Identifying potential patient-specific predictors for anterior cruciate ligament reconstruction outcome – a diagnostic in vitro tissue remodeling platform

Abstract Purpose Upon anterior cruciate ligament (ACL) rupture, reconstruction is often required, with the hamstring tendon autograft as most widely used treatment. Post-operative autograft remodeling enhances graft rupture risk, which occurs in up to 10% of the patient population, increasing up to...

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Main Authors: Marc van Vijven, Bart van Groningen, Joyce N. Kimenai, Maria C. van der Steen, Marina van Doeselaar, Rob P. A. Janssen, Keita Ito, Jasper Foolen
Format: Article
Language:English
Published: Wiley 2020-07-01
Series:Journal of Experimental Orthopaedics
Subjects:
Online Access:http://link.springer.com/article/10.1186/s40634-020-00266-2
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author Marc van Vijven
Bart van Groningen
Joyce N. Kimenai
Maria C. van der Steen
Marina van Doeselaar
Rob P. A. Janssen
Keita Ito
Jasper Foolen
author_facet Marc van Vijven
Bart van Groningen
Joyce N. Kimenai
Maria C. van der Steen
Marina van Doeselaar
Rob P. A. Janssen
Keita Ito
Jasper Foolen
author_sort Marc van Vijven
collection DOAJ
description Abstract Purpose Upon anterior cruciate ligament (ACL) rupture, reconstruction is often required, with the hamstring tendon autograft as most widely used treatment. Post-operative autograft remodeling enhances graft rupture risk, which occurs in up to 10% of the patient population, increasing up to 30% of patients aged under 20 years. Therefore, this research aimed to identify potential biological predictors for graft rupture, derived from patient-specific tissue remodeling-related cell properties in an in vitro micro-tissue platform. Methods Hamstring tendon-derived cells were obtained from remnant autograft tissue after ACL reconstructions (36 patients, aged 12–55 years), and seeded in collagen I gels on a micro-tissue platform. Micro-tissue compaction over time – induced by altering the boundary constraints – was monitored. Pro-collagen I expression was assessed using ELISA, and protein expression of tenomodulin and α-smooth muscle actin were measured using Western blot. Expression and activity of matrix metalloproteinase 2 were determined using gelatin zymography. Results Only micro-tissues corresponding to younger patients occasionally released themselves from the constraining posts. Pro-collagen I expression was significantly higher in younger patients. Differences in α-smooth muscle actin and tenomodulin expression between patients were found, but these were age-independent. Active matrix metalloproteinase 2 expression was slightly more abundant in younger patients. Conclusions The presented micro-tissue platform exposed patient-specific remodeling-related differences between tendon-derived cells, with the micro-tissues that released from constraining posts and pro-collagen I expression best reflecting the clinical age-dependency of graft rupture. These properties can be the starting point in the quest for potential predictors for identifying individual patients at risk for graft rupture.
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spelling doaj.art-258be1a0f702435195e7ea4f37ead5f82024-04-03T08:56:34ZengWileyJournal of Experimental Orthopaedics2197-11532020-07-017111110.1186/s40634-020-00266-2Identifying potential patient-specific predictors for anterior cruciate ligament reconstruction outcome – a diagnostic in vitro tissue remodeling platformMarc van Vijven0Bart van Groningen1Joyce N. Kimenai2Maria C. van der Steen3Marina van Doeselaar4Rob P. A. Janssen5Keita Ito6Jasper Foolen7Orthopaedic Biomechanics, Department of Biomedical Engineering, Eindhoven University of TechnologyDepartment of Orthopaedic Surgery, Máxima MCOrthopaedic Biomechanics, Department of Biomedical Engineering, Eindhoven University of TechnologyDepartment of Orthopaedic Surgery, Máxima MCOrthopaedic Biomechanics, Department of Biomedical Engineering, Eindhoven University of TechnologyOrthopaedic Biomechanics, Department of Biomedical Engineering, Eindhoven University of TechnologyOrthopaedic Biomechanics, Department of Biomedical Engineering, Eindhoven University of TechnologyOrthopaedic Biomechanics, Department of Biomedical Engineering, Eindhoven University of TechnologyAbstract Purpose Upon anterior cruciate ligament (ACL) rupture, reconstruction is often required, with the hamstring tendon autograft as most widely used treatment. Post-operative autograft remodeling enhances graft rupture risk, which occurs in up to 10% of the patient population, increasing up to 30% of patients aged under 20 years. Therefore, this research aimed to identify potential biological predictors for graft rupture, derived from patient-specific tissue remodeling-related cell properties in an in vitro micro-tissue platform. Methods Hamstring tendon-derived cells were obtained from remnant autograft tissue after ACL reconstructions (36 patients, aged 12–55 years), and seeded in collagen I gels on a micro-tissue platform. Micro-tissue compaction over time – induced by altering the boundary constraints – was monitored. Pro-collagen I expression was assessed using ELISA, and protein expression of tenomodulin and α-smooth muscle actin were measured using Western blot. Expression and activity of matrix metalloproteinase 2 were determined using gelatin zymography. Results Only micro-tissues corresponding to younger patients occasionally released themselves from the constraining posts. Pro-collagen I expression was significantly higher in younger patients. Differences in α-smooth muscle actin and tenomodulin expression between patients were found, but these were age-independent. Active matrix metalloproteinase 2 expression was slightly more abundant in younger patients. Conclusions The presented micro-tissue platform exposed patient-specific remodeling-related differences between tendon-derived cells, with the micro-tissues that released from constraining posts and pro-collagen I expression best reflecting the clinical age-dependency of graft rupture. These properties can be the starting point in the quest for potential predictors for identifying individual patients at risk for graft rupture.http://link.springer.com/article/10.1186/s40634-020-00266-2Anterior cruciate ligamentHamstring tendon autograftIn vitro micro-tissue platformPatient-specific cell propertiesTissue remodeling
spellingShingle Marc van Vijven
Bart van Groningen
Joyce N. Kimenai
Maria C. van der Steen
Marina van Doeselaar
Rob P. A. Janssen
Keita Ito
Jasper Foolen
Identifying potential patient-specific predictors for anterior cruciate ligament reconstruction outcome – a diagnostic in vitro tissue remodeling platform
Journal of Experimental Orthopaedics
Anterior cruciate ligament
Hamstring tendon autograft
In vitro micro-tissue platform
Patient-specific cell properties
Tissue remodeling
title Identifying potential patient-specific predictors for anterior cruciate ligament reconstruction outcome – a diagnostic in vitro tissue remodeling platform
title_full Identifying potential patient-specific predictors for anterior cruciate ligament reconstruction outcome – a diagnostic in vitro tissue remodeling platform
title_fullStr Identifying potential patient-specific predictors for anterior cruciate ligament reconstruction outcome – a diagnostic in vitro tissue remodeling platform
title_full_unstemmed Identifying potential patient-specific predictors for anterior cruciate ligament reconstruction outcome – a diagnostic in vitro tissue remodeling platform
title_short Identifying potential patient-specific predictors for anterior cruciate ligament reconstruction outcome – a diagnostic in vitro tissue remodeling platform
title_sort identifying potential patient specific predictors for anterior cruciate ligament reconstruction outcome a diagnostic in vitro tissue remodeling platform
topic Anterior cruciate ligament
Hamstring tendon autograft
In vitro micro-tissue platform
Patient-specific cell properties
Tissue remodeling
url http://link.springer.com/article/10.1186/s40634-020-00266-2
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