A new type of treatment for osteoarthritis, currently in canine clinical trials, shows promise for eventual use in humans.
The treatment, developed by biomedical engineers, is a synthetic version of a naturally occurring joint lubricant that binds to the surface of cartilage in joints and acts as a cushion during high-impact activities, such as running.
"When the production of that specific lubricant goes down, it creates higher contact between the surfaces of the joint and, over time, it leads to osteoarthritis," said the senior author.
The study focuses on a naturally occurring joint lubricant called lubricin, the production of which declines following traumatic injuries to a joint, such as a ligament tear in a knee.
The knee is lubricated in two ways - hydrodynamic mode and boundary mode.
Hydrodynamic mode lubrication occurs when the joint is moving fast and there isn't a strong force pushing down on it. In this mode, joints are lubricated by compounds like hyaluronic acid (HA) that are thick and gooey, like car oil. There are numerous HA products on the market, approved by the Food and Drug Administration, for treating hydrodynamic mode lubrication disorders.
But HA is ineffective when strong forces are pushing down on the joint, such as those that occur during running or jumping. In these instances, thick gooey HA squirts out from between the cartilage surfaces, and boundary mode lubrication is necessary. Under these forces, lubricin binds to the surface of the cartilage. It contains sugars that hold on to water, to cushion hard forces on the knee.
In the paper, the researchers describe a synthetic polymer they developed that mimics the function of lubricin and is much easier to produce. "We are in clinical trials, with dogs that have osteoarthritis, with our collaborators at Cornell's College of Veterinary Medicine," the senior author said.
This diblock copolymer, synthesized by sequential reversible addition–fragmentation chain-transfer polymerization, consists of a cationic cartilage-binding domain and a brush-lubricating domain. It reduces the coefficient of friction of articular cartilage under boundary mode conditions to a level equivalent to that provided by lubricin.
Additionally, both the EC50 and cartilage-binding time constant of the polymer are comparable to purified human and recombinant lubricin. Like lubricin, the tribological properties of this polymer are dependent on molecular architecture.
When the same monomer composition was evaluated either as an AB diblock copolymer or as a random copolymer, the diblock effectively lubricated cartilage under boundary mode conditions whereas the random copolymer did not. Additionally, the individual polymer blocks did not lubricate independently, and lubrication could be competitively inhibited with an excess of binding domain.
"Once we finalize the efficacy study in dogs, we will be in a very good position to market the material for veterinary osteoarthritis treatment," the senior author said. From there, the human market for a lubricin substitute should follow, just as HA has been made available for human use, mainly in knees.
Synthetic joint lubricant holds promise for osteoarthritis
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