Break A Leg And Bioceramics May Mend It

Back in 1967, a young ceramics engineer named Larry L. Hench was designing semiconductor switches for nuclear weapons. His career took a turn on a bus ride to an Army materials conference. A colonel just back from Vietnam told Hench that thousands of soldiers were having limbs amputated because of faulty implants. "Those damn metals and plastics are rejected," Hench recalls him saying. "Why don't young guys like you do something to help people instead of learning how to blow them up better?"

Inspired, the University of Florida scientist decided to try. He began work under a grant from the U.S. Army in September, 1969, and two months later came up with a glass that bonded so well to bones and tissues of rats that experimenters couldn't dislodge it. On analysis, it appeared that Hench's glass was a magnet for bone cells (illustration). In 1985, after lengthy development and testing, the Food & Drug Administration approved the petition of U.S. Biomaterials Corp. in Baltimore, to use Bioglass, as it's now called, to replace the bones of the middle ear to restore hearing. It has since been approved for patching facial bones and repairing diseased gum tissue.

What Hench discovered in 1969 was among the first of a small but important class of medical materials: bioceramics. The category includes all kinds of glasses and ceramics that are implanted in the body. According to Medical Data International, a market-research firm in Irvine, Calif., sales of bioceramics should amount to only $20 million this year in the U.S., the leading market. But the pmtential is much bigger: Americans spend $2 billion a year on dental implants, reconstructive devices such as hip and knee implants, and plates and pins for broken bones. Bioceramics could grab significant chunks of those markets. And they could capture smaller niches as well. For instance, bioceramics can be used to make artificial eyeballs that move in unison with real eyes.

As a sign of the mounting interest, the National Institutes of Health are including money for bioceramics next year as part of $100 million in grants in the broader field of biomaterials, which includes metals and plastics. Britain is funding similar programs. Several large Japanese companies are developing bioceramics, led by giant Kyocera, which has developed a ceramic hip ball replacement.

"PAUSE BUTTON." To be sure, hurdles remain. Getting FDA approval for a new medical device can take $20 million and five years. That aside, it will take time to persuade surgeons and dentists to switch to bioceramics from well-known materials such as titanium alloys. Bioceramics can also be brittle. When used as coatings on metal, they may flake off, causing inflammation. Curing those faults is expensive--and research dollars are scarce. "The health-care-reform environment has been like the pause button on a VCR for biomaterials," says Dr. Harold Alexander, director of the bioengineering department of New York's Hospital for Joint Diseases.

The good news for bioceramics can be summed up in one word: aging. With the population getting older and body parts wearing out, surgeons are performing nearly 500,000 bone grafts and 260,000 hip operations a year, Medical Data International says. Researchers are investigating a wide range of bone substitutes: metal parts with special porous coatings that bond with bone and tissue; polymers derived from human amino acids; and, of course, bioceramics--ranging from ocean coral to glass fibers that the body absorbs.

Bone is particularly difficult for implants or grafts to emulate. It's a tough, resilient composite. Its main component, a calcium-phosphorus compound called hydroxyapatite, gives it strength. Elastic strands of collagen give it flexibility. It is continually eaten away by its own cells--then rebuilt by new bone cells.

CORAL RELIEF. Declaring natural bone to be the gold standard, surgeons generally make grafts from bone harvested from a cadaver or skimmed from a patient's own hip, ribs, or skull. But natural bone has its own problems: Cadaver bone may suffer the same rejection as a transplanted organ would. Because it is living tissue, there's also a slight risk that cadaver bone can transmit diseases such as AIDS and hepatitis B. Harvesting a patient's own bone can be painful and may not yield enough material to mend a fracture. As for implants, metal doesn't always bond well with bone. Plus, metal's stiffness can shield surrounding bone from stress. In the absence of stress, bone has a tendency to break down.

Thus, the search for something new. Among the most creative companies in the field is Interpore International in Irvine, Calif., which makes a bone substitute from coral, the limestone exoskeleton of tiny sea animals called polyps. Interpore harvests unendangered corals from the South Pacific and Indian Oceans and bakes them in a chemical bath to convert the limestone to hydroxyapatite: bone mineral. Three months after an implant, the structure has become filled with bone. Because it's brittle, Interpore's product is best for small patches and nonweight-bearing areas, such as the spongy ends of long bones.

Such mineralized coral is highly adaptable. Besides applying it to jaw and facial bones, Interpore is seeking FDA approval to use it for fusing vertebrae. Coral has also been fashioned into the base of an artificial eye by San Diego's Integrated Orbital Implants, in a procedure patented by Arthur Perry, a San Diego surgeon. With eye muscles attached to a globe made of coral, the fake eye moves more naturally. Soon, tissue and blood vessels grow in, anchoring the implant.

Ideally, implants would go away when their work was done--eliminating the surgery that's needed to retrieve metal parts, for instance. That's the point of work on resorbable composites of polymers reinforced with glass fibers, which could substitute for metal plates, rods, and pins. These materials could be entirely resorbed by the body in a year. Also, the materials transfer needed stress to bone better than metal does, so the bone doesn't dissolve.

Glass and polymers are ideal partners for resorbables. In one effort, William C. LaCourse, a professor of glass science at Alfred University in Alfred, N.Y., is developing glass fibers to reinforce a resorbable polymer developed at Rutgers University. The polymer is made of the amino acid tyrosine and is naturally broken down by the body. Alexander, of the Hospital for Joint Diseases, is coordinating the project under a $2 million grant from Commerce's Advanced Technology Program. "When you consider the cost of the second surgical procedure [to remove the metal parts], we're saving about 40% of the total cost," Alexander says.

Glasses and ceramics have an almost unlimited number of uses. Delbert E. Day and Gary J. Ehrhardt of the University of Missouri have developed glass spheres just a third the width of a human hair to deliver radiation to tough-to-reach liver cancer without damaging nearby organs. Tumors require a large blood flow, so the beads tend to be carried to them rather than to healthy tissue. The spheres are approved to treat liver cancer in Canada and are marketed by Nordion International Inc. in Kanata, Ont.

PLAY-DOH. Many medical researchers believe bioceramics may play their most valuable role as delivery vehicles for human growth factors, the stimulants for regeneration of bone and tissue. DePuy Inc. in Warsaw, Ind., has spent the past two years mixing a unique Play-Doh for surgeons with the help of Genentech Inc. This artificial bone graft combines a growth factor and tricalcium phosphate, a ceramic that releases the growth factor as it dissolves. Animal trials of the bone-graft substitute should be complete in 1995.

Growth factors such as Genentech provides may not always be enough to stimulate bone growth. That's especially true if the body is short on a rare type of bone marrow cell called mesenchymal stem cells, which give rise to new bone, cartilage, ligament, muscle, and tendon. Stephen E. Haynesworth and Arnold I. Caplan of Case Western Reserve University have discovered a way to replicate the rare cells and saturate a bonelike ceramic with them. Since the cells belong to the patient, tissue rejection shouldn't be a problem. Cleveland's Osiris Therapeutics Inc. has licensed the technology and begun large-animal trials.

After nearly 30 years in the field of bioceramics, Larry Hench is still awed by the idea that materials made from such simple components as calcium, phosphorus, and silica could help produce something as vital and complex as human bone. But then, Hench observes, the body itself is made of equally unimpressive ingredients.