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dc.contributor.author
Morel, Alexandre
dc.contributor.supervisor
Ferguson, Stephen John
dc.contributor.supervisor
Fortunato, Giuseppino
dc.contributor.supervisor
Rossi, René
dc.date.accessioned
2020-03-16T06:37:41Z
dc.date.available
2020-03-13T18:09:11Z
dc.date.available
2020-03-16T06:37:41Z
dc.date.issued
2019
dc.identifier.uri
http://hdl.handle.net/20.500.11850/404888
dc.identifier.doi
10.3929/ethz-b-000404888
dc.description.abstract
Tissue engineering is an area of the biomedical and biomaterials fields addressing the development and fabrication of biological tissues used for medical purposes. Combining autologous cells, tailored scaffolds and selected growth factors, these artificial tissues can deliver personalized solutions for the replacement and repair of human diseased tissues e.g. bone, cartilage, blood vessels, bladder, skin, muscle. The successful applications of such biomimetic implants are of high importance nowadays to provide a high-quality health care in spite of the increasing incidence of major diseases related to our ageing society and modern lifestyle. Moreover, engineered tissues can also serve as in vitro biological models using patient cells to screen and select appropriate treatments. With regard to the pharmaceutical industry, they can support the drug development process by replacing part of the animal experiments. A proper functioning of artificial tissues involves, among others, the fabrication of scaffolds that fulfils selected requirements in term of structural and mechanical properties. In principle, these properties should mimic the one of the targeted native tissue to favor a mechanically stable integration of the implant and modulate an adequate cell response for the growth of new functional tissue. In this regard, electrostatic spinning approach (or electrospinning) has attracted increasing interest for the development of such scaffolds. The resulting non-woven membranes composed of nano- to micron scaled polymeric fibers exhibit unique characteristics toward tissue engineering applications. In particular, their microscale architectures resemble the ones of the extracellular matrix composed of collagen and elastin fiber networks and may therefore be suitable to support tissue regeneration. Nevertheless, the control of the structural and mechanical properties of electrospun membranes is still very challenging due to their complex multiscale architectures. The polymeric internal structures providing nanofibers with extraordinary mechanical properties are not fully understood. Moreover, tailoring the properties of the single fiber is difficult due to an un-elucidated fiber formation process by electrospinning procedure. On the other side, fiber-to-fiber interactions are not well characterized and their role in the mechanical deformation of the network is still elusive. The goal of this thesis was to improve the tailoring of electrospun membranes by establishing correlations between the structural and the mechanical properties, from the nanoscale up to the membrane level, as well as the influence of selected fabrication parameters. For this purpose, procedures by needleless electrospinning were elaborated for the production of poly(L-lactide) (PLLA) fibers with different diameters ranging from 200 nm to over one micron. Methods were then developed to investigate the mechanical properties of single nanofibers. In this regard, an AFM-based three-pointbending experiment as well as a micromechanical setup were used to measure the Young's modulus, the yield stress and the hardening of fibers in function of their diameter. The results showed a drastic increase in mechanical properties for decreasing fiber sizes. The analysis of respective fiber internal structures revealed for the first time a linear relationship between the fiber stiffness and their degree of crystallinity and molecular orientation in the amorphous phase. II An approach for the investigation of non-crystalline, mesomorphic superstructures of PLLA fibers was developed based on solvent-induced crystallization. The fiber mesomorphic architectures, which are challenging to investigate due to their low contrast with the surrounding amorphous phase using most of the analytical tools, were revealed after post-treatment in tailored acetone-water blend systems. In this process, the architecture of the superstructures was preserved, while the underlying mesophase were ordered in an α-crystalline phase, enhancing thus their contrast. With this method in place, we demonstrated that a fast evaporation of the electrospinning solvent during the fiber formation favors the growth of fibrillar superstructures, which, in turn, resulted in a higher fiber stiffness. These findings describing the physical properties of single fibers and the influence of the fabrication parameters were used to inform a 3D predictive numerical model of electrospun network, in collaboration with the group of Prof Dr. E. Mazza at ETHZ. These models are of high importance to further understand and predict the mechanical behavior of nanofibrous scaffolds and can assist their development. The virtual networks were compared to real ones by simulating, respectively performing uniaxial tensile testing. In addition, methods to visualize the deformation of real networks upon stretching were developed using a custom-built tensile stage and electron microscopy. These comparisons revealed good agreements between the virtual and real networks. What is more, the numerical models helped elucidating the auxetic behavior of nanofiber networks, which was found to be generated by the buckling of the fibers oriented transversally to the stretching forces and compressed by the lateral contraction of the membrane. In the last part, the methods developed for structural analyses at the fiber and network levels, and the knowledge acquired during the thesis, e.g. concerning the fiber formation process, were applied to closely investigate the multiscale architectures of membranes, from the nano- to the macroscale level. This approach allowed us to demonstrate that the influence of fiber-to-fiber junctions on the macroscopic membrane stiffness can overcome the one from the single fiber Young's modulus. These results draw the attention on important aspects to be accounted for during the development of scaffolds for tissue engineering applications. In conclusion, this thesis provides important points of reference for the production of tailored electrospun PLLA fibers, including by the use of pilot plant needleless equipment, and an extensive understanding of the fiber formation process by the electrospinning procedure. Moreover, a set of methods were established for the characterization of the multiscale architectures of nanofibrous scaffolds. This work contributed as well to the development of a predictive numerical model that already demonstrated its potential toward the understanding of fiber network properties. The newly acquired knowledge will contribute to refine the development of advanced electrospun scaffolds with tailored structural and mechanical properties e.g. for tissue engineering applications.
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
tissue engineering
en_US
dc.subject
Biomaterials
en_US
dc.subject
Electrospinning
en_US
dc.subject
Mechanical characterization
en_US
dc.subject
Multiscale analysis
en_US
dc.title
Understanding and tailoring the multiscale architectural and mechanical properties of electrospun membranes for tissue engineering applications
en_US
dc.type
Doctoral Thesis
dc.rights.license
In Copyright - Non-Commercial Use Permitted
dc.date.published
2020-03-16
ethz.size
115 p.
en_US
ethz.code.ddc
DDC - DDC::5 - Science::570 - Life sciences
en_US
ethz.identifier.diss
26386
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::03915 - Ferguson, Stephen / Ferguson, Stephen
en_US
ethz.date.deposited
2020-03-13T18:09:20Z
ethz.source
FORM
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2020-03-16T06:37:53Z
ethz.rosetta.lastUpdated
2021-02-15T08:45:53Z
ethz.rosetta.versionExported
true
ethz.COinS
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