Dynamic Loading Of Anatomically Shaped Meniscal Constructs Generated Via Mri And micro-Ct Imaging

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Several studies have established that dynamic stimulation by mixing media and dynamic compression enhances the production of extracellular matrix (ECM) and mechanical properties of tissue-engineered (TE) constructs seeded with articular chondrocytes. Very few studies have attempted to engineer a whole meniscus and none have attempted to dynamically stimulate this tissue in vitro. The overall objective of this dissertation was to investigate the effect of dynamic stimulation on the biochemical and mechanical properties of image-guided tissue engineered menisci. The central hypothesis of this dissertation is that mechanical stimulation will alter the ECM assembly and mechanical behavior of anatomically shaped constructs. The first specific aim developed a method of generating patient specific anatomically shaped menisci using an image guided approach and tested the feasibility of culturing these engineered constructs using bovine meniscal fibrochondrocytes. The second specific aim developed a method of quantitatively comparing the shape fidelity of anatomically shaped tissue engineered menisci using various imaging and fabrication techniques. The third specific aim tested the hypothesis that controlled media mixing will enhance tissue formation and mechanical properties of anatomically shaped constructs compared to static controls. The fourth specific aim tested the hypothesis that dynamic compressive loading would improve biochemical and mechanical properties of image-guided tissue engineered menisci. This work represents the first study to dynamically load an anatomically shaped engineered meniscus in vitro. The studies presented in this dissertation are the first attempts to examine the effects of mechanical stimulation on large volume anatomically shaped TE menisci. The findings presented highlight 1) the effectiveness of image-guided fabrication techniques in generating patient specific TE implants and 2) the potential mechanical stimulation has to enhance tissue growth in engineered constructs.

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