Cytocompatibility studies of an in situ photopolymerized thermoresponsive hydrogel nanoparticle system using human aortic smooth muscle cells

We have been investigating thermoresponsive hydrogel nanoparticle composite networks to develop photopolymerized hydrogels to deliver drugs for prevention of restenosis after angioplasty. These composite systems can form a gel under physiological conditions and release drugs in response to temperature changes. Our novel system, consisting of poly(N-isopropylacrylamide) thermoresponsive nanoparticles, photo cross-linker poly(ethylene glycol) diacrylate, and UV photoinitiator, 2-hydroxy-1-[4-(2-hydroxyethoxy) phenyl]-2-methyl-1-propanone-1- one (Irgacure 2959), would be photopolymerized in situ in the presence of UV light. The focus of this study was to evaluate the effects of photoinitiator and UV exposure on human aortic smooth muscle cells (HASMCs). We found that the exposure to UV light did not significantly affect the cellular survival within doses required for photopolymerization. The photoinitiator was cytocompatible at low concentrations (≤0.015% w/v); however, cytotoxicity increased with increasing photoinitiator concentrations. In addition, free radicals formed in the presence of a photoinitiator and UV light caused significant levels of cell death. An antioxidant (free radical scavenger), ascorbic acid, added to the cell media, significantly improved relative cell survival but increased the hydrogel gelation time. Finally, HASMC survival when exposed to all potential cytotoxic components was also evaluated by exposing HASMCs to media incubated with our composite hydrogels. In summary, our studies show that the photoinitiator and free radicals are responsible for the cytotoxicity on HASMCs, and the addition of antioxidants can significantly reduce these harmful effects.