Future Directions - Articular Cartilage Tissue Engineering - page 89

Several cell-scaffold combinations have been examined for resurfacing. BioSeed-C, a fibrin
and polymer-based scaffold (PGLA/polydioxanone), has been able to mitigate pain and improve
knee-related quality of life measures after one-half, one, and four years [ 750 ]. A collagen type I/III
mesh with chondrocyte implantation has shown good or excellent outcomes two years post-operation
in 82% of patients that underwent the procedure although 75% of the defects showed fibrous tissue
formation rather than hyaline [ 751 ]. Hyaff-11, by Fidia Advanced Biopolymers, is an esterified
hyaluronic acid scaffold that could be implanted using an arthroscopic technique to yield formation
of hyaline-like cartilage tissue [ 752 ]. Outcomes for these products and procedures can depend on the
patient population. For instance, young, highly-active patients had better outcomes than less-active
counterparts after treatment with Hyalograft C [ 753 , 754 ].
Future work could take advantage of in vivo tissue engineered constructs using the scaffolds
described above. Alternatively, the scaffoldless self-assembly of chondrocytes may be employed. In
this case, researchers rely only on cells and the biological/mechanical signals that are necessary to
induce a chondrogenic response. Foreign scaffold materials would be unnecessary, and one of the
advantages of in vitro tissue engineering is that a construct with sufficient mechanical properties
would be delivered using such an approach to withstand physiological loading.

5.4 IMMUNE RESPONSE, IMMUNOGENICITY,

TRANSPLANTS

Being alymphatic and avascular, the tough, hyaline matrix of articular cartilage prevents easy access
to cells embedded within, regardless of the origin of these cells. Taking advantage of these character-
istics, proposals have been made to use cartilage matrix as a barrier to protect transplanted cells [ 755 ].
For the same reason, the joint is considered by some to be “immune-privileged” due to the body's
limited ability to detect and reject implanted tissue [ 756 ]. However, cartilage matrix is not itself
without rejection issues [ 756 , 757 ]. Collagens type II, IX, and XI and proteoglycan core proteins
all have antigenic properties [ 758 - 762 ]. The chondrocytes, too, have been found to contain major
histocompatibility complex (MHC) Class II antigens, which can elicit a cell-mediated immune
response as described below [ 763 , 764 ]. Natural killer cells can also attack chondrocytes [ 765 - 767 ].
This section deals with additional therapies and possibilities that follow from the previous sec-
tion. Future clinically applicable treatments may not deal solely with this tissue but the subchondral
bone as well. The rationale for cartilage immuno-privilege will be discussed, and studies involving
cartilage or osteochondral transplantation will also be presented. The difference is that, in this case,
the materials are of a foreign nature whether allogeneic or xenogeneic. These include both cells and
tissues transplanted into the joint, and to understand the body's reaction, we must first have a basic
understanding of the rejection process. First, the mechanism of rejection will be presented in stages.
From this perspective, the reactions to the introduced cartilage grafts will be discussed.