Boning Up: Tissue for grafts grown inside the body

Scientists have discovered a new way to stimulate one part of an animal’s body to grow extra bone tissue that can be transplanted elsewhere. The finding could be a boon for people who require grafts to replace bone segments lost to damage or disease.

The “gold standard” for such grafts is a person’s own bone tissue, says V. Prasad Shastri, a biomedical engineer at Vanderbilt University in Nashville. Unlike synthetic replacements or bone taken from a cadaver, a person’s own bone doesn’t trigger immunological rejection and can adapt to physiological changes within the body.

Surgeons typically harvest bone destined for self-transplantation from a person’s iliac crest, the thickened rim at the top of the hip. However, more than a third of patients who undergo this procedure suffer debilitating pain at the harvest site. “The whole business is very traumatic,” notes Shastri.

Researchers have long sought to solve this problem by engineering bone tissue in the lab, but so far, they have had little success. Seeking an alternative, Shastri and his colleagues tested a new way to prompt the body to create additional pieces of bone.

The researchers performed operations on rabbits to expose one of each of the animals’ tibias, bones that correspond to shins in people. The scientists then slipped a needle underneath the exposed bone’s periosteum, a membrane that covers the bone, and injected a bubble of calcium-containing gel between the periosteum and the bone.

Shastri explains that the periosteum has some qualities in common with adhesive tape: The outside of the membrane is smooth, but the side that touches the bone is sticky. This sticky surface sports a layer of stem cells that produces new bone, a critical part of the healing process that follows a bone injury.

The scientists hypothesized that separating the periosteum from the bone, which mimics an injury, and supplying the cells there with calcium, an important nutrient in bone formation, would induce the stem cells to manufacture new bone tissue.

Sure enough, within 2 weeks of the operation, the researchers found a soft layer of immature bone filling the space occupied by the gel. Six to 8 weeks later, the bone hardened into a mature form with mechanical properties similar to those of adult bone tissue. After nicking a small amount of bone from the tibias of some of the rabbits’ opposite hind legs, the scientists transplanted pieces of the newly grown bone. Within several days, the new tissue integrated itself into the damaged area, making a seamless patch.

Shastri asserts that the new technique, outlined in the Aug. 9 Proceedings of the National Academy of Sciences, could be at work in people within a year.

Creating bone inside a person’s own body is “a clever strategy,” notes Eben Alsberg, a biomedical engineer at Case Western Reserve University in Cleveland. With other scientists encountering snags in their efforts to engineer transplantable bone tissue in the lab, Shastri’s team has “found an alternative approach that circumvents the issue altogether.”

Letter to the editor:
My comments cited in this article were taken out of context. My original comments were: “The authors present a clever strategy to generate autologous bone. … This approach is very promising, since bone tissue for subsequent grafting into defects may be grown within a patient without the need to deliver cells and bioactive factors. As tissue engineers grapple with the problem of choosing an appropriate cell source to generate tissues, Stevens et al. have found an alternative approach that circumvents the issue altogether.”
Eben Alsberg
Case Western Reserve University
Cleveland, Ohio