Photochemical reactions for functional biomaterials development: Thiol-ene and thiol-yne photopolymerizations

Among the areas of particular interest for biomaterial development in recent years are: crosslinked polymers formed via photoinitiated polymerization, fascilitating the in situ fabrication of materials; water-swollen crosslinked polymer hydrogels that can mimic the mechanical properties and microenvironment of many of the body's soft tissues; and degradable, bioresorbable materials that permit and even promote cellular interaction and the body's natural healing processes.;This thesis presents the development and application of a photopolymerization strategy for the synthesis of bioerodable poly(ethylene glycol) (PEG) hydrogels that both permit and promote cellular motility by the inclusion of bioresponsive and bioinstructive peptide elements within the molecular architecture of the hydrogel's polymer network. This was accomplished via the thiol-ene photopolymerization between multi-armed norbornene functionalized PEG and thiol-containing (thiols presented on cysteine residues) peptides. These materials permit the encapsulation and support the viability, migration, in vivo-like morphology and phenotype of multiple cell types including mesenchymal stem cells (MSCs), valve interstitial cells (VICs) and fibrosarcoma HT1080s, making thiol-ene polymerized, PEG-copeptide hydrogels a versatile tool for the 3D study and manipulation of cellular processes and tissue development. Additionally, hybrid networks with 3D patterned biochemical signals were designed and synthesized using thiol-ene photoconjugation to networks prefabricated via copper catalyzed azide-alkyne cycloaddition polymerization. By using separate and semi-orthogonal chemical reactions for the polymerization and biofunctionalization of the hydrogel networks, the hydrogels' mechanical and biochemical properties were independently manipulated.;Analogous to the thiol-ene photopolymerization, the novel thiol-yne photopolymerization was introduced. Whereas in a thiol-ene polymerization one thiol adds to a single ene, in a thiol-yne reaction two thiols may add to a single alkyne resulting in materials of higher crosslinking density. Because of the novelty of the thiol-yne photopolymerization, little is known regarding the effect of substituents on the alkyne reactive groups. To establish guidlines for the future design of monomers for thiol-yne photopolymerization, the reaction of various functional alkynes with octanethiol was characterized. As a result of its unique mechanism, the thiol-yne photopolymerization holds implications for the future development of various classes of functional materials including glassy crosslinked polymers, polymer brushes, dendrimers and biofunctional hydrogels.