{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:01:53Z","timestamp":1790618513778,"version":"4.1.0"},"reference-count":34,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Dural defects, either from trauma, tumor resection, surgical approaches, genetics, or spontaneously represent a significant clinical challenge in neurosurgery. Given the established efficacy of riboflavin-sensitized ultraviolet-A (UVA) photo-crosslinking in ophthalmology, this study investigated its feasibility and dose-response characteristics as a novel strategy to biochemically augment the mechanical integrity and strength of ex-vivo bovine dura mater.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Forty bovine dura mater specimens were treated ex vivo using riboflavin concentrations of 2, 4, or 8 mM combined with UVA irradiation at 0.3 or 3 mW\/cm\n                      <jats:sup>2<\/jats:sup>\n                      . PBS-treated specimens exposed to UVA served as controls. Atomic force microscopy nanoindentation was used to measure the local elastic modulus in matched regions before and after treatment, enabling paired assessment of treatment-induced mechanical changes while minimizing inter-sample variability. Post-treatment stiffness, fold-change from baseline, and riboflavin dose-response relationships were analyzed statistically.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Baseline elastic moduli were equivalent across all groups (mean approximately 52 kPa, p\u2009=\u20090.92). While UVA alone caused a modest approximately 2- to 3-fold stiffness increase, riboflavin-UVA treatment produced a dramatic, concentration-dependent effect. The highest treatment (8 mM RF, 3 mW\/cm\n                      <jats:sup>2<\/jats:sup>\n                      UVA) increased the elastic modulus 150-fold, from approximately 53 kPa to approximately 8,000 kPa. Post-UV stiffness exhibited a strong linear relationship with riboflavin concentration (R\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090.994), indicating a precisely titratable crosslinking effect. All treatment conditions were statistically distinguishable (p\u2009&lt;\u20090.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Riboflavin-sensitized UVA crosslinking substantially increases the nanomechanical strength of ex vivo bovine dura mater in a controllable, dose-dependent manner. These findings establish a proof of concept for biochemical reinforcement of dural tissue that might be used clinically. As a next step evaluation using human dura, macroscopic biomechanical testing, penetration-depth analysis, and safety assessment is warranted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0351819","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:33:50Z","timestamp":1790616830000},"page":"e0351819","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Riboflavin-sensitized UVA collagen crosslinking produced a controllable, dose-dependent increase in the nanomechanical strength of ex vivo bovine dura mater"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5820-1110","authenticated-orcid":true,"given":"Ioannis","family":"Vasilikos","sequence":"first","affiliation":[{"name":"Medical Center - University of Freiburg","place":["Freiburg, Germany"],"department":["Department of Neurosurgery"]},{"name":"University of Freiburg","place":["Freiburg, Germany"],"department":["Faculty of Medicine"]},{"name":"Medical Center - University of Freiburg","place":["Freiburg, Germany"],"department":["CAST, Department of Neurosurgery"]},{"name":"University of Freiburg","place":["Freiburg, Germany"],"department":["Laboratory of Experimental Brain & Spine Surgery (LENS), Medical Center, Faculty of Medicine"]},{"name":"University of Freiburg","place":["Freiburg, Germany"],"department":["Department of Neurosurgery, Faculty of Medicine"]},{"name":"University of Freiburg","place":["Freiburg, Germany"],"department":["Berta-Ottenstein-Program for Clinician Scientists, Faculty of Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sukesh Mysore","family":"Swamy","sequence":"additional","affiliation":[{"name":"Medical Center - University of Freiburg","place":["Freiburg, Germany"],"department":["Neuroelectronic Systems, Department of Neurosurgery"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6264-3701","authenticated-orcid":true,"given":"Ulrich G.","family":"Hofmann","sequence":"additional","affiliation":[{"name":"University of Freiburg","place":["Freiburg, Germany"],"department":["Faculty of Medicine"]},{"name":"Medical Center - University of Freiburg","place":["Freiburg, Germany"],"department":["Neuroelectronic Systems, Department of Neurosurgery"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Hubbe","sequence":"additional","affiliation":[{"name":"Medical Center - University of Freiburg","place":["Freiburg, Germany"],"department":["Department of Neurosurgery"]},{"name":"University of Freiburg","place":["Freiburg, Germany"],"department":["Faculty of Medicine"]},{"name":"University of Freiburg","place":["Freiburg, Germany"],"department":["Laboratory of Experimental Brain & Spine Surgery (LENS), Medical Center, Faculty of Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"R\u00f6lz","sequence":"additional","affiliation":[{"name":"Medical Center - University of Freiburg","place":["Freiburg, Germany"],"department":["Department of Neurosurgery"]},{"name":"University of Freiburg","place":["Freiburg, Germany"],"department":["Faculty of Medicine"]},{"name":"University of Freiburg","place":["Freiburg, Germany"],"department":["Department of Neurosurgery, Faculty of Medicine"]},{"name":"University of Freiburg","place":["Freiburg, Germany"],"department":["Berta-Ottenstein-Program for Clinician Scientists, Faculty of Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angeliki","family":"Stathi","sequence":"additional","affiliation":[{"name":"Medical Center - University of Freiburg","place":["Freiburg, Germany"],"department":["Department of Neurosurgery"]},{"name":"University of Freiburg","place":["Freiburg, Germany"],"department":["Faculty of Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katerina","family":"Wolk","sequence":"additional","affiliation":[{"name":"Medical Center - University of Freiburg","place":["Freiburg, Germany"],"department":["Department of Neurosurgery"]},{"name":"University of Freiburg","place":["Freiburg, Germany"],"department":["Faculty of Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1903-2729","authenticated-orcid":true,"given":"Daniel","family":"Strahnen","sequence":"additional","affiliation":[{"name":"Medical Center - University of Freiburg","place":["Freiburg, Germany"],"department":["Department of Neurosurgery"]},{"name":"University of Freiburg","place":["Freiburg, Germany"],"department":["Faculty of Medicine"]},{"name":"University of Freiburg","place":["Freiburg, Germany"],"department":["Laboratory of Experimental Brain & Spine Surgery (LENS), Medical Center, Faculty of Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"El Rahal","sequence":"additional","affiliation":[{"name":"Medical Center - University of Freiburg","place":["Freiburg, Germany"],"department":["Department of Neurosurgery"]},{"name":"University of Freiburg","place":["Freiburg, Germany"],"department":["Faculty of Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7224-9185","authenticated-orcid":true,"given":"Mukesch J.","family":"Shah","sequence":"additional","affiliation":[{"name":"Medical Center - University of Freiburg","place":["Freiburg, Germany"],"department":["Department of Neurosurgery"]},{"name":"University of Freiburg","place":["Freiburg, Germany"],"department":["Faculty of Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Grauvogel","sequence":"additional","affiliation":[{"name":"Medical Center - University of Freiburg","place":["Freiburg, Germany"],"department":["Department of Neurosurgery"]},{"name":"University of Freiburg","place":["Freiburg, Germany"],"department":["Faculty of Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7274-519X","authenticated-orcid":true,"given":"Florian","family":"Volz","sequence":"additional","affiliation":[{"name":"Medical Center - 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