基于光学相干层析的生物3D打印人工皮肤量化分析

doi:10.3969/j.issn.0258-8021.2020.02.09

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摘要对人工皮肤3D特征的无损定量检测分析,是研究皮肤打印和诱导培养技术须解决的关键问题。利用谱域光学相干层析成像(SD-OCT),对生物3D打印人工皮肤进行无损成像和量化分析。基于光学相干层析成像(OCT)强度信号的自适应峰值检测算法,量化皮肤3D厚度分布和粗糙度变化,通过计算不同位置的皮肤整体厚度及其波动,定量可视化皮肤的空间分辨结构特征。OCT成像人工皮肤的结构特征与切片的苏木精伊红(H&E)染色结果一致,两者实测皮肤整体厚度差异最大为3.59 μm,可验证该方法的可行性和准确性。通过SD-OCT对人工皮肤在培养周期内的持续检测,2D人工皮肤厚度分布检测可以展示皮肤在不同培养时间的厚度增长曲线,而3D空间分辨厚度分布图和表面粗糙图谱能更直观地显示皮肤生长状态。量化统计结果表明,在气液培养过程中,人工皮肤的整体平均厚度不断增长并趋于稳定,皮肤成熟时整体平均厚度为83.91 μm;皮肤表面粗糙度随角质化程度变化先减后增。基于OCT强度信号量化分析的方法能真实有效反映生物3D打印人工皮肤的结构参数变化,可为人工皮肤制备过程中的质量评估提供一种可靠的监测手段。

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	胡杰
	王玲
	徐铭恩
	王中昆

关键词 ：光学相干层析成像, 人工皮肤, 自适应峰值检测, 皮肤厚度, 粗糙度

Abstract：The non-destructive quantitative detection and analysis of the artificial skin three-dimensional features is a key problem to be solved in the research of skin printing and induced culture technology. This paper used spectral domain optical coherence tomography (SD-OCT) to perform non-destructive imaging and quantitative analysis on biological 3D printed artificial skin. The adaptive peak detection algorithm based on OCT intensity signal quantified skin three-dimensional thickness distribution and roughness variation. The overall thickness of the skin at the location and its fluctuation quantitatively visualized the spatially resolved structural features of the skin. The structural characteristics of OCT imaging artificial skin were consistent with the results of sliced hematoxylin and eosin (H&E) staining. The difference between the two measured skin thicknesses was only 3.59 μm, which verified the feasibility and accuracy of the method. Through the continuous detection of artificial skin in the culture period by SD-OCT, the two-dimensional artificial skin thickness distribution detection can show the thickness growth curve of the skin at different culture time, and the three-dimensional spatial resolution thickness distribution map and surface roughness map can be more visually show skin growth status. Quantitative statistical results show that during the gas-liquid culture, the overall average thickness of the artificial skin is constantly increasing and stabilizes. When the skin matures, the overall average thickness is 83.91 μm. The surface roughness of the skin first decreases and then increases with the change of keratinization. Therefore, the method based on OCT intensity signal quantitative analysis can truly and effectively reflect the structural parameter changes of biological 3D printed artificial skin, which provides a reliable monitoring method for quality assessment in artificial skin preparation.

Key words： optical coherence tomography (OCT) artificial skin adaptive peak monitoring skin thickness roughness

收稿日期: 2019-09-17

PACS:

R318

基金资助:国家自然科学基金(61675059,31927801)

通讯作者: ^*E-mail: lingw@hdu.edu.cn;xumingen@hdu.edu.cn

引用本文:

胡杰, 王玲, 徐铭恩, 王中昆. 基于光学相干层析的生物3D打印人工皮肤量化分析[J]. 中国生物医学工程学报, 2020, 39(2): 197-205.
Hu Jie, Wang Ling, Xu Mingen, Wang Zhongkun. Quantitative Analysis of Biological 3D Printed Artificial Skin Using Optical Coherence Tomography. Chinese Journal of Biomedical Engineering, 2020, 39(2): 197-205.

链接本文:

http://cjbme.csbme.org/CN/10.3969/j.issn.0258-8021.2020.02.09 或 http://cjbme.csbme.org/CN/Y2020/V39/I2/197

[1] Casas JW, Lewerenz GM, Rankin EA, et al. In vitro human skin irritation test for evaluation of medical device extracts [J]. Toxicology in Vitro, 2013, 27(8): 2175-2183.
[2] He P, Zhao J, Zhang J, et al. Bioprinting of skin constructs for wound healing [J]. Burns & Trauma, 2018, 6(1):5-15.
[3] Germain L, Larouche D, Nedelec B, et al. Autologous bilayered self-assembled skin substitutes (SASSs) as permanent grafts: a case series of 14 severely burned patients indicating clinical effectiveness [J]. European Cells & Materials, 2018, 36: 128-141.
[4] 胡锦花, 王玲, 石然, 等. 3D打印皮肤组织研究进展 [J]. 中国科学:生命科学, 2017, 4(47): 423-442.
[5] Lee V, Singh G, Trasatti JP, et al. Design and Fabrication of Human Skin by Three-Dimensional Bioprinting [J]. Tissue Engineering Part C: Methods, 2014, 20(6): 473-484.
[6] Koch L, Deiwick A, Schlie S, et al. Skin tissue generation by laser cell printing [J]. Biotechnology and Bioengineering. 2012, 109(7): 1855-1863.
[7] Smith LE, Bonesi M, Smallwood R, et al. Using swept-source optical coherence tomography to monitor the formation of neo-epidermis in tissue-engineered skin [J]. Journal of Tissue Engineering and Regenerative Medicine, 2010, 4(8): 652-658.
[8] Greaves NS, Iqbal SA, Hodgkinson T, et al. Skin substitute-assisted repair shows reduced dermal fibrosis in acute human wounds validated simultaneously by histology and optical coherence tomography [J]. Wound Repair and Regeneration, 2015, 23(4):483-494.
[9] 谢娟英,雷金虎,谢维信. 一种新特征评价方法在红斑鳞状皮肤病诊断中的应用[J]. 中国生物医学工程学报, 2012, 31(1): 59-67.
[10] 武薇,段会龙,李燕,等. 基于光学相干断层扫描成像的眼部3D前房角[J]. 中国生物医学工程学报, 2012, 31(6): 831-838.
[11] Spler F, Frst M, Marquardt Y, et al. High-resolution optical coherence tomography as a non-destructive monitoring tool for the engineering of skin equivalents [J]. Skin Research & Technology, 2010, 12(4): 261-267.
[12] Houcine A, Delalleau A, Heraud S, et al. How biophysical in vivo testing techniques can be used to characterize full thickness skin equivalents [J]. Skin Research and Technology, 2016, 22(3): 284-294.
[13] Schmitt R, Kirkpatrick SJ, Wang R, et al. Optical coherence tomography investigation of growth cycles of engineered skin tissue [C]// Proceedings of SPIE. Bellingham: Schmitt R, 2010, 75660H: 1-10.
[14] Mason C, Markusen JF, Town MA, et al. The potential of optical coherence tomography in the engineering of living tissue [J]. Physics in Medicine and Biology, 2004, 49(7): 1097-1115.
[15] Marx U, Pickert D, heymer A, et al. Non-invasive quality control for production processes of artificial skin equivalents by optical coherence tomography [C]// Procedia CIRP. Amsterdam: Marx U, 2013: 128:132.
[16] Schmitt R, Marx U, Walles H, et al. Validation of artificial skin equivalents as in vitro testing systems [C]. Proceedings of SPIE. Bellingham: Schmitt R, 2011, 78971B: 1-8.
[17] 斯培剑,王玲,徐铭恩. 基于光学相干层析成像技术的肿瘤细胞侵袭成像 [J]. 中国激光, 2019, 46(9):7003-7011.
[18] Knuttel A, Boehlau-Godau M. Spatially confined and temporally resolved refractive index and scattering evaluation in human skin performed with optical coherence tomography [J]. Journal of Biomedical Optics, 2000, 5(1): 83-92.
[19] Robertson C. Optical Coherence Tomography Imaging of Tissue Engineered Skin Cultured Under Perfusion Conditions [D]. Sheffield: University of Sheffield, 2013.
[20] Franois Blateyron. The Areal Field Parameters[M]// Characterisation of areal surface texture. Berlin:Springer Berlin Heidelberg, 2013: 15-43.
[21] Therkildsen P, Haedersdal M, Lock-Andersen J, et al. Epidermal thickness measured by light microscopy: A methodological study [J]. Skin Research & Technology, 2010, 4(4): 174-179.
[22] Sandby-Moller J, Poulsen T, Wulf HC. Epidermal thickness at different body sites: Relationship to age, gender, pigmentation, blood content, skin type and smoking habits [J]. Acta Dermato-Venereologica, 2003, 83(6): 410-413.
[23] Kuranov R, Sapozhnikova V, Prough D, et al. Correlation between optical coherence tomography images and histology of pigskin [J]. Applied Optics, 2007, 46(10): 1782-1786.
[24] Kevin CZ, Ruobing Q, Simone D, et al. Optical coherence refraction tomography [J]. Nature Photonics, 2019,13(11): 794-802.