Ph.D Thesis


Ph.D StudentShitrit Yulia
SubjectHydrogels Physically Cross-Linked with Nanogels
DepartmentDepartment of Chemical Engineering
Supervisor PROF. Havazelet Bianco-Peled
Full Thesis textFull thesis text - English Version


Abstract

Recently there has been wide interest in the field of physically cross-linked hydrogels, termed “supramolecular hydrogels”. These systems are novel class of noncovalently cross- linked polymer material whereas crosslinking is based on hydrogen bonding, metal-ligand coordination, hydrophobic, or electrostatic interactions. The dynamic behaviour of those hydrogels can lead to interesting properties such as stimuli-responsiveness and self-healing that are crucial for a wide variety of emerging applications. Due to the dynamic nature of these weak physical associations, the formed networks can be dissociated under applied shear, allowing the hydrogels to flow and revert into hydrogels when stress is removed. Many examples of physical polymeric hydrogels exist, typically based on biopolymers or polyelectrolytes. Novel hydrogel systems involve the use of cross-linking groups present on the surface of nanoparticle such as clay nano-sheets or silicates. However, hydrogel structure and its mechanical behaviour during and after flow, as well as the mechanisms of gel shear-thinning and rehealing properties unexplored.

In this work the development of a polymer-nanogel hydrogel based on a pair of polysaccharides is reported for the first time. This new hydrogel exhibits self-healing properties due to physical interactions between soluble pectin chains and chitosan nanogels. The nanogels act as crosslinking agents between pectin chains, leading to the formation of thermos-responsive hydrogel. Due to the dynamic interactions between the chains and the nanogels, the formed network dissociates under applied shear, allowing the hydrogel to flow. Moreover, elimination of the applied shear results in exceptionally fast and comprehensive recovery of the storage modulus, reverting the mixture back into solid form. The viscosity and Young modulus increased with the nanogels concentration while the equilibrium swelling decreased as the nanogels concentration increased suggesting a direct relation between the cross-linking degree and nanogel content. This novel hydrogel displays network recovery suitable for injectable biomedical applications, while benefiting from the advantages of nanogels as carriers.

Next, a simple technique for creation of chitosan nanogels with controllable size was developed based on two steps process; physical crosslinking with TPP followed by chemical crosslinking with genipin. The particles were stable at acidic pH that allow hydrogel formation. The influence of the post assembly conditions including exposure to monovalent salts (NaCl, NaI and NaF) and pH (2.5 or 5.5) on the gel swelling and mechanical properties was studied. These experiments provided insights into the influence of hydrogen bonds and electrostatic interactions on the gel network.

At last, dual drug delivery system was examined and exhibit interesting phenomena where the physical separation of the two drugs allowed controlled release profile different than that from the release of the two drugs mixed together in the gel.