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The Growth of Tissue Engineering: Charting new pathways to neural and vascular health

Perched on a shelf in Christine Schmidt's office is a metal hip implant set in clear plastic. For Schmidt, the Laurence E. McMakin Jr. Associate Professor in the Department of Biomedical Engineering at The University of Texas at Austin, the implant serves as a symbol, inspiring her research. As the field of tissue engineering advances—a field in which she is nationally recognized—artificial devices like metal hip implants may become a thing of the past.

Dr. Christine Schmidt
Dr. Christine Schmidt, associate professor of biomedical engineering at The University of Texas at Austin, conducts groundbreaking research in the field of tissue engineering, which has the potential to change the way injuries to the nervous and vascular systems are treated.

Dr. Schmidt describes the new discipline of tissue engineering as a "more natural, biologically based approach to repairing or replacing tissue functions." This interdisciplinary field applies the principles of engineering and the life sciences to the development of bioartificial tissues and organs. Tissue engineering aims to either stimulate the body to regenerate tissue on its own or, depending on the type of injury, to grow tissue outside the body that can then be implanted as natural tissue. This means that ultimately the body can heal itself, vastly improving the treatment options for numerous injuries and illnesses.

Each year, surgeons in the United States perform more than 8 million surgical procedures to treat patients who experience organ failure and tissue loss. These procedures save countless lives, but they're imperfect. Organ transplantation has limited effectiveness, given the insufficient availability of donor organs and the possibility of a body rejecting an organ. Reconstructive surgery, such as the coronary bypass, often depends on moving tissues from one part of the body to another, requiring multiple surgeries and increased risk to the patient. And mechanical devices like kidney dialysis machines cannot perform all of the functions of a particular organ and are often subject to long-term failure. Tissue engineering offers new hope. By allowing the patient to regenerate or re-grow tissues naturally, new possibilities for healing become available.

Schmidt notes that tissue engineers take multiple approaches to their work. The science asks fundamental questions about how the body heals. Tissue engineers must determine how the body normally repairs itself to determine how to encourage a wounded or diseased site to repair itself. They must investigate materials for use in this procedure and how the body interacts with those materials. They must try to understand the body's processes so that they can mimic them, or even improve upon them.

The body is continuously creating new cells, but when it comes to repair, cell growth is often undirected, even scattershot, which inhibits healing. One approach of tissue engineering is to use various biomaterial scaffoldings to help guide the body in repair and regeneration. These scaffoldings, often made with biodegradable plastic or other biocompatible materials, can be molded into any shape, allowing for use in a multitude of situations. Once inserted in the body, the scaffolding provides an actual physical structure for directing the growth of new replacement cells. Eventually, the scaffolding will disintegrate, as with dissolvable stitches, and all that is left is the body's natural tissue.

In addition, the scaffolding offers the opportunity to introduce growth factors into the body. The highly porous materials that are used for scaffolding can be modified with biomolecules, similar to the growth hormones in the body, which enhance the ability of the cells to migrate and grow. In this way, the scaffolding doesn't function simply as a physical structure, but also as a delivery mechanism for factors that trigger the proliferation of cells and encourage the surroundings essential for repair.

Another approach of tissue engineering is to work with the body's tissues in vitro. In this approach, a small sample of cells is taken from the body, usually with a needle, and then the cells are grown in great number in the laboratory. They may still be grown over scaffolding to give them the necessary shape. These tissues can then be transplanted back into the body. The hope is that someday scientists will be able to grow entire organs, such as kidneys and livers, in the lab.

Christine Schmidt's research is focused in two areas: the nervous system and the vascular system. She loves working with these systems because both affect the body as a whole, controlling functions from head to toe. As a tissue engineer, this is more exciting for Schmidt than working with a single tissue type.

A biomaterial scaffold directs growth of the body's own cells in a lab and the cells are then implanted back into the body
One approach to tissue engineering is to use a biomaterial scaffold to direct growth of the body's own cells in a laboratory and then implant the cells back into the body.

Nerve repair

Paralysis due to nerve damage is a devastating injury that debilitates 11,000 Americans each year, and working with the nervous system has long been a challenge for doctors and scientists. The system is complicated, and individual nerve structures themselves are very long.

"All the nerves in your body basically have their origins in the spinal cord," Schmidt explains, "so they're either on the outside of your spinal cord or very near it, and that's how they interface with the brain and allow you to coordinate all of your activities."

Thus, when a nerve is damaged, it is the cellular process or membrane extension that is damaged, because the nerve itself extends beyond the damaged site. If you damage nerves in your arm, they are part of a nerve structure that reaches back to the spine. It's impossible to replace that entire structure without tearing up the body.

Currently, the only hope for repairing severely damaged nerves is by removing a healthy, but less essential, nerve from another part of the body and grafting it to the damaged area. Schmidt's research with tissue engineering focuses on implanting biomaterials that encourage the body to regenerate nerves on its own. She says, "When you have a large defect in the nerve, what happens is when these fibers are regenerating, or trying to regenerate, they go all over the place. They can't find where they are supposed to go. Here we need to physically say, 'You need to go to this muscle target,' physically providing that directionality, and also providing cues that will stimulate predictable growth."

Schmidt has developed an electricity-conducting polymer that, in collaboration with a sugar molecule found in blood vessels and most tissues, can stimulate new growth in peripheral nerves. Hollow tubes made of this polymer bridge gaps in damaged nerves. Once in place, the sugar in the tubes slowly starts to break down, releasing substances that encourage the growth of new blood vessels, which in turn help the nerve to re-grow within the tube. In a period of two to six weeks, the tube itself disintegrates, leaving only the patient's own new nerves.

Endothelial cells reproduce and grow a living blood vessel that could be used in coronary bypass surgery
In tissue engineering, a biomaterial scaffold is created in the lab. Endothelial cells reproduce and grow a living blood vessel that could be used in coronary bypass surgery.
Electrical current has been proven to have a beneficial effect on nerves, so it can also be used in the repair process. The hope behind this research is that peripheral nerve regeneration can be improved and that eventually the regeneration of the spinal cord, where the most debilitating of injuries occur, will be possible.

Vascular regeneration

Schmidt's approach to vascular regeneration is to create a vascular prosthesis that could be used in coronary bypass procedures. With cardiovascular disease the leading cause of death in the United States, and over 1.4 million surgeries required annually to combat this disease, the need is pronounced. Coronary bypass at this time requires that a blood vessel be harvested from elsewhere in the patient, usually from a leg, and used as a graft to bypass occluded arteries. In collaboration with Sulzer Biologics, an Austin-based biomedical company, Schmidt and her researchers are developing in the lab a way of growing living tissue that will ideally behave like a normal blood vessel when implanted into the body.

This process once again requires the use of a biomaterial scaffold, only this time the scaffold is used in the lab. A needle would draw a small sample of blood vessel cells and grow the cells in large numbers. Then those cells would be combined with a physical structure to grow a living blood vessel. The new blood vessel could be used in the coronary bypass, rather than a blood vessel taken from elsewhere in the body. This approach would reduce the need for additional surgeries in patients, hasten healing, and lessen the long-term side effects of bypass surgery.

Taking it to the market

Schmidt's research findings are garnering attention in magazines like Scientific American. It may take a decade or more, however, before the technologies she is developing are actually used in hospitals. Schmidt says that while they have had some "very encouraging animal studies," the technology has not yet gone through clinical trials in human bodies. After more animal studies, they will seek a company sponsor to supply the funding and facilities for clinical studies and begin pursuing FDA approval.

Some practical examples of tissue engineering products are starting to appear on the market. A skin product already exists, and a cartilage product should be available soon. Another company is doing clinical trials on a collagen-based tube for use in repair of very small nerve defects. Schmidt points out that scientists and biomedical companies are beginning with the simplest structures in seeking FDA approval, and that more complicated devices, especially those with biochemical components, are much more difficult to be approved.

Although she acknowledges that the wait can be frustrating, Schmidt finds her work exciting and looks forward to a time when her research can begin trials with The University of Texas M. D. Anderson Cancer Center in Houston. She admits that the slowness of the process leads many scientists to do their research in Europe, where experimental technologies reach the patient more quickly because of the more lenient standards of their FDA equivalent.

(Left to right) Timothy Liu, Jessica Winter, Dr. Christine Schmidt and Dr. Brian Korgel
A team of engineers from The University of Texas at Austin has developed a promising new process for binding tiny semiconductor crystals known as nanocrystals, or "quantum dots," to nerve cells. Their technology could lead to advances in biomedical products ranging from hearing aid implants to robotic prosthetics. (Left to right) Timothy Liu, Jessica Winter, Dr. Christine Schmidt and Dr. Brian Korgel.
Rather than heading overseas, however, Christine Schmidt turned back to her roots. When she arrived at The University of Texas at Austin in 1996 after earning her Ph.D. in chemical engineering at the University of Illinois and completing a NIH Postdoctoral Research Fellowship at MIT, the new appointment was a homecoming for her. Schmidt received her B.S. in chemical engineering here in 1988.

She enjoys the prestige of the College of Engineering and works with outstanding students and fellow researchers. The reputation of the college has opened doors for her in the national research community. She points to the collegial sharing of information and facilities within the university as critical to her progress. "We could not have gotten as much done as we have" without access to this university's world-class resources, she says, and she feels fortunate to be part of a "friendly atmosphere, and a friendly community."

Christine Schmidt has been recognized with a host of teaching awards since returning to The University of Texas at Austin, including the award for "Outstanding Engineering Teaching by an Assistant Professor," conferred by the College of Engineering. In addition to her research, she also serves as graduate advisor in the newly created Department of Biomedical Engineering.

Schmidt's goal is to build a nationally competitive program at The University of Texas at Austin that integrates research and education in the field of molecular and cellular tissue engineering. Her groundbreaking research has the potential to change the way injuries to the nervous and vascular systems are treated, and this will eventually enable doctors to assist patients not only in healing, but in healing themselves.

Vivé Griffith

Diagrams courtesy Dr. Christine Schmidt

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  Updated 2014 October 13
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