Characterization of Cell Activity Distribution in Tissue Engineering Based on Scattering OCT
Lu Ming1, Wang Ling1,2*, Yang Shanshan1,2, Xu Mingen1,2
1(School of Automation, Hangzhou Dianzi University, Hangzhou 310018, China) 2(Zhejiang Provincial Key Lab of Medical Information and Three-Dimensional Bio-Printing,Hangzhou 310018, China)
Abstract Non-invasive and label-free detection of cell activity distribution in tissue engineering is of great significance. This paper proposed a scattering optical coherence tomography (OCT) technology to quantify and characterizing the cell activity distribution in a three-dimensional tissue model, and proposed an optimized depth-resolved (ODR) scattering algorithm to reconstruct the cell/material scatter contrast enhanced images, achieving the quantitative analysis of the correlation between scattering coefficients, cell concentration and activity status, and characterize the cell activity distribution in three-dimensional tissues. The experimental results of multi-layer sample model showed that the ODR scattering algorithm was able to improve the sensitivity and depth of sample scattering imaging. The human hepatocellular carcinoma cell C3A and human dermal fibroblast cell-laden hydrogel were used to verify that the cell concentration and cell activity in the material are linearly correlated with the scattering coefficient (92.07%) and Pearson correlation coefficient (99.13%) respectively, and the scattering coefficient could be used to quantify the cell concentration and survival status in the hydrogel scaffold. ODR-based scattering OCT realized the non-invasive and label-free detect of cell activity distribution in tissue engineering scaffolds, allowing to carry out long-term research on the cell activity distribution of cell-laden scaffolds, therefore, having potentials of a powerful monitoring tool for disease model construction, drug screening and cell therapy.
Lu Ming,Wang Ling,Yang Shanshan, et al. Characterization of Cell Activity Distribution in Tissue Engineering Based on Scattering OCT[J]. Chinese Journal of Biomedical Engineering, 2023, 42(2): 189-200.
[1] Bagnaninchi PO, Dikeakos M, Veres T, et al. Complex permittivity measurement as a new noninvasive tool for monitoring in vitro tissue engineering and cell signature through the detection of cell proliferation, differentiation, and pretissue formation[J]. IEEE Transactions on Nanobioscience, 2004, 3(4): 243-250. [2] 张家盛,吴刚,邱江.组织工程中细胞与生物材料相互作用关键机制研究进展[J].生物工程学报, 2021, 37(8):1-10. [3] Kasibhatla S, Amarante-Mendes GP, Finucane D, et al. Acridine orange/ethidium bromide (AO/EB) staining to detect apoptosis[J]. Cold Spring Harbor Protocols, 2006, 2006(3):4493. [4] Rajaraman R, Rounds DE, Yen SPS, et al. A scanning electron microscope study of cell adhesion and spreading in vitro[J]. Experimental Cell Research, 1974, 88(2): 327-339. [5] Jähn K, Stoddart MJ. Viability assessment of osteocytes using histological lactate dehydrogenase activity staining on human cancellous bone sections[M]//Mammalian Cell Viability. New Jersey: Humana Press, 2011: 141-148. [6] Kumar P, Nagarajan A, Uchil PD. Analysis of cell viability by the MTT assay[J]. Cold Spring Harbor Protocols, 2018, 2018(6): 095505. [7] 张聿全,吴晓静,王弋嘉,等.基于动态光镊技术的卵巢癌SKOV3细胞凋亡检测[J].中国激光, 2014, 41(11): 108-112. [8] Liu MJJ, Chou SM, Chua CK, et al. The development of silk fibroin scaffolds using an indirect rapid prototyping approach: Morphological analysis and cell growth monitoring by spectral-domain optical coherence tomography[J]. Medical Engineering & Physics, 2013, 35(2): 253-262. [9] 沈仁强,王玲,徐铭恩,等.基于光学相干层析成像散射量化表征细胞分布的研究[J].中国激光, 2020, 47(2): 0207039. [10] van der Meer FJ, Faber DJ, Aalders MCG, et al. Apoptosis-and necrosis-induced changes in light attenuation measured by optical coherence tomography[J]. Lasers in Medical Science, 2010, 25(2): 259-267. [11] de Bruin DM, Broekgaarden M, van Gemert MJC, et al. Assesment of apoptosis induced changes in scattering using optical coherence tomography[J]. Journal of Biophotonics, 2016, 9(9): 913-923. [12] Klyen BR, Scolaro L, Shavlakadze T, et al. Optical coherence tomography can assess skeletal muscle tissue from mouse models of muscular dystrophy by parametric imaging of the attenuation coefficient[J]. Biomedical Optics Express, 2014, 5: 1217-1232. [13] Yang Shanshan, Liu Kezhou, Yao Lin, et al. Correlation of optical attenuation coefficient estimated using optical coherence tomography with changes in astrocytes and neurons in a chronic photothrombosis stroke model[J]. Biomedical Optics Express, 2019, 10(12): 6258-6271. [14] Almasian M, Bosschaart N, van Leeuwen TG, et al. Validation of quantitative attenuation and backscattering coefficient measurements by optical coherence tomography in the concentration-dependent and multiple scattering regime[J]. Journal of Biomedical Optics, 2015, 20(12): 121314. [15] Karamata B, Laubscher M, Leutenegger M, et al. Multiple scattering in optical coherence tomography. I. Investigation and modeling[J]. Journal of the Optical Society of America. A, 2005, 22(7): 1369-1379. [16] Karamata B, Leutenegger M, Laubscher M, et al. Multiple scattering in optical coherence tomography. II. Experimental and theoretical investigation of cross talk in wide-field optical coherence tomography[J]. Journal of the Optical Society of America. A, 2005, 22(7): 1380-1388. [17] Munro PRT. Three-dimensional full wave model of image formation in optical coherence tomography[J]. Optics Express, 2016, 24(23): 27016-27031. [18] Munro PRT, Curatolo A, Sampson DD. Full wave model of image formation in optical coherence tomography applicable to general samples[J]. Optics Express, 2015, 23(3): 2541-2556. [19] Gong Peijun, Almasian M, Van Soest G, et al. Parametric imaging of attenuation by optical coherence tomography: review of models, methods, and clinical translation[J]. Journal of Biomedical Optics, 2020, 25(4): 040901. [20] Vermeer KA, Mo J, Weda JJA, et al. Depth-resolved model-based reconstruction of attenuation coefficients in optical coherence tomography[J]. Biomedical Optics Express, 2014, 5: 322-337. [21] Dwork N, Smith GT, Leng T, et al. Automatically determining the confocal parameters from OCT B-scans for quantification of the attenuation coefficients[J]. IEEE Transactions on Medical Imaging, 2018, 38(1): 261-268. [22] 刘斌,李永平.深低温反复冻融对人眼脉络膜黑色素瘤OCM-1细胞内钙离子浓度的影响[J]. 国际眼科杂志, 2006, 6(5): 1005-1007. [23] Li Kaiyan, Liang Wenxuan, Yang Zihan, et al. Robust, accurate depth-resolved attenuation characterization in optical coherence tomography[J]. Biomedical Optics Express, 2020, 11: 672-687. [24] Hölzl K, Lin S, Tytgat L, et al. Bioink properties before, during and after 3D bioprinting[J]. Biofabrication, 2016, 8: 032002.
