A continuing program of research and development focuses on engineering of functional cartilage and cardiac muscle for scientific research and for eventual use in transplants. The program involves the use of cells, polymer scaffolds, and bioreactor vessels. A polymer scaffold serves as a three-dimensional structure to which cells can attach. Once attached, the cells can regenerate full tissues, and then the polymer scaffold becomes biodegraded when no longer needed. A bioreactor provides an appropriate environment and physiological signals during the development of tissues.
Rotating bioreactors were originally developed by NASA to culture cells on Earth in environments that simulate some aspects of microgravity. In one bioreactor configuration, cells are cultured in an annular space between two cylinders that are rotated as a solid body. In the present program, bioreactors of this configuration were adapted for tissue engineering by adjusting the speed of rotation to maintain large tissues (disks 5 to 10 mm in diameter and 1 to 5 mm thick) freely suspended during culturing. Engineered cartilage capable of withstanding mechanical loading and engineered cardiac tissue that contracted in response to electrical stimulation were grown in these reactors.
The cartilage-tissue-engineering mod-el system developed in this program was selected for the first long-term cell-culture study in outer space, using bioreactors developed by NASA that were both rotated and perfused aboard U.S. space shuttles (STS-79 and STS-81) and the Mir space station (September 1996 to January 1997). Tissue mass increased on Mir as well as in control specimens cultured on Earth, and the component cells remained alive and metabolically active. Specimens grown on Earth retained their initial discoid shape, contained high fractions of glycosaminoglycan [GAG (a key cartilage component)] and had high compressive stiffnesses. In contrast, constructs grown on Mir tended to be smaller, to be more nearly spherical, and to have lower GAG fractions and compressive stiffnesses. This study proved the feasibility of long-term cell culture in outer space, and provided a basis for further studies aimed at developing countermeasures for prolonged human spaceflight.
Rotating bioreactors also provide favorable environments for engineering tissues on Earth. Engineered cartilage cultured 6 weeks in rotating bioreactors has slightly higher cellularity, 68 percent as much GAG, 33 percent as much collagen type II, and 19 percent of the compressive stiffness of native cartilage. Composites based on engineered cartilage were recently used to resurface knee joints in adult rabbits. After 6 months, engineered cartilage was preserved at the joint surfaces, where it remodeled to the dimensions of the surrounding host cartilage. The subchon-dral tissue remodeled into mineralized trabecular bone.
Engineered cardiac tissue cultured for 1 week in rotating bioreactors was found to exhibit 26 percent of the cellularity, 90 percent of the conduction velocity, and 65 percent of the maximum capture rate of native neonatal heart tissue. Electrical impulses were found to propagate between extracellular electrodes spaced up to 5 mm apart in tissue up to 0.1 mm thick, and the engineered cardiac tissue could be stimulated to contract at desired frequencies ranging from 60 to 270 beats per minute. However, the dimensions and mechanical properties of engineered cardiac muscle do not yet favor the use of this tissue to repair damaged cardiac tissue in experimental animals.
This work was done by Robert Langer, Lisa E. Freed, and Gordana Vunjak-Novakovic of Massachusetts Institute of Technology for Johnson Space Center.
In accordance with Public Law 96-517, the contractor has elected to retain title to this invention. Inquiries concerning rights for its commercial use should be addressed to
Lisa E. Freed, M.D., Ph.D.
Harvard-MIT Division of Health
Sciences and Technology
77 Massachusetts Avenue
Cambridge, MA 02139
Tel: (617) 253-3858
Fax: (617) 258-8827
Refer to MSC-22715, volume and number of this NASA Tech Briefs issue, and the page number.