In a scientific paper in the International Journal of Oral and Maxillofacial Implants' Novem-ber/December issue, the scientists reported that a large amount of bone -- between 544 and 733 milligrams, or about one cubic centimeter -- was regenerated in the lower jaw bone of rhesus monkeys.
"This is the most new bone ever produced in an attempt at bone regeneration in the jaw bones of a primate," said Michael E. Fritz, who heads the Yerkes Center's dental implant study. Using rhesus monkeys as their model, Fritz and his colleagues attempted bone regeneration as part of their National Institute of Dental Research-funded study designed to determine the most effective approach for dental implants in human patients who have lost their teeth. W.L. Gore and Associates provided supplemental funding for the study.
Bone regeneration is crucial to restoring tissue and ultimately dental function through dental implants, explained Fritz, who is Charles Howard Candler Professor of Dental Medicine at Emory and Yerkes research scientist in pathobiology and immunobiology.
The findings may have application beyond dental implants. "When many types of tumors are removed, large voids in the bone can be created," Fritz explained. "Because the results of the study may provide information on how to fill these voids, our Yerkes work may provide extensive benefits for the health of the human population other than purely dental." About 90 percent of the gap in the lower jaw bone of the three rhesus monkeys involved in the study was filled with new bone. "These results, although preliminary, are very exciting," noted Fritz.
"Until this study, it was not known that this quantity of bone regeneration was possible in chronic jaw bone defects without grafts from another part of the skeleton or the use of biotechnology agents," said Ross Hardwick of W.L. Gore & Associates Inc., one of the co-authors of the scientific paper. "The study shows that there is significant natural biologic potential for bone regeneration."
To foster bone growth, the scientists used a specifically designed membrane to cover the bone defect or gap that was created when the dental implants that they were studying in the animals were surgically removed. The dental implants were extracted so that the scientists could study how well they had functioned in the monkeys' mouths.
Removing the dental implant and surrounding bone tissue created a large void in the animals' lower jaw bone, Fritz said. The gap was allowed to remain for six months to simulate the medical treatment of tumors of the bone or other conditions such as injuries from automobile accidents that destroy bone tissue.
"When bone is lost through such diseases as cancer or by an impact injury, reconstructive surgery is typically not conducted for many months because the physicians' first priority in treatment is other issues including, in the case of cancer, the healing of the wound and the prevention of recurrence of the tumor," said Hardwick.
After the six-month period, a reinforced membrane, designed and manufactured specifically for this type of treatment by W.L. Gore, was placed in the animals' lower jaw bones. The membrane acted as a passive mechanical barrier that prevented undesirable tissues, such as fibrous connective tissue from the gums, from causing scars in the gap and created space into which bone regeneration could occur. Scar tissue could interfere with bone healing and growth, Fritz explained.
The membrane, shaped to fit the gap, was held in place with stainless steel mini screws. The animals were given general anesthesia for the surgery, the placement of the membrane as well as for the periodic evaluations of the membrane site.
"We treated the monkeys very much like we treat our human patients who have dental problems as far as making sure that there is no discomfort during and after the dental procedures," noted Fritz.
The membrane site was monitored by standard X-ray and digital subtractive evaluations. To provide a measure of the amount of bone loss or gain that occurred, X-rays were made when the membrane was placed and at three-month intervals. The X-rays revealed bone gain in each membrane-treated site.
Clinical and histologic evaluations also were conducted over the one year that the membranes were monitored. One year after the membrane was placed in the monkeys' mouths, tests indicated no statistically significant difference in the incremental growth rates of the newly created bone and the old bone in the lower jaw.
In future studies, Fritz and his colleagues will investigate the growth factors and other mechanisms that promote bone regeneration. "Our research at Yerkes may show that by adding growth factors to the membrane, bone regeneration will be much faster," he said. "At this point, it takes 12 months to grow mature bone back. If this time period can be abbreviated to two months, the patients will benefit greatly."
The scientists also will examine the characteristics of loading dental implants -- how the regenerated bone will respond to the stress caused by such normal activities as eating. "To our knowledge, no one has examined the loading characteristics in newly created bone," he added.
- Cathy Yarbrough