Articular cartilage has long been shown to have a limited capacity for healing following traumatic insult or degenerative joint disease. The concept of healing cartilage lesions with allograft materials goes back over a century. The use of viable chondrocytes as a graft material has had mixed results as reported in the literature. Preliminary studies by this group have resulted in a model for healing cartilage lesions in the rabbit. This technique utilizes chondrocytes which have been culture in vitro prior to subsequent autotransplantation. This is a model for intrinsic cartilage healing because the defect which is made does not violate the subchondral plate. The proposed sets of experiments will utilize this model to increase the amount and quality of healing and to increase the surgical efficacy and reproducibility of the procedure. To consolidate and avoid dispersion of grafted cells, chondrocytes will be grown in either collagen sponges or gels. These composite grafts will be autotransplanted into defects in the patellae of New Zealand White rabbits. The chondrocytes in the graft will be radiolabeled. Animals will be sacrificed in short time intervals up to eight weeks to ascertain the mechanism of repair and note changes in cell proliferation. Concurrent to this experiment, monoclonal antibodies to type I and II collagen will be prepared and used to immunolocalize collagen matrix. A third set of experiments will investigate a more controlled and reproducible material to use for fixation of the graft in situ. The previously described model uses periosteum for this purpose. A series of different synthetic and naturally-occurring materials will be tested for their ability to hold a graft in place within the vigorously stressed joint environment. A fourth experiment will evaluate the long-term fate of these autotransplanted grafts. Animals will be sacrificed in groups up to one year postoperatively. At the time of sacrifice, these grafts will be evaluated by quantitative histology, extensive biomechanical testing, and stained for T-cell activation. Grafts will be radiolabeled prior to transplantation to monitor the long-term fate of these graft cells. Clinical application of this work would warrant the use of allografted instead of autografted materials. Therefore, a set of experiments similar to the preceding one for autografts will be conducted to ascertain whether allografted composite grafts will give an acceptable result. The same techniques will be utilized but emphasis will be placed on the monitoring of an immune response.
| Grande, D A; Halberstadt, C; Naughton, G et al. (1997) Evaluation of matrix scaffolds for tissue engineering of articular cartilage grafts. J Biomed Mater Res 34:211-20 |
| Freed, L E; Grande, D A; Lingbin, Z et al. (1994) Joint resurfacing using allograft chondrocytes and synthetic biodegradable polymer scaffolds. J Biomed Mater Res 28:891-9 |
