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Researchers pursue ideal ingredients for cartilage recipe

September 16, 2015

A 5-year, $2 million grant from the National Institutes of Health will allow researchers at Case Western Reserve University and Harvard University to build a microfactory that churns out a formula to produce joint cartilage.

The end product could one day benefit many of the tens of millions of people in the United States who suffer from cartilage loss or damage.

Articular cartilage coats the ends of long bones, bearing loads, absorbing shocks and, with sunovial fluid, enabling knees, hips and shoulders to smoothly bend, lift and rotate. Since the tissue has little ability to repair or heal itself, there is a critical need for new therapeutic strategies.

Artificial substitutes can't match the real thing, and efforts to engineer articular cartilage have been stymied by the complex process of turning stem cells into the desired tissue.

"Cells are very responsive to cues presented to them from their surroundings," said Eben Alsberg, professor of biomedical engineering and orthopedic surgery at Case Western Reserve. "We hope to learn what signals can steer stem cell behavior with the ultimate goal of engineering cartilage quickly with the functionality of natural tissue,"

He's teaming with Ali Khademhosseini, a professor at Harvard-MIT's Division of Health Sciences and Technology, on the research.

"We will do a systematic study of the effects of cellular microenvironmental factors on cellular differentiation and cartilage formation," Khademhosseini said

Alsberg has previously coaxed stem cells obtained from adult bone marrow and fat tissue into cartilage. His lab has designed an array of new materials with controllable characteristics, such as physical properties, cell adhesive properties and the capacity to control the delivery of bioactive factors.

By controlling the presentation of these signals to cells, both independently and in combination, along with the regulated presentation of mechanical signals, his group aims to identify key cues that are important for changing stem cells into cartilage-producing cells.

Khademhosseini is an expert in microfabrication, and his lab specializes in developing micro- and nano-scale technologies to control cell behavior. He will develop a microscale high-throughput system at his lab that will speed testing and analysis of materials engineered in Alsberg's lab.

"The fabrication of such a system that can test many different such combinations in a high throughput manner is rather challenging," Khademhosseini said. "We will use advanced microfluidics and fabrication technologies combined with biomaterials to be able to do this."

The team expects to test and analyze more than 3,000 combinations of factors that may influence cell development, including different types and amounts of biochemicals, extracellular matrix properties, compressive stresses and more. They hope to begin testing conditions identified from these studies in animal models by the end of the grant term.
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Case Western Reserve University

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