Bioactive, semi-degradable hydrogels for cartilage tissue engineering

Poly(vinyl-alcohol) (PVA) hydrogels have long been investigated as replacement materials for articular cartilage, but their lack of bioactivity has impeded their utility. We have prepared bioactive PVA hydrogels by incorporating a degradable phase of poly(lactic-co-glycolic acid) (PLGA) that enhances porosity and controls the release of growth factors. Hydrogel properties such as porosity, pore size, and degradability were dependent on the hydrogel composition and fabrication conditions. Porosity and pore size increased over time in physiological conditions as the PLGA phase degraded within the nondegradable PVA hydrogels. Cell-seeding efficiency and tissue formation in vitro were proportional to the amount of PLGA. When insulin-like growth factor-1 (IGF-1) was incorporated into the degradable PLGA phase, release was controlled over 6 weeks, with no burst effect. Hydrogels containing a low or high dose of IGF-1 were wrapped in PGA fibers, seeded with chondrocytes and implanted subcutaneously into nude mice. After 6 weeks, the amount of cartilage tissue formation and integration with the hydrogels were higher compared to controls without IGF-1, although there were no differences in mass, proteoglycan content or compressive modulus between hydrogels with low and doses of IGF-1. These simple modifications to PVA hydrogels may finally make them suitable as cartilage replacements.