Complete joint replacement, while highly successful, is major surgery with rigorous and often painful therapy regimens and lengthy recovery time. Driven by the need to develop more effective therapies requiring less recovery time for common joint conditions such as osteoarthritis, an international team including National Institute of Biomedical Imaging and Bioengineering (NIBIB)-funded researchers has reportedly developed an integrated two-part scaffold for implantation into damaged joints with cartilage scaffold made from silk, and bone scaffold made from ceramics.

This combination of materials mimics the cartilage and bone of natural joints in both mechanical strength and pore structure. It also allows stem cells to successfully populate the graft and differentiate into cartilage and bone cells. The cells fill the damaged areas to reconstitute the original structure of the joint, after which the scaffold biodegrades, leaving the smooth surface required for a pain-free, functioning interface. The scaffold is a significant step toward improved and lasting treatment of common and often debilitating joint injuries.

“It’s a challenging problem to tackle,” said Rosemarie Hunziker, Ph.D., director for the program for tissue engineering. “One of the big problems in cartilage tissue engineering is that the cartilage does not integrate well with host tissue after implantation, so the graft doesn’t ‘take.’ In this new approach, there is a greater chance of success because the materials have architectures and physical properties that more closely resemble the native tissue.”

Existing clinical treatments generally fall into two categories. Non-surgical treatment involves immobilization and restricted weight-bearing, with gradual progression of weight-bearing and physical therapy. Current surgical treatments include debriding (removing injured cartilage and bone), or grafting of new bone and cartilage. Both surgical techniques are aimed at restoring the natural shape and gliding surface of the cartilage. The existing approaches are typically successful at alleviating pain and restoring some function in the short term, but rarely achieve full restoration of functional osteochondral tissue in the long term. In particular, poor healing of bones that were cut in surgery is a common problem.

NIBIB-funded researchers at Tufts University in Medford, Mass., and researchers at the Biomaterials and Tissue Engineering Research Unit at the University of Sydney, Australia, teamed up to develop materials that mimic the unique and complex nature of osteochondral tissue. The goal was to develop an artificial scaffold with mechanical and bioactive properties that successfully promotes healing of damaged tissue to restore a fully functional joint. Bioactive properties include having a scaffold with the correct pore sizes that allow cells to enter and populate the scaffold after implantation, and being fully degradable over time to remove barriers to tissue regeneration. 

In tests that measure how the materials hold up under stretch and compression forces, the biphasic scaffold maintained its structural integrity under forces that were much higher than would be encountered in the body under physiological conditions. Also, the bonding between the two phases remained intact under very high stretch and compression tests. Tested in cell culture, the researchers found that each phase of the scaffold promoted population by human mesenchymal stem cells and their differentiation into the proper cell type. The interface between the two phases also allowed cell migration and interaction between phases. Tests of gene expression in tissue culture revealed that the genes expressed from the cells populating the silk and ceramic phases were indeed those expected from cartilage and bone, respectively.

“We are extremely encouraged by the outstanding mechanical and bioactive properties present in these materials that also feature relatively simple and reproducible fabrication methods,” said David L. Kaplan, Ph.D., chair of the department of biomedical engineering at Tufts University.

For more information, visit www.nibib.nih.gov.