood into the heart and the other two control the blood leaving the heart. Problems can arise with the heart valves if they become structurally damaged by disease affecting the opening and closing mechanisms.

The early prostheses developed in the 1960s for valve replacement were based on a stainless steel ball- in-cage or polysiloxane ball in a Co–Cr alloy cage (see Figure 13.9). These restrict the blood flow, even

in the open position, and were superseded by a tilt- (b) ing disc device which opens and closes to the beat

of the heart to allow the required blood flow. The Figure 13.9 Photographs of replacement heart valves: (a) ball in a cage type (courtesy Institute of Materials, major problem with valves arose from the tendency

London), and (b) pyrolitic carbon disc type (courtesy P. to initiate a blood clot and thus it was found necessary

Marquis, Dental School, Birmingham) .

Biomaterials 403

a reduced risk of thrombosis. Unfortunately two prob- it is necessary to use artificial arteries made from poly- lems have hindered this development. The first is that

mers; such arteries must be tough and flexible enough the collagen valve material suffers from slow calcifi-

to avoid kinking, with the added requirement of avoid- cation whereby hard deposits form on the surface of

ing the formation of blood clots. In modern surgery, the valves causing them to stick and tear. The use of

the blood clotting tendency can be removed by anti- anticalcification drugs are a possibility but the second

coagulants, such as heparin, but the ultimate goal is to problem has thrown the whole area of implant surgery

provide artificial arteries with natural clot resistance. using animal tissue in doubt. This problem is the emer-

Several different polymers have been used to make gence of BSE (mad cow disease) in cattle, which has

blood vessels but none is entirely satisfactory. led to restrictions and worries in the use of animal tis-

The polyester Dacron, can make small tubes but sue for reconstructive implant surgery because of the

these have porous walls which have to be sealed. This fear of transmission of viral illness from animal tissue

is achieved by treating with the protein albumin and to humans.

heating it to form a coagulated coating. In the body, the albumin degrades and is replaced by the natural protein

collagen forming a smooth lining (pseudointima). This Other developments in improving heart performance

13.7.2 Pacemakers

process leads to some initial inflammation which is include the use of cardiac pacemakers which produces

one disadvantage of this biomaterial. Woven Dacron

a 5V electrical impulse for 1/500 second at regular is quite rigid and unsuitable for small arteries and is heartbeat rate. These devices have been available for

difficult to suture; it is mostly used for resected aortic some time but have improved significantly over recent

aneurysms. Knitted Dacron is easier to suture. It may years. The basic requirement is to provide electrical

be coated with polyurethane, tetrafluoroethylene, or signals to the heart at the appropriate level to stim-

heparin to reduce the thrombogenic tendency. The use ulate the patient’s own electrical activity to produce

of poly(hydroxyethyl methacrylate) coating establishes the proper physiological change, normally linking the

an endothelial-like cell layer in a few weeks. pacemaker into the cardiac system so that it works

Other arterial polymers include PTFE and polyure- when needed. The biomaterial aspects of the pace-

thanes. PTFE is used as an expanded foam to form maker are, however, also important, not only in over-

the porous tubes. These rapidly develop a smooth coming the problems introduced by any device/body

neointima layer and thus acquire blood compatibility. environmental interaction, but also in designing the

Polyurethanes have a natural compatibility with proper electrical supply and insulation. Power sup-

blood and are tough and flexible in tube form but plies have advanced considerably in the last few years

unfortunately slowly degrade in the body producing and lithium cells are now exclusively used. Titanium

toxic products. PTFE coatings on polyester and is again the most common biomaterial to encase the

polyurethane vessels have also been tried. Silicone- device, manufactured and electron beam welded to seal

lined tubing has been used for extra-corporeal it hermetically. Polymers have been used for encapsu-

circulation during open-heart surgery. lation, e.g. epoxy resin or silicone rubber but these

To produce artificial arteries with built-in clot resis- materials do not completely prevent moisture from

tance, heparin molecules have been attached to their entering the pacemaker and shortening the lifetime

surface either directly by chemical bonds or by cross- of the device. These have now been superseded by

linking to form a polymerized heparin film. To mimic titanium alloys because of their better strength and

total thrombosis resistance, however, requires not only environmental properties. These are sutured into the

anticoagulation but also avoidance of platelet deposi- aorta with a Dacron sleeve.

tion normally achieved by the endothelial cells lining Another problem area is that provided by the elec-

the blood vessel releasing the protein prostacyclin. trodes which have to flex with every heartbeat and

Ideal artificial arteries should have both of these anti- hence are liable to fatigue failure (see Chapter 7).

clotting agents attached at their surface. Good design and choice of electrode materials can

minimize this problem. The electrical supply passes through the titanium casing via a ceramic insulator

13.8 Tissue repair and growth

and the leads to the heart are insulated with a poly- mer (polyetherurethane). Degradation with time is still

Tissues include skin, tendons, ligaments and cartilages.

a possibility and has to be considered in an effective Skin has the dual property of keeping the body fluids design.

in while allowing the outward movement of moisture through a porous membrane, which is important in

13.7.3 Artificial arteries

cooling and maintaining the body temperature. Skin also protects against infections, such as bacteria but is

In branches of surgery, particularly cardiovascular not, of course, particularly strong. It is made up of lay- surgery, there is often a need to replace arteries

ers including an outer epidermis and an inner dermis, blocked by atherosclerosis. Sometimes this can be

a dense network of nerve and blood vessels. It is there- achieved by using tissue grafts from the patients,

fore virtually impossible to make an artificial skin from thereby avoiding any immune response. In other cases

biomaterials to match this complexity. Nevertheless

404 Modern Physical Metallurgy and Materials Engineering skin replacements have been made from polymers with

rigid, compressive load fixing. By contrast, Ni –Ti rods an open structure which provides a basic framework

can be programmed to provide traction on local heating. onto which real skin is able to grow. Moreover, with a

In other applications Ni –Ti has been used in artificial biodegradable polymer the framework degrades as the

heart muscles, teeth-straightening devices, intrauterine new tissue regrows. The porous film can be coated

contraceptive devices and as a filter in the vena cava with silicone rubber to provide infection protection

(inserted cold the filter opens its mesh at the temper- and retain fluids while the skin grows. When sutured

ature of the deoxygenated blood flowing back to the in place, tissue-forming cells (fibroblasts) migrate into

heart).

the porous polymer framework to generate new skin In spinal surgery, commercially pure titanium cables layers. For severe burns, artificial skin can be made

and screws have been used for the correction of sco- by growing epidermal skin cells within a biodegrad-

liosis by gradual tightening of the cable to straighten able collagen mesh in a culture medium. The syn-

the spine. A big advantage of Ti for these devices is thetic skin can then be grafted onto the patient. Other

its resistance to crevice corrosion. biodegradable products include the copolymers lactic

acid–glycolic acid and lysine–lactic acid. The adhe- sion of the polymer framework can be improved by incorporating an adhesive protein fibronectin.

13.10 Ophthalmics

Other tissues such as ligaments and cartilages are largely elastic filaments of fibrous proteins. Synthetic

The main usage of biomaterials in ophthalmics is for substitutes have included Dacron polyesters, PTFE

hard contact lenses, soft contact lenses, disposable fibres and pyrolyzed carbon fibres, with mixed success.

contact lenses and artificial interocular lenses. Apart The fibres may be coated with polylactic acid polymer

from being easier to wear soft contact lenses have which breaks down in the body to be replaced by col-

several advantages over hard lenses. Soft lenses ride lagen. At this stage such techniques are relatively new

on a thinner tear film fitting closer to the shape of but it does suggest that in future the growth of cells in

the cornea generally giving better corneal health, less

a culture vessel may possibly supply complex bioma- irritation from dust under the lens and less likelihood terials for various implanted functions. This approach

of being dislodged.

is termed tissue engineering and together with biomet- For satisfactory lens performance the biomaterial rics, i.e. the mimicking of the working of biological

must be inert, dimensionally stable to retain its optical systems, offers a way of producing materials which

properties, have a low density (¾1g cm 3 ), a refractive totally synergize with the human body.

index close to that of the cornea (1.37) and good oxy- gen permeability to maintain a healthy cornea. Hard contact lenses first became available using PMMA

because it was light (density 1.19g cm 3 ), easy to Polymers are used in a wide variety of surgical appli-

13.9 Other surgical applications

shape, has a refractive index of 1.49 and is reasonably cations. Polyurethane has good tissue and blood con-

biocompatible. They are, however, difficult to wear for tact properties and is used in both short-term applica-

long periods because PMMA is (i) hydrophobic and tions, e.g. catheters, endotracteal tubes, vascular tub-

not easily wetted by eye fluids and (ii) has a very low ing, haemodialysis parts, and long-term applications,

oxygen permeability. These have now been superseded

e.g. heart-assist devices. Dacron is used in composite

by soft lenses.

form with a poly(2-hyroxyethyl methacrylate) matrix

A wide variety of materials have been used for soft for orthopaedic tendon reconstruction. Varying the

lenses including silicones, hydroxyethyl methacrylate composite mix can alter the properties to match the

(HEMA) and copolymers with HEMA as the major requirements. Reinforced, Dacron fabric is used for

component and vinyl pyrrolidine to increase the water reconstructing the trachea and, in woven Dacron form,

content. Most soft lenses are made from hydrogels; for small bowel repair or replacement. It is also used

poly(2-hydroxyethyl methacrylate) is still the most in the genitourinary systems, in mesh form in repair-

popular, containing a small amount of ethylene glycol ing hernias and abdominal wall defects. Polysiloxanes

dimethacrylate to act as a cross-linking agent. These are used in neurological surgery, e.g. in valves to drain

hydrogel materials have excellent compatibility and fluids produced intercranially and also as tubes to drain

other properties but even with good oxygen permeabil- other canals such as the middle ear. Not having a

ity (100 times better than PMMA) additional oxygen porous structure, these tubes resist bacterial contam-

transplant via tear exchange is necessary. To increase ination.

the permeability the water content of the lens is raised Shape–memory–effect (SME) alloys (see Chapter 9,

but too high a water content can result in reduced section 9.6.4), particularly Ni –Ti, have been used

strength and poor handleability. in several biomedical applications because of their

After cataract surgery and removal, polysiloxane unique behaviour and for their biocompatibility. In

coated with wetting agents such as polyvinyl pyrro- orthopaedics, for example, pre-stressed fracture bone

lidine (PVP) has been used. For intraocular problems, plates can be made to shrink on heating to provide a

silicone injectable has been used.

Biomaterials 405

13.11 Drug delivery systems

consists of a titanium reservoir of insulin together with

a micro-pump which delivers the insulin via a fine Oral administration of tablets is a familiar method

catheter. In principle, a glucose sensor could provide for taking medicine. Less familiar is regular injection.

a feedback control to the reservoir to complete the Both methods have many disadvantages not least of

creation of an artificial pancreas. which is that the drug is being used as a general body

medicine when, ideally, it is required only at some specific site in the body. A second disadvantage is the variation in drug level with time, as it is metabolized

Further reading

from a high to an insignificant rate rather than a steady, Ball, P. (1998). Spare parts—biomedical materials, in Chap- more moderate rate. Nowadays, these disadvantages

ter 5, Measure for Measure, Princeton University Press, are being addressed by developing controlled drug

Princeton, NJ, USA.

delivery; in some cases to specified tissues or organs. Bhumbra, R. S. et al., (1998). Enhanced bone regeneration One form of controlled drug delivery and targeting

and formation around implants. J. Biomed. Mater. Res. system uses polymeric biomaterial to contain the drug

(Appl. Biomater.) , 43, 162–167. which then escapes by diffusion. The diffusion path-

Bonfield, W. (1992). Can materials stimulate advances in way through the polymer is provided by the gaps in the

orthopaedics? p. 168, Science of New Materials, Blackwell, chain-like structure which may be varied to control the Oxford, UK. Bonfield, W. (1997). Biomaterials—a new generation. Mate-

release rate. One such release system uses a copoly- rials World , January, p. 18, Institute of Materials. mer of lactic and glycolic acids to target peptide-based

Brown, D. (1994). Polymers in dentistry. Progress in Rubber drugs to reduce prostate cancer. Another approach uses

and Plastics Technology , 10, 185.

a biodegradable material chemically bonded to the Brown, D. (1996). Filling the gap. Materials World, May, drug. In the body the drug is gradually released as

p. 259, Institute of Materials. the material degrades, giving a continued release over

Helson, J. E. F. A. and J¨urgan Brime, H. (eds) (1998). Met-

a known degradation period at a specific site within als as Biomaterials . John Wiley and Sons Ltd. the body.

Ratner, B. (ed.) (1996). Biomaterials Science. Academic

A more ambitious system delivers a drug in response Press, New York, USA. Vincent, J. (1990). Materials technology from nature. Metals to blood chemistry levels, such as the release of insulin

and Materials , June, p. 395, Institute of Materials. in response to glucose level and has been used with

Williams, D. F. (1991). Materials for surgical implants. Met- some success. The implanted micro-infusion system

als and Materials , January, p. 24, Institute of Materials.