{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T15:40:23Z","timestamp":1792683623061,"version":"4.5.0"},"reference-count":72,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,12,28]],"date-time":"2024-12-28T00:00:00Z","timestamp":1735344000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,12,28]],"date-time":"2024-12-28T00:00:00Z","timestamp":1735344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000266","name":"Engineering and Physical Sciences Research Council","doi-asserted-by":"publisher","award":["EP\/T020997\/1"],"award-info":[{"award-number":["EP\/T020997\/1"]}],"id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000266","name":"Engineering and Physical Sciences Research Council","doi-asserted-by":"publisher","award":["EP\/T020997\/1"],"award-info":[{"award-number":["EP\/T020997\/1"]}],"id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000266","name":"Engineering and Physical Sciences Research Council","doi-asserted-by":"publisher","award":["EP\/T020997\/1"],"award-info":[{"award-number":["EP\/T020997\/1"]}],"id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000266","name":"Engineering and Physical Sciences Research Council","doi-asserted-by":"publisher","award":["EP\/T020997\/1"],"award-info":[{"award-number":["EP\/T020997\/1"]}],"id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000266","name":"Engineering and Physical Sciences Research Council","doi-asserted-by":"publisher","award":["EP\/T020997\/1"],"award-info":[{"award-number":["EP\/T020997\/1"]}],"id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000266","name":"Engineering and Physical Sciences Research Council","doi-asserted-by":"publisher","award":["EP\/T020997\/1"],"award-info":[{"award-number":["EP\/T020997\/1"]}],"id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Osteoarthritis (OA) is a complex disease of cartilage characterised by joint pain, functional limitation, and reduced quality of life with affected joint movement leading to pain and limited mobility. Current methods to diagnose OA are predominantly limited to X-ray, MRI and invasive joint fluid analysis, all of which lack chemical or molecular specificity and are limited to detection of the disease at later stages. A rapid minimally invasive and non-destructive approach to disease diagnosis is a critical unmet need. Label-free techniques such as Raman Spectroscopy (RS), Coherent anti-Stokes Raman scattering (CARS), Second Harmonic Generation (SHG) and Two Photon Fluorescence (TPF) are increasingly being used to characterise cartilage tissue. However, current studies are based on whole tissue analysis and do not consider the different and structurally distinct layers in cartilage. In this work, we use Raman spectroscopy to obtain signatures from the superficial (top) and deep (bottom) layer of healthy and osteoarthritic cartilage samples from 64 patients (19 control and 45 OA). Spectra were acquired both in the \u2018fingerprint\u2019 region from 700 to 1720\u00a0cm\n                    <jats:sup>\u2212\u20091<\/jats:sup>\n                    and high-frequency stretching region from 2500 to 3300\u00a0cm\n                    <jats:sup>\u2212\u20091<\/jats:sup>\n                    . Principal component and linear discriminant analysis was used to identify the peaks that contributed significantly to classification accuracy of the different samples. The most pronounced differences were observed at the proline (855\u00a0cm\n                    <jats:sup>\u2212\u20091<\/jats:sup>\n                    and 921\u00a0cm\n                    <jats:sup>\u2212\u20091<\/jats:sup>\n                    ) and hydroxyproline (877\u00a0cm\n                    <jats:sup>\u2212\u20091<\/jats:sup>\n                    and 938\u00a0cm\n                    <jats:sup>\u2212\u20091<\/jats:sup>\n                    ), sulphated glycosaminoglycan (sGAG) (1064\u00a0cm\n                    <jats:sup>\u2212\u20091<\/jats:sup>\n                    and 1380\u00a0cm\n                    <jats:sup>\u2212\u20091<\/jats:sup>\n                    ) frequencies for both control and OA as well as the 1245\u00a0cm\n                    <jats:sup>\u2212\u20091<\/jats:sup>\n                    and 1272\u00a0cm\n                    <jats:sup>\u2212\u20091<\/jats:sup>\n                    , 1320\u00a0cm\n                    <jats:sup>\u2212\u20091<\/jats:sup>\n                    and 1345\u00a0cm\n                    <jats:sup>\u2212\u20091<\/jats:sup>\n                    , 1451\u00a0cm\n                    <jats:sup>\u2212\u20091<\/jats:sup>\n                    collagen modes were altered in OA samples, consistent with expected collagen structural changes. Classification accuracy based on Raman fingerprint spectral analysis of superficial and deep layer cartilage for controls was found to be 97% and 93% on using individual\/all spectra and, 100% and 95% on using mean spectra per patient, respectively. OA diseased cartilage was classified with an accuracy of 88% and 84% for individual\/all spectra, and 96% and 95% for mean spectra per patient based on analysis of the superficial and the deep layers, respectively. Raman spectra from the C-H stretching region (2500\u20133300\u00a0cm\n                    <jats:sup>\u2212\u20091<\/jats:sup>\n                    ) resulted in high classification accuracy for identification of different layers and OA diseased cartilage but low accuracy for controls. Differential changes in superficial and deep layer cartilage signatures were observed with age (under 60 and over 60 years), in contrast, less significant differences were observed with gender. Prominent chemical changes in the different layers of cartilage were preliminarily imaged using CARS, SHG and TPF. Cell clustering was observed in OA together with differences in pericellular matrix and collagen structure in the superficial and the deep layers correlating with the Raman spectral analysis. The current study demonstrates the potential of Raman Spectroscopy and multimodal imaging to interrogate cartilage tissue and provides insight into the chemical and structural composition of its different layers with significant implications for OA diagnosis for an increasing aging demographic.\n                  <\/jats:p>","DOI":"10.1038\/s41598-024-83155-3","type":"journal-article","created":{"date-parts":[[2024,12,28]],"date-time":"2024-12-28T03:44:03Z","timestamp":1735357443000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Harnessing Raman spectroscopy and multimodal imaging of cartilage for osteoarthritis diagnosis"],"prefix":"10.1038","volume":"14","author":[{"given":"Anna","family":"Crisford","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Cook","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Bourdakos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seshasailam","family":"Venkateswaran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas","family":"Dunlop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard O. C.","family":"Oreffo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumeet","family":"Mahajan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,12,28]]},"reference":[{"key":"83155_CR1","doi-asserted-by":"publisher","first-page":"1711","DOI":"10.1016\/S0140-6736(20)32230-3","volume":"396","author":"DJ Hunter","year":"2020","unstructured":"Hunter, D. J., March, L. & Chew, M. Osteoarthritis in 2020 and beyond: a Lancet Commission. Lancet 396, 1711\u20131712. https:\/\/doi.org\/10.1016\/S0140-6736(20)32230-3 (2020).","journal-title":"Lancet"},{"key":"83155_CR2","unstructured":"Wittenauer, R., Smith, L. & Aden K. M."},{"key":"83155_CR3","doi-asserted-by":"publisher","first-page":"s207","DOI":"10.3928\/0147-7447-20050202-05","volume":"28","author":"B Mandelbaum","year":"2005","unstructured":"Mandelbaum, B. & Waddell, D. Etiology and pathophysiology of osteoarthritis. Orthopedics 28, s207\u2013214. https:\/\/doi.org\/10.3928\/0147-7447-20050202-05 (2005).","journal-title":"Orthopedics"},{"key":"83155_CR4","doi-asserted-by":"publisher","first-page":"1561","DOI":"10.1016\/0021-9290(95)00103-4","volume":"28","author":"NM Bachrach","year":"1995","unstructured":"Bachrach, N. M. et al. Changes in proteoglycan synthesis of chondrocytes in articular cartilage are associated with the time-dependent changes in their mechanical environment. J. Biomech. 28, 1561\u20131569. https:\/\/doi.org\/10.1016\/0021-9290(95)00103-4 (1995).","journal-title":"J. Biomech."},{"key":"83155_CR5","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/0142-9612(92)90001-5","volume":"13","author":"VC Mow","year":"1992","unstructured":"Mow, V. C., Ratcliffe, A. & Poole, A. R. Cartilage and diarthrodial joints as paradigms for hierarchical materials and structures. Biomaterials 13, 67\u201397. https:\/\/doi.org\/10.1016\/0142-9612(92)90001-5 (1992).","journal-title":"Biomaterials"},{"key":"83155_CR6","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1186\/ar326","volume":"3","author":"PJ Roughley","year":"2001","unstructured":"Roughley, P. J. Articular cartilage and changes in arthritis: noncollagenous proteins and proteoglycans in the extracellular matrix of cartilage. Arthritis Res. 3, 342\u2013347. https:\/\/doi.org\/10.1186\/ar326 (2001).","journal-title":"Arthritis Res."},{"key":"83155_CR7","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1177\/1941738109350438","volume":"1","author":"AJ Sophia Fox","year":"2009","unstructured":"Sophia Fox, A. J., Bedi, A. & Rodeo, S. A. The basic science of articular cartilage: structure, composition, and function. Sports Health. 1, 461\u2013468. https:\/\/doi.org\/10.1177\/1941738109350438 (2009).","journal-title":"Sports Health"},{"key":"83155_CR8","doi-asserted-by":"publisher","first-page":"1904","DOI":"10.1016\/j.joca.2013.09.011","volume":"21","author":"TM Quinn","year":"2013","unstructured":"Quinn, T. M., H\u00e4uselmann, H. J., Shintani, N. & Hunziker, E. B. Cell and matrix morphology in articular cartilage from adult human knee and ankle joints suggests depth-associated adaptations to biomechanical and anatomical roles. Osteoarthr. Cartil. 21, 1904\u20131912. https:\/\/doi.org\/10.1016\/j.joca.2013.09.011 (2013).","journal-title":"Osteoarthr. Cartil."},{"key":"83155_CR9","doi-asserted-by":"publisher","first-page":"116002","DOI":"10.1117\/1.3643721","volume":"16","author":"PG Ellingsen","year":"2011","unstructured":"Ellingsen, P. G., Lilledahl, M. B., Aas, L. M., Cde, D., Kildemo, M. & L. & Quantitative characterization of articular cartilage using Mueller matrix imaging and multiphoton microscopy. J. Biomed. Opt. 16, 116002. https:\/\/doi.org\/10.1117\/1.3643721 (2011).","journal-title":"J. Biomed. Opt."},{"key":"83155_CR10","doi-asserted-by":"publisher","unstructured":"M\u00fcller, C. et al. Quantitative proteomics of different zones in human articular cartilage reveals unique patterns of protein distribution. Osteoarthr. Cartil. 20 https:\/\/doi.org\/10.1016\/j.joca.2012.02.564 (2014).","DOI":"10.1016\/j.joca.2012.02.564"},{"key":"83155_CR11","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/0272-0590(88)90276-X","volume":"11","author":"M Kato","year":"1988","unstructured":"Kato, M. & Onodera, T. Morphological investigation of osteochondrosis induced by ofloxacin in rats. Fundam. Appl. Toxicol. 11, 120\u2013131. https:\/\/doi.org\/10.1016\/0272-0590(88)90276-X (1988).","journal-title":"Fundam. Appl. Toxicol."},{"key":"83155_CR12","first-page":"487","volume":"47","author":"JA Buckwalter","year":"1998","unstructured":"Buckwalter, J. A. & Mankin, H. J. Articular cartilage: degeneration and osteoarthritis, repair, regeneration, and transplantation. Instr Course Lect. 47, 487\u2013504 (1998).","journal-title":"Instr Course Lect"},{"key":"83155_CR13","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1053\/joca.2002.0801","volume":"10","author":"EB Hunziker","year":"2002","unstructured":"Hunziker, E. B. Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects. Osteoarthr. Cartil. 10, 432\u2013463. https:\/\/doi.org\/10.1053\/joca.2002.0801 (2002).","journal-title":"Osteoarthr. Cartil."},{"key":"83155_CR14","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1093\/bmb\/ldn025","volume":"87","author":"AM Bhosale","year":"2008","unstructured":"Bhosale, A. M. & Richardson, J. B. Articular cartilage: structure, injuries and review of management. Br. Med. Bull. 87, 77\u201395. https:\/\/doi.org\/10.1093\/bmb\/ldn025 (2008).","journal-title":"Br. Med. Bull."},{"key":"83155_CR15","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.1016\/j.berh.2006.06.003","volume":"20","author":"MB Goldring","year":"2006","unstructured":"Goldring, M. B. Update on the biology of the chondrocyte and new approaches to treating cartilage diseases. Best Pract. Res. Clin. Rheumatol. 20, 1003\u20131025. https:\/\/doi.org\/10.1016\/j.berh.2006.06.003 (2006).","journal-title":"Best Pract. Res. Clin. Rheumatol."},{"key":"83155_CR16","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1186\/ar148","volume":"3","author":"LJ Sandell","year":"2001","unstructured":"Sandell, L. J. & Aigner, T. Articular cartilage and changes in arthritis: cell biology of osteoarthritis. Arthritis Res. Therapy. 3, 107. https:\/\/doi.org\/10.1186\/ar148 (2001).","journal-title":"Arthritis Res. Therapy"},{"key":"83155_CR17","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1038\/s41578-020-0213-1","volume":"5","author":"BJ Bielajew","year":"2020","unstructured":"Bielajew, B. J., Hu, J. C. & Athanasiou, K. A. Collagen: quantification, biomechanics and role of minor subtypes in cartilage. Nat. Reviews Mater. 5, 730\u2013747. https:\/\/doi.org\/10.1038\/s41578-020-0213-1 (2020).","journal-title":"Nat. Reviews Mater."},{"key":"83155_CR18","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/ar380","volume":"4","author":"D Eyre","year":"2002","unstructured":"Eyre, D. Collagen of articular cartilage. Arthritis Res. 4, 30\u201335. https:\/\/doi.org\/10.1186\/ar380 (2002).","journal-title":"Arthritis Res."},{"key":"83155_CR19","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1038\/nprot.2012.009","volume":"7","author":"X Chen","year":"2012","unstructured":"Chen, X., Nadiarynkh, O., Plotnikov, S. & Campagnola, P. J. Second harmonic generation microscopy for quantitative analysis of collagen fibrillar structure. Nat. Protoc. 7, 654\u2013669. https:\/\/doi.org\/10.1038\/nprot.2012.009 (2012).","journal-title":"Nat. Protoc."},{"key":"83155_CR20","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1089\/ten.teb.2014.0286","volume":"21","author":"Z Zhang","year":"2015","unstructured":"Zhang, Z. Chondrons and the pericellular matrix of chondrocytes. Tissue Eng. Part. B Rev. 21, 267\u2013277. https:\/\/doi.org\/10.1089\/ten.teb.2014.0286 (2015).","journal-title":"Tissue Eng. Part. B Rev."},{"key":"83155_CR21","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.bcp.2019.02.036","volume":"165","author":"E Charlier","year":"2019","unstructured":"Charlier, E. et al. Chondrocyte dedifferentiation and osteoarthritis (OA). Biochem. Pharmacol. 165, 49\u201365. https:\/\/doi.org\/10.1016\/j.bcp.2019.02.036 (2019).","journal-title":"Biochem. Pharmacol."},{"key":"83155_CR22","doi-asserted-by":"publisher","first-page":"R36","DOI":"10.1186\/ar2172","volume":"9","author":"R Gobezie","year":"2007","unstructured":"Gobezie, R. et al. High abundance synovial fluid proteome: distinct profiles in health and osteoarthritis. Arthritis Res. Ther. 9, R36. https:\/\/doi.org\/10.1186\/ar2172 (2007).","journal-title":"Arthritis Res. Ther."},{"key":"83155_CR23","doi-asserted-by":"publisher","first-page":"R7","DOI":"10.1186\/ar3555","volume":"14","author":"DH Sohn","year":"2012","unstructured":"Sohn, D. H. et al. Plasma proteins present in osteoarthritic synovial fluid can stimulate cytokine production via Toll-like receptor 4. Arthritis Res. Ther. 14, R7. https:\/\/doi.org\/10.1186\/ar3555 (2012).","journal-title":"Arthritis Res. Ther."},{"key":"83155_CR24","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1097\/00002281-200309000-00017","volume":"15","author":"S Laufer","year":"2003","unstructured":"Laufer, S. Role of eicosanoids in structural degradation in osteoarthritis. Curr. Opin. Rheumatol. 15, 623\u2013627. https:\/\/doi.org\/10.1097\/00002281-200309000-00017 (2003).","journal-title":"Curr. Opin. Rheumatol."},{"key":"83155_CR25","doi-asserted-by":"publisher","first-page":"1444","DOI":"10.1002\/art.1780361017","volume":"36","author":"RH Wittenberg","year":"1993","unstructured":"Wittenberg, R. H., Willburger, R. E., Kleemeyer, K. S. & Peskar, B. A. In vitro release of prostaglandins and leukotrienes from synovial tissue, cartilage, and bone in degenerative joint diseases. Arthritis Rheum. 36, 1444\u20131450. https:\/\/doi.org\/10.1002\/art.1780361017 (1993).","journal-title":"Arthritis Rheum."},{"key":"83155_CR26","doi-asserted-by":"publisher","first-page":"1403","DOI":"10.1136\/ard.2006.061994","volume":"65","author":"P Pottie","year":"2006","unstructured":"Pottie, P. et al. Obesity and osteoarthritis: more complex than predicted! Ann. Rheum. Dis. 65, 1403\u20131405. https:\/\/doi.org\/10.1136\/ard.2006.061994 (2006).","journal-title":"Ann. Rheum. Dis."},{"key":"83155_CR27","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.joca.2005.07.014","volume":"14","author":"KPH Pritzker","year":"2006","unstructured":"Pritzker, K. P. H. et al. Osteoarthritis cartilage histopathology: grading and staging. Osteoarthr. Cartil. 14, 13\u201329. https:\/\/doi.org\/10.1016\/j.joca.2005.07.014 (2006).","journal-title":"Osteoarthr. Cartil."},{"key":"83155_CR28","doi-asserted-by":"crossref","unstructured":"Mankin, H. J., Dorfman, H., Lippiello, L. & Zarins, A. Biochemical and metabolic abnormalities in articular cartilage from osteo-arthritic human hips: II. JBJS 53 (1971).","DOI":"10.2106\/00004623-197153030-00009"},{"key":"83155_CR29","doi-asserted-by":"publisher","first-page":"16044","DOI":"10.1038\/boneres.2016.44","volume":"5","author":"D Chen","year":"2017","unstructured":"Chen, D. et al. Osteoarthritis: toward a comprehensive understanding of pathological mechanism. Bone Res. 5, 16044. https:\/\/doi.org\/10.1038\/boneres.2016.44 (2017).","journal-title":"Bone Res."},{"key":"83155_CR30","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1038\/s41413-022-00226-9","volume":"10","author":"L Tong","year":"2022","unstructured":"Tong, L. et al. Current understanding of osteoarthritis pathogenesis and relevant new approaches. Bone Res. 10, 60. https:\/\/doi.org\/10.1038\/s41413-022-00226-9 (2022).","journal-title":"Bone Res."},{"key":"83155_CR31","doi-asserted-by":"publisher","first-page":"383","DOI":"10.2217\/17460816.1.4.383","volume":"1","author":"MD Morris","year":"2006","unstructured":"Morris, M. D. & Roessler, B. J. Future spectroscopic diagnostics in osteoarthritis. Future Rheumatol. 1, 383 (2006).","journal-title":"Future Rheumatol."},{"key":"83155_CR32","doi-asserted-by":"publisher","first-page":"19443","DOI":"10.1038\/s41598-020-76337-2","volume":"10","author":"MK Nieuwoudt","year":"2020","unstructured":"Nieuwoudt, M. K. et al. Raman spectroscopy reveals age- and sex-related differences in cortical bone from people with osteoarthritis. Sci. Rep. 10, 19443. https:\/\/doi.org\/10.1038\/s41598-020-76337-2 (2020).","journal-title":"Sci. Rep."},{"key":"83155_CR33","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1111\/joa.12624","volume":"231","author":"JC Mansfield","year":"2017","unstructured":"Mansfield, J. C. & Winlove, C. P. Lipid distribution, composition and uptake in bovine articular cartilage studied using Raman micro-spectrometry and confocal microscopy. J. Anat. 231, 156\u2013166. https:\/\/doi.org\/10.1111\/joa.12624 (2017).","journal-title":"J. Anat."},{"key":"83155_CR34","doi-asserted-by":"publisher","first-page":"8067","DOI":"10.1007\/s00216-015-8979-5","volume":"407","author":"R Kumar","year":"2015","unstructured":"Kumar, R. et al. Optical investigation of osteoarthritic human cartilage (ICRS grade) by confocal Raman spectroscopy: a pilot study. Anal. Bioanal. Chem. 407, 8067\u20138077. https:\/\/doi.org\/10.1007\/s00216-015-8979-5 (2015).","journal-title":"Anal. Bioanal. Chem."},{"key":"83155_CR35","doi-asserted-by":"publisher","first-page":"100210","DOI":"10.1016\/j.mtbio.2022.100210","volume":"13","author":"G Pezzotti","year":"2022","unstructured":"Pezzotti, G. et al. Raman spectroscopic insight into osteoarthritic cartilage regeneration by mRNA therapeutics encoding cartilage-anabolic transcription factor Runx1. Mater. Today Bio. 13, 100210. https:\/\/doi.org\/10.1016\/j.mtbio.2022.100210 (2022).","journal-title":"Mater. Today Bio"},{"key":"83155_CR36","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1080\/05704928.2018.1506799","volume":"54","author":"MG Martinez","year":"2019","unstructured":"Martinez, M. G., Bullock, A. J., MacNeil, S. & Rehman, I. U. Characterisation of structural changes in collagen with Raman spectroscopy. Appl. Spectrosc. Rev. 54, 509\u2013542. https:\/\/doi.org\/10.1080\/05704928.2018.1506799 (2019).","journal-title":"Appl. Spectrosc. Rev."},{"key":"83155_CR37","doi-asserted-by":"publisher","first-page":"9417","DOI":"10.1038\/s41598-018-27752-z","volume":"8","author":"M Khalid","year":"2018","unstructured":"Khalid, M., Bora, T., Ghaithi, A. A., Thukral, S. & Dutta, J. Raman spectroscopy detects changes in bone mineral quality and collagen cross-linkage in Staphylococcus infected human bone. Sci. Rep. 8, 9417. https:\/\/doi.org\/10.1038\/s41598-018-27752-z (2018).","journal-title":"Sci. Rep."},{"key":"83155_CR38","doi-asserted-by":"publisher","unstructured":"Gao, T. et al. Non-destructive spatial mapping of glycosaminoglycan loss in native and degraded articular cartilage using confocal Raman microspectroscopy. Front. Bioeng. Biotechnol. 9 https:\/\/doi.org\/10.3389\/fbioe.2021.744197 (2021).","DOI":"10.3389\/fbioe.2021.744197"},{"key":"83155_CR39","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.jmbbm.2013.02.014","volume":"31","author":"Y Takahashi","year":"2014","unstructured":"Takahashi, Y. et al. Raman spectroscopy investigation of load-assisted microstructural alterations in human knee cartilage: Preliminary study into diagnostic potential for osteoarthritis. J. Mech. Behav. Biomed. Mater. 31, 77\u201385. https:\/\/doi.org\/10.1016\/j.jmbbm.2013.02.014 (2014).","journal-title":"J. Mech. Behav. Biomed. Mater."},{"key":"83155_CR40","doi-asserted-by":"publisher","first-page":"546","DOI":"10.3390\/diagnostics11030546","volume":"11","author":"P Casal-Beiroa","year":"2021","unstructured":"Casal-Beiroa, P. et al. Optical biomarkers for the diagnosis of osteoarthritis through Raman spectroscopy: radiological and biochemical validation using ex vivo human cartilage samples. Diagnostics 11, 546. https:\/\/doi.org\/10.3390\/diagnostics11030546 (2021).","journal-title":"Diagnostics"},{"key":"83155_CR41","doi-asserted-by":"publisher","first-page":"20299","DOI":"10.1038\/s41598-021-99569-2","volume":"11","author":"N Prokopi","year":"2021","unstructured":"Prokopi, N., Andrikopoulos, K. S., Beobide, A. S., Voyiatzis, G. A. & Papachristou, D. J. Collagen orientation probed by polarized Raman spectra can serve as differential diagnosis indicator between different grades of meniscus degeneration. Sci. Rep. 11, 20299. https:\/\/doi.org\/10.1038\/s41598-021-99569-2 (2021).","journal-title":"Sci. Rep."},{"key":"83155_CR42","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1016\/j.saa.2011.10.049","volume":"86","author":"JJ C\u00e1rcamo","year":"2012","unstructured":"C\u00e1rcamo, J. J., Aliaga, A. E., Clavijo, R. E., Bra\u00f1es, M. R. & Campos-Vallette, M. M. Raman study of the shockwave effect on collagens. Spectrochim Acta Mol. Biomol. Spectrosc. 86, 360\u2013365. https:\/\/doi.org\/10.1016\/j.saa.2011.10.049 (2012).","journal-title":"Spectrochim Acta Mol. Biomol. Spectrosc."},{"key":"83155_CR43","doi-asserted-by":"publisher","unstructured":"Asaoka, R. et al. Prognostic potential and pathological validation of a diagnostic application using Raman spectroscopy in the characterization of degenerative changes in the cartilage of the humeral head. J. Biomed. Opt. 27 https:\/\/doi.org\/10.1117\/1.Jbo.27.11.115002 (2022).","DOI":"10.1117\/1.Jbo.27.11.115002"},{"key":"83155_CR44","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1021\/acscentsci.6b00222","volume":"2","author":"MS Bergholt","year":"2016","unstructured":"Bergholt, M. S. et al. Raman spectroscopy reveals new insights into the zonal organization of native and tissue-engineered articular cartilage. ACS Cent. Sci. 2, 885\u2013895. https:\/\/doi.org\/10.1021\/acscentsci.6b00222 (2016).","journal-title":"ACS Cent. Sci."},{"key":"83155_CR45","doi-asserted-by":"publisher","first-page":"034013","DOI":"10.1117\/1.3130338","volume":"14","author":"KA Esmonde-White","year":"2009","unstructured":"Esmonde-White, K. A. et al. Raman spectroscopy of synovial fluid as a tool for diagnosing osteoarthritis. J. Biomed. Opt. 14, 034013. https:\/\/doi.org\/10.1117\/1.3130338 (2009).","journal-title":"J. Biomed. Opt."},{"key":"83155_CR46","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1002\/jrs.6062","volume":"52","author":"R Shaikh","year":"2021","unstructured":"Shaikh, R. et al. Raman spectroscopy is sensitive to biochemical changes related to various cartilage injuries. J. Raman Spectrosc. 52, 796\u2013804. https:\/\/doi.org\/10.1002\/jrs.6062 (2021).","journal-title":"J. Raman Spectrosc."},{"key":"83155_CR47","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.1093\/bioinformatics\/btt084","volume":"29","author":"J Trevisan","year":"2013","unstructured":"Trevisan, J., Angelov, P. P., Scott, A. D., Carmichael, P. L. & Martin, F. L. IRootLab: a free and open-source MATLAB toolbox for vibrational biospectroscopy data analysis. Bioinformatics 29, 1095\u20131097. https:\/\/doi.org\/10.1093\/bioinformatics\/btt084 (2013).","journal-title":"Bioinformatics"},{"key":"83155_CR48","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1038\/nmeth.4346","volume":"14","author":"J Lever","year":"2017","unstructured":"Lever, J., Krzywinski, M. & Altman, N. Principal component analysis. Nat. Methods. 14, 641\u2013642. https:\/\/doi.org\/10.1038\/nmeth.4346 (2017).","journal-title":"Nat. Methods"},{"key":"83155_CR49","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1039\/c8ib00050f","volume":"10","author":"C Costa Moura","year":"2018","unstructured":"Costa Moura, C. et al. Quantitative temporal interrogation in 3D of bioengineered human cartilage using multimodal label-free imaging. Integr. Biology. 10, 635\u2013645. https:\/\/doi.org\/10.1039\/c8ib00050f (2018).","journal-title":"Integr. Biology"},{"key":"83155_CR50","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/1475-925x-2-13","volume":"2","author":"TA Pologruto","year":"2003","unstructured":"Pologruto, T. A., Sabatini, B. L. & Svoboda, K. ScanImage: flexible software for operating laser scanning microscopes. Biomed. Eng. Online. 2, 13. https:\/\/doi.org\/10.1186\/1475-925x-2-13 (2003).","journal-title":"Biomed. Eng. Online"},{"key":"83155_CR51","doi-asserted-by":"publisher","unstructured":"Qin, Y. & Xia, Y. Simultaneous two-photon fluorescence microscopy of NADH and FAD using pixel-to-pixel wavelength-switching. Front. Phys. 9 https:\/\/doi.org\/10.3389\/fphy.2021.642302 (2021).","DOI":"10.3389\/fphy.2021.642302"},{"key":"83155_CR52","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1002\/cyto.a.23597","volume":"95","author":"PM Schaefer","year":"2019","unstructured":"Schaefer, P. M., Kalinina, S., Rueck, A., von Arnim, C. A. F. & Einem, B. NADH autofluorescence\u2014a marker on its way to boost bioenergetic research. Cytometry Part. A. 95, 34\u201346. https:\/\/doi.org\/10.1002\/cyto.a.23597 (2019). von.","journal-title":"Cytometry Part. A"},{"key":"83155_CR53","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1016\/j.jbiomech.2005.11.002","volume":"40","author":"TJ Klein","year":"2007","unstructured":"Klein, T. J., Chaudhry, M., Bae, W. C. & Sah, R. L. Depth-dependent biomechanical and biochemical properties of fetal, newborn, and tissue-engineered articular cartilage. J. Biomech. 40, 182\u2013190. https:\/\/doi.org\/10.1016\/j.jbiomech.2005.11.002 (2007).","journal-title":"J. Biomech."},{"key":"83155_CR54","doi-asserted-by":"publisher","first-page":"R79","DOI":"10.1186\/ar2278","volume":"9","author":"A Sharma","year":"2007","unstructured":"Sharma, A., Wood, L. D., Richardson, J. B., Roberts, S. & Kuiper, N. J. Glycosaminoglycan profiles of repair tissue formed following autologous chondrocyte implantation differ from control cartilage. Arthritis Res. Therapy. 9, R79. https:\/\/doi.org\/10.1186\/ar2278 (2007).","journal-title":"Arthritis Res. Therapy"},{"key":"83155_CR55","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/s40634-014-0008-7","volume":"1","author":"PJ Roughley","year":"2014","unstructured":"Roughley, P. J. & Mort, J. S. The role of aggrecan in normal and osteoarthritic cartilage. J. Experimental Orthop. 1, 8. https:\/\/doi.org\/10.1186\/s40634-014-0008-7 (2014).","journal-title":"J. Experimental Orthop."},{"key":"83155_CR56","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1002\/ar.1092240207","volume":"224","author":"A Robin Poole","year":"1989","unstructured":"Robin Poole, A., Matsui, Y., Hinek, A. & Lee, E. Cartilage macromolecules and the calcification of cartilage matrix. Anat. Rec. 224, 167\u2013179. https:\/\/doi.org\/10.1002\/ar.1092240207 (1989).","journal-title":"Anat. Rec."},{"key":"83155_CR57","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1002\/jor.1100140313","volume":"14","author":"M Wong","year":"1996","unstructured":"Wong, M., Wuethrich, P., Eggli, P. & Hunziker, E. Zone-specific cell biosynthetic activity in mature bovine articular cartilage: A new method using confocal microscopic stereology and quantitative autoradiography. J. Orthop. Res. 14, 424\u2013432. https:\/\/doi.org\/10.1002\/jor.1100140313 (1996).","journal-title":"J. Orthop. Res."},{"key":"83155_CR58","doi-asserted-by":"publisher","first-page":"100012","DOI":"10.1016\/j.clispe.2021.100012","volume":"3","author":"R Gaifulina","year":"2021","unstructured":"Gaifulina, R. et al. Intra-operative Raman spectroscopy and ex vivo Raman mapping for assessment of cartilage degradation. Clin. Spectrosc. 3, 100012. https:\/\/doi.org\/10.1016\/j.clispe.2021.100012 (2021).","journal-title":"Clin. Spectrosc."},{"key":"83155_CR59","doi-asserted-by":"publisher","unstructured":"Unal, M., Jung, H. & Akkus, O. Novel Raman spectroscopic biomarkers indicate that post-yield damage denatures bone\u2019s collagen. J. Bone Miner. Res. 31 https:\/\/doi.org\/10.1002\/jbmr.2768 (2015).","DOI":"10.1002\/jbmr.2768"},{"key":"83155_CR60","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1016\/S0731-7085(03)00359-5","volume":"33","author":"E Kindt","year":"2003","unstructured":"Kindt, E., Gueneva-Boucheva, K., Rekhter, M. D., Humphries, J. & Hallak, H. Determination of hydroxyproline in plasma and tissue using electrospray mass spectrometry. J. Pharm. Biomed. Anal. 33, 1081\u20131092. https:\/\/doi.org\/10.1016\/S0731-7085(03)00359-5 (2003).","journal-title":"J. Pharm. Biomed. Anal."},{"key":"83155_CR61","doi-asserted-by":"publisher","first-page":"596","DOI":"10.2174\/1389203717666151201192247","volume":"17","author":"AK Srivastava","year":"2016","unstructured":"Srivastava, A. K. et al. A potential biochemical marker and its role in the pathogenesis of different diseases. Curr. Protein Pept. Sci. 17, 596\u2013602. https:\/\/doi.org\/10.2174\/1389203717666151201192247 (2016).","journal-title":"Curr. Protein Pept. Sci."},{"key":"83155_CR62","doi-asserted-by":"publisher","first-page":"2011","DOI":"10.3945\/jn.117.256404","volume":"147","author":"VL Albaugh","year":"2017","unstructured":"Albaugh, V. L., Mukherjee, K. & Barbul, A. Proline precursors and collagen synthesis: biochemical challenges of nutrient supplementation and wound healing. J. Nutr. 147, 2011\u20132017. https:\/\/doi.org\/10.3945\/jn.117.256404 (2017).","journal-title":"J. Nutr."},{"key":"83155_CR63","doi-asserted-by":"publisher","first-page":"3193","DOI":"10.1039\/C0AN00459F","volume":"135","author":"A Bonifacio","year":"2010","unstructured":"Bonifacio, A. et al. Chemical imaging of articular cartilage sections with Raman mapping, employing uni- and multi-variate methods for data analysis. Analyst 135, 3193\u20133204. https:\/\/doi.org\/10.1039\/C0AN00459F (2010).","journal-title":"Analyst"},{"key":"83155_CR64","doi-asserted-by":"publisher","first-page":"4264","DOI":"10.1364\/boe.520171","volume":"15","author":"H Cook","year":"2024","unstructured":"Cook, H. et al. Holistic vibrational spectromics assessment of human cartilage for osteoarthritis diagnosis. Biomed. Opt. Express. 15, 4264\u20134280. https:\/\/doi.org\/10.1364\/boe.520171 (2024).","journal-title":"Biomed. Opt. Express"},{"key":"83155_CR65","doi-asserted-by":"publisher","unstructured":"Afara, I. O., Oloyede, A. & 729S-737S. Resolving the near-infrared spectrum of articular cartilage. Cartilage 13 https:\/\/doi.org\/10.1177\/19476035211035417 (2021).","DOI":"10.1177\/19476035211035417"},{"key":"83155_CR66","doi-asserted-by":"publisher","first-page":"1913","DOI":"10.1088\/0967-3334\/36\/9\/1913","volume":"36","author":"IO Afara","year":"2015","unstructured":"Afara, I. O., Hauta-Kasari, M., Jurvelin, J. S., Oloyede, A. & T\u00f6yr\u00e4s, J. Optical absorption spectra of human articular cartilage correlate with biomechanical properties, histological score and biochemical composition. Physiol. Meas. 36, 1913\u20131928 (2015).","journal-title":"Physiol. Meas."},{"key":"83155_CR67","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1080\/05704928.2016.1250010","volume":"52","author":"IA Olumegbon","year":"2017","unstructured":"Olumegbon, I. A., Oloyede, A. & Afara, I. O. Near-infrared (NIR) spectroscopic evaluation of articular cartilage: A review of current and future trends. Appl. Spectrosc. Rev. 52, 541\u2013559. https:\/\/doi.org\/10.1080\/05704928.2016.1250010 (2017).","journal-title":"Appl. Spectrosc. Rev."},{"key":"83155_CR68","doi-asserted-by":"publisher","first-page":"11463","DOI":"10.1038\/s41598-017-11844-3","volume":"7","author":"IO Afara","year":"2017","unstructured":"Afara, I. O., Prasadam, I., Arabshahi, Z., Xiao, Y. & Oloyede, A. Monitoring osteoarthritis progression using near infrared (NIR) spectroscopy. Sci. Rep. 7, 11463. https:\/\/doi.org\/10.1038\/s41598-017-11844-3 (2017).","journal-title":"Sci. Rep."},{"key":"83155_CR69","doi-asserted-by":"publisher","first-page":"2245","DOI":"10.1007\/s10439-023-03261-7","volume":"51","author":"A Linus","year":"2023","unstructured":"Linus, A. et al. Visible and near-infrared spectroscopy enables differentiation of normal and early osteoarthritic human knee joint articular cartilage. Ann. Biomed. Eng. 51, 2245\u20132257. https:\/\/doi.org\/10.1007\/s10439-023-03261-7 (2023).","journal-title":"Ann. Biomed. Eng."},{"key":"83155_CR70","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1038\/s41584-024-01118-4","volume":"20","author":"RC Nordberg","year":"2024","unstructured":"Nordberg, R. C. et al. Recent advancements in cartilage tissue engineering innovation and translation. Nat. Rev. Rheumatol. 20, 323\u2013346. https:\/\/doi.org\/10.1038\/s41584-024-01118-4 (2024).","journal-title":"Nat. Rev. Rheumatol."},{"key":"83155_CR71","doi-asserted-by":"publisher","first-page":"6755","DOI":"10.1021\/acs.analchem.1c00490","volume":"93","author":"S Mosca","year":"2021","unstructured":"Mosca, S. et al. Spatially offset Raman spectroscopy\u2014how deep? Anal. Chem. 93, 6755\u20136762. https:\/\/doi.org\/10.1021\/acs.analchem.1c00490 (2021).","journal-title":"Anal. Chem."},{"key":"83155_CR72","doi-asserted-by":"publisher","first-page":"3794","DOI":"10.1021\/acssensors.4c01242","volume":"9","author":"P Raj","year":"2024","unstructured":"Raj, P. et al. Shining light on osteoarthritis: spatially offset Raman spectroscopy as a window into cartilage health. ACS Sens. 9, 3794\u20133804. https:\/\/doi.org\/10.1021\/acssensors.4c01242 (2024).","journal-title":"ACS Sens."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-83155-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-83155-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-83155-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,28]],"date-time":"2024-12-28T18:03:49Z","timestamp":1735409029000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-83155-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,28]]},"references-count":72,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["83155"],"URL":"https:\/\/doi.org\/10.1038\/s41598-024-83155-3","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-3961763\/v1","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,28]]},"assertion":[{"value":"16 February 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 December 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 December 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"31466"}}