MSE Seminar: “Dynamic Biomaterials Enabling Innovations in Cell and Drug Delivery” – Eric Appel – Stanford University

Dynamic biomaterials exhibit highly useful properties that are impossible with traditional materials but crucial for a wide variety of emerging applications in biomedicine. These materials typically employ enthalpy-dominated crosslinking interactions that become weaker at elevated temperatures, leading to significant softening. Herein, we will discuss the development of a physical hydrogel platform exploiting dynamic and multivalent interactions between biopolymers and nanoparticles that are strongly entropically driven, providing alternative temperature dependencies than typical for materials of this type. We will discuss the implications of these crosslinking thermodynamics on the observed mechanical properties and discuss the desired mechanical properties for injectability, including viscous flow under shear stress (shear-thinning) and rapid recovery of mechanical properties when the applied stress is relaxed (self-healing). Moreover, the hierarchical construction of these biphasic hydrogels enables innovative approaches to formulation and delivery of a diverse array of compounds over user-defined timeframes ranging from days to months. In one example application, we demonstrate that these unique material characteristics can be leveraged for controlled locoregional exposure of immunomodulatory cargo to greatly enhance anti-cancer immune responses. In another example, we demonstrate that the dynamic structure of these materials can be leveraged for co-delivery of immunostimulatory cytokines and CAR-T cells to improve cancer treatments. Overall, this talk will illustrate our recent efforts exploiting dynamic and multivalent interactions between polymers and nanoparticles to generate injectable hydrogel depot technologies exhibiting properties not previously observed in biomaterials and affording unique opportunities in biomedicine.