Nerve regeneration

Bellamkonda studies hydrogels for nerve regeneration

by Kathleen McDermott

Ravi Bellamkonda is a little like a matchmaker. He has to pair the right material with nerve tissue to regenerate the spinal cord.

Finding the right material has been the biggest hurdle in tissue regeneration, according to the CWRU biomedical engineer. Overcoming this obstacle could offer real hope to thousands of paralyzed people. Each year, spinal cord injuries cause paralysis in as many as 12,000 Americans.

"Nerves like to grow on things," says Bellamkonda, the Elmer Lindseth Assistant Professor of Biomedical Engineering. "They don't just float around in the body. They are anchored."

Bellamkonda believes hydrogels, a jellylike material that traps water, might be the right foundation on which nerves can grow. The three-dimensional polymer is similar to a net that allows the nerves to grow through the material. He is working to design a matrix with the right dimensions that would accomplish this.

To date, he says, most research has focused on flat plastic tissues, not three-dimensional materials.

Nerves in the peripheral nervous system regenerate better than those in the central nervous system, which includes the brain and spinal cord. Unlike the central nervous system, the peripheral nervous system has Schwann cells, which secrete molecules that promote nerve regeneration.

When nerves in the central nervous system are cut, they will not grow back, Bellamkonda said. Something switches off. By discovering what molecules are involved in that switch, researchers hope to turn that switch back on through some artificial means.

"If we can find out what the Schwann cells secrete, we can try to link this to our gels without the need for the actual Schwann cells themselves," Bellamkonda said.

He and other CWRU researchers are experimenting with natural sources such as sugar molecules for the hydrogels because the body would be less likely to reject them.

"We are trying to tailor the gel to the nerve we are trying to repair," Bellamkonda says.

The researchers are part of a new breed of tissue engineers that take cells that are useful, and organize them inside or outside the body, and then transplant those cells.

The CWRU researchers are also investigating both adhesion-promoting molecules that would attract nerves and ones that would repel nerves.

The molecules would be like traffic signals directing the nerves' actions. They would guide the nerves and their growth. The gel would serve as the physical foundation for the molecules.

"Nerves are soft tissues. The challenge is to find a material that is stiff enough for nerves to attach and grow, but at the same time, is not so stiff that it obstructs nerve growth," Bellamkonda said.

Spinal cord injuries create a cavity where scar tissue forms. This scar tissue is extremely dense and impedes nerve regeneration. Once the researchers develop the optimum gel, it can be injected in a lesion or cavity to prevent scar tissue from forming.

"The gel is a structure that permits nerve growth. What you bind your gel with determines what you want your gel to do," Bellamkonda said. "If you have a bioactive gel, you could bind scar-tissue-inhibiting molecules or nerve-growth-stimulating molecules."

In the case of the spinal cord, Bellamkonda hopes to develop a gel to regenerate nerve tissue that would not require adding cells which the immune system could reject.

He has already demonstrated through tissue culture that he can generate different responses depending on what he binds to the gel.

"By binding pieces of laminin to the gel, we have shown that we can stimulate growth from certain kinds of cells and inhibit growth from other kinds of cells," he said.

Laminin is a protein in the extracellular matrix that allows brain cells or neurons to adhere to connective tissue.

Bellamkonda plans to develop a degradable gel that would disappear once the nerve mends. Natural materials will degrade, but some synthetic ones won't. He hopes to develop a gel for clinical use in about 10 years.