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UCLA Researchers Discover New Method to Generate Bone
Protein Found by UCLA Shows Promise for Generation of New Bone, as
Well as Faster,
More Reliable Healing of Fractures
By studying diseases in which the human body generates too much bone, UCLA researchers
have discovered and isolated a natural molecule that can be used to heal fractures
and generate new bone growth in patients who lack it.
Bioengineering Professor Ben Wu at the UCLA Henry Samueli School of Engineering and Applied Science, and Thomas R. Bales Professor Kang Ting at the School of Dentistry are developing a new molecule they have named UCB, or University of California Bone.
The core technology developed by Ting and Wu is potentially the most significant advancement in bone regeneration since the discovery of bone morphogenetic proteins (BMPs) by Dr. Marshall Urist at UCLA in the 1960s.
Professors Kang Ting and Ben Wu. |
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“For the average person, this new development potentially means faster, more reliable bone healing with fewer side effects at a lower cost,” says Ting. “In more severe cases, such as in children born with congenital anomalies, the new protein may offer an advanced solution to repair cleft palates, which involves bone deficiencies, and also aid in repairing other bone defects such as fractures, spinal fusion and implant integration.”
The key to success for these proteins is designing the right carrier – using the protein alone is not effective. Currently BMPs are delivered with a collagen-sponge into the area where bone growth is needed. The sponge offers little biological benefits for the surgeon, and proteins can migrate away from the sponge. In contrast, the team at UCLA is developing a carrier that is engineered for UCB activities in the biological environment.
By mimicking the formation of biominerals that occur during natural bone wound healing, Wu’s team has developed a bone-forming carrier to serve several important functions. In addition to delivering the UCB protein at predetermined rates, the carrier itself also provides cues at the cellular level to assist in bone formation.
“By controlling the material’s microstructure,” explains Wu, “our team demonstrated that adjusting the processing parameters significantly affects the behavior of mature bone-forming cells.”
Wu’s group recently reported in Nature Biotechnology that the cellular
environment alone, without the addition of expensive and exotic biochemicals,
can stimulate progenitor cells derived from fat or marrow to differentiate into
bone-forming cells to heal defects. This finding has motivated efforts
to understand how minute changes in the microenvironment can regulate the fate
of cells. Wu believes that fine-tuning the carrier for UCB will lead to optimal
delivery of the molecule in
a wide range of environments.
UCB differs significantly from BMPs, the protein currently used by orthopedic surgeons to aid in bone repair, in that UCB has potentially fewer side effects. With BMPs, bone formation has been observed to occur at locations outside of the intended implant site, and tissue other than bone also has been reported. In contrast, UCB’s main effects appear to be more specific towards bone formation process, giving surgeons increased control over where bone forms.
Says Wu, UCB is more specific because it works downstream from the body’s “master switch” for bone formation. Because the two molecules act on different targets, UCB also works synergistically with BMPs to form more bone than is typically possible with BMPs alone.
BMPs, found in demineralized bone, were discovered in the 1960s, but until the advent of biotechnology, the arduous process and high cost associated with making BMPs from animal-derived bone was deemed too difficult. To date, only two companies have received FDA approval for BMPs, making the product cost high, and the treatment prohibitive for many.
Ting, who works frequently with children who have congenital anomalies, began his bone research eight years ago. Wu joined him three years ago, and their collaboration resulted in the recent discovery.
“I thought it was important to understand how accelerated bone growth in one situation might be applied to situations where more bone growth could accelerate healing in those patients who lacked normal or necessary bone formation,” says Ting. “This discovery will provide another option for patients. Competition will make treatment options safer, less expensive, and more accessible for those families who really need it.”
The team of UCLA researchers, under the business name Bone Biologics, already has begun forming partnerships that may assist in the development of appropriate carriers for UCB. The Musculoskeletal Transplant Foundation (MTF), the nation’s largest tissue bank, has signed a collaborative development agreement with Wu and Ting to provide customized tissue forms to support the delivery of UCB.
Wu and Ting anticipate FDA approval and first sales of the product in the next seven to nine years. Other collaborators on this technology include Dr. Xinli Zhang and Dr. Chia Soo at UCLA, and Dr. Shunichi Kuroda at Osaka University. The new technology recently has been awarded the prestigious 2005 Hatton Award from the International Association of Dental Research.
For additional information on the project, please contact Professor Ben Wu at benwu@ucla.edu.
-Melissa Abraham |
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