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- Genre: Masters Thesis
Description
Cardiac tissue engineering has major applications in regenerative medicine, disease modeling and fundamental biological studies. Despite the significance, numerous questions still need to be explored to enhance the functionalities of the engineered tissue substitutes. In this study, three dimensional (3D) cardiac micro-tissues were developed through encapsulating co-culture of cardiomyocytes and cardiac fibroblasts, as the main cellular components of native myocardium, within photocrosslinkable gelatin-based hydrogels. Different co-culture ratios were assessed to optimize the functional properties of constructs. The geometry of the micro-tissues was precisely controlled using micro-patterning techniques in order to evaluate their role on synchronous contraction of the cells. Cardiomyocytes exhibited a native-like phenotype when co-cultured with cardiac fibroblasts as compared to the mono-culture condition. Particularly, elongated F-actin fibers with abundance of sarcomeric α-actinin and troponin-I were observed within all layers of the hydrogel constructs. Higher expressions of connexin-43 and integrin β1 indicated improved cell-cell and cell-matrix interactions. Amongst co-culture conditions, 2:1 (cardiomyocytes: cardiac fibroblasts) ratio exhibited enhanced functionalities, whereas decreasing the construct size adversely affected the synchronous contraction of the cells. Therefore, this study indicated that cell-cell ratio as well as the geometrical features of the micropatterned constructs are among crucial parameters, which need to be optimized in order to enhance the functionalities of engineered tissue substitutes and cardiac patches.
ContributorsSaini, Harpinder (Author) / Nikkhah, Mehdi (Thesis advisor) / Vernon, Brent (Committee member) / Towe, Bruce (Committee member) / Arizona State University (Publisher)
Created2015
Description
Combining 3D bio-printing and drug delivery are promising techniques tofabricate scaffolds with well controlled and patient-specific structures for tissue
engineering. In this study, silk derivatives of bioink were developed consisting of
silk fibroin and gelatin then 3D printed into scaffolds. The scaffolds would be
evaluated for small molecule release, cell growth, degradation, and morphology.
Preparations and design of the scaffolds are major parts of engineering and tissue
engineering. Scaffolds are designed to mimic extracellular matrix by providing
structural support as well as promoting cell attachment and proliferation with
minimum inflammation while degrading at a controlled rate. Scaffolds offers new
potentials in medicine by aiding in the preparation of personalized and controlled
release therapeutic systems.
ContributorsNg, Johnny (Author) / Rege, Kaushal (Thesis advisor) / Holloway, Julianne (Committee member) / Jin, Kailong (Committee member) / Arizona State University (Publisher)
Created2022
Description
Breast cancer cell invasion is a highly orchestrated process driven by a myriad of complex microenvironmental stimuli. These complexities make it difficult to isolate and assess the effects of specific parameters including matrix stiffness and tumor architecture on disease progression. In this regard, morphologically accurate tumor models are becoming instrumental to perform fundamental studies on cancer cell invasion within well-controlled conditions. In this study, the use of photocrosslinkable hydrogels and a novel, two-step photolithography technique was explored to microengineer a 3D breast tumor model. The microfabrication process presented herein enabled precise localization of the cells and creation of high stiffness constructs adjacent to a low stiffness matrix. To validate the model, breast cancer cell lines (MDA-MB-231, MCF7) and normal mammary epithelial cells (MCF10A) were embedded separately within the tumor model and cellular proliferation, migration and cytoskeletal organization were assessed. Proliferation of metastatic MDA-MB-231 cells was significantly higher than tumorigenic MCF7 and normal mammary MCF10A cells. MDA-MB-231 exhibited highly migratory behavior and invaded the surrounding matrix, whereas MCF7 or MCF10A cells formed clusters that were confined within the micropatterned circular features. F-actin staining revealed unique 3D protrusions in MDA-MB-231 cells as they migrated throughout the surrounding matrix. Alternatively, there were abundance of 3D clusters formed by MCF7 and MCF10A cells. The results revealed that gelatin methacrylate (GelMA) hydrogel, integrated with the two-step photolithography technique, has great promise in creating 3D tumor models with well-defined features and tunable stiffness for detailed studies on cancer cell invasion and drug responsiveness.
ContributorsSam, Feba Susan (Author) / Nikkhah, Mehdi (Thesis advisor) / Ros, Robert (Committee member) / Smith, Barbara (Committee member) / Arizona State University (Publisher)
Created2015
Description
Glioblastoma Multiforme (GBM) is a grade IV astrocytoma and the most aggressive form of cancer that begins within the brain. The two-year average survival rate of GBM in the United States of America is 25%, and it has a higher incidence in individuals within the ages of 45 - 60 years. GBM Tumor formation can either begin as normal brain cells or develop from an existing low-grade astrocytoma and are housed by the perivascular niche in the brain microenvironment. This niche allows for the persistence of a population of cells known as glioma stem cells (GSC) by supplying optimum growth conditions that build chemoresistance and cause recurrence of the tumor within two to five years of treatment. It has therefore become imperative to understand the role of the perivascular niche on GSCs through in vitro modelling in order to improve the efficiency of therapeutic treatment and increase the survival rate of patients with GBM.
In this study, a unique three dimensional (3D) microfluidic platform that permitted the study of intercellular interactions between three different cell types in the perivascular niche of the brain was developed and utilized for the first time. Specifically, human endothelial cells were embedded in a fibrin matrix and introduced into the vascular layer of the microfluidic platform.
After spontaneous formation of a vascular layer, Normal Human Astrocytes and Patient derived GSC were embedded in a Matrigel® matrix and incorporated in the stroma and tumor regions of the microfluidic device respectively.
Using the established platform, migration, proliferation and stemness of GSCs studies were conducted. The findings obtained indicate that astrocytes in the perivascular niche significantly increase the migratory and proliferative properties of GSCs in the tumor microenvironment, consistent with previous in vivo findings.
The novel GBM tumor microenvironment developed herein, could be utilized for further
in-depth cellular and molecular level studies to dissect the influence of individual factors within the tumor niche on GSCs biology, and could serve as a model for developing targeted therapies.
In this study, a unique three dimensional (3D) microfluidic platform that permitted the study of intercellular interactions between three different cell types in the perivascular niche of the brain was developed and utilized for the first time. Specifically, human endothelial cells were embedded in a fibrin matrix and introduced into the vascular layer of the microfluidic platform.
After spontaneous formation of a vascular layer, Normal Human Astrocytes and Patient derived GSC were embedded in a Matrigel® matrix and incorporated in the stroma and tumor regions of the microfluidic device respectively.
Using the established platform, migration, proliferation and stemness of GSCs studies were conducted. The findings obtained indicate that astrocytes in the perivascular niche significantly increase the migratory and proliferative properties of GSCs in the tumor microenvironment, consistent with previous in vivo findings.
The novel GBM tumor microenvironment developed herein, could be utilized for further
in-depth cellular and molecular level studies to dissect the influence of individual factors within the tumor niche on GSCs biology, and could serve as a model for developing targeted therapies.
ContributorsAdjei-Sowah, Emmanuella Akweley (Author) / Nikkhah, Mehdi (Thesis advisor) / Plaisier, Christopher (Committee member) / Mehta, Shwetal (Committee member) / Arizona State University (Publisher)
Created2020