Bioengineering the body

Artificial skin, a biocomposite pancreas, nev bones for the inner ear: Regenerative medicine will build us a full set of spare parts.

Many of us will remember a time in our youth when everything about our bodies worked perfectly: We could see without glasses, our hair was all there and its original color, our muscles and joints never ached, sleep came easily, and everything worked just as nature apparently had designed. Many of us will also remember that bittersweet point at which some part of our once maintenance-free body changed or broke permanently. For some it was the need for vision correction, for others the loss of a tooth, for yet others a newly dysfunctional joint. Fortunately, in many cases bioengineers have designed pretty good medical work-arounds that limit the impact of bodily deterioration. But the body's capacity for self-repair is not limitless, and the available replacement parts are not nearly as good, in many cases, as the factory-equipped version.

Bioengineering innovators are as creative as any engine tinkerer— witness the adaptation of a bottle closure design to a heart valve. But while the first pioneers, groping around for solutions, used materials like mercury that seemed good but weren't, the science and technology have now progressed to the point that bioengineers manufacture new materials fully cognizant of the potential roles that stress, friction, corrosion, immune response, clotting, and other body-biomaterial interactions will play in the success or failure of the new part.

Artificial organs have been designed to replace most of our own. The artificial kidney, or dialysis machine, is arguably the most successful and certainly the oldest, dating back to the 1940s. Many of us also remember the Jarvik artificial heart implanted in Barney Clark, a 61-year-old retired dentist, in 1982. Clark survived for 112 days, tethered to a drive mechanism the size of a refrigerator, and eventually died from a blood clot in the brain.

While Robert Jarvik is popularly credited with the invention of the artificial heart, his design was largely based on patents assigned to the University of Utah by a ventriloquist, dancer, actor, and inventor named Paul Winchell. Winchell's roles included Fleegle in the American television series The Banana Splits and Tigger in the Disney movie Winnie the Pooh. Clark's heart was a clunky device made of plastic, polyurethane, and metal; today`s totally implantable artificial heart wejghs two pounds, has internal surfaces that are resistance clot formation, and is made titanium and a proprietary polyurethane plastic that inhibits clot formation.

No artificial lung or livers have yet been designed for general use, but solutions are on the non'zon tnat could be used as a bridge to transplantation, much as temporary heart-support devices do now. The pancreas can also be transplantable, but a prototype biocomposite pancreas now exists. It sequesters living pancreas cells inside of a silicon and titanium chamber etched with pores that are large enough to allow the passage of glucose, insulin, and oxygen but too small to let immune components by. A device like this may soon be implanted as a permanent artificial alternative to a real pancreas.

Advances in laser technology have enabled us to sculpt the human lens for better visual acuity, and bioengineers have developed implant-able artificial lenses made of biologically inert polymers. However, the approaches used to replace skin and restore hearing give us the best clues about what bioengineering will look like in the future.

Conducting hearing loss results from damage to one or more of the three bones of the middle ear, collectively known as ossicles, or "little bones." The bones conduct sound impulses from the eardrum to the inner ear, where they are translated into the nerve signals that are subsequently processed by the brain. The scientific names of the bones are the malleus, the incus, and the stapes, taken from the Latin words for hammer, anvil, and stirrup. When the eardrum vibrates, it moves the hammer, which acts with the anvil, like a lever, to move the stirrup. The middle-ear bones translate air-based sound waves into a fluid wave in the inner ear, dampening excessively loud sounds when necessary to protect the inner ear.

The materials that bioengineers and surgeons originally used to replace damaged ossicles included titanium, Teflon, platinum, and plastics. Today's replacement ossicles, however, have been engineered to more closely adhere to natural design principles and are made of composites of plastic or glass with biologically active materials that stimulate bone growth. After implantation, the new ossicles become covered with new bone and eventually become superficially indistinguishable from the original ones. The first words heard by the recipient of one of these new prototype middle ears were "Hamburger, hot dog, ice cream."

Biocomposite materials that integrate natural and man-made features, similar to those used in the ear, are also being used to manufacture new skin for badly burned patients who lack enough of their own that's suitable for grafting. Collagen, one of the body's natural connective tissues, is bound to silicone in a two-layer sheet. This artificial skin material is applied to a burned area with the silicone on top; new skin eventually grows into the collagen over a period of weeks while the silicone protects the vulnerable area. The silicone is eventually peeled off when the new skin is mature. The collagen underlayer serves as scaffolding through and over which the new skin grows, like ivy on a trellis.

Huge advances have been made in the development of inert materials that can duplicate or replace functions in the human body without triggering the immune system, but the holy grail for bioengineers is organ engineering, or the de novo construction of living, functional organs and components that can regenerate or replace damaged tissues in the body. In order to be successful, organ engineering will require the isolation, proliferation, and differentiation of various component stem cells and the design of scaffolds, or framing, to coordinate the growth of three-dimensional tis*sue°6rgaTi structures. In effect, organ engineers will need to function as architects. Their organ buildings must be structurally sound; a variety of scaffolding materials have become available, some of which are permanent, such as nanofibers or porous textiles. Others are resorbable or biodegradable. Chitin, for example, is the principal component in crab shells and squid beaks, and yet it is also used to make resorbable surgical sutures. The bricks and mortar of the organ are its constituent cells, which may come from mature cells grown in cultures, like crops, or may proliferate from precursor cells, like stem cells. Finally, the bioengineered organ must be designed with provision for utilities—in this case, blood and lymphatic vessels rather than plumbing and HVAC.

Intuitively, it seems almost inconceivable that human engineers would be able to re-create, say, a kidney, which is a complex organ with a complicated and highly sophisticated internal architecture of arteries, arterioles, capillaries, venules, veins, urinary conduits, and lymphatics. A neokidney of the future, however, doesn't have to look like a kidney, which is admittedly odd looking. There's no anatomic reason that the neokidney couldn't be shaped to look like the corporate logo of its manufacturer. And while the artificial assembly of an organ of such complexity would certainly be challenging, the challenges are no greater than those involved in the design and assembly of modern computer microchips. In fact, some of the techniques used in computer chip design are just what will be required for organ engineering. Computer-assisted design and manufacturing (CAD/CAM) can be used to create an appropriate three-dimensional organ scaffold that can then be populated with cells, using techniques very similar to ink-jet printing technology.

We humans have been endlessly inventive in finding ways to use natural materials (such as shell fragments) to alter our own cells and tissues and, increasingly, to design new materials (like pyrolytic carbon, similar to graphite) in the service of human appearance and health. Advances in bioengineering, miniaturization, nanotechnology, and stem cells are | converging, and we are on the verge of an era in which we'll be able to ' repair or replace injured or aging organs, tissues, and joints.

Man-made prosthetic materials will eventually transition seamlessly into our own tissues—exactly as the squid's beak gradually hardens to the tip—turning today's cosmetic, orthopedic, and cardiovascular implants into antiquated museum artifacts.