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UNT System: Resource magazine >> Tissue engineering

Tissue engineering: Sci-fi becomes reality as scientists produce new skin, corneas and moreThe future of medicine has already begun at the University of North Texas Health Science Center at Fort Worth. The emerging field of tissue engineering once the stuff of science fiction and Star Trek episodes is taking shape in the center's Cardiovascular Research Institute.
    To describe what tissue engineering is, it may be helpful to say what it is not.
Dan Dimitrijevich retrieves cells, stored in liquid nitrogen.    "It's a common misconception that tissue engineering is the same as bioengineering," says Dan Dimitrijevich, Ph.D., director of CRI's Laboratories of Human Cell and Tissue Engineering. "Bioengineering involves the use of manmade materials such as plastics and metals in living systems. The artificial heart is a bioengineered product. Tissue engineering is the construction of living tissue. It's natural vs. manmade."
    Unlike prostheses made of manmade materials, engineered tissue becomes an integrated part of the patient.

The growing field
   The young but growing field of tissue engineering is truly a multidisciplinary one, with cell and molecular biologists, biomaterial and robotics engineers, designers, imaging specialists, materials scientists and others working together to develop materials that can replace or support diseased or damaged tissues and restore or improve their function.
Cells of human tissue are used to seed a “scaffold,” which is then bathed with growth factors, causing the cells to produce three-dimensional tissue.    So exactly how does one engineer tissue? "You take human tissue skin, for example and you dissociate it into its cellular components," Dimitrijevich says. These cells are used to seed a "scaffold" made of natural or synthetic materials such as collagen or a biodegradable polymer. The scaffold is bathed with growth factors, causing the cells to grow and adapt to produce three-dimensional tissue. When this engineered tissue is implanted in the body, the cells assume their intended tissue functions, and the body's own systems help it grow and form new tissues. The scaffold is gradually absorbed while the new tissue blends in with its environment.
    "We've done it with skin and corneas," Dimitrijevich says, "and we're trying to do it with blood vessels; several groups have constructed cartilage." Other researchers are working to develop strategies to repair bone, muscle, intervertebral discs and connective tissue.
    People with skin damaged by burns, cancer or diabetic ulcers are all potential beneficiaries of tissue engineering.
    "We started with skin because it's readily available," Dimitrijevich says. Plastic surgery is a major source. "But skin is a very complex tissue. The skin equivalent developed so far is not as close to skin as we would like: no hair, no sweat glands. A better target is the cornea, because it's much simpler in terms of cellular components."

Replacement vessels
   Cardiovascular disease, says Dimitrijevich, is the catalyst for the development of blood vessel replacements.
Anti-adhesion patches derived from engineered tissue may one day benefit surgeons and their patients.    "An artery is not just a pipe," he says. "If you replace it with a synthetic material, it plugs up; it doesn't become a living tissue. Even the most elaborate materials fail under the mechanical stress to which we subject our biologically produced parts."
    The use of a blood vessel taken from elsewhere in the body to replace a diseased vessel is also problematic.
    "What if the obstruction is the result of a general vascular disease in the body?" Dimitrijevich asks. "Perhaps the piece you're installing will eventually be just as troublesome as the piece being replaced."
In addition, the vessels usually available from the patient are veins, which are about one-third the thickness of arteries.
   "They're not high-pressure systems, so they can't take the stress forever," Dimitrijevich says. "We need something else, and we need more of it. Our concern is to try to engineer an arterial-type tissue for replacement in a situation like a coronary bypass."

Battling scar tissue
   The prevention of adhesions is another area in which Dimitrijevich and Health Science Center colleagues have made great strides. Adhesions, an almost inevitable result of surgery, are scar tissues that form during the healing process and glue together tissues or structures that are not supposed to be connected.
Cultures are grown from human tissue broken down to the cellular level, in preparation for engineering new tissue.     "We're not meant to be wide open, subject to probing, gloved hands, instruments and gauze," says Dimitrijevich. The injury to the exposed surfaces creates a "glue" that becomes "a surgeon's nightmare if he has to go back into the body cavity." An anti-adhesion material used in the chest cavity and other surgery sites would be a boon to surgeons and their patients.
    Dimitrijevich and his staff are studying an anti-adhesion patch derived from engineered tissue.
    "We know that the anti-adhesion patches have resolved adhesions in four to six months," he says. "We know the protected areas are free of adhesions, and the unprotected areas form adhesions."
    If warranted, three or four such patches could be used in a surgery, he says.

Challenges and possibilities
   Even with the recent success in the field of tissue engineering, obstacles remain. Cells must be expanded and introduced back into their three-dimensional architecture without being genetically altered or contaminated.
  "This is a very serious quality-control criterion," Dimitrijevich says. "You don't want to implant anything that has a predisposition to be abnormal."
    And there's the problem of rejection by the host.
    "How do we make these implants invisible or tolerated by the immune system?" Dimitrijevich asks. "Today we can give you a new heart, but then we put you on immuno-suppressive drugs that will damage your liver. We'll develop methods of disguising or screening the implant, perhaps by secreting compounds that say to the immune system, 'Don't come here ... there's nothing wrong here.' This is not impossible."
    With tissue engineering, few things, it seems, are impossible. Also under development are artificial organs such as hearts and livers, as well as restoration of cells that produce important hormones or enzymes. The day grows nearer when surgeons will routinely repair or replace body parts that have failed due to disease, injury or aging.
    "It really is Star Trek stuff," Dimitrijevich says. "Wave a wand and you're healed. It's still a dream, but a dream that is clearly in the realm of possibility."

 Institutes for Discovery?

Cardiovascular Research Institute at the University of North Texas Health Science Center at Fort Worth is one of the center's six institutes created to conduct leading-edge research on health issues that include heart disease, cancer, vision, physical medicine, public health and aging. Through these institutes, Health Science Center biomedical scientists and clinical faculty members team up with scientists and physicians from other academic institutions, government laboratories and the pharmaceutical, medical device and biotechnology industries.
The research institutes have multidisciplinary teams involved in everything from basic discovery and clinical research to clinical trials, outcomes research and, ultimately, translational research and product development.
    Funding for clinical research comes from the federal government through the National Institutes of Health and from the private sector through pharmaceutical and biotech companies. The sponsor of the research hires physicians to conduct the clinical trial in a variety of health-care settings.
    Industry licenses intellectual property from the institution and develops drugs; royalties go back to the institutions and the individuals who did the research.
    Before a pharmaceutical company can begin testing in humans, it must conduct extensive preclinical research typically involving years of experiments. The company provides this data to the Food and Drug Administration and requests approval to begin testing the drug in humans.
Clinical testing in humans is usually done in three phases, with each successive phase involving a larger number of people. Phase one studies are primarily concerned with assessing the drug's safety, and phase two with its effectiveness. Phase three involves large-scale testing of the drug for a better understanding of its effectiveness and possible adverse reactions.
    A biotech center will eventually be built in Fort Worth to house the research institutes. In addition to the Cardiovascular Research Institute, the list includes the Institute for Cancer Research, the North Texas Eye Research Institute, the Physical Medicine Institute, the Institute for Public Health Research and the Institute for Aging and Alzheimer's Disease Research.




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