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@PHDTHESIS{Kittel:993685,
author = {Kittel, Yonca},
othercontributors = {De Laporte, Laura and Kühne, Alexander J. C.},
title = {{M}icrofluidic synthesis of multifunctional microgels for
treatment of inflammatory bowel syndrome},
school = {RWTH Aachen University},
type = {Dissertation},
address = {Aachen},
publisher = {RWTH Aachen University},
reportid = {RWTH-2024-08919},
pages = {1 Online-Ressource : Illustrationen},
year = {2024},
note = {Veröffentlicht auf dem Publikationsserver der RWTH Aachen
University 2025; Dissertation, RWTH Aachen University, 2024},
abstract = {The overall goal of my thesis is to develop
inflammation-targeting multifunctional star-shaped
poly(ethylene glycol) (sPEG)-based microgels as novel
combinatorial therapy for local treatment of non-microbial
inflammatory bowel diseases (IBD). In Chapter 1, I describe
the motivation of my work on how three different key
challenges of IBD treatment are addressed by altering the
microgel properties as desired. Chapter 2 discusses the
state of the art of microgel requirements for clinical
applications by giving an overview of key attributes, such
as biocompatibility, biodegradability, mechanical stability
and softness, loading capacity, chemical functionality, and
cell interaction. Moreover, different microgel fabrication,
as well characterization, techniques are discussed in
detail. In Chapter 3, I make use of the existing systemic
TNFα antibody therapy in clinics for IBD treatment –
however, I incorporate TNFα antibodies (adalimumab) in
sPEG-based microgels for non-systemic but local specific
scavenging of the inflammation-mediating cytokine TNFα to
inhibit the inflammation in the intestine. Spherical
microgels are synthesized via droplet-based microfluidics
with a diameter of around 25 μm. I have systematically
investigated the diffusion of TNFα antibody, as well as
TNFα itself, inside the microgels made from different
sPEG-Ac building blocks and GMA as co-polymer. In
particular, the high loading of TNFα antibody inside the
microgels and sequential TNFα binding capacity of the
microgels, due to their high accessibility of internal
surface, is shown in the presence of human colorectal
adenocarcinoma cells HT29. Furthermore, the microgels
scavenge TNFα produced by human macrophages to mimic the in
vivo situation of IBD. In fact, the microgels scavenge TNFα
at concentrations that are far beyond disease relevant
levels. Chapter 4 addresses another major challenge in IBD
therapy: the repair of damaged epithelial intestinal
barrier. For this purpose, I have produced hyaluronic acid
(HA)-functionalized microgels that specifically target and
bind CD44 receptor-expressing inflamed intestinal epithelial
cells. Therefore, I have investigated the stiffness and
viscoelastic properties of the microgels to mimic the
mucosal ECM. By active targeting and binding to inflamed
intestinal cells, the microgels form a layer on the
epithelial surface to replace the degraded mucus and shield
the tissue from harmful bacteria. Finally, Chapter 5 gives a
deeper insight of the importance of mechanical, biochemical,
and structural properties of microgels, when they are
applied in cell culture to be able to better design and
employ microgels as building blocks for engineered tissues.
For this purpose, I have systematically investigated how the
concentration, molecular weight, and architecture of the
molecular building blocks influence the internal structure
of rod-shaped microgels, and thus their mechanical and
diffusion properties. Furthermore, I have characterized how
the internal structure, as well as the functionalization of
the microgels with cell-adhesive peptide RGD, affect the
interaction with cells. In conclusion, this thesis provides
a comprehensive overview of the interplay of mechanical,
biochemical, and structural properties of microgels when
applied for biomedical application, in particular for the
treatment of IBD.},
cin = {150000 / 154610 / 154005 / 156420 / 052200},
ddc = {540},
cid = {$I:(DE-82)150000_20140620$ / $I:(DE-82)154610_20140620$ /
$I:(DE-82)154005_20140620$ / $I:(DE-82)156420_20190828$ /
$I:(DE-82)052200_20140620$},
pnm = {SFB 985 C03 - Zielgerichtete multi-funktionalisierte
Mikrogele für entzündliche Darmerkrankungen (C03)
(221477736) / SFB 985 B05 - Anisometrische Mikrogele für
die Konstruktion 3D-responsiver makroporöser Strukturen zur
Ausrichtung und mechanischen Stimulation von Zellen (B05)
(221474668) / SFB 985: Funktionelle Mikrogele und
Mikrogelsysteme (191948804)},
pid = {G:(GEPRIS)221477736 / G:(GEPRIS)221474668 /
G:(GEPRIS)191948804},
typ = {PUB:(DE-HGF)11},
doi = {10.18154/RWTH-2024-08919},
url = {https://publications.rwth-aachen.de/record/993685},
}
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