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dc.creatorNikolaev, N. I.
dc.creatorObradović, Bojana
dc.creatorVersteeg, H. K.
dc.creatorLemon, G.
dc.creatorWilliams, D.J.
dc.date.accessioned2021-03-10T11:23:45Z
dc.date.available2021-03-10T11:23:45Z
dc.date.issued2010
dc.identifier.issn0006-3592
dc.identifier.urihttp://TechnoRep.tmf.bg.ac.rs/handle/123456789/1711
dc.description.abstractIn this work a new phenomenological model of growth of cartilage tissue cultured in a rotating bioreactor is developed. It represents an advancement of a previously derived model of deposition of glycosaminoglycan (GAG) in engineered cartilage by (i) introduction of physiological mechanisms of proteoglycan accumulation in the extracellular matrix (ECM) as well as by correlating (ii) local cell densities and (iii) tissue growth to the ECM composition. In particular, previously established predictions and correlations of local oxygen concentrations and GAG synthesis rates are extended to distinguish cell secreted proteoglycan monomers free to diffuse in cell surroundings and outside from the engineered construct, from large aggrecan molecules, which are constrained within the ECM and practically immovable. The model includes kinetics of aggregation, that is, transformation of mobile GAG species into immobile aggregates as well as maintenance of the normal ECM composition after the physiological GAG concentration is reached by incorporation of a product inhibition term. The model also includes mechanisms of the temporal evolution of cell density distributions and tissue growth under in vitro conditions. After a short initial proliferation phase the total cell number in the construct remains constant, but the local cell distribution is leveled out by GAG accumulation and repulsion due to negative molecular charges. Furthermore, strong repulsive forces result in expansion of the local tissue elements observed macroscopically as tissue growth (i.e., construct enlargement). The model is validated by comparison with experimental data of (i) GAG distribution and leakage, (ii) spatial-temporal distributions of cells, and (iii) tissue growth reported in previous works. Validation of the model predictive capability-against a selection of measured data that were not used to construct the model-suggests that the model successfully describes the interplay of several simultaneous processes carried out during in vitro cartilage tissue regeneration and indicates that this approach could also be attractive for application in other tissue engineering systems. Biotechnol. Bioeng. 2010;105: 842-853.en
dc.publisherJohn Wiley & Sons Inc, Hoboken
dc.relationUK EPSRCEngineering & Physical Sciences Research Council (EPSRC)
dc.relationinfo:eu-repo/grantAgreement/MESTD/MPN2006-2010/142075/RS//
dc.relationBiotechnology and Biological Sciences Research CouncilBiotechnology and Biological Sciences Research Council (BBSRC) [BB/D008522/1] Funding Source: researchfish
dc.relationEngineering and Physical Sciences Research CouncilEngineering & Physical Sciences Research Council (EPSRC) [EP/C534247/1] Funding Source: researchfish
dc.rightsrestrictedAccess
dc.sourceBiotechnology and Bioengineering
dc.subjectmathematical modelen
dc.subjectcartilage tissue engineeringen
dc.subjecttissue growthen
dc.subjectglycosaminoglycan depositionen
dc.subjectcell distributionen
dc.titleA Validated Model of GAG Deposition, Cell Distribution, and Growth of Tissue Engineered Cartilage Cultured in a Rotating Bioreactoren
dc.typearticle
dc.rights.licenseARR
dc.citation.epage853
dc.citation.issue4
dc.citation.other105(4): 842-853
dc.citation.rankM21
dc.citation.spage842
dc.citation.volume105
dc.identifier.doi10.1002/bit.22581
dc.identifier.pmid19845002
dc.identifier.rcubconv_3337
dc.identifier.scopus2-s2.0-77449089927
dc.identifier.wos000274742200019
dc.type.versionpublishedVersion


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