Chen Leng-Chun, Lloyd William R, Kuo Shiuhyang, Kim Hyungjin Myra, Marcelo Cynthia L, Feinberg Stephen E, Mycek Mary-Ann
Department of Biomedical Engineering, University of Michigan College of Engineering & Medical School, 1101 Beal Avenue, Ann Arbor, MI 48109-2110, USA.
Department of Oral and Maxillofacial Surgery, University of Michigan School of Dentistry, 1150 W. Medical Center Drive, Ann Arbor, MI 48109, USA.
Biomaterials. 2014 Aug;35(25):6667-76. doi: 10.1016/j.biomaterials.2014.04.080. Epub 2014 May 20.
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.
非线性光学分子成像和定量分析方法被开发用于非侵入性评估由原代人类细胞制造的组织工程构建体的活力。局部组织结构和生物化学的无标记光学测量表征了对照构建体和应激构建体之间的形态和功能差异。严格的统计分析考虑了人类患者之间的变异性。基于荧光强度的空间评估和代谢传感区分了对照构建体与热应激构建体以及代谢应激构建体。基于荧光寿命的传感区分了对照构建体与热应激构建体。与传统的组织学分析（发现通常可靠但具有破坏性）和生化分析（非侵入性但不可靠）不同，无标记光学评估具有非侵入性和可靠的优点。因此，这种光学测量可以作为基于细胞的组织工程构建体在人体植入前可靠的生产放行标准，从而满足再生医学中的一项关键监管需求。
