UC Riverside

Hyaluronic acid (HyA) hydrogels are promising in various biomedical applications such as tissue regeneration, drug delivery, cell therapy, and biosensing. Three-dimensional printing (3D printing) can precisely control the structures and properties of the HyA hydrogels, which is highly desirable for many biomedical applications. However, the crosslinking and 3D printing of HyA hydrogels usually require chemical modifications. This may raise toxicity concerns on the hydrogels, especially when regulatory approval is required for the clinical translation of the final products. This dissertation investigated the mechanisms of dynamic coordination and the relationships among the key parameters in controlling the tunable crosslinking, reversible phase transition, and 3D printing of HyA hydrogels for biomedical applications, without blending with other polymers or adding new functional groups. In the first part, tunable crosslinking and reversible phase transition of HyA hydrogels were achieved and demonstrated via dynamic coordination of Fe3+ ions with innate carboxyl groups. The concentrations of Fe3+ and H+ ions and the reaction time determine the coordination state, leading to the low-to-high crosslinking densities and reversible solid-liquid phase transition of HyA hydrogels. In chapters 3 and 4, three different 3D printing approaches for HyA hydrogels were developed, for the first time. Two 3D printing strategies, namely cold-stage and direct-writing methods, were achieved based on the tunable crosslinking and reversible phase transition of the HyA hydrogel. Direct writing of HyA solution in FeCl3 solution was also achieved by decelerating the solidification process of the hydrogel in FeCl3 solution. In chapter 5, the cytocompatibility of HyA hydrogels with different crosslinking densities and 3D-printed HyA constructs was investigated via the direct exposure culture method with bone marrow-derived mesenchymal stem cells (BMSCs). The last part of this dissertation investigated the incorporation of magnetic nanoparticles (MNPs) in the HyA hydrogels in situ. The MNP content and agglomeration in the magnetic hydrogels were tunable by controlling concentrations of Fe3+ and Fe2+ ions. Cell study results indicated that BMSC adhesion density decreased when increasing the MNP content in HyA hydrogels.