Nanostructured Biomaterials for Immunomodulation and Cellular Therapy

A high level of spatial and temporal control over the presentation of biomolecules is essential for immune cell modulation. Nanostructured materials can be designed to provide efficient and tunable protein presentation. These structures can be tuned in terms of geometry allowing for greater residence time and modified to allow site-specific coupling to therapeutic proteins. In particular, nanowires and nanoparticles conjugated with antibodies can be designed to capture and potentiate endogenous cytokines demonstrating both tissue- and cell- specific immune activation. We show that the density and ratiometric control of immunomodulatory proteins such as costimulatory ligands and cytokines on can significantly impact human primary T cell activation phenotypes. This platform can be used to improve the safety of chimeric antigen receptor (CAR) T cell therapies by providing localized and specific cell activation for in vivo tumor clearance. Moveover, these tunable nanostructures can be used to modulate the microenvironment after injury, diminishing the fibrotic response. Our work highlights the role of tunable nanostructured biomaterials for immune modulation and cell based therapies.