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Hydrogels with Controlled Physical and Biochemical Properties to Direct Cell Behavior for Applications in Bone Tissue Engineering

Samorezov, Julia Elizabeth
http://rave.ohiolink.edu/etdc/view?acc_num=case1435241088

Abstract Details

2015, Doctor of Philosophy, Case Western Reserve University, Biomedical Engineering.
Tissue engineered bone grafts using biomaterials, autologous cells and bioactive factors seek to address the clinical need for replacement bone tissue to treat musculoskeletal injuries. This dissertation aimed to use hydrogel biomaterial scaffolds to present either biochemical signals or patterns of physical properties to influence the behavior of cells with known osteogenic potential, with the ultimate goal of expanding knowledge of the cells’ responses to such signals and developing instructive biomaterials for bone regeneration. Human adipose-derived stem cells (hASCs) were used because of their known capacity for osteogenic differentiation, but there are conflicting data on their response to specific potentially osteogenic soluble factors. To address this, dexamethasone and bone morphogenetic protein-2 (BMP-2) were examined for their effects on osteogenic differentiation of hASCs from three donors in 2D culture and in 3D methacrylated gelatin (GelMA) hydrogels. Culture medium with a lower calcium concentration than standard DMEM was shown to be beneficial in revealing these effects. Media supplementation with BMP-2 did not improve hASC osteogenesis. Dexamethasone was shown to be highly osteogenic, but the addition of BMP-2 to culture media inhibited this dexamethasone-driven hASC osteogenic differentiation. It was next examined if sustained, localized presentation of BMP-2 could enhance its osteogenic potential compared to exogenous presentation from culture medium. When BMP-2 was mixed into GelMA hydrogels prior to crosslinking, approximately one third of the loaded growth factor was retained in the hydrogels for seven weeks. Delivery from the hydrogel did improve BMP-2 bioactivity, leading to statistically increased calcium deposition compared to similar amounts of growth factor supplied exogenously in culture medium. Lastly, a dual-crosslinked alginate hydrogel system was developed to spatially control hydrogel physical properties or presentation of covalently coupled cell adhesive peptides. Changes in biomaterial stiffness and swelling significantly affected preosteoblast cell proliferation, and spatial control over RGD cell adhesion peptide presentation directed both cell adhesion and proliferation. This system can easily be applied to control the spatial presentation of osteogenic signals to hASCs, providing a platform to study cell response to patterned physical and biochemical signals or serving as an instructive biomaterial to guide hASC osteogenesis.
Eben Alsberg (Advisor)
Erin Lavik (Committee Member)
Guang Zhou (Committee Member)
Umut Gurkan (Committee Member)
347 p.
Biomedical Engineering

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Citations

  • Samorezov, J. E. (2015). Hydrogels with Controlled Physical and Biochemical Properties to Direct Cell Behavior for Applications in Bone Tissue Engineering [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1435241088

    APA Style (7th edition)

  • Samorezov, Julia. Hydrogels with Controlled Physical and Biochemical Properties to Direct Cell Behavior for Applications in Bone Tissue Engineering. 2015. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1435241088.

    MLA Style (8th edition)

  • Samorezov, Julia. "Hydrogels with Controlled Physical and Biochemical Properties to Direct Cell Behavior for Applications in Bone Tissue Engineering." Doctoral dissertation, Case Western Reserve University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=case1435241088

    Chicago Manual of Style (17th edition)

case1435241088
822
© 2015, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.