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dc.contributor.advisorKelly, Daniel
dc.contributor.authorAPRILE, PAOLA
dc.date.accessioned2019-12-17T10:39:06Z
dc.date.available2019-12-17T10:39:06Z
dc.date.issued2019en
dc.date.submitted2019
dc.identifier.citationAPRILE, PAOLA, Unravelling the role of mechanical cues on the chondrogenic differentiation of stem cells, Trinity College Dublin.School of Engineering, 2019en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/91120
dc.descriptionAPPROVEDen
dc.description.abstractThe inability of adult articular cartilage to regenerate has motivated the development of tissue engineering strategies to repair cartilage defects before they progress to osteoarthritis. Common cell based strategies employing autologous chondrocytes to treat cartilage lesions, often fail to promote hyaline cartilage repair. Mesenchymal stem cells / stromal cells (MSC) represent a promising cell type for cartilage tissue engineering, due to their relative ease of isolation, ability to proliferate extensively in vitro and differentiate along multiple pathways1-3. MSC differentiation can be influenced by the mechanical properties of their environment4. The objective of this dissertation was to examine the influence of intrinsic and extrinsic mechanical cues on the initiation of chondrogenesis of MSC seeded on top (2-Dimension) or encapsulated within (3-Dimension) hydrogels of defined stiffness. The development of an Interpenetrating Network (IPN) hydrogel system able to support cell growth in 2D and 3D, enabled the independent control of substrate rigidity (2D and 3D) and cell morphology (3D). A softer environment (2D and 3D) was correlated to enhanced upregulation of key chondrogenic markers and cell condensation. Contrary to the expectations, allowing the cells to spread in a soft 3D context greatly improved this chondrogenic response. Finally, the effect of biomaterial's mechanical properties and external forces was combined to the application of a physiological magnitude of Hydrostatic Pressure (HP) to mimic the physiological environment of a loaded knee joint. In this case, the chondrogenic differentiation of HP-stimulated cells resulted enhanced to a greater extent, when the mechanical perturbation was applied after the initiation of their chondrogenic commitment. Mechanical forces and local morphogen gradients greatly influence cartilage development, hence biomimetic cartilage repair strategies aiming to recapitulate the complex interplay of biophysical and biochemical cues, would open new possibilities for cartilage tissue regeneration5,6. The results described in this work evidenced the fundamental role of biophysical cues in regulating MSC biology and the importance of this information to inspire new biomimetic strategies for stem cell based cartilage regeneration procedures. REFERENCES 1. Johnstone, B., Hering, T. M., Caplan, A. I., Goldberg, V. M. & Yoo, J. U. In VitroChondrogenesis of Bone Marrow-Derived Mesenchymal Progenitor Cells. Exp. Cell Res. 238, 265-272 (1998). 2. Caplan, A. I. Mesenchymal stem cells. J. Orthop. Res. 9, 641-650 (1991). 3. Badylak, S. F., Weiss, D. J., Caplan, A. & Macchiarini, P. Engineered whole organs and complex tissues. Lancet 379, 943-52 (2012). 4. Engler, A. J., Sen, S., Sweeney, H. L. & Discher, D. E. Matrix Elasticity Directs Stem Cell Lineage Specification. Cell 126, 677-689 (2006). 5. Ingber, D. E. et al. Tissue Engineering and Developmental Biology: Going Biomimetic. Tissue Eng. 12, 3265-3283 (2007). 6. Mammoto, T., Mammoto, A. & Ingber, D. E. Mechanobiology and developmental control. Annu. Rev. Cell Dev. Biol. 29, 27-61 (2013).en
dc.language.isoenen
dc.publisherTrinity College Dublin. School of Engineering. Discipline of Mechanical & Manuf. Engen
dc.rightsYen
dc.subjectHydrostatic pressureen
dc.subjectMechanobiologyen
dc.subjectYAPen
dc.subjectN-cadherinen
dc.titleUnravelling the role of mechanical cues on the chondrogenic differentiation of stem cellsen
dc.typeThesisen
dc.type.supercollectionthesis_dissertationsen
dc.type.supercollectionrefereed_publicationsen
dc.type.qualificationlevelDoctoralen
dc.identifier.peoplefinderurlhttps://tcdlocalportal.tcd.ie/pls/EnterApex/f?p=800:71:0::::P71_USERNAME:APRILEPen
dc.identifier.rssinternalid209153en
dc.rights.ecaccessrightsopenAccess
dc.contributor.sponsorScience Foundation Ireland (SFI)en


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