Development of Polymeric Networks for Drug Delivery and Tissue Engineering Applications



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The synthetic versatility of polymeric networks provide the opportunity to use organic and polymer chemistry for the precise synthesis of macromolecular building blocks to form a host of materials that can be tuned for specific biomedical applications. This dissertation focuses on the development of polymeric networks ranging in size from bulk materials as hydrogels, to discrete micron structures and nanoparticles for applications in tissue engineering and drug delivery. The development of a novel hydrogel material based on a suitable poly(ethylene glycol) (PEG) alternative, polyglycidol, is described. Incorporation of THF as a comonomer in the ring opening polymerization of glycidol reducing the branching in the structure providing a semi-branched architecture. Upon functionalization with ketone and aminooxy groups, these derivatives are brought together to produce hydrogels with great promise for tissue engineering applications. Later, poly(dimethyl acrylamide-co-diacetone acrylamide) copolymers were cross-linked with a variety of synthesized aminooxy-PEG cross-linkers to produce an oxime-based host hydrogel tuned in its hydrophilicity and elasticity. An interpenetrated network consisting of self-assembled peptides within the host hydrogel was established. Results demonstrated the self-assembled peptide network was exclusively responsible for triggering cell adhesion while the dense oxime-based network provided the mechanically stable environment required by the bioactive system. To further evolve nanoparticle platforms previously developed, a novel second-generation particle system was established to create particles ranging in size from the nanoscale to the microscale in a simple, robust one pot synthetic method. By utilizing acyclic diene metathesis (ADMET) polymerization, high molecular weight polyesters possessing backbone functionalities were synthesized for intermolecular cross-linking via thiol-Michael addition chemistry with a dithiol linker for particle formation. Variations in the degree of functionalization and reaction concentration led to particles tuned in their cross-linking density in well-defined size dimensions. This practical synthetic approach combined with tunable drug release profiles based on cross-linking density makes this system a promising platform for drug delivery applications. Lastly, to broaden the applications of this new particle platform for potential use in tissue engineering, progress towards incorporating these particles in organo/hydrogels as reinforcement agents to improve the overall mechanical properties of the network is discussed.



Polymeric Nanoparticles, Hydrogels


Portions of this document appear in: Criado-Gonzalez, Miryam, Breyinn Loftin, Jennifer Rodon Fores, Dominique Vautier, Leyla Kocgozlu, Loic Jierry, Pierre Schaaf, Fouzia Boulmedais, and Eva Harth. "Enzyme assisted peptide self-assemblies trigger cell adhesion in high density oxime based host gels." Journal of Materials Chemistry B 8, no. 20 (2020): 4419-4427.