{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T03:44:19Z","timestamp":1792640659035,"version":"4.5.0"},"reference-count":40,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2020,10,6]],"date-time":"2020-10-06T00:00:00Z","timestamp":1601942400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["4145\/4-1"],"award-info":[{"award-number":["4145\/4-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["409\/2-1"],"award-info":[{"award-number":["409\/2-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["150\/10-1"],"award-info":[{"award-number":["150\/10-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005341","name":"Bayerisches Staatsministerium f\u00fcr Wissenschaft, Forschung und Kunst","doi-asserted-by":"publisher","award":["CANTER Research Focus"],"award-info":[{"award-number":["CANTER Research Focus"]}],"id":[{"id":"10.13039\/501100005341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005341","name":"Bayerisches Staatsministerium f\u00fcr Wissenschaft, Forschung und Kunst","doi-asserted-by":"publisher","award":["BayWISS - Verbundkolleg Gesundheit"],"award-info":[{"award-number":["BayWISS - Verbundkolleg Gesundheit"]}],"id":[{"id":"10.13039\/501100005341","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We have determined the sensitivity and detection limit of a new fiber Bragg grating (FBG)-based optoelectronic micro-indenter for biomechanical testing of cartilage and compared the results to indentation-type atomic force microscopy (IT-AFM) and histological staining. As test samples, we used bovine articular cartilage, which was enzymatically degraded ex vivo for five minutes using different concentrations of collagenase (5, 50, 100 and 500 \u00b5g\/mL) to mimic moderate extracellular matrix deterioration seen in early-stage osteoarthritis (OA). Picrosirius Red staining and polarization microscopy demonstrated gradual, concentration-dependent disorganization of the collagen fibrillar network in the superficial zone of the explants. Osteoarthritis Research Society International (OARSI) grading of histopathological changes did not discriminate between undigested and enzymatically degraded explants. IT-AFM was the most sensitive method for detecting minute changes in cartilage biomechanics induced by the lowest collagenase concentration, however, it did not distinguish different levels of cartilage degeneration for collagenase concentrations higher than 5 \u00b5g\/mL. The FBG micro-indenter provided a better and more precise assessment of the level of cartilage degeneration than the OARSI histological grading system but it was less sensitive at detecting mechanical changes than IT-AFM. The FBG-sensor allowed us to observe differences in cartilage biomechanics for collagenase concentrations of 100 and 500 \u00b5g\/mL. Our results confirm that the FBG sensor is capable of detecting small changes in articular cartilage stiffness, which may be associated with initial cartilage degeneration caused by early OA.<\/jats:p>","DOI":"10.3390\/ijms21197384","type":"journal-article","created":{"date-parts":[[2020,10,7]],"date-time":"2020-10-07T09:12:58Z","timestamp":1602061978000},"page":"7384","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Early Detection of Cartilage Degeneration: A Comparison of Histology, Fiber Bragg Grating-Based Micro-Indentation, and Atomic Force Microscopy-Based Nano-Indentation"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9928-0860","authenticated-orcid":false,"given":"Bastian","family":"Hartmann","sequence":"first","affiliation":[{"name":"Center for Applied Tissue Engineering and Regenerative Medicine\u2013CANTER, Munich University of Applied Sciences, 80335 Munich, Germany"},{"name":"Laboratory of Experimental Surgery and Regenerative Medicine (ExperiMed), Clinic for General, Trauma and Reconstructive Surgery, University of Munich, 82152 Planegg, Germany"},{"name":"Center for Nanoscience (CeNS), University of Munich, 80331 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Marchi","sequence":"additional","affiliation":[{"name":"Photonics Laboratory, Department of Applied Sciences and Mechatronics, Munich University of Applied Sciences, 80335 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Alberton","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Surgery and Regenerative Medicine (ExperiMed), Clinic for General, Trauma and Reconstructive Surgery, University of Munich, 82152 Planegg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsuzsanna","family":"Farkas","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Surgery and Regenerative Medicine (ExperiMed), Clinic for General, Trauma and Reconstructive Surgery, University of Munich, 82152 Planegg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3569-6557","authenticated-orcid":false,"given":"Attila","family":"Aszodi","sequence":"additional","affiliation":[{"name":"Center for Applied Tissue Engineering and Regenerative Medicine\u2013CANTER, Munich University of Applied Sciences, 80335 Munich, Germany"},{"name":"Laboratory of Experimental Surgery and Regenerative Medicine (ExperiMed), Clinic for General, Trauma and Reconstructive Surgery, University of Munich, 82152 Planegg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6525-4544","authenticated-orcid":false,"given":"Johannes","family":"Roths","sequence":"additional","affiliation":[{"name":"Photonics Laboratory, Department of Applied Sciences and Mechatronics, Munich University of Applied Sciences, 80335 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9413-0310","authenticated-orcid":false,"given":"Hauke","family":"Clausen-Schaumann","sequence":"additional","affiliation":[{"name":"Center for Applied Tissue Engineering and Regenerative Medicine\u2013CANTER, Munich University of Applied Sciences, 80335 Munich, Germany"},{"name":"Center for Nanoscience (CeNS), University of Munich, 80331 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3382","DOI":"10.1002\/art.11347","article-title":"Indentation testing of human cartilage: Sensitivity to articular surface degeneration","volume":"48","author":"Bae","year":"2003","journal-title":"Arthritis Rheum."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1016\/j.joca.2005.06.008","article-title":"Altered cartilage mechanics and histology in knee osteoarthritis: Relation to clinical assessment (ICRS Grade)","volume":"13","author":"Kleemann","year":"2005","journal-title":"Osteoarthr. Cartil."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Alberton, P., Dugonitsch, H.C., Hartmann, B., Li, P., Farkas, Z., Saller, M.M., Clausen-Schaumann, H., and Aszodi, A. (2019). Aggrecan Hypomorphism Compromises Articular Cartilage Biomechanical Properties and Is Associated with Increased Incidence of Spontaneous Osteoarthritis. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20051008"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/nnano.2008.410","article-title":"Early detection of aging cartilage and osteoarthritis in mice and patient samples using atomic force microscopy","volume":"4","author":"Stolz","year":"2009","journal-title":"Nat. Nanotechnol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Chae, S., Jung, S.W., and Park, H.S. (2018). In vivo biomechanical measurement and haptic simulation of portal placement procedure in shoulder arthroscopic surgery. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0193736"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1016\/j.arthro.2017.11.028","article-title":"Fundamentals of Arthroscopic Surgery Training Program Improves Knee Arthroscopy Simulator Performance in Arthroscopic Trainees","volume":"34","author":"Cychosz","year":"2018","journal-title":"Arthroscopy"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1007\/s00402-009-0868-y","article-title":"How valid is the arthroscopic diagnosis of cartilage lesions? Results of an opinion survey among highly experienced arthroscopic surgeons","volume":"129","author":"Spahn","year":"2009","journal-title":"Arch. Orthop. Trauma Surg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1088\/0031-9155\/46\/2\/319","article-title":"The accuracy and reliability of a novel handheld dynamic indentation probe for analysing articular cartilage","volume":"46","author":"Appleyard","year":"2001","journal-title":"Phys. Med. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"054303","DOI":"10.1063\/1.3127602","article-title":"The tissue diagnostic instrument","volume":"80","author":"Hansma","year":"2009","journal-title":"Rev. Sci. Instrum."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/1350-4533(95)97322-G","article-title":"Indentation instrument for the measurement of cartilage stiffness under arthroscopic control","volume":"17","author":"Lyyra","year":"1995","journal-title":"Med. Eng. Phys."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1926","DOI":"10.1016\/j.joca.2014.08.008","article-title":"Non-destructive electromechanical assessment (Arthro-BST) of human articular cartilage correlates with histological scores and biomechanical properties","volume":"22","author":"Sim","year":"2014","journal-title":"Osteoarthr. Cartil."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1007\/s00132-012-1953-4","article-title":"Hochdynamisches Pr\u00fcfsystem zur biomechanischen Charakterisierung von Knorpel und seinen Regeneraten","volume":"41","author":"Hautmann","year":"2012","journal-title":"Der. Orthop\u00e4de."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.snb.2017.05.156","article-title":"Microindentation sensor system based on an optical fiber Bragg grating for the mechanical characterization of articular cartilage by stress-relaxation","volume":"252","author":"Marchi","year":"2017","journal-title":"Sens. Actuators B"},{"key":"ref_14","unstructured":"Roths, R., Clausen-Schaumann, H., Marchi, G., and Aszodi, A. (2016). Indentierungsvorrichtung Mit Piezoelektrischem Stellelement. (DE 10 2015 003433 B3)."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.jmbbm.2019.07.005","article-title":"Discrimination between healthy and degenerated bovine articular cartilage with a fiber Bragg grating based microindenter","volume":"99","author":"Marchi","year":"2019","journal-title":"J. Mech. Behav. Biomed. Mater."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"523","DOI":"10.2106\/00004623-197153030-00009","article-title":"Biochemical and metabolic abnormalities in articular cartilage from osteo-arthritic human hips. II. Correlation of morphology with biochemical and metabolic data","volume":"53","author":"Mankin","year":"1971","journal-title":"J. Bone Jt. Surg. Am."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.joca.2005.07.014","article-title":"Osteoarthritis cartilage histopathology: Grading and staging","volume":"14","author":"Pritzker","year":"2006","journal-title":"Osteoarthr. Cartil."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Mieloch, A.A., Richter, M., Trzeciak, T., Giersig, M., and Rybka, J.D. (2019). Osteoarthritis Severely Decreases the Elasticity and Hardness of Knee Joint Cartilage: A Nanoindentation Study. J. Clin. Med., 8.","DOI":"10.3390\/jcm8111865"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.joca.2016.08.008","article-title":"Nanoindentation modulus of murine cartilage: A sensitive indicator of the initiation and progression of post-traumatic osteoarthritis","volume":"25","author":"Doyran","year":"2017","journal-title":"Osteoarthr. Cartil."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2319","DOI":"10.1143\/JJAP.45.2319","article-title":"Development of Atomic Force Microscope for Arthroscopic Knee Cartilage Inspection","volume":"45","author":"Imer","year":"2006","journal-title":"Jpn. J. Appl. Phys."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1679\/aohc.72.251","article-title":"The measurement of biomechanical properties of porcine articular cartilage using atomic force microscopy","volume":"72","author":"Imer","year":"2009","journal-title":"Arch. Histol. Cytol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Javadzadeh Kalahrodi, A., Marchi, G., M\u00f6ller, J., Nolte, S., and Roths, J. (2019). 2D stiffness mapping for localizing osteoarthritic degenerated cartilage by using a fast indentation system based on fiber Bragg gratings. Seventh European Workshop on Optical Fibre Sensors, SPIE.","DOI":"10.1117\/12.2539252"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.jbiomech.2013.11.050","article-title":"An in vitro model for the pathological degradation of articular cartilage in osteoarthritis","volume":"47","author":"Grenier","year":"2014","journal-title":"J. Biomech."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3269","DOI":"10.1016\/S0006-3495(04)74375-1","article-title":"Dynamic Elastic Modulus of Porcine Articular Cartilage Determined at Two Different Levels of Tissue Organization by Indentation-Type Atomic Force Microscopy","volume":"86","author":"Stolz","year":"2004","journal-title":"Biophys. J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.jmbbm.2019.05.040","article-title":"Combined enzymatic degradation of proteoglycans and collagen significantly alters intratissue strains in articular cartilage during cyclic compression","volume":"98","author":"Pastrama","year":"2019","journal-title":"J. Mech. Behav. Biomed. Mater."},{"key":"ref_26","unstructured":"Marchi, G., Canti, O., Baier, V., Micallef, W., Hartmann, B., Alberton, P., Aszodi, A., Clausen-Schaumann, H., and Roths, J. (February, January 27). Cartilage microindentation using cylindrical and spherical optical fiber indenters with integrated Bragg gratings as force sensors. Proceedings of the SPIE Volume 10496 in Optical Elastography and Tissue Biomechanics V, San Francisco, CA, USA."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.matbio.2015.10.001","article-title":"Structural and mechanical properties of the proliferative zone of the developing murine growth plate cartilage assessed by atomic force microscopy","volume":"50","author":"Prein","year":"2016","journal-title":"Matrix Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1002\/jcp.21258","article-title":"Osteoarthritis","volume":"213","author":"Goldring","year":"2007","journal-title":"J. Cell. Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.21037\/aoj.2018.12.05","article-title":"The diagnosis of early osteoarthritis of the knee using magnetic resonance imaging","volume":"3","author":"Nagai","year":"2018","journal-title":"Ann. Jt."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"88","DOI":"10.2106\/00004623-198264010-00013","article-title":"Variations in the intrinsic mechanical properties of human articular cartilage with age, degeneration, and water content","volume":"64","author":"Armstrong","year":"1982","journal-title":"J. Bone Jt. Surg. Am."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1053\/joca.1998.0202","article-title":"Biomechanical, histological and immunohistological studies of patellar cartilage in an ovine model of osteoarthritis induced by lateral meniscectomy","volume":"7","author":"Appleyard","year":"1999","journal-title":"Osteoarthr. Cartil."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1016\/j.clinbiomech.2006.07.001","article-title":"A review on the mechanical quality of articular cartilage\u2014Implications for the diagnosis of osteoarthritis","volume":"21","author":"Knecht","year":"2006","journal-title":"Clin. Biomech."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1038\/nnano.2009.29","article-title":"AFM tackles osteoarthritis","volume":"4","author":"Aigner","year":"2009","journal-title":"Nat. Nanotechnol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s10544-019-0359-z","article-title":"Fiberoptic microindentation technique for early osteoarthritis diagnosis: An in vitro study on human cartilage","volume":"21","author":"Marchi","year":"2019","journal-title":"Biomed. Microdevices"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Ihnatouski, M., Pauk, J., Karev, D., and Karev, B. (2020). AFM-Based Method for Measurement of Normal and Osteoarthritic Human Articular Cartilage Surface Roughness. Materials, 13.","DOI":"10.3390\/ma13102302"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1007\/s10439-010-9921-9","article-title":"Freeze\u2013Thaw Induced Biomechanical Changes in Arteries: Role of Collagen Matrix and Smooth Muscle Cells","volume":"38","author":"Venkatasubramanian","year":"2010","journal-title":"Ann. Biomed. Eng."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2731","DOI":"10.1016\/j.bpj.2010.02.013","article-title":"Micro- and nanomechanical analysis of articular cartilage by indentation-type atomic force microscopy: Validation with a gel-microfiber composite","volume":"98","author":"Loparic","year":"2010","journal-title":"Biophys. J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2010\/243150","article-title":"Properties of Cartilage on Micro- and Nanolevel","volume":"2010","author":"Chizhik","year":"2010","journal-title":"Adv. Tribol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1115\/1.2893754","article-title":"Regular Pyramid Punch Problem","volume":"59","author":"Bilodeau","year":"1992","journal-title":"J. Appl. Mech."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.jmbbm.2016.01.015","article-title":"Mechanical properties of normal and osteoarthritic human articular cartilage","volume":"61","author":"Robinson","year":"2016","journal-title":"J. Mech. Behav. Biomed. Mater."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/19\/7384\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:16:58Z","timestamp":1760177818000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/19\/7384"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,6]]},"references-count":40,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2020,10]]}},"alternative-id":["ijms21197384"],"URL":"https:\/\/doi.org\/10.3390\/ijms21197384","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,6]]}}}