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Synthesis and Modification of Biomaterials for Tissue Engineering Applications

Zheng, Jukuan
http://rave.ohiolink.edu/etdc/view?acc_num=akron1427581327

Abstract Details

2015, Doctor of Philosophy, University of Akron, Polymer Science.
Various materials have been utilized for tissue engineering applications to induce the desired cellular response. To achieve better cellular performance, bioactive molecules are needed to dictate cellular activity. Efficient and additive-free methods are needed to attach bioactive motifs. This dissertation demonstrates the application of efficient chemical methods, such as strain-promoted azide alkyne cycloaddition (SPAAC), oxime reaction and copper-catalyzed azide alkyne cycloaddition (CuAAC), to introduce biomolecules. Cellular responses to these bioactive moities were also studied. This dissertation is separated into three parts. The first part describes efforts to modify electrospun nanofibers post-fabrication and how these materials are useful for tissue engineering. We demonstrated that an amine derivatized 4-dibenzocyclooctynol (DIBO) initiated the ring-opening polymerization of benzyl-L-glutamate-N- carboxyanhydride (Bz-L-GluNCA), which yielded high molecular mass DIBO terminated poly(benzyl-L-glutamate) (DIBO-PBLG). Nanofibers were generated via electrospinning and the reactivity of DIBO groups on the surface of nanofibers were demonstrated using a fluorescence conjugation experiment and a gold nanoparticle attachment study. This initiator was then applied to make high molecular weight polyesters, like DIBO-poly(lactide) (DIBO-PLA), DIBO-poly(carprolactone) (DIBO-PCL) and DIBO-poly(caprolactone-co-2-oxepane-1,5-dione) (DIBO-(P(CL- co-OPD))). These polymers were synthesized and nanofibers were electrospun. These electrospun nanofibers were modified with neuron inductive peptides and their applications for neuron differentiation and Schwann cell proliferation were tested in vitro. For the second part, a chemically crosslinked hydrogel was fabricated based on Strain-Promoted Azide Alkyne Cycloaddition (SPAAC). Poly(ethylene glycol) diamine was functionalized with DIBO and the generated DIBO-PEG was crosslinked with PEG tri-arm azide to form a covalently connected network. This chemically crosslinked hydrogel was quite soft, with a storage modulus around 800 Pa. Its cytotoxicity was evaluated with human mesenchymal stem cells. After 24h of culture, cell viability was 88%, which was no different than controls. This soft, PEG-based hydrogel is being studied for its neuron differentiation application combining neuron inductive protein. The third part of my research was focused on modification of surfaces by combining SPAAC and dopamine. Since poly(dopamine) was found to be a surface-independent coating material, the combination of dopamine and DIBO yielded an adhesion-click kit enabled versatile surface modification. This molecule was applied for modification of PDMS, silicon oxide, aluminum oxide, gold and titanium oxide. Combined with contact printing, nano-patterns based on fluorescence and gold nanoparticles were fabricated on these surfaces. This method enabled versatile surface functionalization for introducing biomolecules, and pattern fabrication.
Matthew Becker, Dr. (Advisor)
Abraham Joy, Dr. (Committee Member)
Darrell Reneker, Dr. (Committee Member)
Rebecca Willits, Dr. (Committee Member)
Chrys Wesdemiotis, Dr. (Committee Member)
236 p.
Polymer Chemistry; Polymers
click chemistry, oxime reaction, electrospin, nanofiber functionalization, di-functionalization, tri-functionalization, dopamine

Recommended Citations

Citations

  • Zheng, J. (2015). Synthesis and Modification of Biomaterials for Tissue Engineering Applications [Doctoral dissertation, University of Akron]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=akron1427581327

    APA Style (7th edition)

  • Zheng, Jukuan. Synthesis and Modification of Biomaterials for Tissue Engineering Applications. 2015. University of Akron, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=akron1427581327.

    MLA Style (8th edition)

  • Zheng, Jukuan. "Synthesis and Modification of Biomaterials for Tissue Engineering Applications." Doctoral dissertation, University of Akron, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=akron1427581327

    Chicago Manual of Style (17th edition)

akron1427581327
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© 2015, all rights reserved.
This open access ETD is published by University of Akron and OhioLINK.