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
| Authors | Zhang, Yuezhou, Hollis, Dave, Ross, Rosie, Snow, T., Terrill, N., Lu, Yongjie, Wang, Wen, Connelly, John, Tozzi, Gianluca and Gupta, H. |
|---|---|
| Abstract | Fibrotic 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. |
| Keywords | small-angle X-ray scattering; keloids; extracellular matrix; hypertrophic scarring; synchrotron X-ray imaging; collagen fibrils; digital image correlation; nanomechanics |
| Year | 2022 |
| Journal | Materials |
| Journal citation | 15 (5) |
| Publisher | MDPI |
| ISSN | 1996-1944 |
| Digital Object Identifier (DOI) | https://doi.org/ma15051836 |
| https://doi.org/10.3390/ma15051836 | |
| Funder/Client | Engineering and Physical Sciences Research Council |
| Biotechnology and Biological Sciences Research Council | |
| Medical Research Council | |
| Science and Technology Facilities Council | |
| Publication dates | |
| Online | 01 Mar 2022 |
| Publication process dates | |
| Deposited | 04 Feb 2022 |
| Accepted | 21 Jan 2022 |
| Publisher's version | License File Access Level Open |
| Accepted author manuscript | License File description Accepted manuscript File Access Level Controlled |
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