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Science: Protein putty mends broken bones

A genetically engineered protein that heals fractured bones and damaged
teeth is being tested in the US. The compound is a natural human protein
that appears to trigger the regrowth of bone in injuries called 鈥榥on-union
fractures鈥�, where the two parts of a broken bone fail to join up. The same
protein can stimulate the recovery of tooth tissue in decayed teeth.

Creative BioMolecules of Hopkinton, near Boston in Massachusetts, has
been testing the bone-healing capabilities of the protein, code named OP-1,
in a trial due to end in a few months鈥� time. Charles Cohen, the chairman
of the company, explains that the compound is being tested against traditional
grafts, in which surgeons bridge non-union fractures with fragments of bone
taken from the patient鈥檚 hip.

Cohen says that the trial involves 鈥榯ens of patients鈥�. All the participants
had non-union fractures persisting for at least nine months after the original
break. 鈥榃e鈥檙e very encouraged by the results so far,鈥� says Cohen.

Company researchers mix the protein compound with natural, biodegradable
connective tissue from cattle, called type-1 collagen. They then grind
up the mixture to form a fine powder.

During operations, surgeons mix the powder with a saline solution to
form a putty-like material that they smear into the gap between the fractured
bones. After a few days, cells from the bloodstream called mesenchymal stem
cells begin to accumulate in the 鈥榩utty鈥�.

Within a few weeks, the mesenchymal stem cells have been modified to
form cartilage tissue, and within months, the site becomes calcified, forming
natural bone containing bone marrow cells. In its initial trials with monkeys,
the company found that at the end of the treatment, the new tissue was indistinguishable
from the original.

Cohen suspects that the protein triggers off a sequence of events by
which the raw stem cells 鈥� the 鈥榓ncestors鈥� of bone, cartilage, skin, ligament,
marrow, muscle and tendon cells 鈥� are converted into bone cells. 鈥業t appears
to commit the stem cell to the creation of a certain type of tissue, in
this case bone,鈥� says Cohen. 鈥榃e think the protein acts as the priming signal
to start the process.鈥�

The same compound promotes the growth of tooth tissue called dentine
鈥� a protective material between the sensitive pulp inside a tooth and the
enamel on its surface 鈥� so Cohen believes that the type of tissue formed
partly depends on the neighbouring cells. He says this explains why dentine
has never appeared in bones, and bone has never appeared in teeth. 鈥楴o bone
has grown where it shouldn鈥檛. The safety of the trials is exceptional.鈥�

The company expects to finish the trial in teeth by the end of next
year. The research was financed by Stryker of Kalamazoo in Michigan, which
has so far spent $20 million on the project.

Cohen says there are 40 000 cases of non-union fractures each year in
the US, and more than 400 000 other bone defects and accidents that could
be treated with the protein. US dentists also drill 4.2 million root canals
each year, and fit more than a million pulp caps.