In this study, we used an in vitro model to test the capacity of tissue transglutaminase to increase the adhesive strength at a cartilage-cartilage interface. Full-thickness cartilage-bone cylinders were prepared from fresh adult bovine shoulder joints, and the superficial half of the hyaline cartilage was then removed to provide a plane surface. Tissue transglutaminase was applied to the freshly cut surface of one cylinder, and a calcium-chloride solution (to act as an activating agent) was applied to that of the other. The cartilage surfaces were immediately apposed, one on top of the other, and an eighty-gram weight was applied to the upper cylinder for ten minutes at 37 degrees Celsius under defined humidity conditions. A measured force was then applied transversely to the upper cylinder until it was displaced from the lower one (which was clamped in a holding device), and the force recorded at this point was taken as a measure of the adhesive strength achieved at the cartilage-cartilage interface. The adhesive strength increased linearly with an increasing concentration of tissue transglutaminase (0.25 to 2.75 milligrams per milliliter) and was enhanced by increasing the duration of incubation, but it was not influenced by the level of humidity. The adhesive strength was improved by as much as 40 per cent when the cartilage surfaces had been pretreated with chondroitinase AC or hyaluronidase to remove glycosaminoglycan chains of proteoglycans, which are largely responsible for the intrinsic anti-adhesive properties of cartilage.CLINICAL RELEVANCE: The mechanical fixation of cartilage fragments in diarthrodial joints and the fixation and immobilization of cartilage transplant materials or biodegradable matrices containing chondrogenic cells pose serious problems for the orthopaedic surgeon. In the present study, the adhesive strength achieved with use of tissue transglutaminase at the cartilage-cartilage interface was greater than that obtained with use of Tissucol, a commercially available fibrin sealant. Tissue transglutaminase thus has great promise for practical application in clinical orthopaedics. Because this material has a relatively simple single-polypeptide-chain structure, production of the substance in large quantities with use of recombinant DNA technology is feasible. As a biological adhesive, it thus offers new possibilities for improving the repertoire for the treatment of chondral lesions.