Technion breakthrough improves chances tissue grafts will survive and thrive

tissue grafts
This figure shows the blood vessels in the abdominal muscle of mice (red) and the engineered tissue grafts implanted into this muscle (green). Before the transplant the engineered blood vessels underwent static stretching, which brought about the arrangement of the vessels to grow in the parallel direction of the stretching regimens. As you can see, after implantation a very good connection was forged between the engineered blood vessels and the host vessels because of matching network arrangements

Researchers from the Technion-Israel Institute of Technology and colleagues in the U.S. have developed technology to tailor grafted tissues that can respond to certain natural forces affecting blood vessels. The researchers also found that matching the structure of the engineered vessels to the structure of the host tissues at the site of implantation helps the tissue implant integration, improving the chances that grafted tissues will survive better. The findings were published recently in The Proceedings of the National Academy of Sciences (PNAS).

tissue grafts
Prof. Shulamit Levenberg

“Developing functional and mature three-dimensional (3D) blood vessel networks in implantable tissues is critical when using these engineered tissues to treat a number of conditions, such as cardiovascular disease and trauma injuries,” said lead researcher Prof. Shulamit Levenberg of the Technion Department of Biomedical Engineering. “Matching the tissue structures will improve the long term viability and strength of tissue grafts when new blood vessel growth – called ‘angiogenesis’ – can be manipulated and exploited for the purpose of attaining optimal blood supply.”

tissue grafts
Fig 1: The figure presents the blood vessel arrangement under static stretching and under the influence of materials inhibiting both: (1) the ability of the cell to activate force or (2) the ability to form vessel networks. The findings showed that there is a correlation between the ability of cells to activate force and the cell’s ability to form blood vessel networks

The team’s laboratory studies were aimed at determining just how vascular networks are regulated by various kinds of “tensile forces”- by stretching the constructs (3D engineered tissues).

“Although mechanical forces play a central role in all biological processes as well as influence the shape and organization of cells, mechanical forces had not been previously investigated in relation to vascular networks in 3D,” explained Prof. Levenberg. “Our study used a number of techniques to monitor the impact of tensile forces on vascular network construction and properties.”

The researchers examined the effects of cell-induced forces on vascular networks by applying variety of stretching forces, both cyclic (on-and-off) and static (constant) forces.  The researchers found that the vessels aligned in response to the stretch.

To test the effects vessel alignments on tissue integration, the researchers grafted engineered tissues into mouse abdominal muscles with the vessel direction placed both parallel and vertically to the natural mouse muscle fibers (host tissues).  They found that tissues with vertically implanted blood vessels had greater stiffness and strength when they corresponded to the vertical direction of the host tissue fibers.

This study was conducted in collaboration with Professor Dave Mooney, of Harvard University, who hosted Prof. Levenberg during her sabbatical year. The project was carried out by Dr. Dekel Dado-Rosenfeld as part of her PhD thesis, under the mentorship of Prof. Levenberg. Dr. Dado-Rosenfeld is currently a postdoc at the Massachusetts Institute of Technology, under the auspices of the MIT-Technion Post-Doctoral Fellowship