Amorphous calcium phosphate scaffold and osteoblasts may enhance bone formation

Researchers are attempting to design a composite material for oral reconstruction. Orthopedic applications include treating nonunion.

Amorphous calcium phosphates, an inorganic host material, may prove effective in promoting bone formation. Virginia and Maryland researchers are trying to design a composite material for oral reconstruction resulting from oral and pharyngeal cancers. Repairing diseased tissue from those cancers often requires bone reconstruction.

Potential orthopedic applications include treating bony abscesses and nonunion, the lead researcher said.

A National Institutes of Health grant is funding the study, which has taken about two years. The researchers now are preparing to enter animal and clinical studies.

Two Virginia Polytechnic Institute and State University researchers — Brian Love, PhD, professor of materials science and engineering, and Aaron Goldstein, PhD, assistant professor of chemical engineering — are collaborating with Drago Skrtic, PhD, of the American Dental Association’s Paffenbarger Research Center in Gaithersburg, MD, and Peter Shires, BVSc, MS, of the Virginia-Maryland Regional College of Veterinary Medicine. Love is principal investigator. Goldstein is a co-principal investigator.

Love and his colleagues believe combining amorphous calcium phosphates (ACPs) and osteoblasts may provide a better host material than other substances, offering rapid and effective bone formation.

Timing the ACP release

Researchers aim to design a scaffold that will regulate how fast ACPs dissolve and mix with the osteoblasts, Love told Orthopedics Today.

“We’re basically trying to keep cells viable and contained within the structure and then, secondarily, we’re trying to regulate when this dissolution plume occurs,” Love said. “There are some engineering ways we can manipulate how that occurs and then we're trying to control the plume in such a way that we're actually releasing ions at the right time in the cell cycle.”

Love described two possible ways of regulating ACP release: adding a stabilizing compound that controls how long the ACP dissolves, or designing a time-release capsule filled with a shielding chemical that regulates ACP dissolution.

“The real challenge is to get the timing and sequence figured out,” Shires said. “At this point we are still at ground zero, trying to document the efficacy of Zinc stabilized ACP on osteoblasts ... .”

Potential orthopedic applications

Love described the scaffold’s potential orthopedic uses, particularly nonunion.

“While we've been focused on oral cancers and bone reconstruction associated with those, there’s no reason to suggest that the same methodology couldn’t be applied for things like bony abcesses, where there’s essentially a bone gap, or nonunions,” Love said. “If you were to take out the bone segments that were associated with the nonunion and then stick in a plug of this particular type of scaffold material, you could basically create the same mechanism here.”

Love and fellow researchers aim to fuse different orthopedic defect types in a “demonstration” study, he said.

“We’ve actually talked about a specific animal model and trying to look at one type of defect,” Love said. “We’ve been looking around for the right type of defect model to actually use that would help us to be able to not only advance veterinary science in a way but to actually learn something about the performance characteristics of the bone scaffold material at the same time ... . We’re really much more at the scientific stage at this point, looking at trying to at least tweak the characteristics of the system to the point where we think it’s going to be the most successful and will lead us to the fewest number of clinical experiments necessary to do.”