Investigating the Fibrillar Ultrastructure and Mechanics in Keloid Scars Using In Situ Synchrotron X-ray Nanomechanical Imaging.

Journal article


Zhang, Yuezhou, Hollis, Dave, Ross, Rosie, Snow, T., Terrill, N., Lu, Yongjie, Wang, Wen, Connelly, John, Tozzi, Gianluca and Gupta, H. (2022). Investigating the Fibrillar Ultrastructure and Mechanics in Keloid Scars Using In Situ Synchrotron X-ray Nanomechanical Imaging. Materials. 15 (5). https://doi.org/ma15051836
AuthorsZhang, Yuezhou, Hollis, Dave, Ross, Rosie, Snow, T., Terrill, N., Lu, Yongjie, Wang, Wen, Connelly, John, Tozzi, Gianluca and Gupta, H.
AbstractFibrotic scarring is prevalent in a range of collagenous tissue disorders. Understanding the role of matrix biophysics in contributing to fibrotic progression is important to develop therapies, as well as to elucidate biological mechanisms. Here, we demonstrate how microfocus small-angle X-ray scattering (SAXS), with in situ mechanics and correlative imaging, can provide quantitative and position-resolved information on the fibrotic matrix nanostructure and its mechanical properties. We use as an example the case of keloid scarring in skin. SAXS mapping reveals heterogeneous gradients in collagen fibrillar concentration, fibril pre-strain (variations in D-period) and a new interfibrillar component likely linked to proteoglycans, indicating evidence of a complex 3D structure at the nanoscale. Furthermore, we demonstrate a proof-of-principle for a diffraction-contrast correlative imaging technique, incorporating, for the first time, DIC and SAXS, and providing an initial estimate for measuring spatially resolved fibrillar-level strain and reorientation in such heterogeneous tissues. By application of the method, we quantify (at the microscale) fibrillar reorientations, increases in fibrillar D-period variance, and increases in mean D-period under macroscopic tissue strains of ~20%. Our results open the opportunity of using synchrotron X-ray nanomechanical imaging as a quantitative tool to probe structure-function relations in keloid and other fibrotic disorders in situ.
Keywordssmall-angle X-ray scattering; keloids; extracellular matrix; hypertrophic scarring; synchrotron X-ray imaging; collagen fibrils; digital image correlation; nanomechanics
Year2022
JournalMaterials
Journal citation15 (5)
PublisherMDPI
ISSN1996-1944
Digital Object Identifier (DOI)https://doi.org/ma15051836
https://doi.org/10.3390/ma15051836
Funder/ClientEngineering and Physical Sciences Research Council
Biotechnology and Biological Sciences Research Council
Medical Research Council
Science and Technology Facilities Council
Publication dates
Online01 Mar 2022
Publication process dates
Deposited04 Feb 2022
Accepted21 Jan 2022
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