Development of Cell - laden Hydrogels with High Mechanical Strength for Tissue Engineering Applications

The development of materials with biomimetic mechanical and biological properties is of great interest for regenerative medicine applications. Hydrogels are a promising class of biomaterials due to several advantages, however, the mechanical weakness remains a critical challenge for applications as tissue scaffolds. Particularly, scaffolds for load-bearing tissues such as cartilage and bone need to have great strength to keep their integrity after implantation. This thesis focused on the development of cell-laden hydrogels that have high mechanical strength and good biological properties. The first work of the thesis was to synthesize a biodegradable hydrogel, poly(glucose malate)methacrylate (PGMma), from two natural monomers glucose and malic acid. The PGMma hydrogels were cell-adhesive, and mechanically tunable by altering the formulation. In the second work, double-network (DN) hydrogels were prepared from two biomacromolecules, gellan gum and gelatin. The DN hydrogels prepared exhibited much higher strength than traditional hydrogels, the maximal strength being 6.9MPa. By using a cell-compatible two-step photocrosslinking process, it was also possible to encapsulate cells with high viability. Further research into the materials as tissue scaffolds showed that the DN hydrogels weakened when they were prepared at cell-compatible conditions, and stronger cell-hydrogel interaction is needed to improve the function of the encapsulated cells. Therefore in the last work, microgel-reinforced (MR) hydrogels that have better mechanical strength and biological properties in comparison to DN hydrogels were prepared by embedding stiff GG microgels into soft and ductile gelatin hydrogels. The MR hydrogels exhibited higher strength than the DN hydrogels and the gelatin hydrogels. The cells encapsulated in MR hydrogels showed high metabolic activity and high level of osteogenic behaviors similar to the cells encapsulated in gelatin hydrogels, which was not the case for DN hydrogels. The MR hydrogels, the final product of all these works could be potentially useful for load-bearing tissue scaffolds. Thesis Supervisor: Ali Khademhosseini Title: Associate professor of Medicine and Health Sciences and Technology, Harvard Medical School