Kinetics and Retention of Polystyrenesulfonate for Proteoglycan Replacement in Cartilage

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dc.contributor.authorSundar, Shalini
dc.contributor.authorKoopman, Allison
dc.contributor.authorManzoni, Thomas J.
dc.contributor.authorXie, Weiran
dc.contributor.authorBhatti, Qurat-Ul-Ain
dc.contributor.authorLo, Chun-Yuan
dc.contributor.authorDamani, Vidhika S.
dc.contributor.authorYang, Ai Nin
dc.contributor.authorPochan, Darrin
dc.contributor.authorParreno, Justin
dc.contributor.authorEngiles, Julie B.
dc.contributor.authorKayser, Laure V.
dc.contributor.authorDhong, Charles
dc.date.accessioned2024-09-13T17:43:46Z
dc.date.available2024-09-13T17:43:46Z
dc.date.issued2024-08-14
dc.descriptionThis document is the Accepted Manuscript version of a Published Work that appeared in final form in Biomacromolecules, copyright © 2024 The Authors. Published by American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://www.doi.org/10.1021/acs.biomac.4c00479. This article will be embargoed until 08/14/2025.
dc.description.abstractTissue hydration provides articular cartilage with dynamic viscoelastic properties. Early stage osteoarthritis (OA) is marked by loss of proteoglycans and glycosaminoglycans (GAG), lowering fixed charge density, and impairing tissue osmotic function. The most common GAG replacement, chondroitin sulfate (CS), has failed to show effectiveness. Here, we investigated a synthetic polyelectrolyte, poly(styrenesulfonate) (PSS), both as a model compound to investigate polyelectrolyte transport in cartilage, and as a potential candidate to restore bulk fixed charge density in cartilage with GAG loss. Through bovine explants and histology, we determined zonal-based effective diffusion coefficients for three different molecular weights of PSS. Compared to CS, PSS was retained longer in GAG-depleted cartilage in static and compression-based desorption experiments. We explained enhanced solute performance of PSS by its more compact morphology and higher charge density by small-angle X-ray scattering. This study may improve design of GAG mimetic molecules for repairing osmotic function in OA cartilage.
dc.description.sponsorshipThis project was supported by the DCMR COBRE program, with a grant from the National Institute of General Medical Sciences and from the National Institutes of Health (NIH-NIGMS COBRE, P20GM139760) to C.D., L.V.K., J.P. and J.E. T.J.M. and J.P. acknowledge funding from NIGMS P20GM103446. W.X. and D.P. acknowledge funding from the National Science Foundation (NSF) through the University of Delaware Materials Research Science and Engineering Center, DMR-2011824. L.V.K., A.K., C.Y.L., V.S.D., and A.N.Y. thank the University of Delaware Research Foundation-Strategic Initiative (UDRF-SI) for seed funding and the NSF (CAREER grant No. DMR-2237888) for providing funding for the PSS synthesis. Histology was performed by the DCMR Histology Core, University of Delaware, Newark, DE. SAXS experiments were performed at LiX beamline of the National Synchrotron Light Source II, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Brookhaven National Laboratory under Contract no. DE-SC0012704. The LiX beamline is part of the Center for BioMolecular Structure (CBMS) which is primarily supported by the National Institutes of Health, National Institute of General Medical Sciences (NIGMS) through a Center Core P30 Grant (P30GM133893), and by the DOE Office of Biological and Environmental Research (KP1607011). The authors would like to thank Dr. Kyla Ortved (University of Pennsylvania School of Veterinary Medicine) for her insights on OA. The authors would also like to thank Dr. David Martin (University of Delaware) and his lab for access to their microplate reader. Notes The authors declare the following competing financial interest(s): C.D., L.V.K., S.S., Q.B., A.N.Y, and V.S.D. are inventors on a U.S. provisional patent related to the use of synthetic polyelectrolytes for restoration of glycosaminoglycan and proteoglycan function in soft tissue (Application 63/595,625).
dc.identifier.citationSundar, Shalini, Allison Koopman, Thomas J. Manzoni, Weiran Xie, Qurat-Ul-Ain Bhatti, Chun-Yuan Lo, Vidhika S. Damani, et al. “Kinetics and Retention of Polystyrenesulfonate for Proteoglycan Replacement in Cartilage.” Biomacromolecules 25, no. 9 (September 9, 2024): 5819–33. https://doi.org/10.1021/acs.biomac.4c00479.
dc.identifier.issn1526-4602
dc.identifier.urihttps://udspace.udel.edu/handle/19716/34961
dc.language.isoen_US
dc.publisherBiomacromolecules
dc.subjectGAG replacement
dc.subjectproteoglycan replacement
dc.subjectosteoarthritis
dc.subjectfixed charge density
dc.subjectsynthetic polyelectrolytes
dc.titleKinetics and Retention of Polystyrenesulfonate for Proteoglycan Replacement in Cartilage
dc.typeArticle

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