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Friday, September 24, 2021

Putting the bite back in the bark

In medicine, the road from laboratory research to clinical application is often a long and complicated route. But sometimes, it’s no farther than a five-minute walk.

Such is the unique advantage enjoyed by doctors at UC Davis Veterinary Teaching Hospital, nestled among a complex of biomedical research facilities on the southwestern edge of campus that includes the Musculoskeletal Bioengineering lab of Kyriacos Athanasiou. The partnership between the lab and the hospital has produced a successful new treatment for regenerating bones that have been fractured or surgically removed in the jaws of dogs, a technique that may eventually be applied to human patients.

“This kind of work exemplifies the collaboration that happens at UC Davis,” said Boaz Arzi, a veterinary surgeon who is also a member of the Athanasiou lab. “Basically, magic can be done.”

The new surgical technique was put to its most challenging test in the case of Whiskey, a 10-year-old Munsterlander dog who needed almost half his lower right jawbone removed because of a type of cancer called squamous cell carcinoma, the most common type of oral cancer in humans.

After surgically removing the infected portion of Whiskey’s jaw, Arzi, along with a team that included the hospital’s Dentistry and Oral Surgery Service Head Frank Verstraete and Athanasiou lab tissue engineer Dan Huey, attached a titanium rod shaped to match the jaw line to the remaining bone, bridging the 6-centimeter gap.

“Formerly, when we had to remove a portion of the bone we were forced to leave the defect in the jaw because there was no better alternative,” Verstraete said.

A specially constructed sponge-like scaffold composed of collagen and the mineral hydroxyapatite, both constituents of normal bone tissue, and infused with a precise dose of a growth-promoting protein, was then inserted into the gap and attached to the titanium rod. Bone morphogenetic protein – first purified for clinical use in the 1980s by UC Davis orthopedic surgeon A. Hari Redi – is responsible for helping to recruit stem cells in the surrounding bone and tissue to differentiate into new bone cells.

“It’s not very difficult to regenerate bone,” Arzi said. “It’s difficult to regenerate bone over a large, critical-sized defect. And it’s more difficult to try to get it right without side effects.”

After three months, the scaffolding in Whiskey’s jaw had been almost entirely replaced by new bone growth, marking a triumph of the delicate refinements needed to coordinate scaffolding and protein for the specific requirements of a dog’s jawbone.

“The thing with bone morphogenetic protein is that it’s dose dependent, scaffold dependent and species dependent,” said Arzi. “So, for example, the same doses we use for dogs is different from the dose we would use for humans. So it really needs to be tailored per animal, per procedure, per bone event. It’s finding the right recipe which makes this [procedure] unique.”

With eight out of eight successful surgeries, the team is now publishing its results. Arzi sees great promise in similar collaboration for future projects, including ongoing work on disorders of the temporomandibular joint connecting the jaw to the skull, which are common in both dogs and humans.

“Taking people like those at the Athanasiou lab, with their knowledge base and understanding of the material, and combining it with our surgical expertise makes it really fertile ground,” Arzi said.  “It’s exciting; it’s definitely changed the way we think. I think that the team approach, with easy access to each other’s expertise, is what makes it successful.”

OYANG TENG can be reached at science@theaggie.org.

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