Synthesis and fabrication of a degradable poly(N-isopropyl acrylamide) scaffold for tissue engineering applications

Biodegradable poly(N-isopropyl acrylamide) (polyNIPAM) hydrogels with controlled molecular weight of the parent polymer and its degradation products were synthesized by atom transfer radical polymerization in the presence of a polycaprolactone-based di-chlorinated macroinitiator and polycaprolactone dimethacrylate. The phase transition temperature, swelling, hydrolytic degradability, and mechanical properties at 25 and 37 degrees C were explored. A cytocompatibility study showed good NIH3T3 cell response over 5 days culture on the surface of the hydrogels, demonstrated by a consistent increase in cell proliferation detected by an Alamar Blue assay. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] results suggested that the hydrogels and their degradation products in the concentration range of 125 mg/mL were not cytotoxic to NIH3T3 cells. A sphere-templating technique was utilized to fabricate biodegradable polyNIPAM scaffolds with monodisperse, pore size. Scaffolds with pore diameter of 48 +/- 6 mu m were loaded with A-10 smooth muscle cells and then warmed to 37 degrees C entrapping cells in pores approximately 40 mu m in diameter, a size we have found to be optimal for angiogenesis and biointegration. Due to their degradable nature, tunable molecular weight, highly interconnected morphology, thermally controlled monodisperse pore size, and temperature-induced volume expansioncontraction, the polyNIPAM-based scaffolds developed in this work will be valuable in tissue engineering. (C) 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A: 775-786, 2013.