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dc.contributor.advisorZeugolis, Dimitrios
dc.contributor.authorKumar, Pramod
dc.description.abstractTherapeutic strategies based on the principles of tissue engineering by self-assembly put forward the notion that functional regeneration can be achieved by utilising the inherent capacity of cells to create highly sophisticated supramolecular assemblies. However, in dilute ex vivo microenvironments, prolonged culture time is required to develop extracellular matrix-rich implantable devices. Herein, we assessed the influence of macromolecular crowding, a biophysical phenomenon that regulates intra- and extra-cellular activities in multicellular organisms, in human corneal fibroblast culture. In the presence of neutral macromolecules, abundant extracellular matrix deposition was evidenced as fast as 48 hours in culture, even at low serum concentration. The addition of negative charged galactose derivative (carrageenan) in human corneal fibroblast culture, even at 0.5% serum, increases by 12-fold tissue-specific matrix deposition, whilst maintaining physiological cell morphology and protein / gene expression. Gene analysis indicates that a glucose derivative (dextran sulphate) may drive corneal fibroblasts towards a myofibroblast lineage. Temperature responsive copolymers allowed the detachment of dense and cohesive supramolecularly assembled living substitutes within 6 days in culture, with morphological and histological properties similar to native tissue. Collectively, these results indicate that macromolecular crowding may be suitable not only for clinical translation and commercialisation of tissue engineering by self-assembly therapies, but also for the development of in vitro pathophysiology models.en_US
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 Ireland
dc.subjectMacromolecular crowdingen_US
dc.subjectHuman corneal fibroblastsen_US
dc.subjectIn vitroen_US
dc.subjectExtracellular matrixen_US
dc.subjectCell sheet technologyen_US
dc.subjectRegenerative, Modular & Developmental Engineering Laboratory (REMODEL)en_US
dc.subjectNetwork of Excellence for Functional Biomaterials (NFB)en_US
dc.subjectCentre for Research in Medical Devices (CURAM)en_US
dc.titleCell sheet technology meets macromolecular crowding: The self-ssembly approach for corneal stromal developmenten_US
dc.contributor.funderCollege of Engineering & Informatics NUI Galway & Science Foundation Irelanden_US
dc.local.noteIt has been demonstrated that functional tissue regeneration can be achieved by utilising the inherent capacity of cells to create highly sophisticated supramolecular assemblies similar to the that of native tissue. The current thesis describes the application of scaffold-free self assembly approaches, macromolecular crowding and cell sheet technology for the development of extracellular matrix rich corneal fibroblasts cell sheets within 2-6 days of in vitro culture, without affecting the light transmittance of the developed corneal stromal tissue substitute.en_US

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Attribution-NonCommercial-NoDerivs 3.0 Ireland
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivs 3.0 Ireland