Scaffold-based non-viral gene delivery in granular hydrogels for tissue repair

Work leading up to my PhD thesis has looked to optimizing and understanding non-viral nucleic delivery to cells in 3D culture and in vivo mouse models using microporous annealed particle (MAP) hydrogels and my own developed flowable linked irregular particle (FLIP) scaffolds. From microgel properties (stiffness, size, adhesion ligand), and pathways regulating the uptake of polyplexes from the 3D environment, non-viral delivery can be enhanced to provide a sustained and repeated transfection as cells remodel the scaffold. I have looked to both surface coating of the microgels and encapsulation of lyophilized, coating-stabilized nanoparticles to improve sterics and prevent aggregation or inactivation.

Currently, my platform is adaptable across a wide range of nucleic acid vectors and nonviral cationic vehicles, and give highly efficient, sustained, persistent delivery in vitro. Challenges remain in vivo, including tissue infiltration and immunogenicity, particular with delivery of viral vectors. Studies are ongoing in this area. However, I also study applications including in vitro biologics manufacturing from my nonviral scaffold system, as well as vaccine applications.