34 CHAPTER 3. IN VITRO TISSUE ENGINEERING
Due to limits on the availability of human tissue, some have suggested that cross-species cell
implantations might be an alternative option. Xenogeneic transplants have been successfully used
in sheep [296], goats [297], and rabbits [298]. However, similar difficulties exist with xenogeneic
transplants as with allogeneic transplants, namely immunogenicity concerns. Further complications
could arise with cross-species compatibility issues at the cellular and molecular level.
A promising cell source for cartilage tissue engineering is autologous progenitor/stem cell pop-
ulations [299]. Adult progenitor cells reside throughout the body and can be differentiated along
many different lineages. Progenitor cells from bone marrow and fat tissue have been extensively in-
vestigated for their promising application to cartilage regeneration [300]. Also, dermis-derived cells
exhibit significant promise [301]. If autologous cells are used, minimal problems with immuno-
genicity exist. Progenitor/stem cells show a large capacity for proliferation, so only small samples are
needed to obtain enough cells to grow the large populations necessary for tissue engineering. Donor
site morbidity and patient pain are dependent on the site of harvest, but for some cell types this is
minimal (i.e., adipose-derived stem cells).
Another possible cell source akin to progenitor populations is embryonic stem cells.While pro-
genitor cells can proliferate extensively, extensive expansion in monolayer culture can have negative
effects on proliferative rates, telomere shortening, and loss of multipotency [302306]. Embryonic
stem cells, however, have an unlimited capacity for proliferation, and hence, are attractive for tis-
sue engineering endeavors that require large cell numbers [286]. These cells are truly pluripotent,
showing a capacity to differentiate into any cell type in the body. However, researchers do not cur-
rently know the best ways to differentiate embryonic stem cells along every lineage. Some protocols
are more defined than others, though, and good results have been obtained for the chondrocytic
lineage [299, 307310]. As with all cell therapies using embryonic stem cells, there are potential
problems with teratoma formation, poorly controlled cell proliferation or differentiation, and pos-
sible immunogenicity problems since the cells come from an allogeneic source. A more detailed
description of the use of these alternative cell sources is provided in the Future Directions section.
3.3 SCAFFOLD DESIGN
For functional tissue engineering, biocompatible scaffolds are chosen to best fulfill a role in im-
proving the regeneration of a damaged or diseased tissue. While recent studies have indicated that
cartilage constructs can be formed in vitro using only cells [311314], traditional tissue engineering
approaches have seeded cells on scaffolds to provide structure to the neocartilage. The architec-
tural structure of the scaffold can affect the mechanical properties of the construct, cell seeding
distributions, and diffusional characteristics. Furthermore, the material itself can help or hinder cell
attachment, proliferation, and synthesis over the lifetime of the implant.
The base scaffold material can be considered the central component of a tissue engineered
implant. The scaffold should fulfill three main requirements: 1) have an interconnected network
that allows efficient diffusion of nutrients and wastes; 2) be biocompatible and bioresorbable, with
a degradation rate that ideally matches the rate of tissue growth; 3) and allow for cell attachment,

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