Zwitterionic poly-carboxybetaine-dexamethasone conjugates do not alleviate cartilage degeneration and synovitis in the collagenase-induced osteoarthritis model in rats
Abstract Osteoarthritis is a degenerative joint disease for which there is yet to be a disease-modifying drug available in clinics. New drug candidates often fail due to a combination of poor pharmacokinetics as well as an inability to address the complex, multifactorial nature of osteoarthritis. To...
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Nature Portfolio
2025-07-01
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| Online Access: | https://doi.org/10.1038/s41598-025-93247-3 |
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| author | Patrick Weber Maryam Asadikorayem Shipin Zhang David Fercher Kajetana Bevc Sami Kauppinen Tuomas Frondelius Tianqi Zhang Marina Fonti Gonçalo Barreto Mikko A.J. Finnilä Marcy Zenobi-Wong |
| author_facet | Patrick Weber Maryam Asadikorayem Shipin Zhang David Fercher Kajetana Bevc Sami Kauppinen Tuomas Frondelius Tianqi Zhang Marina Fonti Gonçalo Barreto Mikko A.J. Finnilä Marcy Zenobi-Wong |
| author_sort | Patrick Weber |
| collection | DOAJ |
| description | Abstract Osteoarthritis is a degenerative joint disease for which there is yet to be a disease-modifying drug available in clinics. New drug candidates often fail due to a combination of poor pharmacokinetics as well as an inability to address the complex, multifactorial nature of osteoarthritis. To address these issues, we developed a zwitterionic poly-carboxybetaine acrylamide-dexamethasone (pCBAA-DEX) conjugate showing good cartilage penetration as well as anti-inflammatory and lubricating properties in previous in vitro studies. Here, we investigate the therapeutic potential of pCBAA-DEX in the collagenase-induced osteoarthritis (CIOA) model in rats. Upon induction of the model, animals received one-time, unilateral injections of either saline, DEX or pCBAA-DEX on day 4 (N = 8). On day 70, joint tissues were harvested and analyzed. While pCBAA-DEX achieved ~ 50% cartilage retention at the terminal timepoint, it did not prevent cartilage degeneration, synovial inflammation and synovial fibrosis, nor did DEX alone. Nevertheless, DEX and pCBAA-DEX slightly decreased the fibrosis levels in the synovium with DEX also decreasing the number of synovial lining layers. For the cartilage, DEX did not cause any notable differences, instead we observed an increase in cartilage degeneration in the pCBAA-DEX group. These findings challenge the previous in vitro results and motivate a substantial redesign of these conjugates and associated in vitro methods to reconsider them for the treatment of osteoarthritis. |
| format | Article |
| id | doaj-art-57bf03d59bbf4c92a395b039954bd7c6 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-57bf03d59bbf4c92a395b039954bd7c62025-08-20T04:01:34ZengNature PortfolioScientific Reports2045-23222025-07-0115111410.1038/s41598-025-93247-3Zwitterionic poly-carboxybetaine-dexamethasone conjugates do not alleviate cartilage degeneration and synovitis in the collagenase-induced osteoarthritis model in ratsPatrick Weber0Maryam Asadikorayem1Shipin Zhang2David Fercher3Kajetana Bevc4Sami Kauppinen5Tuomas Frondelius6Tianqi Zhang7Marina Fonti8Gonçalo Barreto9Mikko A.J. Finnilä10Marcy Zenobi-Wong11Tissue Engineering + Biofabrication Laboratory, Department of Health Sciences and Technology, ETH ZürichTissue Engineering + Biofabrication Laboratory, Department of Health Sciences and Technology, ETH ZürichTissue Engineering + Biofabrication Laboratory, Department of Health Sciences and Technology, ETH ZürichTissue Engineering + Biofabrication Laboratory, Department of Health Sciences and Technology, ETH ZürichTissue Engineering + Biofabrication Laboratory, Department of Health Sciences and Technology, ETH ZürichResearch Unit of Health Sciences and Technology, University of OuluResearch Unit of Health Sciences and Technology, University of OuluResearch Unit of Health Sciences and Technology, University of OuluTissue Engineering + Biofabrication Laboratory, Department of Health Sciences and Technology, ETH ZürichClinicum, Faculty of Medicine, University of Helsinki and Helsinki University HospitalResearch Unit of Health Sciences and Technology, University of OuluTissue Engineering + Biofabrication Laboratory, Department of Health Sciences and Technology, ETH ZürichAbstract Osteoarthritis is a degenerative joint disease for which there is yet to be a disease-modifying drug available in clinics. New drug candidates often fail due to a combination of poor pharmacokinetics as well as an inability to address the complex, multifactorial nature of osteoarthritis. To address these issues, we developed a zwitterionic poly-carboxybetaine acrylamide-dexamethasone (pCBAA-DEX) conjugate showing good cartilage penetration as well as anti-inflammatory and lubricating properties in previous in vitro studies. Here, we investigate the therapeutic potential of pCBAA-DEX in the collagenase-induced osteoarthritis (CIOA) model in rats. Upon induction of the model, animals received one-time, unilateral injections of either saline, DEX or pCBAA-DEX on day 4 (N = 8). On day 70, joint tissues were harvested and analyzed. While pCBAA-DEX achieved ~ 50% cartilage retention at the terminal timepoint, it did not prevent cartilage degeneration, synovial inflammation and synovial fibrosis, nor did DEX alone. Nevertheless, DEX and pCBAA-DEX slightly decreased the fibrosis levels in the synovium with DEX also decreasing the number of synovial lining layers. For the cartilage, DEX did not cause any notable differences, instead we observed an increase in cartilage degeneration in the pCBAA-DEX group. These findings challenge the previous in vitro results and motivate a substantial redesign of these conjugates and associated in vitro methods to reconsider them for the treatment of osteoarthritis.https://doi.org/10.1038/s41598-025-93247-3Zwitterionic polymersDexamethasoneCIOAComputed tomographySynovitis |
| spellingShingle | Patrick Weber Maryam Asadikorayem Shipin Zhang David Fercher Kajetana Bevc Sami Kauppinen Tuomas Frondelius Tianqi Zhang Marina Fonti Gonçalo Barreto Mikko A.J. Finnilä Marcy Zenobi-Wong Zwitterionic poly-carboxybetaine-dexamethasone conjugates do not alleviate cartilage degeneration and synovitis in the collagenase-induced osteoarthritis model in rats Scientific Reports Zwitterionic polymers Dexamethasone CIOA Computed tomography Synovitis |
| title | Zwitterionic poly-carboxybetaine-dexamethasone conjugates do not alleviate cartilage degeneration and synovitis in the collagenase-induced osteoarthritis model in rats |
| title_full | Zwitterionic poly-carboxybetaine-dexamethasone conjugates do not alleviate cartilage degeneration and synovitis in the collagenase-induced osteoarthritis model in rats |
| title_fullStr | Zwitterionic poly-carboxybetaine-dexamethasone conjugates do not alleviate cartilage degeneration and synovitis in the collagenase-induced osteoarthritis model in rats |
| title_full_unstemmed | Zwitterionic poly-carboxybetaine-dexamethasone conjugates do not alleviate cartilage degeneration and synovitis in the collagenase-induced osteoarthritis model in rats |
| title_short | Zwitterionic poly-carboxybetaine-dexamethasone conjugates do not alleviate cartilage degeneration and synovitis in the collagenase-induced osteoarthritis model in rats |
| title_sort | zwitterionic poly carboxybetaine dexamethasone conjugates do not alleviate cartilage degeneration and synovitis in the collagenase induced osteoarthritis model in rats |
| topic | Zwitterionic polymers Dexamethasone CIOA Computed tomography Synovitis |
| url | https://doi.org/10.1038/s41598-025-93247-3 |
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