title: Micro- and nano-mechanics of osteoarthritic cartilage: The effects of tonicity and disease severity.
abstract: The present study aims to discover the contribution of glycosaminoglycans (GAGs) and collagen fibers to the mechanical properties of the osteoarthritic (OA) cartilage tissue. We used nanoindentation experiments to understand the mechanical behavior of mild and severe osteoarthritic cartilage at micro- and nano-scale at different swelling conditions. Contrast enhanced micro-computed tomography (EPIC-μCT) was used to confirm that mild OA specimens had significantly higher GAGs content compared to severe OA specimens. In micro-scale, the semi-equilibrium modulus of mild OA specimens significantly dropped after immersion in a hypertonic solution and at nano-scale, the histograms of the measured elastic modulus revealed three to four components. Comparing the peaks with those observed for healthy cartilage in a previous study indicated that the first and third peaks represent the mechanical properties of GAGs and the collagen network. The third peak shows considerably stiffer elastic modulus for mild OA samples as compared to the severe OA samples in isotonic conditions. Furthermore, this peak clearly dropped when the tonicity increased, indicating the loss of collagen (pre-) stress in the shrunk specimen. Our observations support the association of the third peak with the collagen network. However, our results did not provide any direct evidence to support the association of the first peak with GAGs. For severe OA specimens, the peak associated with the collagen network did not drop when the tonicity increased, indicating a change in the response of OA cartilage to hypertonicity, likely collagen damage, as the disease progresses to its latest stages.
authors.affiliation: Faculty of Mechanical, Maritime, and Materials Engineering, Delft University of Technology (TU Delft), Mekelweg 2, 2628 CD, Delft, The Netherlands; Department of Orthopaedics, University Medical Center Utrecht, Q.03.2.103-1, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands. Electronic address: P.Rahnamaymoshtagh@umcutrecht.nl.
authors.forename: P R
authors.initials: PR
authors.lastname: Moshtagh
authors.affiliation: Faculty of Mechanical, Maritime, and Materials Engineering, Delft University of Technology (TU Delft), Mekelweg 2, 2628 CD, Delft, The Netherlands; Department of Orthopaedics, University Medical Center Utrecht, Q.03.2.103-1, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands. Electronic address: B.Pouran@umcutrecht.nl.
authors.forename: B
authors.initials: B
authors.lastname: Pouran
authors.affiliation: Department of Orthopaedics and Radiology, Erasmus Medical Centre, Rotterdam, The Netherlands. Electronic address: J.Vantiel@erasmusmc.nl.
authors.forename: J
authors.initials: J
authors.lastname: van Tiel
authors.affiliation: Faculty of Mechanical, Maritime, and Materials Engineering, Delft University of Technology (TU Delft), Mekelweg 2, 2628 CD, Delft, The Netherlands. Electronic address: Jrauker@m3dd.com.
authors.forename: J
authors.initials: J
authors.lastname: Rauker
authors.affiliation: Kavli Institute of Nanoscience, Delft University of Technology, Lorentzweg 1, 2628 CJ, Delft, The Netherlands. Electronic address: M.R.Zuiddam@tudelft.nl.
authors.forename: M R
authors.initials: MR
authors.lastname: Zuiddam
authors.affiliation: Faculty of Mechanical, Maritime, and Materials Engineering, Delft University of Technology (TU Delft), Mekelweg 2, 2628 CD, Delft, The Netherlands. Electronic address: V.arbabi-21@tudelft.nl.
authors.forename: V
authors.initials: V
authors.lastname: Arbabi
authors.affiliation: Department of Orthopaedics, University Medical Center Utrecht, Q.03.2.103-1, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands; Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands. Electronic address: N.M.Korthagen@uu.nl.
authors.forename: N M
authors.initials: NM
authors.lastname: Korthagen
authors.affiliation: Faculty of Mechanical, Maritime, and Materials Engineering, Delft University of Technology (TU Delft), Mekelweg 2, 2628 CD, Delft, The Netherlands; Department of Orthopaedics, University Medical Center Utrecht, Q.03.2.103-1, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands; Department of Rheumatology, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address: H.H.Weinans@umcutrecht.nl.
authors.forename: H
authors.initials: H
authors.lastname: Weinans
authors.affiliation: Faculty of Mechanical, Maritime, and Materials Engineering, Delft University of Technology (TU Delft), Mekelweg 2, 2628 CD, Delft, The Netherlands. Electronic address: A.A.Zadpoor@tudelft.nl.
authors.forename: A A
authors.initials: AA
authors.lastname: Zadpoor
mesh_terms: D002358:Cartilage, Articular / Q000473:pathology / Q000648:ultrastructure*; D003094:Collagen / Q000737:chemistry; D055119:Elastic Modulus; D006025:Glycosaminoglycans / Q000737:chemistry*; D006801:Humans; D010003:Osteoarthritis / Q000473:pathology*; D055114:X-Ray Microtomography
chemical_list: D006025:Glycosaminoglycans; D003094:Collagen
keywords: Articular cartilage; Biophysics; EPIC-µCT; Micro-stiffness; Nano-stiffness; Osmolality