Ph.D. Theses
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Browsing Ph.D. Theses by Subject "Biomedical materials."
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Item Linear and multi-arm functionalizable polymeric constructs for targeted drug delivery and imaging applications(Thesis (Ph.D.) - Bogazici University. Institute for Graduate Studies in Science and Engineering, 2014., 2014.) Gök, Özgül.; Sanyal, Rana.; Sanyal, Amitav.Multifunctional polymers with different architectures were designed as macromolecular carriers for drug delivery and imaging applications. To this end, linear and multiarm copolymers incorporated with reactive groups were synthesized. The first study outlines the design of a thiol-reactive water soluble maleimide-based copolymer that can be utilized for targeted delivery system. Water soluble thiol-reactive linear copolymers were conjugated with a thiol-containing hydrophobic fluorescent dye and a peptide based targeting group. In vitro studies over both cancerous and healthy cells demonstrated non-toxicity of the polymeric carrier and enhanced uptake for polymers containing the targeting group. The second project involves the synthesis of polymer-drug conjugates where a chemotherapy drug was attached to linear polymers. These were investigated for in vitro cytotoxicity and in vivo pharmacokinetic profiles to demonstrate benefits of drug conjugation to polymers. The third project involves development of polymers containing clusters of functional groups as side chains at precise location along the polymer backbone. Linear copolymers of styrene and maleimide containing polyester dendrons were synthesized via nitroxide-mediated radical polymerization. Successful incorporation of dendrons containing alkene units was undertaken and these were modified with thiol-containing molecules. Fourth part of thesis focuses on the design of orthogonally reactive multiarm star polymers as drug delivery vehicles. Polyester dendrons containing initiators were designed to obtain multiarm copolymers. Obtained copolymers contained thiol reactive maleimide group at the core and activated esters along the polymeric arms. These copolymers were efficiently conjugated with a hydrophobic fluorescent dye at the core and an anti-cancer drug gemcitabine along the side chains. In vitro studies over cancerous cells displayed the reduced toxicity of drug upon polymer conjugation. Final project outlines the design of multiarm water soluble polymers containing a pyridyl disulfide based reversible linker for conjugation of peptides and small molecules. In summary, various linear and multiarm functional polymers were designed for facile conjugation of drugs, imaging and targeting groups to fabricate ideal drug delivery systems.Item Reactive and 'clickable' hydrophilic nanofibers as novel biomaterials(Thesis (Ph.D.)-Bogazici University. Institute for Graduate Studies in Science and Engineering, 2017., 2017.) Kalaoğlu Altan, Özlem İpek.; Sanyal, Rana.; Sanyal, Amitav.Among many other nanomaterials, polymeric nanofibers have gained attraction in biomedical applications due to their unique properties such as high surface area, porosity and physical resemblance to the extracellular matrix. Electrospinning is the most commonly used method for producing nanofibers due to its low-cost, simplicity and efficiency. These nanofibers usually need to be modified with a biological material for bioapplications in order to enhance their biocompatibility, cell-adhesivity and stimuli-responsivity. Recently, ‘click’ chemistry, in particular metal-free click reactions, has emerged as a preferred method for the functionalization of electrospun nanofibers as it enables efficient and orthogonal functionalization under mild reaction conditions. In this thesis, clickable polymers with various reactive groups were designed and electrospun into reactive nanofibers which were aimed to be used for the reagent-free (bio)functionalization of nanofibers under mild reaction conditions. In the first project, furan-bearing acrylate-based non-biodegradable nanofibers were produced and modified with maleimide-containing fluorescent dye and biotin ligand via Diels-Alder reaction. In the second project, maleimide-containing acrylate-based non-biodegradable nanofibers were obtained and photo-patterned. The patterned nanofibers were biofunctionalized with a thiol-bearing oligonucleotide via Michael reaction, followed with hybridization with its complementary sequence. The third project involved the in situ crosslinking of polyoxazoline-based nanofibers. The alkene unit on the polymer was used for modification of the crosslinked nanofibers via thiol-ene reaction. In the fourth project, furan-bearing biodegradable polylactide nanofibers were produced and modified with a maleimide-containing RGD peptide via Diels-Alder reaction, followed by cell culture on the modified nanofibers. In the last project, dual-functional biodegradable polylactide nanofibers were obtained and modified with fluorescent dyes and biomolecules using strain-promoted azide-alkyne cycloaddition and inverse electron-demand Diels-Alder reaction.Item Stimuli responsive functional polymeric materials for biomedical applications(Thesis (Ph.D.) - Bogazici University. Institute for Graduate Studies in Science and Engineering, 2019., 2019.) Demirer, Hatice Betül.; Avcı, Duygu.This work consists of synthesis, structural characterization and evaluation of stimuliresponsive functional polymers and hydrogels designed for biomedical applications. In the first project pH and redox responsive degradable gels and cryogels were synthesized from phosphonate-functionalized poly(-aminoester) macromers as potential materials for tissue engineering applications. Then injectable poly(-aminoester) based hydrogels were fabricated by a facile one-step method and a photosensitizer released from these hydrogels showed promising activity in phtodynamic therapy. Phosphonic acid containing acrylamides were synthesized and evaluated as self-etching dental adhesives. Furthermore, these acrylamides were used to make hydrogels which were then successfully mineralized to make bone-like composite materials. Lastly carboxylic acid-functional crosslinkers were fabricated into hydrogels, and the pH/redox response of these hydrogels were demonstrated through controlled release studies of R6G dye and resorcinol.