Hylan gel biomaterial: dermal and immunologic compatibility

Hylan, a hyaluronan derivative, was chemically cross-linked with divinyl sulfone to produce a water-insoluble gel. This gel was fragmented into a gel slurry and evaluated for particle size, biocompatibility, and residence times in selected tissues. Hylan gels used in this study are made up of pseudoplastic, deformable gel particles with greater elasticity (at all frequencies) and greater viscosity (shear rates, 0.01 sec-1) than the water soluble hylan polymer. Hylan gel was injected intradermally and subdermally in mice and was found to produce a minimal reaction at 24 h; thereafter (up to 7 weeks) there was no significant tissue reaction. Intradermal injection of [3H]-hylan gel in guinea pigs revealed a minimal tissue reaction after 1 week, and measurement of radioactivity in the tissue at 1, 2, and 4 weeks revealed only a slight decrease in the total amount of injected radioactivity. The immunogenic activity of hylan gel was evaluated in rabbits; unmodified hylan gel, degraded hylan gel, and hylan gel ovalbumin conjugate were used to immunize rabbits. No antibody production to any hylan gel sample was detected, although control rabbits immunized with ovalbumin developed titers > 400 of antiovalbumin antibodies by day 21, as measured by the passive cutaneous anaphylaxis assay (PCA). Last, serum from owl monkeys (Aotus trivirgatus) in which hylan gel had been placed intravitreally for up to 3 years contained no detectable anti-hylan gel antibodies (PCA assay). Skin tests on these monkeys were also negative.