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    Stem cell-based scaffolds for orthopedic applications

    Author
    Gharat, Tanmay Pradip
    View/Open
    177452_Gharat_rpi_0185E_10951.pdf (1.149Mb)
    Other Contributors
    Hahn, Mariah; Cramer, Steven M.; Karande, Pankaj; Koffas, Mattheos A. G.;
    Date Issued
    2016-08
    Subject
    Chemical engineering
    Degree
    PhD;
    Terms of Use
    This electronic version is a licensed copy owned by Rensselaer Polytechnic Institute, Troy, NY. Copyright of original work retained by author.;
    Metadata
    Show full item record
    URI
    https://hdl.handle.net/20.500.13015/1742
    Abstract
    In the proposed work, we fabricated bioactive scaffolds in combination with stem cells and growth factors. Towards this goal, we made use tunable polyethylene glycol diacrylate (PEGDA)-based scaffolds. Mesenchymal stem cells (MSCs) as well as embryonic stem cells (ESCs) were encapsulated in PEGDA-based scaffolds in separate studies. Initially, bone marrow-derived MSCs were encapsulated in PEGDA-polydimethylsiloxane (PDMS) scaffolds along with bone morphogenetic protein-2 (BMP-2) for specific osteoblastic differentiation. Low dosage levels of BMP-2 appeared to significantly enhance PEG-PDMS osteoinductivity. Subsequently, in the following study, transforming growth factor-beta1 (TGF-β1) was incorporated in PEGDA-chondroitin sulfate (CSC) scaffolds for driving chondrocytic differentiation of synovium-derived MSCs (SMSCs). In addition, intermediate levels of TGF-β1, PDMS and BMP-2 appeared to induce mix ‘cartilage/bone’ cell behavior in SMSCs. Overall, SMSCs appeared to be spatially guided for layer-specific differentiation depending on the initial biochemical composition of PEGDA scaffolds. In addition, the second study also established SMSCs as a viable MSC alternative for osteochondral repair.; As a whole, the current work adds to the existing knowledge of stem cell—based therapies that are emerging as potential strategies for treating musculoskeletal conditions. The understanding from this work will take us one step forward in the rational development of promising scaffolds to treat the affected patients.; Human ESCs (hESCs) were investigated for directed osteoblastic differentiation using step-wise differentiation involving an intermediate mesodermal lineage. Enhancement of FOXD3 expression in transfected hESCs using doxycycline (DOX) treatment followed by 3D osteogenic culture appeared to downregulate pluripotency levels and increase mesodermal commitment. Moreover, 48h of initial DOX treatment in 2D culture appeared to significantly upregulate osteoblastic marker expression suggesting directed differentiation.; Musculoskeletal diseases are becoming one of the major concerns in the US due the aging population, increasing cases of congenital defects, and trauma-related incidents. Drug therapies and exercise could provide temporary relief but do not heal the injured tissue. Surgical treatments and autologous grafts are common strategies used to treat these defects; however, they are inefficient at restoring full tissue function. The current study aims at providing potential stem cell-based tissue engineering strategies that could be used for osteochondral and skeletal repair.;
    Description
    August 2016; School of Engineering
    Department
    Dept. of Chemical and Biological Engineering;
    Publisher
    Rensselaer Polytechnic Institute, Troy, NY
    Relationships
    Rensselaer Theses and Dissertations Online Collection;
    Access
    Restricted to current Rensselaer faculty, staff and students. Access inquiries may be directed to the Rensselaer Libraries.;
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