Design Synthesis And Characterization Of Biomimetic Oligomers

Author : Ting-Bin Yu
Publisher :
ISBN 13 : 9781124522159
Total Pages : 368 pages
Book Rating : 4.5/5 (221 download)

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Download or read book Design and Synthesis of Biomimetic Polymers as Biomaterials written by Ting-Bin Yu and published by . This book was released on 2011 with total page 368 pages. Available in PDF, EPUB and Kindle. Book excerpt: The first four chapters of this dissertation describes the application of alkyne-azide cycloaddition (the so-called "click" chemistry) to efficiently construct a beta-sheet polymer. Inspired by nature, there had been much interest in the development of synthetic peptides that have the beta-sheet secondary structure which can undergo self-assembly to prepare of well-defined materials with advanced properties. Despite significant progress being made in the area of designing discrete short peptidomimetic oligomers with beta-sheet structures, design of synthetic polymers that can efficiently self-assembly into predictable well-defined beta-sheets and hierarchical nanostructures remains elusive. Herein, we have demonstrated the first example of Cu(I)-catalyzed azide-alkyne cycloaddition-induced folding of a synthetic polymer into well-defined beta-sheets and further assembly into hierarchical nanofibrils. Furthermore, by simply switching to hydrophilic strand of the monomer, the network of nanofibrils can further constitute a rigid hydrogel. The efficiency and versatility of the click chemistry also allows us for further design of more complex polymer materials. A de novo designed copolymer that is composed of the beta-sheet motif with other elastic folding motifs (beta-spiral structure) has been prepared to mimic spider-silk structure with tunable advanced physical properties. The last chapter of this dissertation describes the development of a new synthetic saccharride-peptide copolymer as a highly functional extracellular matrices for tissue engineering application. For tissue engineering applications, the ideal synthetic scaffolds should be biocompatible, non-immunogenic, pathogen-free, be biochemically defined for reproducibility and support the regeneration of the specific tissue type. Here, we have combined the positive properties of both natural and synthetic biomaterials and generated a saccharide-peptide hydrogel that is synthetically simple and highly functional. Composed of all natural building blocks, namely galataric acid and lysine, tyrosine was incorporated onto the backbone as a handle for crosslinking the polymer through the formation of dityrosine, a naturally occurring crosslinker found in proteins. By simply varying the crosslinking time, the resulting hydrogel is able to induce tailored cellular responses with minimal cytotoxic. Due to the versatility of our biomaterials, thiol-ene crosslinking chemistry was also utilized in saccharride-peptide copolymer to facilitate the hydrogel formation. Thiol-ene conjugated addition reaction has been known as "click" process that occurs without any additives. Hydrogel mechanical properties were tunable by varying vinyl sulfone (VS): cysteine (Cys) ratio as well as pH of the cross-linking components. In addition, mesenchymal stem cells (MSCs) were cultured in 3D for up to 28 days in vitro without deleterious effects on cell viability. These will allow us to program chemical, physical, and biological information into our hydrogels to control stem cell differentiation.