Synthesis and characterization of injectable poly(N-isopropylacrylamide)-based hydrogels that support tissue formation in vitro

Hydrogels that support tissue formation in vitro were developed using poly(N-isopropylacrylamide) [P(NIPAAm)]. Loosely cross-linked P(NIPAAm) and poly(NIPAAm-co-acrylic acid) [P(NIPAAm-co-AAc)] hydrogels were synthesized with N,N′-methylenebis(acrylamide) cross-linker. At room temperature (RT), the hydrogels were transparent and extremely pliable, while at 37°C, the matrices became opaque and were significantly more rigid. The P(NIPAAm-co-AAc) hydrogel demonstrated significantly less volume change between RT and 37°C, contained significantly more water at 37°C, and had a lower critical solution temperature which was significantly higher, as compared to that of the P(NIPAAm) hydrogel. The hydrogels supported bovine articular chondrocyte viability for at least 28 days of in vitro culture, and cartilage-like tissue was formed in the matrices. These hydrogels can be injected through a small-diameter aperture and offer the benefit of in situ stabilization without the possible deleterious effects of in situ polymerization. Thus, these hydrogels have the potential to be used as injectable scaffolds for tissue engineering applications.