A newly discovered osteoinductive protein dubbed University of California Bone (UCB) may one day help heal fractures, generate new bone growth, and revolutionize spinal fusion. Scientists first isolated the molecule when they were studying a disease marked by accelerated bone growth, and are currently in the process of refining it for clinical use.

While full regulatory approval is most likely about 7 to 9 years away, "the first use may be spinal fusion, but can certainly be used in other orthopaedic surgeries, including non-union fractures and dental applications such as ridge augmentation and sinus lifts," says Ben Wu, PhD, bioengineer at the University of California, Los Angeles' (UCLA) Henry Samueli School of Engineering and Applied Science.

 

Better than BMP?

UCB is more specific than bone morphogenetic proteins (BMPs), and may have fewer side effects, Dr. Wu says. Several BMPs are being studied for orthopaedic applications, including human BMP-2, which can be administered laparoscopically, and which is currently approved as a bone graft replacement for anterior lumbar spinal fusions. BMP-7 and BMP-14 are being investigated for similar indications.

BMPs can cause undesirable bone formation at locations outside of the implant site, however. UCB is more specific for osteoblastic cells, which decreases the possibility of heterotopic bone formation because fibroblasts, pericytes and other non-committed cells would not be stimulated to form bone, Dr. Wu tells CIAOMed.

"In one of the pathways that lead to bone formation, BMP is an upstream regulator of core binding factor alpha-1 (CBFα1), an essential transcription factor for osteoblast differentiation and bone formation," he says. "In contrast, [UCB] acts downstream of CBFα1," enhancing its specificity.

The new protein may also be used along with BMP, Dr Wu predicts. "Because of the different molecular targets, UCB and BMP may act synergistically, and the combination may greatly reduce the dosage of BMPs currently employed."

 

Seeking the Ideal Carrier

One of the remaining goals is to design a suitable carrier for UCB, as the protein administered alone is not effective. BMPs are delivered with a collagen sponge into the area where bone growth is needed, but proteins can diffuse away from the sponge, diminishing the effectiveness of the treatment. To counter this issue, Dr. Wu and his collaborators are developing biological carriers.

"For moderate weight-bearing applications, we are designing moldable carriers that will expose pores and release the growth factors over time," Dr. Wu says. "For non-weight-bearing applications with limited surgical access, we are designing injectable carriers to minimize surgical trauma." For heavy weight-bearing applications, Dr. Wu says, either of these approaches will need to be combined with stronger biomaterials such as metals or advanced composites.

"I believe these proteins will become the standard of care in the future," says Jeffrey Wang, MD, the chief of Orthopaedic Spine Service at the UCLA Comprehensive Spine Center. "UCB has the potential to substitute for [autologous] bone grafts, minimizing pain and recovery to patient," he says, adding that "it could minimize and decrease fracture healing time, and provide excellent treatments for fracture non-unions."

Reference:

UCLA Researchers Discover New Method to generate Human Bone [press release]. 4/21/05.