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dc.contributor.author
Trachsel, Lucca
dc.contributor.supervisor
Zenobi-Wong, Marcy
dc.contributor.supervisor
Benetti, Edmondo Maria
dc.contributor.supervisor
Hoogenboom, Richard
dc.date.accessioned
2021-02-18T07:54:11Z
dc.date.available
2021-02-17T18:24:13Z
dc.date.available
2021-02-18T07:54:11Z
dc.date.issued
2020
dc.identifier.uri
http://hdl.handle.net/20.500.11850/470118
dc.identifier.doi
10.3929/ethz-b-000470118
dc.description.abstract
Poly(2-alkyl-2-oxazoline)s (PAOXAs) offer a plethora of attractive features, such as broad chemical versatility, biocompatibility, hydrolytic and oxidative stability, and tuneable physical properties. In the biomedical field, these characteristics have been exploited for numerous potential applications, such as for the generation of self-assembling nanoparticles, polymer-drug conjugates, hydrogels, carrier materials for additive manufacturing and bioinert surface coatings. This doctoral thesis aimed to molecularly engineer PAOXA building blocks for the fabrication of biomaterials and biointerfaces. In the first part of the thesis, I exploited the broad synthetic flexibility and biocompatibility of PAOXA to generate enzymatically crosslinked hydrogels for 3D cell culture of human chondrocytes and bioinks for 3D bioprinting. In the second part, functional cyclic polymers based on PAOXA were synthesized to yield topologically unique hydrogels and nanoassemblies on surfaces. Synthetic hydrogels can be engineered to mimic the natural extracellular matrix (ECM) by providing an adequate mechanical and biochemical environment for the encapsulated cells. The type of crosslinking used to form such hydrogels in the presence of cells is particularly critical to ensure a high cell viability. Since enzymate-mediated crosslinking is known to be a highly cell-friendly approach, I synthesized PAOXA-peptide conjugates that were crosslinked by a bacterial enzyme, sortase A (SA), in the presence of human chondrocytes, generating hydrogels with tuneable mechanical properties and crosslinking kinetics and excellent cell viability. The lack of mechanical strength and toughness is a common issue of biocompatible hydrogels designed for load-bearing applications such as for articular cartilage. To mechanically reinforce the enzymatically crosslinked single network PAOXA hydrogel, a double network (DN) hydrogel was formed by introducing ionically crosslinked alginate into the PAOXA hydrogel. The resulting DN hydrogel featured significantly higher storage and compressive moduli while still maintaining high cell viability. Moreover, a DN hydrogel bioink was developed enabling 3D bioprinting in the presence of human chondrocytes to yield printed DN hydrogel structures with good shape fidelity and cell viability. The second part of the thesis focused on the synthesis of functional cyclic macromolecules based on PAOXA to exploit the unique intrinsic characteristics of cyclic polymers and the distinct physicochemical and interfacial properties of surfaces that were coated with cyclic adsorbates. I hypothesized that the enhanced intramolecular steric repulsion generated within cyclic polymers would lead to stiffer and tougher gels with respect to gels made from their linear analogs. In theory, the crosslinking of cyclic macromolecules would provide a polymer network topology without structural defects such as dangling chain ends. Hence, I synthesized crosslinkable functional cyclic copolymer based on poly(2-ethyl-2-oxazoline) (PEOXA), yielding hydrogels that are solely composed of crosslinked cyclic PEOXA. Remarkably, these “cyclic” gels exhibited up to 42% higher stiffness and larger mesh size at a concomitant higher swelling ratio, with respect to hydrogels formed from their linear analogs with identical molecular weight and composition. Finally, motivated by previous studies that showed enhanced physicochemical and interfacial properties of surfaces that were grafted with chemically inert, cyclic PAOXA adsorbates, I advanced to grafting functional cyclic adsorbates based on PAOXA, forming cyclic nanoassemblies that featured a functional character. Relevantly, these nanoassemblies of cyclic PAOXA-based polyacid brushes showed an amplified pH responsiveness and cyclic glycopolymer brushes derived from polyacids displayed an increased lectin-binding ability with respect to their linear counterparts. These findings indicate that the functional groups within cyclic glycopolymers are more exposed and available when compared to those within linear-brush analogues. As a result, the functional moiteties along cyclic grafts tended to interact more favorably with sourrounding lectin proteins instead of coiling or associating with neighboring functions
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
ETH Zurich
en_US
dc.rights.uri
http://rightsstatements.org/page/InC-NC/1.0/
dc.subject
polyoxazoline
en_US
dc.subject
Polymer chemistry
en_US
dc.subject
tissue engineering
en_US
dc.subject
biomaterials
en_US
dc.subject
biointerfaces
en_US
dc.subject
biomedical engineering
en_US
dc.title
Molecularly Engineered POLY(2-OXAZOLINE)S as Building Blocks for the Fabrication of Biomaterials and Biointerfaces
en_US
dc.type
Doctoral Thesis
dc.rights.license
In Copyright - Non-Commercial Use Permitted
dc.date.published
2021-02-18
ethz.size
213 p.
en_US
ethz.code.ddc
DDC - DDC::5 - Science::540 - Chemistry
en_US
ethz.grant
Chondrogenic Bioinks for Bioprinting Stable Cartilage Grafts
en_US
ethz.identifier.diss
27100
en_US
ethz.publication.place
Zurich
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02070 - Dep. Gesundheitswiss. und Technologie / Dep. of Health Sciences and Technology::02518 - Institut für Biomechanik / Institute for Biomechanics::03949 - Zenobi-Wong, Marcy / Zenobi-Wong, Marcy
en_US
ethz.grant.agreementno
166052
ethz.grant.fundername
SNF
ethz.grant.funderDoi
10.13039/501100001711
ethz.grant.program
Interdisziplinäres Projekt
ethz.date.deposited
2021-02-17T18:24:23Z
ethz.source
FORM
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2021-02-18T07:54:23Z
ethz.rosetta.lastUpdated
2021-02-18T07:54:23Z
ethz.rosetta.versionExported
true
ethz.COinS
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