BIOACTIVE SELF-FORMING HYDROGELS FOR BIOMEDICAL APPLICATIONS

Hydrogels are soft biomaterials that feature a wide range of physical and biochemical properties. Although highly versatile, hydrogels typically require an exogeneous input (e.g., light, pH, temperature) to form, and this limits their use to conditions where a catalyst is present. The goal of this dissertation is to expand the use of catalyst-based hydrogels by developing hydrogels with independently tunable properties which gel in situ without external stimuli. This new class of hydrogels was developed by first modifying macromers with norbornene (Nor) or tetrazine (Tet) moieties. Macromers containing Nor or Tet remain liquid when dissolved, and upon mixing self-form into Nor-Tet hydrogels. Hydrogels with broad mechanical properties are obtained, and peptide functionalization has no effect on mechanics or gelation time. Nor-Tet hydrogels functionalized with adhesive RGD peptides exhibit exceptional cell-matrix interactions, and stem cells in Nor-Tet solutions are protected from shear forces cells experience during liquid cell injections. Nor-Tet hydrogels functionalized with peptides containing active motifs of bone morphogenetic protein 2 (BMP2) also induce 3D osteogenic differentiation, and BMP2 Nor-Tet hydrogel injections into medullary cavities result in nascent trabecular bone growth in femurs. Taken together, the self-forming Nor-Tet hydrogels developed can be used to safely deliver cells in vivo and can serve as a targeted therapeutic to locally treat degenerative musculoskeletal diseases including osteoporosis