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Bioinspired Multiscale Biomaterials for Cell-Based Medicine

Zhao, Shuting, zhao
http://rave.ohiolink.edu/etdc/view?acc_num=osu1469100304

Abstract Details

2016, Doctor of Philosophy, Ohio State University, Biomedical Engineering.
Cell-based medicine is recently attracting extensive attention as a potential therapeutic approach for various diseases. However, major hurdles have prevented their widespread application including but not limited to, the difficulty to expand stem cells while maintaining their pluripotency, dismal cell retention after implanting cells in vivo, and damage induced by the interactions between host and the implanted cells. This dissertation research is aimed to address some of these major challenges facing cell-based medicine. Inspired by the core-shell configuration of early mammalian embryos, we developed a novel coaxial electrospray technology to generate microcapsules with a hydrogel shell of alginate that mimics the zona pellucida, surrounding an aqueous liquid core of living cells in one step. Specifically, murine embryonic stem (ES) cells are encapsulated in the core while maintaining high viability. After expansion in vitro, these cells form a single aggregate in each microcapsule and maintain significantly higher pluripotency with higher capacity for cardiac differentiation than the cells conventionally cultured on 2D substrate or in the homogeneous hydrogel microbeads without a core-shell architecture. It was further found that the bioinspired core-shell microcapsule system encapsulated with cancer cells is significantly better than the conventional suspension culture in ultralow attachment plate (ULAP) for enriching cancer stem-like cells (CSCs). The time for enriching CSCs can be unprecedentedly shortened from 7-10 days to only 2 days with better CSC quality in terms of the expression of surface receptor markers, dye exclusion, gene at the transcript and protein level, and in vivo tumorigenicity. Therefore, this novel approach for enriching CSCS should greatly facilitate cancer research and therapy development, as the CSCs are also known as the tumor reinitiating cells that induce cancer relapse. Further inspired by the natural processes of hatching to release stem cell aggregates out of the zona pellucida and re-encapsulating the cell aggregates in blastocyst for implantation, we released the aggregates out of the alginate hydrogel shell and re-encapsulated each aggregate in a biocompatible and biodegradable micromatrix for injectable delivery to replace myocardial cell lost during experimental myocardial infarction. This method significantly enhances the long-term survival of animals with MI as a result of the temporary immunoisolation of the micromatrix, as well as in situ cardiac regeneration to improve cardiac function by the injected cells. The long-term benefit of temporary immunosuppression as a result of cell encapsulation in biomaterials was also tested with allogeneic T cell transplantation for cancer therapy. We conformally encapsulated the donor T cells within a porous film of chitosan and alginate, and the nanoencapsulation was found not to affect the phenotype of T cells in terms of size, viability, proliferation, cytokine secretion, and cytotoxicity against tumor cells. Leukemic mice transplanted with bone marrow cells (BMCs) and the conformally encapsulated allogeneic T cells exhibited significantly improved survival, due to reduced Graft-versus-Host-Diseases (GVHD) associated with uncompromised Graft-versus-Leukemia (GVL) effect of the donor T cells. This dissertation research demonstrates the great potential of producing bioinspired micro and nanoscale biomaterials for engineering various living cells to facilitate the widespread application of modern cell-based medicine.
Xiaoming He (Advisor)
Noah Weisledar (Committee Member)
Jianhua Yu (Committee Member)
Keith Gooch (Committee Member)
168 p.
Biomedical Engineering
Biomaterials, alginate, chitosan, microencapsulation, electrospray, conformal nanoencapsulation

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Citations

  • Zhao, zhao, S. (2016). Bioinspired Multiscale Biomaterials for Cell-Based Medicine [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1469100304

    APA Style (7th edition)

  • Zhao, zhao, Shuting. Bioinspired Multiscale Biomaterials for Cell-Based Medicine . 2016. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1469100304.

    MLA Style (8th edition)

  • Zhao, zhao, Shuting. "Bioinspired Multiscale Biomaterials for Cell-Based Medicine ." Doctoral dissertation, Ohio State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=osu1469100304

    Chicago Manual of Style (17th edition)

osu1469100304
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© 2016, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.