Mapping the 3D remodeling of the extracellular matrix in human hypertrophic scar by multi-parametric multiphoton imaging using endogenous contrast
Shenyi Jiang,
Shuhao Qian,
Lingxi Zhou,
Jia Meng,
Rushan Jiang,
Chuncheng Wang,
Xinguo Fang,
Chen Yang,
Zhihua Ding,
Shuangmu Zhuo,
Zhiyi Liu
Affiliations
Shenyi Jiang
State Key Laboratory of Modern Optical Instrumentation, College of Optical Science and Engineering, International Research Center for Advanced Photonics, Zhejiang University, Hangzhou, Zhejiang, 310027, China
Shuhao Qian
State Key Laboratory of Modern Optical Instrumentation, College of Optical Science and Engineering, International Research Center for Advanced Photonics, Zhejiang University, Hangzhou, Zhejiang, 310027, China
Lingxi Zhou
State Key Laboratory of Modern Optical Instrumentation, College of Optical Science and Engineering, International Research Center for Advanced Photonics, Zhejiang University, Hangzhou, Zhejiang, 310027, China
Jia Meng
State Key Laboratory of Modern Optical Instrumentation, College of Optical Science and Engineering, International Research Center for Advanced Photonics, Zhejiang University, Hangzhou, Zhejiang, 310027, China
Rushan Jiang
State Key Laboratory of Modern Optical Instrumentation, College of Optical Science and Engineering, International Research Center for Advanced Photonics, Zhejiang University, Hangzhou, Zhejiang, 310027, China
Chuncheng Wang
State Key Laboratory of Modern Optical Instrumentation, College of Optical Science and Engineering, International Research Center for Advanced Photonics, Zhejiang University, Hangzhou, Zhejiang, 310027, China
Xinguo Fang
State Key Laboratory of Modern Optical Instrumentation, College of Optical Science and Engineering, International Research Center for Advanced Photonics, Zhejiang University, Hangzhou, Zhejiang, 310027, China
Chen Yang
State Key Laboratory of Modern Optical Instrumentation, College of Optical Science and Engineering, International Research Center for Advanced Photonics, Zhejiang University, Hangzhou, Zhejiang, 310027, China
Zhihua Ding
State Key Laboratory of Modern Optical Instrumentation, College of Optical Science and Engineering, International Research Center for Advanced Photonics, Zhejiang University, Hangzhou, Zhejiang, 310027, China
Shuangmu Zhuo
School of Science, Jimei University, Xiamen, Fujian, 361021, China; Corresponding author. School of Science, Jimei University, Xiamen, Fujian, 361021, China.
Zhiyi Liu
State Key Laboratory of Modern Optical Instrumentation, College of Optical Science and Engineering, International Research Center for Advanced Photonics, Zhejiang University, Hangzhou, Zhejiang, 310027, China; Jiaxing Key Laboratory of Photonic Sensing & Intelligent Imaging, Jiaxing, 314000, China; Intelligent Optics & Photonics Research Center, Jiaxing Research Institute, Zhejiang University, Jiaxing, 314000, China; Corresponding author. State Key Laboratory of Modern Optical Instrumentation, College of Optical Science and Engineering; International Research Center for Advanced Photonics, Zhejiang University, Hangzhou, Zhejiang, 310027, China.
The hypertrophic scar is an aberrant form of wound healing process, whose clinical efficacy is limited by a lack of understanding of its pathophysiology. Remodeling of collagen and elastin fibers in the extracellular matrix (ECM) is closely associated with scar progression. Herein, we perform label-free multiphoton microscopy (MPM) of both fiber components from human skin specimens and propose a multi-fiber metrics (MFM) analysis model for mapping the structural remodeling of the ECM in hypertrophic scars in a highly-sensitive, three-dimensional (3D) manner. We find that both fiber components become wavier and more disorganized in scar tissues, while content accumulation is observed from elastin fibers only. The 3D MFM analysis can effectively distinguish normal and scar tissues with better than 95% in accuracy and 0.999 in the area under the curve value of the receiver operating characteristic curve. Further, unique organizational features with orderly alignment of both fibers are observed in scar-normal adjacent regions, and an optimized combination of features from 3D MFM analysis enables successful identification of all the boundaries. This imaging and analysis system uncovers the 3D architecture of the ECM in hypertrophic scars and exhibits great translational potential for evaluating scars in vivo and identifying individualized treatment targets.
