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University of Iowa News Release


Feb. 5, 2008

UI, ISU team aims for new therapies for post-traumatic osteoarthritis

University of Iowa orthopedics experts are joining forces with biomaterials specialists from Iowa State University to develop an entirely new approach to preventing post-traumatic osteoarthritis (PTOA).

PTOA -- the pain and stiffness that often develops after serious joint injuries -- is a debilitating condition that affects as many as six million Americans and annually costs about $12 billion in direct medical costs and indirect costs, including lost wages.

The new approach combines biomaterials technology with recent advances in understanding the biological mechanisms underpinning PTOA. These advances, many from UI studies, suggest that severe joint injury initiates a cascade of cartilage cell death and dysfunction, which leads to PTOA.

Translating these research findings into potential treatments is at the heart of the collaborative effort spearheaded by Todd McKinley, M.D., UI associate professor of orthopaedics and rehabilitation, and James Martin, Ph.D., UI research scientist; and by ISU researchers Surya Mallapragada, Ph.D., professor of chemical and biological engineering, and program director of materials chemistry and biomolecular materials; Mufit Akinc, Ph.D., professor of materials science and engineering; and Zhiqun Lin, Ph.D., ISU assistant professor of materials science and engineering.

"Our idea is to develop biomaterials capable of treating the acute mechanical damage of the cartilage at the time of injury, or what I call 'time-zero' treatments," McKinley said. "These treatments aim to prevent cartilage cell death and dysfunction and rescue the cells, which will, in turn, prevent arthritis from developing."

"This is an exciting opportunity for an interdisciplinary collaboration between researchers at the University of Iowa and Iowa State University to develop new technologies and methods to potentially make an impact on post-traumatic osteoarthritis," Mallapragada said.

If the team is successful, the collaborative effort could also have significant economic benefits.

"This collaboration brings the best of two complementary disciplines -- orthopedic surgery from the University of Iowa and materials science from Iowa State University -- to address a significant unmet medical need," said Thomas Sharpe, Ph.D., associate vice president for economic development at the UI's IOWA Centers for Enterprise. "The commercial potential for the results of this collaboration is tremendous."

PTOA is a "huge problem" according to McKinley. It accounts for almost 12 percent of all arthritis cases, and it disproportionately affects young people, who are more likely to sustain major joint fractures from motor vehicle accidents or severe sports injuries.

"If you get arthritis when you are 55 or 60, joint replacement is a great option," McKinley said. "But if you get arthritis in your 20s or 30s, there is no good bailout. These people will generally face lifelong pain, disability and loss of function. So, anything we can do to better understand and treat PTOA will really help this group of patients."

For more than a century, standard treatment for severe joint fractures has been to repair, as well as possible, the gross anatomy of the joint. The idea was that mending bones, realigning joints and smoothing joint surfaces would restore normal weight-bearing capabilities and prevent arthritis. Unfortunately, despite refinements in the surgical techniques used, the incidence of PTOA has not improved significantly.

Recent studies have shown that severe joint injury is especially damaging to cartilage, the tough yet flexible connective tissue that forms a smooth, semi-compressible, shock-absorbing gel in all the joints of the body. In particular, chondrocytes -- critical cells within cartilage that produce the molecules that make up and maintain the tissue -- are disrupted and destroyed by joint fractures. Chrondrocyte death, which occurs in several stages over a period of hours to days after the injury, appears to be the staring point of PTOA.

To directly treat at-risk chondrocytes -- those cells at the injured joint surfaces and near the cracks in the damaged cartilage -- the research team aims to develop biomaterials that can be injected directly into the injured joint. These biomaterials will accomplish two potentially therapeutic functions: recreate a near-normal physical environment for the chondrocytes, and deliver therapeutic substances to inhibit the cell-killing processes that are initiated after injury.

"We need a material that not only can seep into the cracks but can form bonds with the surrounding tissue and assume a stiffness that mimics the normal cartilage tissue," McKinley explained. "We also want the materials to deliver bioactive agents that directly target treatments to the cells most affected by the injury.

"These are significant biomaterials challenges, and we are really fortunate that we can collaborate with our colleagues at ISU, who have enormous expertise and experience in biomaterials development," he added.

Although the collaboration is just getting stared, McKinley is optimistic about the team's ability to make real progress toward developing new PTOA treatments.

"Hopefully, within a year, we might have a basic material with desirable mechanical, biocompatible and bioactive delivery properties that we can test in preclinical models," McKinley said. "If we can get that far, I think our collaborative strengths and results will put us in a great position to apply for major funding to develop this as a treatment. I would love to think we might have testable material within five years."

STORY SOURCE: University of Iowa Health Science Relations, 5135 Westlawn, Iowa City, Iowa 52242-1178

CONTACT: Jennifer Brown, 319-335-9917