The Progress and Promise of Tissue Engineering
A NextGen Free-Standing Perspective Article
Once confined to the realm of science fiction, the creation of replacement human body parts has become reality. A term coined in the 1980s, "tissue engineering," also often referred to as "regenerative medicine," was defined by two of its earliest pioneers, chemical engineer Robert Langer and transplant surgeon Joseph P. Vacanti as "an interdisciplinary field that applies the principles of engineering and life sciences toward the development of biological substitutes that restore, maintain, or improve tissue function or a whole organ." (1)
Advancements in the field have been motivated in no small part by the growing demand for organ transplants, as approximately 15% of the candidates for a liver or heart transplant in the United States die while waiting for a suitable donor, and the demand for transplants seems to be steadily increasing. In 2003, there were 82,867 patients on waiting lists for organ transplants between January and July, but less than 15,000 patients actually received them. (2)
Bringing together biologists, chemical engineers, materials scientists, surgeons, and other clinical researchers, tissue engineering lies at the forefront of the next generation of cutting-edge, multidisciplinary biomedical research. The raw materials used in the creation of engineered tissues are cells, biomaterial scaffolds, and bioactive molecules. Ideally, a small sample of the patient's own cells would be expanded ex vivo, or outside of the body in laboratory culture, for subsequent seeding and transplantation in order to avoid complications of immune rejection. The biomaterial scaffold serves to house the cells and direct their three-dimensional growth, exposing them to an adequate perfusion of nutrients, oxygen, metabolic products, and a cocktail of appropriate growth factors to guide their differentiation and function. (3) The polymeric chemical composition of the biomaterial scaffold is tailored to achieve the desired biodegradability (such that the scaffold may be removed naturally by the body), mechanical properties, porosity, and lack of immunogenicity (the effect of causing an immune response from the host).
The greatest success in the field thus far has been in the realm of skin tissue engineering. Complete epidermal and dermal bi-layer tissue mimetics have successfully made their way from the laboratory bench to patient treatment. FDA-approved products such as Dermagraft (Smith & Nephew) and Appligraf (Organogenesis) have found their way into the clinical treatment of burn victims and other patients afflicted with skin disorders that require skin graft treatment. (4) The skin substitutes usually consist of an ex vivo-expanded population of the patient's own skin cells seeded atop a layer of chemically engineered collagen or other cell-friendly polymers.
Despite this remarkable success, skin tissue engineering is a relatively simple feat when compared to the fabrication of other tissues, such as nerve, pancreas, or liver tissue. An interview with Dr. Joseph Vacanti, principal investigator at the Laboratory for Tissue Engineering and Organ Fabrication in the Center for Regenerative Medicine at Massachusetts General Hospital, brought to light some of the major hurdles which need to be overcome for these other tissues. Success in skin tissue engineering, he maintains, is attributable to the fact that epidermal keratinocytes and the skin's extracellular matrix primarily plays a structural rather than metabolic role. This is in stark contrast to liver cells (hepatocytes), the focus of Vacanti's laboratory, in which the complexity of hepatocytes is orders of magnitude greater than skin cells due to their chemical processing functions and their close integration into the blood vessel network. According to Dr. Vacanti, for a tissue-engineered device seeded with hepatocytes to be feasible over time, researchers face the challenge of creating a vascular network to support the cells. The current technology aimed at doing this is known as microelectromechanical systems (MEMS). MEMS consists of a polymer-based, three-dimensional capillary bed system separated from a hepatocyte-containing chamber by a semipermeable membrane that creates a size barrier to allow small molecules such as oxygen, nutrients, and other metabolites to selectively diffuse through. Surgical trials of animal implantation are underway.
The greatest hurdles facing tissue engineering as a long-term viable biotechnology are those of immunogenicity and off-the-shelf availability. (6) While skin tissue engineering has been successful in the engineering of artificial grafts using a patient's own cells, other cell types are much less amenable to ex vivo expansion, such as liver cells. Moreover, the time required to create patient-specific constructs is long and requires more than one surgical procedure. This raises serious questions concerning the cost, efficiency, and feasibility of large-scale manufacturing of tissue-engineered medical products. Donor cells also face the inherent problem of immune rejection when implanted into another patient's body, thus limiting the off-the-shelf availability of current cell-based devices. The solution, however, may lie within the realms of genetic engineering and stem cells, which offer strategies to circumvent such issues. Still in its infancy, tissue engineering holds great promise for the future of transplant medicine. 
Elie R. Balesh is a writer for the Next Generation and a member of the Harvard College Class of 2007.
Joseph P. Vacanti, M.D. is John Homans Professor of Surgery at Harvard Medical School, Surgeon in Chief at Massachusetts General Hospital for Children, and Director of the Laboratory for Tissue Engineering and Organ Fabrication at Massachusetts General Hospital.
Work Cited- Fuchs, J., Nasseri, B., Vacanti, J. Tissue engineering: a 21st century solution to surgical reconstruction. Ann Thorac Surg 2001;72:577-91.(Text)
- Stock UA, Vacanti JP (2001) Tissue engineering: current state and prospects. Annu Rev Med 2001;52: 443-451.(Text)
- Moreno-Borchart, A. Building organs piece by piece. EMBO Reports 2004;5;1025-1028.(Text)
- Horch, R., Kopp, J., Kneser, U., Beier, J., Bach, A. Tissue engineering of cultured skin substitutes. J Cell Molec Med 2005;9;592-608.(Text)
- Laboratory for Tissue Engineering and Organ Fabrication Web Site. <http://www.mgh.harvard.edu/tissue/projects/mains/mmain.html> (Text)
- Ahsan, T., Nerem, R. Bioengineered tissues: the science, the technology, and the industry. Orthod Craniofacial Res 2005;8;134-140.(Text)