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

820 Tissue Engineering

cell types. Although the initial motivation for these Matrices derived of naturally occuring tissues, such
studies was to undertand the mechanisms of embryonic as animal-derivedheart valves, acellular dermis, and bone-
development, the derivations are also relevant to the derived matrices, are typically of allogeneic and xeno-
engineering of tissues for clinical applications. In the geneic origin. They are prepared via physical and chem-
1970s, several studies by Douglas A. Lauffenburger (then ical treatments, such as freeze-drying, cross-linking by
at the University of Illinois, now at M.I.T.) and Robert T. glutaraldehyde, and detergent-mediated removal of cells,
Tranquillo (University of Minnesota) set the stage for the in order to enhance their physical properties and remove
modeling of intracellular signaling processes as well as any antigen-bearing cells which could trigger undesirable
cell-migration phenomena. immune responses. These materials retain the chemical
composition and microarchitecture proper to the tissue
that they are derived from, which can enhance their func-
II. FUNDAMENTALS OF TISSUE tion. For example, blood vessel growth into an acellular
ENGINEERING dermis applied onto a burn wound will preferentially oc-
cur in the spaces formerly occupied by the blood ves-
A. Biomaterial Design sels in the original intact tissue. Soluble factors are often
retained within the matrix and can have pro-angiogenic
1. Materials Used in Tissue Engineering
(small intestinal mucosa) or anti-angiogenic (amniotic
The vast majority of mammalian cells are anchorage de- membrane) properties. A disadvantage of these materials
pendent and therefore must attach and spread onto a sub- is that their chemical composition is often only partially
strate to proliferate and function normally. While in tra- known, availability may be limited, and issues such as
ditional tissue culture systems two-dimensional surfaces batch-to-batch variation and potential contamination with
are used to grow cells, tissue engineering often requires pathogens must be addressed on a continuous basis.
the use of three-dimensional matrices which allow cell Most of the natural extracellular matrix materials, ex-
ingrowth and organization reminiscent of actual tissues cept bone, can be at least partially solubilized by chemical
found in vivo. The choice of extracellular matrix mate- processing and reconstituted into three-dimensional gels
rial is highly dependent on the intended use of the tissue of any shape or form. Although the microarchitecture is
(whether its function is structural or biochemical or both) lost, these reconstituted matrices retain many chemical
and on the respective roles of materials and cells in the features of the extracellular matrix proteins including
reconstructed tissue. A list of three-dimensional materials bound growth factors found in the original material. Com-
used in tissue engineering is given in Table II. monly used reconstituted matrices include type I collagen

TABLE II Materials Commonly Used in Tissue Engineering
Name Composition Applications
Intact extracellular matrices
Amniotic membrane Collagen, fibronectin, laminin, GAG, growth Corneal epithelium
factors
Acellular dermis Collagen, laminin, elastin Skin epithelium
Small intestinal mucosa Collagen, fibronectin, GAG, growth factors Smooth muscle (vascular, urogenital)
Carbonate apatite (dahllite) Calcium/magnesium carbonate/phosphate Bone
Reconstituted extracellular matrices
Type I collagen gel Collagen Skin dermis, tendon, hepatocyte
a
Collagen–GAG complexes Collagen, GAG Skin dermis, tendon, nerve guidance
Engelbreth–Holm–Swarm tumor matrix Collagen, laminin, GAG, growth factors Hepatocyte
gel (Matrigel)
Synthetic matrices
Carbonate apatite Calcium/magnesium carbonate/phosphate Bone
pLA/pLGA co-polymer Poly(lactic-co-glycolic) acid Cartilage, bone, epithelium (gut, urogenital),
hepatocyte
Dacron ® Polyethylene teraphtalate Vascular endothelium
Gore-Tex ® Expanded polytetrafluoroethylene Vascular endothelium
pHEMA/MMA co-polymer Poly(hydroxyethyl methacrylate) Vascular endothelium
a
GAG = glycosaminoglycan.