biostudies-literatureZhang YBarts CharityScience and Technology Facilities CouncilMedical Research CouncilBiotechnology and Biological Sciences Research CouncilEngineering and Physical Sciences Research Council1836https://www.ebi.ac.uk/biostudies/studies/S-EPMC8911729biostudies-literatureUnknown15(5)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 nanoscalMaterials (Basel, Switzerland)Investigating the Fibrillar Ultrastructure and Mechanics in Keloid Scars Using In Situ Synchrotron X-ray Nanomechanical Imaging.PMC8911729EP/V011383/1G-002184BB/R003610/1MR/R025673/1EP/V011235/1BB/R003610/1, BB/R003610/1BB/R004773/1EP/V011006/1SM-18524-2Ross RTozzi GTerrill NJHollis DSnow TZhang YLu YGupta HSWang WConnelly JfalseInvestigating the Fibrillar Ultrastructure and Mechanics in Keloid Scars Using In Situ Synchrotron X-ray Nanomechanical Imaging.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 nanoscal2022-01-01T00:00:00Z2022 Mar2025-04-22T13:01:12.099Z2025-04-06T00:25:42.318ZS-EPMC89117293526906710.3390/ma15051836