In the artificial bone yard

Bones made of coral, cartilages grown in test-tubes, arteries fashioned from Gore-Tex: science fiction? Not so, says Roger Dobson. Bio- technology is making enormous advances
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The Independent Culture
IN A laboratory in Cambridge, Massachusetts, a physician deposits a few dozen cells from the skin of a human donor on to a structure made of what looks like layer upon layer of fine plastic netting. He repeats the process with muscle, bone and blood cells, placing them at various points on the tube-like structure, which is a metre long.

When the work is complete, the tube is moved to a special culturing area where a pump is attached to feed the cells with nutrients; over the next few days they will divide and assemble in groups and shapes, following the intricate shape of the plastic scaffolding. Six weeks or so later, the matrix of polymer scaffolding and cells will have become a living human arm ready for a limb transplant.

That, according to Dr Joseph Vacanti, isn't science fiction but a taste of things to come - and soon - in the rapidly expanding world of bio-engineering and tissue fabrication. "It is do-able," he says. "The only real hurdle is nerve regeneration, which is still being worked on. But we have grown all the rest - skin, bone, cartilage and so on."

As associate professor of surgery at Harvard Medical School, and director of the Laboratory for Transplan-tation and Tissue Engineering at the Boston Children's Hospital, Dr Vacanti is at the leading edge of his field - in which human parts are being grown or manufactured rather than transplanted from donor humans or animals. Sometimes high-tech artificial substitutes such as Gore-Tex are used; sometimes the body parts are cultured from living human or other cells.

Teams around the world are currently growing or manufacturing a variety of tissues, including skin, bone and liver. At the same time, specialists in the US and Canada are trying to make battery-powered artificial hearts and other organs. This is a world of cartilages grown in test tubes; artificial arteries made from Gore-Tex (a plastic originally developed for anoraks); human cells coated with special plastic to deceive immune systems; and artificial bones made from processing coral taken from the South Pacific.

Some of the leading practitioners of tissue fabrication believe that, in 50 years time, ''traditional'' transplants will be as out-of-date as leeches and lobotomies. They say the future lies in off-the-shelf bones, limbs, and ready-made artificial organs. "We can already produce many of these, so why move it when you can make it?" asks Dr Vacanti.

While many of these projects are still at the research stage, or even less advanced, some are well under way. In London, a British invention leads the world in artificial bone production, and has already been implanted in more than 100 patients here and in the United States. The bone material, developed by Professor William Bonfield of Lon-don University's Queen Mary and Westfield College, is made from a mixture of synthetic hydroxyapatite, the major natural ingredient of human bone, and polyethylene.

"It is a composite material with tailor-made properties that make it very strong. Natural bone accepts it and will grow up to the surface of the implant, which then becomes part of the structure," Professor Bonfield says. One of the material's main uses so far has been as an implant in the middle ear to replace a missing or diseased bone in patients with a specific hearing problem. It has been found to be more successful than other types of material. "What was needed was a material that the tissue considered to be the same as itself; ours has the properties of bone, and has been very successful."

Professor Bonfield's team is now working on other uses for the material, such as joint replacements. One of the problems with hip and knee replacements in particular is that the metal or ceramic fixings used at present alter the stresses in the living bone tissue in which they sit. As a result, the bone grows away from the fixing, eventually leading to failure and a repeat operation.

Professor Bonfield says the ultimate aim is to use the material his team is working on in highly loaded areas such as hips and knees. He believes it will be particularly useful in repeat operations where, because more of the original bone has worn away, there is a need for firmer fixing. "If you had sterile, artificial bone on the shelf which you could easily make into the shape you wanted, it would be a much better prospect and would be permanent. "

The idea of creating artificial bone is being worked on by a number of other groups, particularly in France and the US. In California, coral - the limestone material that is made up of the external skeletons of tiny creatures, called polyps - is proving a useful starting point. Coral taken from the South Pacific and the Indian Ocean is being baked in a chemical bath to convert its limestone deposits into hydroxyapatite. Interpore Inter-national, the company behind the development, is using the new material to patch up broken bones. Several months after it is implanted, real bone grows into and around the porous substitute.

At the De Puy Laboratories in Warsaw, Indiana, another type of bone material is being produced from a mixture of hydroxyapatite and a ceramic, tricalcium phosphate. "We call it our play dough, because it can be moulded into any shape," says the research manager, Pam Lougher. "We use a biological molecule found in large concentrations of bone, which is then isolated, cultured and synthesised." The idea is that the surgeon can mould and shape it - using it to treat large breaks, for example, where part of the natural bone has been lost. The real bone will grow up to the ceramic and form around the material, which slowly degrades. "Our goal," says Pam Lougher, "is to provide off-the-shelf bone for surgeons to replace the present practice of harvesting it from the patient - which is complicated and painful - or taking it from bone banks, with the slight risk of hepatitis or HIV." De Puy is about to seek formal go-ahead for clinical trials on human patients.

Valuable though these synthetic bone substitutes may be, Professor Bonfield at Queen Mary's in London believes the future lies in a combination of materials and techniques, some of them entirely synthetic, others grown from natural tissue and bone. "What we are going to see is a combination of the best that bio-engineering can offer with the best of the artificial materials," he says.

The growing of human skin on plastic scaffolding has proved the success of the mixed approach for tissue production. Designed primarily for the treatment of burns victims, the process involves placing human skin cells on to a polymer matrix and culturing them. Over several days the skin grows along the matrix; when the patient is ready, the "patch" is transferred to the wound. Eric Freed-lander, a plastic surgeon at the Northern General Hospital in Sheffield, has taken the process one stage further by using sterile human skin as the scaffolding rather than a polymer, and has treated more than a dozen patients.

At Harvard, Dr Vacanti has also grown skin, as well as cartilage and liver tissue. "We can grow new cartilage, new bone, new tendon, new liver tissue and new urological tubes. We are at an advanced stage with cartilage and relatively close with bone and tendon. Clinical trials are now being designed."

What he and his researchers have found is that cells communicate and grow to the design, partially dictated by the polymer scaffolding. They have been able to produce cartilage in the shape of an ear and a nose to prove the point. "We think we will implant grown cartilage into a patient within two to three years," he says. "Eventually, entire organs will be designed and fabricated in this way and transferred to patients." His team is working with Advanced Tissue Sciences (ATS) - a California-based company - and with Smith and Nephew in the UK. Both companies can see the potential of growing human cartilage material.

There is as yet no commercially available synthetic or natural product that works as a substitute for damaged cartilage. Cartilage damage leads to both short- and long-term problems, and can eventually result in the need for a knee replacement. With growing numbers of people active, and with increased longevity, the number of injury cases is growing rapidly. The cartilage tissue serves a range of functions in the human body, from providing a gliding surface for smooth joint movement and impact absorption, as in the knee, to giving body organs and tissue their shape and flexibility.

Dr Gareth Lloyd-Jones is head of research for Smith and Nephew, based in York. "The work we are interested in," he says, "is engineering cartilage from cells that are derived from a donor, or from the subjects themselves. The cells are cultured in a laboratory for four to six weeks, and what you then have is a button of tissue that you can shape and implant into the patient's knee to repair the cartilage."

The main causes of cartilage damage, Dr Lloyd-Jones explains, are sports injuries and osteo-arthritis. Laboratory tests have shown that, where you put a piece of the new cartilage in, it remodels itself and integrates into the existing cartilage. "The treatment available at present is largely limited to removing the loosened tissue and advising the patient to adopt a more gentle lifestyle," he says. "We think our development will enable people to return to normal active life."

At the Massachusetts Institute of Technology, injectable cartilage from ATS in San Diego is also being developed for use in plastic and reconstructive surgery for reshaping faces. One of the main advantages of using fabricated tissue is that there is little or no risk of rejection, a problem encountered with transplants and also with the use of some artificial aids and devices.

A similar problem is faced in the treatment of disorders like diabetes, where the body cannot produce enough insulin. Insulin-producing cells could be transplanted from healthy donors, were it not for the patient's ever-watchful immune system, which rejects them. One solution is to disguise the implanted cells with a plastic coating, containing holes too small for the immune-system molecules to penetrate but large enough for the insulin molecules to pass through.

Such materials are currently being developed, says Professor David Williams of the clinical engineering department at the Royal Liverpool University Hospital. "In some diseases where certain types of cell are not functioning properly," he explains, "it is now possible to take cells and encapsulate them in polymers so that cells can be transplanted from one patient to another. The encapsulation protects the cell from the immune system, and we can get the cell performing."

The main area of interest is the treatment of diabetes, as described above. Suitable "selective permeability" materials are being developed in the US and a number of other countries, with all kinds of medical applications in mind. Work is already underway on coating nerve cells, with implications for the treatment of neurological diseases where a specific molecule deficiency has been identified - such as the nerve transmitter dopamine in Parkinson's disease.

Many tissue fabricators believe that the idea of building spare parts on scaffolding is the biggest development in medicine for some time, offering almost limitless potential. One possibility, still at the drawing- board stage, is that after a mastectomy cells could be grown on a polymer scaffolding to produce a natural breast replacement.

Ian Pearson is a futurologist employed by British Telecom, with the job of predicting future developments in technology. He believes there is going to be an escalation in fabrication and replacement over the next few years. By the year 2020, he believes, 95 per cent of body parts will be replaceable. At present, about 50 percent of body parts (as a percentage of body weight) are replaceable. "Soon," he says, "add-on parts may become everyday accessories, allowing people to select and optimise their abilities for the day. Body spare-part technology, together with a new range of sensors, could lead to the emergence of a true bionic man." !