Research concerning articular cartilage repair using novel growth factor

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AG-041R is a cholecystokinin-B/gastrin receptor antagonist, which was originally developed to treat gastric ulcers. In a preclinical toxicological study on rats, oral administration of a high dose of AG-041R was found to stimulate systemic cartilage hyperplasia, including the articular cartilage.1 ; The first aim of this study is to develop the way of local administration for articular cartilage.PDLLA microspheres containing AG-041R were prepared by the solvent-evaporation method. Many kinds of microspheres was made by mixing various amounts of AG-01R and various kinds of PL(G)A. We indeed implanted the collagen containing microsphere into the 5 mm-diameter full-thickness articular cartilage defect of rabbit patellar groove. After certain weeks, we sacrificed the rabbit and measure the AG-041R content in synovial fluid and reparative tissue by HPLC. We could confirm that PLA0020 microsphere containing 40% AG-04R remained in reparative tissue for 4 weeks, which we thought ideal periods.2 ; The second aim is to verify the effectiveness ofAG-041R for articular cartilage repair and to examine it histologically.We made the same cartilage defect as above in both knee. Collagen gel mixed with 0.5 or 2.5mg PLA microspheres containing 40% were implanted into the left knee, as experimental group, and collagen gel mixed with same volume of just PLA microsphere, as control group. 4, 8, 12 weeks after implantation, reparative tissues were examined histologically by Toluidin Blue and immunofistochemistoly of type I and II collagen. 12 weeks after implantation, the reparative tissues of experimental group implanted with 2.5mg PLA microspheres containing 40 % were well repaired and the tissue were confined type II collagen positive and type I collagen negative.As future direction, we planed the more detailed histologically examination by BrdU stain for proliferating cell and TUNEL stain for apoptosis.