Future Directions - Articular Cartilage Tissue Engineering - page 91

however, were relatively safe. Implantation of chondrocytes versus chondrocytes allowed to first
produce matrix has shown that the immune response was greatly diminished in the latter case [ 777 ].
In animal models, when allogeneic chondrocytes are implanted with their ECM into rat,
rabbits, or dogs, neither significant leukocyte migration nor cytotoxic humoral antibodies were ob-
served for several studies [ 772 , 778 , 779 ] while others have shown increased presence of inflammatory
mononuclear cells and less repair cartilage in defects filled with antigen-mismatched transplants in
dogs [ 780 ]. Due to the potential for immune responses, and due to the lack of availability of fresh
cadaveric donor tissue, frozen or pressure washed osteochondral allografts have been examined. In
these cases, the cells are likely dead, thus reducing the immunogenic response [ 781 , 782 ], but the
grafts are biochemically and histologically inferior to fresh grafts. Cryopreservation does allow for
tissues to be banked, giving greater time for screening of diseases in the tissue [ 783 , 784 ].
Allografts have shown considerable success; long-term follow-ups of up to fifteen years of
patients receiving fresh osteochondral allografts revealed allograft survival rates of 75%-95% at
five years, 64%-80% at ten years, and greater than 60% during fourteen and fifteen years [ 785 , 786 ].
However, compared to unipolar repairs, clinical trials have demonstrated that allograft implantation
is unsuitable for bipolar lesion repairs, with 50% of grafts failing at six years (as compared to 84%
in unipolar repairs) [ 787 , 788 ]. Cryopreserved and frozen allografts have yielded good to excellent
scores following transplantation in roughly 70% of patients up to four years. It is worth noting
that, while success has been demonstrated in the treatment of condylar lesions using allografts, the
procedure is still considered to be a salvage operation and is currently only suited for young, active
patients with isolated patellofemoral articular cartilage disease, for whom previous procedures have
failed.
Though currently not available as therapies, emerging technologies employing in vitro tissue
engineering has shown much success when allogeneic cells are combined with scaffolds. Implantation
of allogeneic chondrocytes embedded in collagen [ 789 - 791 ], agarose [ 792 ], and PGA [ 352 , 793 ],
among others, have been examined in various animal models. In general, the hyaline histological
appearances were found with little to no sign of immunologic reactions. Similarly, the implantation
of allogeneic MSCs in a hyaluronic acid-based gel in a caprine model has shown only mild immuno-
logic rejection [ 794 ]. As seen with the contrast between chondrocytes alone and chondrocytes with
associated matrix, in vitro seeding and culture of these tissue engineered constructs allow for the
formation of a protective, hyaline-like matrix around the cells prior to implantation, boding well for
the future of tissue engineering therapies utilizing allogeneic cells.
5.4.3 XENOGENEICTRANSPLANTS
While allogeneic tissues are more easily procured than autologous tissues, xenogeneic tissues are of
even greater abundance. In this case, the source is of a different species, and immunological concerns
are further heightened. No cartilage product using live xenogenic cells currently exists though the
methodology is being examined in several animal models. Rat chondrocytes implanted in rabbit
muscle resulted in the complete destruction of the implant by macrophages and giant foreign body