Formation of Robust Supramolecular Hydrogels using MonofunctionalizedCucurbit[6]uril Derivatives and Its Applications

Abstract

This thesis describes the synthesis, characterization and applications of a robust supramolecular hydrogel formed by a strong host-guest interaction of cucurbit[6]uril to polyamine as a noncovalentcrosslinker. Here, water soluble monoallyoxylatedcucurbit[6]uril derivative (monoCB[6] having single reactive site) wasutilized as a host moiety which can be efficiently conjugated to thiolatedhyalruronic acid (HA) via thiol-ene photoreaction to providemonoCB[6]-tethered biocompatible polymers. Taking advantage of strong host-guest interactions between CB[6] and diaminohexane(DAH) moieties separately conjugated to HA, arobust and stable supramolecular hydrogel was prepared by simple mixing and its application in cellular engineering was studied. In chapter 1, a brief summary of the recent development ofhydrogels as artificial extracellular matrixes (ECMs) isdescribed. To mimic 3D environment of ECMs, a robustin situ forming hydrogel is required for efficient cell encapsulation. A recent report aboutin situ forming supramolecular hydrogels utilizing strong host-guest interactions between CB and polyamine as noncovalentcrosslinkers is also described. In chapter 2, preparation of the robust supramolecular hydrogel usingmonoCB[6] and polyamine conjugated polymers is described. Feasibility of this synthetic hydrogels as artificial ECMs has been extensively investigated for different applications, which are described in details.Synthetic hydrogels as artificial ECMs have been extensively investigated for protecting cells from immune systems, and the differentiation of mesenchymalstem cells (MSCs) to specific cells and tissues depending on the provided environments. For the purpose of tissue engineering, physical properties of hydrogels are important factors tomodulate the 3D cellular environment which affects to the fate of encapsulated stem cells. For example, variousmechanical properties with a different cross-linking density leadto the alteration of morphologies and functionsof encapsulated cells.Here, I describemonoCB[6]which can be more efficiently conjugated to HA than the previously reported multi-allyoxylated CB[6] due to the enhanced solubility in water in which HA is also well solubilized.Utilizing the good solubility of monoCB[6] in water, I prepared a various conjugation degree of monoCB[6] to HA to provide monoCB[6]/DAH-HA hydrogels with controlled crosslinking density and physical property, and further studied their applicability to tissue engineering and cell therapy.