Cutting Edge: David Williams

July 6, 2001

When I started to work on reconstructing the body, well over 30 years ago, I had one objective: to find the most inert synthetic substances that could restore some bodily function without doing any harm. Those were the exciting days of the first hip replacements, artificial heart valves and arteries. Enormous strides have been made since then, and we can now replace many parts of the body with implants to treat arthritis, cataracts and so on.

It is perhaps obvious, however, that a materials scientist was never going to be able to address problems nature had failed to resolve in years of evolution. If the cartilage of our joints cannot always sustain the loads we place on it, why should we expect a synthetic version to do any better? How can we possibly replace bone, a living collagen and apatite composite that has an extraordinarily complex microstructure and architecture, with a simple isotropic, homogeneous, non-living piece of engineering alloy?

The answer is that we get away with it, but only just. Implants do not always last long and may have side effects. They are limited in terms of the quality of life they can produce and the diseases they can address. Because of this, there has been a radical change in the thinking behind tissue reconstruction, coincident with the emergence of cell therapy to treat disease.

There have always been alternatives to synthetic tissue replacements. However, living transplants have inherent problems of donor supply and immunological rejection, while grafts have limited applicability. Cells, on the other hand, have had little role in this process until recently because it was not possible to persuade them to grow into replacement tissue or organs. The diseased, traumatised or simply aged tissue that needs replacing is much more than a collection of cells.

To grow cells into a functioning form has necessitated persuading cells to do things they were not intended to do, or at least were not designed to do under those conditions. The first major issue - where the cells come from - is both technical and ethical. It is feasible to take specialised cells from the patient and by delivering appropriate biological and mechanical signals, arrange for them to produce new tissue. Much more attention has been focused on the use of stem cells, and especially embryonic stem cells, that can be directed to produce any new tissue. Harvesting cells from the eventual recipient of the new tissue has limitations. Embryonic stem cells are far more challenging ethically, but offer enormous hope for the treatment of degenerative diseases.

The second challenge is concerned with treating the cells to ensure they produce the right tissue. This is what tissue engineering is all about. We need to create the ideal environment for cells to grow and generate new tissue, which may be done partly in the laboratory and partly in the body. It involves the development of physical scaffolds and the creation of bioreactors in which the cells, seeded into the matrix, are stimulated with molecules. We have to consider the implications of artificially creating new tissue - can we turn off growth mechanisms just as we hope to switch them on; will the new tissue be strong enough; will it be more susceptible to disease? It is possible that to achieve these goals, the cells will have to be genetically modified, with all of the ethical dilemmas this brings.

Much progress has been made in the past couple of years. "Laboratory grown" arteries, valves, joints, teeth, ligaments and cartilage are all on the horizon.

David Williams is head of the department of clinical engineering at Liverpool University and deputy director of the United Kingdom Centre for Tissue Engineering.

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