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

838 Tissue Engineering

FIGURE 18 Possible equilibrium configurations of two cell types A and B mixed together depending on the relative
tissue surface tension of each tissue. Cells will not remain mixed unless the adhesion force of A to B exceeds the
average cohesion of tissues A and B (left-most case). Otherwise, cells segregate and the most cohesive tissue will
tend to remain in the center while the other tissue spreads around it.
host’s vascular system in order to provide efficient nutri- skin has several applications, including the treatment of
ent supply and waste removal. burn wounds and nonhealing diabetic and venous leg ul-
cers, as well as pressure sores. Bioartificial skin consists
of a dermal equivalent made by seeding collagen gels or
III. APPLICATIONS OF TISSUE meshes made of biodegradable polymers with dermal fi-
ENGINEERING
broblasts. The dermal equivalent may have an overlay of
silicone sheeting to prevent evaporative loss of water (a
A. Connective Tissues
function normally performed by the missing epidermis).
1. In Vitro Construction of Connective Tissues After take, the grafted material is suitable for grafting
an epidermis, either in the form of a split-thickness skin
Connective tissues can be reconstructed in vitro by in-
graft or cultured layer of epidermal cells (keratinocytes).
corporation of connective tissue cells within a porous
Bioartificial skin is also available as a complete dermal–
biomaterial or a loose network of extracellular matrix
epidermal composite comprising the dermal equivalent on
components. The resulting geometry and organization of
top of which keratinocytes have been cultured to conflu-
thetissueequivalentaresimilartothoseoftheparenttissue
ence. Differentiation of the epidermal layer into a func-
in vivo. Several different types of connective tissues have
tional epidermis with a cornified layer that exhibits a high
been built using this approach (Table VIII). The mechani-
resistance to chemical damage is induced by exposure to
cal properties of the original biomaterial are dramatically
the air–liquid interface during the culturing process. The
altered by the embedded cells, due either to cell-generated
composites are then grafted onto the wound site in a single
forces causing contraction of the matrix material or depo-
operation.
sition of extracellular matrix generated by the cells them-
Metabolic engineering of connective tissue cells such as
selves. This remodeling is often important for the eventual
fibroblasts and smooth muscle cells via addition of ascor-
function of the tissue construct.
bic acid to the culture medium has been shown to pro-
The only engineered connective tissue equivalent cur-
mote the production of large quantities of extracellular
rently used clinically is bioartificial skin. Bioengineered
matrix, such that the cells produce their own scaffolding
material. This is an efficient method to generate sheets
TABLE VIII Examples of Connective Tissues Made in vitro
of cells that can then be layered on top of each other
Tissue Biomaterial Cell type or rolled around a mandrill to form thicker tissue con-
structs. Although still in early experimental stages, this
Dermis Collagen Fibroblast
approach has been used to form tubes that can withstand
Vascular Collagen, endogenously Smooth muscle cell
significant mechanical stress and is currently being evalu-
media produced matrix and fibroblast
ated for the generation of media for bioengineered blood
Cartilage Collagen–glycosaminoglycan Chondrocyte
vessels.
complex, polylactic–glycolic
copolymer Connective tissues that must bear significant loads must
Meniscus Collagen–glycosaminoglycan Fibrochondrocyte exhibit specific mechanical properties. This is the case
complex of bioartificial cartilage, which would be best implanted
Bone Calcium phosphate, polylactic– Mesenchymal stem once its mechanical properties are similar to that of the
glycolic copolymer cell from periosteum
authentic tissue. Chondrocytes seeded at high density
Tendon Collagen Tenocyte (tendon (10 cells/cm ) in agarose gels retain their phenotype and
7
3
fibroblast)
remain viable for up to 6 months. In this system, the