A Degradable Thermo-sensitive Poly(N-isopropyl acrylamide)-Based Scaffold with Controlled Porosity for Tissue Engineering Applications

摘要

We have developed a thermoresponsive poly(N-isopropyl acrylamide)-based scaffold with degradability and controlled porosity. Biodegradable poly(N-isopropyl acrylamide) hydrogels were synthesized by photo-copolymerization of N-isopropylacrylamide with 2-methylene-1,3-dioxepane and polycaprolactone dimethacrylate. The hydrogels’ phase transition temperature, swelling and viscoelastic properties, as well as hydrolytic degradability at 25 and 37°C, were explored. A sphere-templating technique was applied to fabricate hydrogel scaffolds with controllable pore size and a highly interconnected porous structure. The scaffold pore diameter change as a function of temperature was evaluated and, as expected, pores decreased in diameter when the temperature was raised to 37°C. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test results suggested neither the scaffolds nor their degradation products were cytotoxic to NIH3T3 cells. Scaffolds with 55±5 μm pore diameter were loaded with NIH3T3 cells and then were warmed to 37°C entrapping cells in pores approximately 39 μm in diameter, a size range we have found to be optimal for angiogenesis and biointegration. Cells showed uniform infiltration and an elongated morphology after 7 days of culture. Due to the controlled monodisperse pore diameter, highly interconnected architecture, fully degradable chemistry and thermoresponsive properties, the polyNIPAM-based scaffolds developed here are attractive for applications in tissue engineering.