In general, the most common approach in tissue engineering is to develop tools as needed. Physicians treat patients and define the requirements for a better cure. Then, biologists study the targeted problem and learn what the mechanism is that caused the failure. Later, chemists and materials scientists manufacture the tools needed to treat the problem. Finally, the tools are delivered to doctors to treat the patients. Thus, tissue engineering requires a good understanding of how body parts work and come into existence, and this involves precise and sensitive application. Precise, aware and regular study of the interactions involved in tissues and organs must be practiced by the researchers who are interested in developing techniques for the manufacture of potential body parts. One of the first scientific approaches used for tissue engineering is to simply inject the body with molecules, such as growth factors, which are known to promote organ formation.
The growth factors are naturally occurring proteins which are assigned for cell proliferation and differentiation. Different parts of the body require different types of growth factors to signal to the cells to multiply or to replace the cells which have died or have been damaged. For example, it has been discovered that bone morphogenic proteins are responsible for the beginning of bone cell reproduction. For someone with a fractured bone that can not heal on its own within a reasonable period of time, the injection of bone growth factors to the site can direct the body to where bone cells are needed to be produced to repair the fracture.
In more severe conditions, the body may not receive the signal only with a simple injection of the growth factors. In this case, there is a need for more intricate treatment. Another way to treat organ malfunction starts with the harvesting of cells from the patient. The harvested cells can be multiplied in an artificial scaffold to eventually be implanted into the wound site. Because cells inhabit a different world than we do, we need a way to speak their language. The artificial scaffold should provide everything a cell needs and be able to direct the targeted cells toward the desired purpose. Basic knowledge gained from biology can help us to design potential artificial environments for cells.
A critical challenge in tissue engineering is how to design and make the artificial scaffolds. The cells must be fed through the blood vessel and are grown in the scaffold by the body; the scaffold should be able to communicate with the cells and finally the scaffold should disappear when its mission has been completed. The best example of a perfect scaffold is the natural environment of the cells, the extracellular matrix (ECM). The ECM provides support and anchorage for the cells and regulates communication between cells. There are various biological signals found in the ECM that help cell survival. For example, proteins called collagens provide mechanical support for cells through adhesive proteins in the ECM and the handles on the cell surface, known as integrins. Cell adhesion is crucial for cell survival and proliferation. Growth factors are also found in the ECM for cell organization. Some growth factors promote blood vessel formation, which can provide nutrients for cells. Therefore, a simple artificial environment should include various biological signals found in the ECM.
Currently, there are natural and synthetic scaffolds that are being used to generate the optimal environment for cells. Natural polymers such as collagen, chitosan or glycosaminoglycans, and synthetic polymers, including polylactic acid, polyglycolic acid, polycaprolactone or self-assembled nanofibers, are some of the materials used or considered for scaffold production. Natural polymers can be obtained easily, however biological contamination is a concern since they are produced using components from animals or microorganisms. Synthetic polymers can usually avoid the problem of contamination. Sometimes the ability to process the polymers can be problematic. Researchers have developed self-assembled nanofibers to overcome the problems that arise with synthetic and natural polymers. These nanofibers are composed of small molecules which are programmed to come together under control and to form larger structures. The nanofibers in the solution can form a three-dimensional network and convert into a self-supporting gel which can encapsulate cells as an artificial scaffold. In general, small bioactive molecules can be conjugated to the self-assembled molecules or can be encapsulated in situ in the 3-D network of fibers.
One of the recent uses of tissue engineering is to replace tissue that has been damaged by cancer. Cancer surgery is one of the most challenging types of surgery in that the defective tissue must be reconstructed afterwards. Improvement in surgical technology gives the chance of transferring a tissue from different sites of the body but unfortunately most of the time it is not the same tissue, and does not have the same texture or function. Reconstructing a resected tongue or the feeding tube is possible with the use of skin from the leg or forearm. But this skin does not provide the normal mucosal function, so it does not enable taste or sense to be perceived in the same way nor does it produce mucus in the same way. Together with advances in tissue engineering surgeons have started using the tissue-engineered mucosa of patients to reconstruct the mouth and feeding passage defects, instead of using the skin from chest, leg or forearm skin. These clinical applications of tissue engineering are in their very early stages, but it would not be surprising if we were able to reconstruct a lost organ from a similar one in the future. It would be exciting to be able to replace the tongue of a tongue cancer patient with a brand new tongue grown from his/her own tissues produced in a laboratory. Tasting the same…sensing the same…moving and even articulating the same…instead of having a piece of meat from another part of the body…
Innovative and imaginative work which has been inspired by natural materials demonstrates how the treatment of organ malfunctions is feasible. Efforts in biotechnology to develop tissue-engineered products will benefit many people who are searching for a healthier life. Potentially, in the near future, tissue-engineered products will be more widely used to treat bone fractures, serious skin burns, spinal cord injuries, diabetes, and heart diseases. Before implanting the tissue-engineered products, it is vital that there be extensive testing of the materials to be used. Toxicology and efficacy studies should be performed on the materials to prevent damage to the original healthy cells, and the new cells and regenerated tissue must be compared to original healthy cells and tissue.
Mustafa Guler has a PhD in chemistry. He is currently a research associate at Northwestern University, Chicago, IL. Joseph Coreman is a medical doctor at the Ohio State University Medical College, Columbus, OH.
Khariwala SS, Vivek PP, Lorenz RR, Esclamado RM, Wood B, Strome M, Alam DS. Swallowing outcomes after microvascular head and neck reconstruction: a prospective review of 191 cases. Laryngoscope. 2007 Aug; 117(8):1359-63.
Sauerbier S, Gutwald R, Wiedmann-Al-Ahmad M, Lauer G, Schmelzeisen R. Clinical application of tissue-engineered transplants. Part I: mucosa. Clin Oral Implants Res. 2006 Dec; 17(6):625-32.
Hotta T, Yokoo S, Terashi H, Komori T. Clinical and histopathological analysis of healing process of intraoral reconstruction with ex vivo produced oral mucosa equivalent. Kobe J Med Sci. 2007;53(1-2):1-14.
Ratner, Buddy D. “Biomaterials Science – An Introduction to Materials in Medicine” Elsevier, 2004.
Lanza, Robert P., Robert S. Langer, William L. Chick, “Principles of Tissue Engineering”, Academic Press, 1997.
Alberts, Bruce, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, Peter Walter, “Molecular Biology of the Cell” Garland Science, 2002.