The present study presents a new approach for evaluating in vitro cytotoxicity of nanoparticles. The approach is based on American National Standard ISO 10993-5. Hepatoma HepG2 and fibroblast NIH3T3 cell lines were incubated with nanoparticles, and their associated extracts were derived at 70 and 121 degrees C. Nanoparticles proposed as potential biomedical imaging probes were evaluated on the basis of the detection of metabolic activities and cell-morphology changes. In general, nanoparticles incubated directly with cells showed higher cytotoxicity than their associated extracts. CdSe and core-shell CdSe@ZnS quantum dots resulted in low cell viability for both cell lines. The cytotoxicity of the quantum dots was attributed to the Cd ion and the presence of the nanoparticle itself. A statistically significant (p < 0.05) decrease in cell viability was found in higher dosage concentrations. Rare earth nanoparticles and their extracts appear to affect NIH3T3 cells only, with cell viability as low as 71.4% +/- 4.8%. Magnetic nanoparticles have no observable effects on the cell viabilities for both cell lines. In summary, we found the following: (1) both direct incubation and extracts of nanoparticles are required for complete assessment of nanoparticle cytotoxicity, (2) the rare earth oxide nanoparticles are less cytotoxic than the Cd-based quantum dots, and (3) the extent of cytotoxicity is dependent upon the cell line.

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Developments in bioprocessing technology play an important role for overcoming challenges in cardiac tissue engineering. To this end, our laboratory has developed a novel rotary perfused bioreactor for supporting three-dimensional cardiac tissue engineering. The dynamic culture environments provided by our novel perfused rotary bioreactor and/or the high-aspect rotating vessel produced constructs with higher viability and significantly higher cell numbers (up to 4 × 10(5) cells/bead) than static tissue culture flasks. Furthermore, cells in the perfused rotary bioreactor showed earlier gene expressions of cardiac troponin-T, α- and β-myosin heavy chains with higher percentages of cardiac troponin-I-positive cells and better uniformity of sacromeric α-actinin expression. A dynamic and perfused environment, as provided by this bioreactor, provides a superior culture performance in cardiac differentiation for embryonic stem cells particularly for larger 3D constructs.