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dc.contributor.authorGarcia, João P
dc.contributor.authorLongoni, Alessia
dc.contributor.authorGawlitta, Debby
dc.contributor.authorRosenberg, Antoine J W P
dc.contributor.authorGrinstaff, Mark W
dc.contributor.authorTöyräs, Juha
dc.contributor.authorWeinans, Harrie
dc.contributor.authorCreemers, Laura B
dc.contributor.authorPouran, Behdad
dc.date.accessioned2019-12-10T11:29:29Z
dc.date.available2019-12-10T11:29:29Z
dc.date.issued2019
dc.identifier.urihttps://erepo.uef.fi/handle/123456789/7859
dc.description.abstractTissue engineering and regenerative medicine are two therapeutic strategies to treat, and to potentially cure, diseases affecting cartilaginous tissues, such as osteoarthritis and cartilage defects. Insights into the processes occurring during regeneration are essential to steer and inform development of the envisaged regenerative strategy, however tools are needed for longitudinal and quantitative monitoring of cartilage matrix components. In this study, we introduce a contrast-enhanced computed tomography (CECT)-based method using a cationic iodinated contrast agent (CA4+) for longitudinal quantification of glycosaminoglycans (GAG) in cartilage-engineered constructs. CA4+ concentration and scanning protocols were first optimized to ensure no cytotoxicity and a facile procedure with minimal radiation dose. Chondrocyte and mesenchymal stem cell pellets, containing different GAG content were generated and exposed to CA4+. The CA4+ content in the pellets, as determined by micro computed tomography, was plotted against GAG content, as measured by 1,9-dimethylmethylene blue analysis, and showed a high linear correlation. The established equation was used for longitudinal measurements of GAG content over 28 days of pellet culture. Importantly, this method did not adversely affect cell viability or chondrogenesis. Additionally, the CA4+ distribution accurately matched safranin-O staining on histological sections. Hence, we show proof-of-concept for the application of CECT, utilizing a positively charged contrast agent, for longitudinal and quantitative imaging of GAG distribution in cartilage tissue-engineered constructs. Statement of Significance Tissue engineering and regenerative medicine are promising therapeutic strategies for different joint pathologies such as cartilage defects or osteoarthritis. Currently, in vitro assessment on the quality and composition of the engineered cartilage mainly relies on destructive methods. Therefore, there is a need for the development of techniques that allow for longitudinal and quantitative imaging and monitoring of cartilage-engineered constructs. This work harnesses the electrostatic interactions between the negatively-charged glycosaminoglycans (GAGs) and a positively-charged contrast agent for longitudinal and non-destructive quantification of GAGs, providing valuable insight on GAG development and distribution in cartilage engineered constructs. Such technique can advance the development of regenerative strategies, not only by allowing continuous monitoring but also by serving as a pre-implantation screening tool.
dc.language.isoenglanti
dc.publisherElsevier BV
dc.relation.ispartofseriesActa biomaterialia
dc.relation.urihttp://dx.doi.org/10.1016/j.actbio.2019.09.014
dc.rightsCC BY-NC-ND https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjecttissue engineering
dc.subjectcartilage regeneration
dc.subjectglycosaminoglycans
dc.subject3D imaging
dc.subjectcomputed tomography
dc.titleContrast enhanced computed tomography for real-time quantification of glycosaminoglycans in cartilage tissue engineered constructs
dc.description.versionfinal draft
dc.contributor.departmentDepartment of Applied Physics, activities
uef.solecris.id65612746en
dc.type.publicationTieteelliset aikakauslehtiartikkelit
dc.rights.accessrights© Acta Materialia Inc
dc.relation.projectidinfo:eu-repo/grantAgreement/EC/H2020-EU.1.3.1./642414/EU/Targeting Cartilage Regeneration in joint and intervertebral disc diseases/TargetCaRe
dc.relation.doi10.1016/j.actbio.2019.09.014
dc.description.reviewstatuspeerReviewed
dc.format.pagerange202-212
dc.relation.issn1742-7061
dc.relation.volume100
dc.rights.accesslevelopenAccess
dc.type.okmA1
uef.solecris.openaccessEi


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