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Inside Iowa State
April 28, 2000

Nerves of ... plastic

Scientist finds attention to details is paying off

by Skip Derra
Attention to detail is earning a big name for Surya Mallapragada (Sur-yah Mah-lah-prah-gada). The assistant professor of chemical engineering is getting recognition for her research into biodegradable polymer materials that could aid nerve regeneration.

Recently, Mallapragada learned that she will receive a National Science Foundation Faculty Early Career Development award for a project she is working on in micro-patterning techniques for biopolymers. The award brings with it $200,000 over four years.

Using biopolymers in nerve regeneration is not new. What is new is the level at which Mallapragada is attempting to make this happen. She is using biodegradable polymers, basically specialty plastics, to help severed nerves regenerate and reconnect cell by cell. Her work is also finding other potential medical uses (see story at right).

"As a polymer person, my focus has been on micro-patterning of degradable polymers, which is the new aspect to this," Mallapragada said.

Previous work in this area has focused on directing two severed nerve endings toward each other so they eventually link up and mend themselves. In these attempts, a conduit, or sleeve, is put over the two nerve endings to physically direct them toward each other.

While promising, the approach is limited to the ability of the nerve endings to sense each other and grow toward the other end. In humans, that limit is about 1 centimeter.

Mallapragada's work -- funded by the U.S. Department of Energy and the National Science Foundation -- goes a major step deeper, down to the cellular level of nerve regeneration. Her goal is not only to point the nerves in the right direction, but to coax them with physical, chemical and cellular cues to grow back toward the other end. She uses a conduit, but it's what she puts inside the conduit -- the micro- patterned biodegradable polymer surfaces -- that makes the difference.

"The micro-patterns on the biodegradable polymers provide channels along which the neurons regenerate," she said.

Mallapragada and her colleagues have developed methods for making minutely patterned surfaces on incredibly thin materials. The biodegradable polymer films are only a few hundred microns thick (100 microns equals 0.004 in.), significantly less than the thickness of a human hair or a single layer of skin.

On that delicate surface, Mallapragada's group makes a pattern of indentations. Each groove is roughly the size of a cell, a few microns in width.

While technologies exist to make these tiny patterns, they aren't ideal for making grooves directly on the delicate surface of biodegradable polymers. So the team is exploring new ways to make the tiny grooves.

One is to use an advanced analytical instrument called an atomic force microscope to basically scratch in the grooves. Another approach is direct laser etching of the biopolymer.

"We developed a couple of ways to do it that seem to work well," Mallapragada said. "Now we can make these patterns with adhesive protein coatings at the bottom of the grooves and use those."

In addition to the protein coatings, Mallapragada's team adds Schwann cells (living cells that promote nerve regeneration) to the polymer to encourage nerve growth. Results have been promising.

In in vitro tests so far, Mallapragada's team has found that when the grooves are at an optimal depth, are pointed in the right direction, and have the protein adhesive and the Schwann cells added, the nerves regenerate in a highly focused manner.

"There is minimal branching," Mallapragada said. "When they are growing along the grooves, they don't have the capacity to branch out a whole lot. We want them to grow toward the other side as quickly and as directly as possible."

In a few weeks, a new round of tests will determine how well the materials work in rats. The studies, Mallapragada said, will be a true test for the method because the nerve regeneration will have to be coaxed within a body, on the molecular level, in which anything can happen.



On the scientific horizon


While a major focus of Surya Mallapragada's research group is nerve regeneration, her expertise in polymer materials is branching her work into other medical directions. The ability to get tissue to grow on biodegradable polymers could lead to new ways of encouraging human tissue growth. Mallapragada also is working on sophisticated, yet easily implantable, drug delivery systems. Here's a look at what could result from those projects.

Breast replacement tissue
Mallapragada's team is exploring the possibility of using biodegradable polymers to grow breast tissue outside of the body. The work currently focuses on rat tissue but the technology, if transferred to human tissue, could be useful in reconstructive breast tissue implantation.

The idea is to provide a "polymer scaffolding" on which mammary cells would grow, providing more compatible tissue for reconstructive surgery. Methods today include taking tissue from other parts of the body or using saline implants.

"Ideally, we would take cells from the patient and we would grow and multiply them on these scaffolds, so there wouldn't be immune rejection problems," she said. "The goal is to get replacement tissue as close to natural tissue as possible."


Drug delivery
Mallapragada also has been working for a couple of years on developing more sophisticated drug delivery systems. The idea is to use a polymer that is liquid at room temperature, but becomes a gel at slightly higher temperatures. This would allow it to be injected into the body as a liquid, but harden and act as a drug dispenser once in the body.

The envisioned polymer would respond to changes and body chemistry and would dissolve into the body after it completes its dosages.

"The target molecule is insulin," Mallapragada said. "So instead of having to give yourself an injection, say at noon or before you eat, you'd get one injection every one or two weeks and it would release insulin on its own in response to changes in the body."

Mallapragada said the team still is in exploratory stages and has yet to work with insulin. "We are just tinkering around with the polymers," she said.

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