Bionic man, heal thyself

Advances in the science of biomaterials make rebuilding the body more than the stuff of science fiction.

To many ‘biomaterials’ is a vague concept. Yet low-tech biomaterials are now an accepted part of healthcare. Examples range from tinted polymer contact lenses to wounds being healed with resorbable polymer sutures, or chipped teeth replaced by a ceramic tooth attached to the jaw by a titanium screw.

Any material that can be used to repair, replace or add to the functioning of a body part is termed a biomaterial by virtue of its biocompatibility: its ability to be tolerated by the immune system and the body’s physical make-up.

But scientists are now developing ‘third-generation’ biomaterials which, by taking the concept of working positively with the body further than ever before, are opening up staggering new possibilities for treating illness and injury.

The financial potential of biomaterial is also large, as a recent survey by Kalorama Information states: ‘The market potential for tissue-engineered healthcare solutions has been estimated at over $80bn (£55bn),’ with high potential in ’tissue engineering and transplant medicine, devices that deliver pharmaceuticals, and specialised polymer coatings that allow for more complex device design’.

The market for drug-coated stents (used instead of open-heart surgery), which prevent arteries from refurring, has alone been predicted to be worth $5bn (£3.5bn) within a few years.

Forty years ago when the first implants were placed in the human body, the holy grail was an ‘inert’ biomaterial – one that co-existed in harmony with the body, mimicking the tissue that it replaced and not evoking a toxic response.

Unfortunately, as Dr John Hunt from the University of Liverpool’s Department of Clinical Engineering explains, ‘There is no such thing as an inert material. As soon as a surgeon’s knife enters the body he has caused a trauma and there will be a response. The important thing is to control that response.’

And so the second generation of biomaterials was born, taking materials such as stainless steel, titanium and a host of polymers, and adapting them. One example is the use of coatings of hydroxyapatite, a synthetic material that strongly resembles bone, on titanium implants to cause a bioactive response towards the material and aid integration with the existing bone.

Lessons from a jellyfish

A novel type of polymeric material, hydrogels are one of the most versatile biomaterials in development.

Imagine a jellyfish: it’s just a lump of jelly but it can sense its environment and react to it, using its body as a muscle. Synthetic hydrogels are an example of biomimetics, harnessing concepts from nature such as the sensory capabilities of jellyfish. Smart hydrogels can sense and react – they respond to stimuli such as pH and heat, have a shape memory and change their structures reversibly, such as by swelling or contracting. When the gels swell due to osmosis they can apply a pressure and do work.

Hydrogels are now being made that are stronger than silicone rubber when swollen. At the Johns Hopkins University in Baltimore, Maryland, they are being researched as a possible artificial muscle, though at present the pressures exerted are too small for useful clinical application.

One use of hydrogels that has already received UK and FDA licences is that of controlled drug delivery. Prof Neil Graham at the University of Strathclyde Department of Chemistry has developed a responsive system using hydrogels based on polyethylene glycols, which release a drug when in their expanded state. It has been reported that accelerated drug release could be achieved by warming the skin or using ultrasonic vibration.

Graham says: ‘We are just beginning to address the enormity of the changes and properties you can get with hydrogels.’ One application he thinks may be possible is an artificial pancreas for diabetics, with pancreatic cells growing in a hydrogel enclosure membrane. It would respond to changes in body chemicals to release insulin by swelling and shrinking.

The new generation of biomaterials is all about ‘systems that are not only accepted by the body but interact with the body’, Graham says, and they also ‘provide a mechanism for the body to heal itself’.

Other applications include wound healing and, potentially, repairing holes in the bladder, which has already been achieved with a biodegradable matrix hydrogel supplementing missing tissue in the bladder wall. Because the gel is permeable to nutrients it can turn into tissue, and within a few weeks is indistinguishable from the natural bladder wall tissue.

Non-clinical applications include robots with simulated muscles (where the robot can make ratchet-like movements when a current is fed to hydrogel ‘muscles’) and using hydrogels to prevent barnacle adhesion on boat hulls.

New bone for old

Hydroxyapatite is just one of the materials that can be used to rebuild bone. A step further is bone-replacement technology using synthetic calcium phosphate. The US orthopaedic biomaterials company Orthovita has recently been granted a patent for production methods and uses of its nano-structured calcium phosphate bone void filler, Vitoss. The material is a resorbable scaffold that ‘mimics the chemical composition and structure of human cancellous bone’ (the honeycomb-like interior).

The structure is bioactive, encouraging growth of bone cells within the honeycomb, and resorbing it as new bone is laid down, aiding repair.

This synthetic bone has already been cleared for sale in the US, Australia and Europe. Still under development is a preformed, injection-moulded composite, Rhakoss. The dual nature of natural bone – the hard outer cortical bone and internal honeycomb cancellous bone – is mimicked by this material, designed for spinal implants. To give some idea of the similarity of these substances to natural bone, Orthovita claims that in laboratory tests Cortoss, a cortical bone void filler, exhibits compressive strength similar to human bone.

Third-generation biomaterials take the idea of a material working with the body even further. Failure rates for mechanical implants such as heart valves and hip prostheses are as high as a third to a half within 10-25 years, with revision surgery both painful and costly to an ageing population.

Having realised that any synthetic material will always play second fiddle to the highly specialised and adaptable tissues of our bodies, research has become highly interdisciplinary. Biologists and chemists work with geneticists and even electronics engineers to develop materials that can invoke healing responses in the body.

A good example of interdisciplinary collaboration is bioelectronics, which almost enters the realm of science fiction. An unlikely coupling has been achieved between biological substances such as neurons in the brain and electronic transducers such as piezoelectric crystals and electrodes.

A leader in this field, Dr Shlomo Yitzchaik, of the department of inorganic and analytical chemistry at the Hebrew University of Jerusalem, described how ‘neurocompatible surfaces were obtained by grafting charged polymers on various surfaces’ at the Bio-Tech Israel 2002 Conference in March. Cultured neurons were persuaded to grow on a silicon surface and communication was achieved between the biological and electronic interface by the movement of electrons. This process has huge implications for anyone with a sensory disability such as blindness. Prostheses could be developed using artificial organs to see, hear and smell for a person.

In the same research group as Yitzchaik, another expert, Prof Itamar Willner, is working on nano-architectured biomaterials with surface coatings of enzymes, antigen-antibodies or DNA on an electronic transducer. The surfaces are engineered to control the properties of the interface between the biological and transducer materials, and electronic messages of, for example, pH value have been sent between the two.

Future applications include a self-powered insulin pump, and using coated DNA transducers to detect drug resistance in HIV patients. Rapid identification of viral infection would also be possible. Electronic circuits can be made with building blocks of semiconductors using nanowire formed by combining nanoparticles with strands of DNA.

Custom design of body parts using a patient’s own cells is now a reality. Cells are transplanted on to a resorbable polymeric scaffold in the lab, and the resulting structure grows to mimic natural tissue. When transplanted into the patient to replace damaged tissue, the scaffold becomes integrated into the blood supply and nervous system. This can be used for skin, cartilage and vein repairs.

Another theoretically possible method for creating replacement tissues using biomaterials comes from the automotive industry. Rapid prototyping could be used with biodegradable polymers such as polylactic acid and the caprolactones to form a scaffold on to which stem cells (from lab-grown embryo cells which could theoretically develop into any organ) are placed. If this process is fully developed it holds endless possibilities for the generation of made-to-measure body parts, though the ethical implications of using stem cells are far from resolved.

Bioactive glasses and foams can activate genes to encourage regrowth of natural tissue. One possibility is cell transplants to treat illnesses such as Parkinson’s disease. A resorbable polymer surface can have cells incorporated on to it that are attractive to brain cells and promote regrowth and stimulation of neurons.

Before the excitement of having your mental capacity increased by a brain cell transplant gets too much, it’s worth noting that these processes are in their infancy.

Biomaterials is a fast-moving field but, even with significant investment, in some areas the future will partly depend on the ethical decisions reached. Nonetheless, their potential has developed unimaginably in 20 years ago and offers new hope in caring for an ageing population, and in the treatment of disease and injury.