Organizational Unit:
Wallace H. Coulter Department of Biomedical Engineering

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Now showing 1 - 3 of 3
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    Heparin and PEG-based hydrogels to modulate and interrogate dynamic cell behavior
    (Georgia Institute of Technology, 2016-10-14) Rinker, Torri Elise
    Hydrogel-based biomaterials are often used for biomolecule delivery or encapsulation of cells for tissue engineering and regenerative medicine applications. However, utilizing hydrogels in dynamic cell systems can be challenging, as hydrogels must be engineered to account for changes in cellular behavior. For example, the hydrogel cell culture platforms and analyses techniques employed to investigate cell response to disease conditions should account for variations in cellular communication. In addition, hydrogels used to modulate cellular differentiation, either through protein delivery or direct interactions with cells, should account for evolving cell phenotype. Thus, in this work, hydrogel-based technologies were developed and utilized to interrogate and modulate dynamic cellular behavior. A PEG-based platform was designed and utilized to interrogate MSCs, adipocytes, and osteoblasts under hyperglycemic conditions via multivariate analyses, as these three cell types are implicated in abnormal deposition of marrow adipose tissue and bone in diabetes and osteoporosis. Then, as heparin binds many growth factors involved in cellular differentiation processes, heparin-based MPs were used to temporally modulate endochondral ossification in ATDC5 cells, possibly through heparin-mediated protein sequestration. To further modulate the timing of protein sequestration, heparin-PEG core-shell MPs were designed to enable sequestration and temporally controlled redelivery of protein. Finally, hydrolytically degradable heparin-PEG-based MPs were engineered with tunable heparin content and degradation rate, to enable temporally controlled protein release. Overall, this work demonstrates the ability of PEG and heparin-based hydrogels to investigate and regulate evolving cellular processes.
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    Incorporation of bio-inspired microparticles within embryonnic stem cell aggregates for directed differentiation
    (Georgia Institute of Technology, 2015-08-04) Sullivan, Denise D.
    Embryonic stem cells (ESCs) are a unique cell population that can differentiate into all three embryonic germ layers (endoderm, mesoderm, and ectoderm), rendering them an invaluable cell source for studying the molecular mechanisms of embryogenesis. Signaling molecules that direct tissue patterning during embryonic development are secreted by ESC aggregates, known as embryoid bodies (EBs). As many of these signaling proteins interact with the extracellular matrix (ECM), manipulation of the ESC extracellular environment provides a means to direct differentiation. ECM components, such as glycosaminoglycans (GAGs), play crucial roles in cell signaling and regulation of morphogen gradients during early development through binding and concentration of secreted growth factors. Thus, engineered biomaterials fabricated from highly sulfated GAGs, such as heparin, provide matrices for manipulation and efficient capture of ESC morphogens via reversible electrostatic and affinity interactions. Ultimately, biomaterials designed to efficiently capture and retain morphogenic factors offer an attractive platform to enhance the differentiation of ESCs toward defined cell types. The overall objective of this work was to examine the ability of microparticles synthesized from both synthetic and naturally-derived materials to enhance the local presentation of morphogens to direct ESC differentiation. The overall hypothesis was that microparticles that mimic the ECM can modulate ESC differentiation through sequestration of endogenous morphogens present within the EB microenvironment.
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    Chondroitin sulfate microparticles modulate TGF-B1-induced chondrogenesis in human mesenchymal stem cell spheroids
    (Georgia Institute of Technology, 2014-04-28) Goude, Melissa Chou
    Due to the limited intrinsic healing ability of mature cartilage tissue, stem cell therapies offer the potential to restore cartilage lost due to trauma or arthritis. Mesenchymal stem cells (MSCs) are a promising cell source due to their ability to differentiate into various adult tissues under specific biochemical and physical cues. Current MSC chondrogenic differentiation strategies employ large pellets, however, we have previously developed a high-throughput technique to form small MSC aggregates (500-1,000 cells) that may reduce diffusion barriers while maintaining a multicellular structure that is analogous to cartilaginous condensations. The objective of this study was to examine the effects on chondrogenesis of incorporating chondroitin sulfate methacrylate (CSMA) microparticles (MPs) within these small MSC spheroids when cultured in the presence of transforming growth factor-β1 (TGF-β1) over 21 days. Spheroids +MP induced earlier increases in collagen II and aggrecan gene expression (chondrogenic markers) than spheroids -MP, although no large differences in immunostaining for these matrix molecules were observed by day 21. Collagen I and X was also detected in the ECM of all spheroids by immunostaining. Interestingly, histology revealed that CSMA MPs clustered together near the center of the MSC spheroids and induced circumferential alignment of cells and ECM around the material core. Because chondrogenesis was not hindered by the presence of CSMA MPs, this study demonstrates the utility of this culture system to further examine the effects of matrix molecules on MSC phenotype, as well as potentially direct differentiation in a more spatially controlled manner that better mimics the architecture of specific target tissues.