Page 267 - Academic Press Encyclopedia of Physical Science and Technology 3rd BioTechnology

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Encyclopedia of Physical Science and Technology EN016J-783 August 1, 2001 10:58

818 Tissue Engineering

Stem cell An undifferentiated cell which has a high The first man-made material designed to promote cell
replicative potential and has the ability to convert into ingrowth and permanent incorporation into the body was
a wide variety of cell types expressing differentiated developed by Ioannis V. Yannas (Massachusetts Institute
functions. of Technology) and John F. Burke (Massachusetts General
Xenogeneic Qualifies tissues used for transplantation Hospital and Shriners Burns Hospital, Boston) in 1980. It
across species. consists of a bovine collagen–glycosaminoglycan matrix
made from chemical extracts of bovine skin and shark
cartilage overlaid with a thin silicone membrane. This
TISSUE ENGINEERING can be defined as the appli- construct is applied onto deep burn wounds to faciltate
cation of scientific principles to the design, construction, the regeneration of the dermal layer of skin, after which
modification, growth, and maintenance of living tissues. the silicone sheeting is removed and replaced by a skin
The main goals of tissue engineering are to help with the graft. This product was approved by the U.S. Food and
repair and regeneration of tissues in vivo and to grow Drug Administration (FDA) for clinical use in 1996 and
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tissues in vitro for use as models for physiological and is commercialized under the name of Integra (manufac-
pathophysiological studies, as well as to provide replace- tured by Integra LifeSciences, Inc.).
ment parts for the body. Sometimes, tissues will repair Advances in cell culture techniques have also played
and form scar tissue or tissue which does not exhibit a a pivotal role in the development of tissue engineered
normal function and/or appearance. For example, tissue products. A landmark discovery by Howard Green and
engineers have implanted polymeric tubes to promote the James Rheinwald (Harvard Medical School) in 1975 is
growth and reconnection of damaged nerves and used the demonstration that keratinocytes from the skin epi-
cultured skin grafts to cover deep burn wounds. Some- dermis could be cultured in vitro using a “feeder layer”
times, the normal tissue regeneration process is too slow of mouse fibroblasts. Keratinocytes were harvested from
and temporary palliative care must be used to supply the patients with extensive burns and propagated in vitro un-
vital missing functions to the patient. For example, tissue til the available surface area of cultured skin was suffi-
engineers are currently developing bioartificial liver as- cient to use as an autologous grafting material. In 1988,
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sist devices for acute liver failure patients. Such devices Genzyme Corp. began the Epicel service and more re-
may be used to buy time until a transplantable organ is cently extended this concept to the propagation of chon-
available or may allow the patient’s own liver function drocytesforthetreatmentofcartilagedefectsinkneejoints
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to return to recover, thereby obviating the need for liver (Carticel ).
transplantation altogether. Other pioneering work in tissue engineering includes
studies published by Eugene Bell (Massachusetts Institute
of Technology) between 1979 and 1981 describing the first
I. A BRIEF HISTORY OF TISSUE matrix–cell composite grown in vitro prior to in vivo im-
ENGINEERING plantation. Human dermal fibroblasts were seeded into
collagen gels to produce a bioartificial dermis, which
The use of materials derived from animal sources for mak- was then overlayed with a monolayer of epidermal cells
ing tissue replacement parts has been common practice (keratinocytes) to generate a full-thickness skin equiva-
for over 25 years with the use of bovine and porcine heart lent. This product, available under the name of Apligraf ®
valves in cardiovascular surgery procedures. The source (Organogenesis, Inc.), was approved by the FDA in 1998
materials require special chemical processing and trim- for treating nonhealing venous ulcers and, more recently,
ming before they are ready for use, all of which require diabetic foot ulcers. Unlike autologous skin grafts, which
extensive research and development. These devices may require several weeks to become available after harvesting
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thereforearguablybeconsideredthefirsttissueengineered the source cells from the patient, Apligraf is made of al-
devices used clinically. The function of these devices, logeneic cells obtained from donated human foreskins and
however, is primarily a mechanical one and such implants is a ready- to-use product available within a short notice.
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do not significantly become repopulated with the host’s On the other hand, since Apligraf contains allogeneic
cells (or, if they do, they do not significantly contribute cells, it eventually becomes rejected by the recipient’s im-
to their function). More recently, biologically derived ma- mune system, and repeated treatments may be necessary
trices, such as acellular human dermis (AlloDerm , Life- until the ulcer heals on its own.
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Cell, Inc.), which is made by treating human cadaver skin Beyond the few tissue engineered products which are
in such a way that no cells but the extracellular matrix re- currently used clinically, there are many others in the
main, have been used in order to promote the regeneration pipeline of biotechnology companies as well as research
of tissue in deep burn wounds. laboratoriesaroundtheworld.Oneimportantareaoftissue