NIH-Funded Researchers Make Progress Toward Regenerating Tissue to Replace Joints

A team of NIH-funded researchers has successfully regenerated rabbit joints using a cutting edge process to form the joint inside the body, or in vivo. Regenerative in vivo procedures are performed by stimulating previously irreparable organs or tissues to heal themselves. In this study, bioscaffolds, or three-dimensional structures made of biocompatible and biodegradable materials in the shape of the tissue, were infused with a protein to promote growth of the rabbit joint.

The experiment demonstrated the feasibility of an approach to growing dissimilar tissues, such as cartilage and bone, derived entirely from the host’s own cells. Results of the study are in the July 29 issue of The Lancet.

Regeneration activity relied on the host's supply of cells to the joint, local tissue response, and functional stimulation to recreate the entire surface of the joint cartilage together with the bone. The approach sidesteps problems encountered in transplantation of cells grown ex vivo, such as immunological rejection, pathogen transmission, and potential formation of tumors.

The research team laser-scanned the surface contours of a rabbit forelimb joint and made a 3-D model that was used to create an anatomically dimensioned bioscaffold. Some rabbits in the study received a bioscaffold infused with a collagen gel loaded with the protein, called transforming growth factor beta 3 (TGFB3), while other rabbits received bioscaffolds without TGFB3.

Bioscaffolds infused with TGFB3 recruited 130 percent more cells and grew a whole layer of cartilage tissue with greater compressive and shear properties than those who received the bioscaffold without the TGFB3. Rabbits with TGFB3-infused bioscaffolds resumed weight-bearing activity and locomotion three to four weeks after joint replacement. At five to eight weeks after surgery, these rabbits moved nearly as well as the control rabbits. By contrast, rabbits whose bioscaffolds did not contain TGFB3 continued to limp.

The research team included Chang H. Lee, Avital Mendelson, Eduardo K. Moioli, and Jeremy J. Mao of Columbia University Medical Center Tissue Engineering and Regenerative Medicine Laboratory, New York City; James L. Cook, University of Missouri School of Veterinary Medicine, Columbia; and Hai Yao, Clemson University and Medical University of South Carolina Department of Bioengineering, Charleston.

"Cartilage is one of the most resistant tissues for regeneration. This is the first time an entire cartilage joint was regenerated. By successfully regenerating cartilage in this way, we hope that this approach would work with other tissues without cell transplantation," Dr. Mao said.

Future work could replace arthritic joints in pre-clinical animal models and ultimately in arthritis patients who need total joint replacement.

Osteoarthritis is the world's leading cause of chronic disabilities. The disease involves structural breakdown of cartilage and bone, and affects approximately 80 million people in the United States.

"The aging population with arthritis is expected to double by 2030, when the last of the baby boomers become seniors," adds Dr. Mao. Current joint replacements have only a 10–15 year lifespan which may not be long enough for the increasing numbers of arthritis patients who are 65 years old or younger.

"The potential for in vivo tissue regeneration is enormous," says Dr. Christine Kelley, director of the NIBIB Division of Discovery Science and Technology. "Dr. Mao's work with repairing damaged bone and cartilage by recruiting host cells within a living animal could help pave the way for advanced treatment of arthritis and other diseases in humans."

This work was supported by grants from the National Institute of Biomedical Imaging and Bioengineering (NIBIB) (National Institutes of Health grant R01EB002332) and New York State Stem Cell Science.

NIBIB, a component of NIH, is dedicated to improving health by bridging the physical and biological sciences to develop and apply new biomedical technologies. Additional information and publications are available at http://www.nibib.nih.gov.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

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