Huebner, Anna
Submitted to the University of New Hampshire in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy in Chemistry.
DISSERTATION ABSTRACT:
Since the late 1980’s tissue engineering has become an important field in regenerative medicine. Tissue engineering aims to create scaffolds designed to mimic the extracellular matrix (ECM) of human tissue, which is a complex, heterogeneous system. While there are a variety of approaches for scaffold fabrication, it is difficult to mimic the heterogeneity of the natural ECM. NH BioMade proposed a tissue engineering scaffold design to address these limitations, where multi-lobed particles can be 3D-printed to form a scaffold, providing heterogeneity in pore size by the incorporation of different-sized multi-lobed particles. In order for particles to be 3D printed into a structure they need to be a stable dispersed latex while printing that can then be triggered to assemble once printed. This work focuses on investigating the use of light as a trigger to assemble nanoparticles for further applications in tissue engineering. Light is an attractive stimulus as it is noninvasive and has excellent spatial and temporal resolution.
Photochemical cycloadditions have been previously used to assemble nanoparticles through dimerization of photoresponsive moieties like cinnamyl and coumarin. These dimerization reactions rely on the absorption of light to create excited states, which can react with ground states to form dimers. While inter-particle dimerization has been previously achieved in literature through photochemical cycloadditions, the particles typically used are gold nanoparticles on the order of 5-50 nm. In this work we investigated the use of the [4+4] cycloadditions of anthracene to cause particle assembly via inter-particle dimerization to occur in polymer latexes, varying the amount of the anthracene, particle size, and the softness of the particle. When these approaches did not allow for inter-particle dimerization, we investigated the use of polymer tethers terminated in the photoresponsive moiety grafted to particles to provide a greater degree of freedom and to move the reactive group further out from the particle. These systems did not work, due to premature particle clustering due to interactions of the tethers.
An alternative approach to generating light-responsive systems is to use radical-mediated photochemistry. Exposure of a photoinitiator to UV light results in radicals, which can mediate thiol-disulfide exchanges. A significant difference is that this approach possesses a longer lifetime of the reactive species than in photochemical cycloadditions. We investigated the use of a dithiol linker in the presence of a photoinitiator to induce thiol-disulfide exchanges with disulfide-containing particles, exploring the importance of dithiol concentration and the number of tethering sites in favoring inter-particle exchange. Inter-particle disulfide exchange was observed at specific concentrations of each, resulting in a light-induced assembly of nanoparticles. Learnings from this approach can be used in the development of a biocompatible system for tissue engineering applications.