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%0 Thesis %A Kittel, Yonca %T Microfluidic synthesis of multifunctional microgels for treatment of inflammatory bowel syndrome %I RWTH Aachen University %V Dissertation %C Aachen %M RWTH-2024-08919 %P 1 Online-Ressource : Illustrationen %D 2024 %Z Veröffentlicht auf dem Publikationsserver der RWTH Aachen University 2025 %Z Dissertation, RWTH Aachen University, 2024 %X 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. %F PUB:(DE-HGF)11 %9 Dissertation / PhD Thesis %R 10.18154/RWTH-2024-08919 %U https://publications.rwth-aachen.de/record/993685