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Mechanical and Hydromechanical Stimulation of Chondrocytes for Articular Cartilage Tissue Engineering

dc.contributor.authorPourmohammadali, Homeyra
dc.date.accessioned2014-05-01T17:43:40Z
dc.date.available2014-05-01T17:43:40Z
dc.date.issued2014-05-01
dc.date.submitted2014-05-01
dc.description.abstractTissue engineering approaches have attempted to address some of the problems associated with articular cartilage defect repair, but grafts with sufficient functional properties have yet to reach clinical practice. Mechanical loads are properly controlled in the body to maintain the functional properties of articular cartilage. This inspires the inclusion of mechanical stimulation in any in vitro production of tissue engineered constructs for defect repair. This mechanical stimulation must improve the functional properties (both biochemical and structural) of engineered articular cartilage tissue. Only a few studies have applied more than two loading types to mimic the complex in vivo load/flow conditions. The general hypothesis of the present thesis proposes that the generation of functional articular cartilage substitute tissue in vitro benefits from load and fluid flow conditions similar to those occurring in vivo. It is specifically hypothesized that application of compression, shear and perfusion on chondrocyte-seeded constructs will improve their properties. It is also hypothesized that protein production of the cell-seeded constructs can be improved in a depth-dependent manner with some loading combinations. Thus, a hydromechanical stimulator system was developed that was capable of simultaneously applying compression, shear and perfusion. Functionality of system was tested by series of short-term pilot studies to optimize some of the system parameters. In these studies, agarose-chondrocytes constructs were stimulated for 2 weeks. Then, longer-term (21- 31 days) studies were performed to examine the effects of both mechanical (compression and dynamic shear) and hydromechanical (compression, dynamic shear and fluid flow) stimulation on glycosaminoglycan and collagen production. The effects of these loading conditions were also investigated for three layers of construct to find out if protein could be localized differently depth-wise. In one of the longer-term studies, the chosen mechanical and hydromechanical stimulation conditions increased total collagen production, with higher amount of collagen for hydromechanical compared with mechanical loading condition. However, their effectiveness in increasing total glycosaminoglycan production was inconclusive with the current loading regimes. The hydromechanically stimulated construct could localize higher collagen production to the top layer compared with middle and bottom layers. Some effectiveness of hydromechanical stimulation was demonstrated in this thesis. Future studies will be directed towards further optimization of parameters such as stimulation frequency and duration as well as fluid perfusion rate to produce constructs with more glycosaminoglycan and collagen.en
dc.identifier.urihttp://hdl.handle.net/10012/8408
dc.language.isoenen
dc.pendingfalse
dc.publisherUniversity of Waterlooen
dc.subjectarticular cartilageen
dc.subjectchondrocyteen
dc.subjecttissue engineeringen
dc.subjectmechanical stimulationen
dc.subjecthydromechanical stimulationen
dc.subjectagaroseen
dc.subject.programMechanical Engineeringen
dc.titleMechanical and Hydromechanical Stimulation of Chondrocytes for Articular Cartilage Tissue Engineeringen
dc.typeDoctoral Thesisen
uws-etd.degreeDoctor of Philosophyen
uws-etd.degree.departmentMechanical and Mechatronics Engineeringen
uws.peerReviewStatusUnrevieweden
uws.scholarLevelGraduateen
uws.typeOfResourceTexten

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