Nonlinear optical molecular imaging and quantitative analytic methods were developed to non-invasively assess the viability of tissue-engineered constructs manufactured from primary human cells. Label-free optical measures of local tissue structure and biochemistry characterized morphologic and functional differences between controls and stressed constructs. Rigorous statistical analysis accounted for variability between human patients. Fluorescence intensity-based spatial assessment and metabolic sensing differentiated controls from thermally-stressed and from metabolically-stressed constructs. Fluorescence lifetime-based sensing differentiated controls from thermally-stressed constructs. Unlike traditional histological (found to be generally reliable, but destructive) and biochemical (non-invasive, but found to be unreliable) tissue analyses, label-free optical assessments had the advantages of being both non-invasive and reliable. Thus, such optical measures could serve as reliable manufacturing release criteria for cell-based tissue-engineered constructs prior to human implantation, thereby addressing a critical regulatory need in regenerative medicine. © 2014 The Authors.
Chen, L. C., Lloyd, W. R., Kuo, S., Kim, H. M., Marcelo, C. L., Feinberg, S. E., & Mycek, M. A. (2014). The potential of label-free nonlinear optical molecular microscopy to non-invasively characterize the viability of engineered human tissue constructs. Biomaterials, 35(25), 6667–6676. https://doi.org/10.1016/j.biomaterials.2014.04.080