Advanced Biomaterials Technologies for Improving Biopharmaceutical Formulation and Delivery

• Discussion of the design criteria for injectable hydrogels for use as sustained release depot technologies
• Defining “injectability” in shear-thinning hydrogels
• Sustained co-delivery of subunit vaccine components improves the potency, durability and breadth of vaccine responses
• Sustained co-delivery of cytokines and CAR-T cells enhances in vivo expansion and activation of the adoptive cells and improves therapeutic efficacy

Supramolecular (bio)materials exhibit highly useful properties that are impossible with traditional materials but crucial for a wide variety of emerging applications in industry or biomedicine. These materials typically employ enthalpy-dominated crosslinking interactions that become more dynamic at elevated temperatures, leading to significant softening. Herein, we will discuss the development of a supramolecular 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 how tuning the thermodynamics and kinetics of these crosslinking interactions enable broad modulation of the mechanical properties of these materials, including their cargo encapsulation and controlled release. In particular, these materials exhibit viscous flow under shear stress (shear-thinning) and rapid recovery of mechanical properties when the applied stress is relaxed (self-healing), affording facile processing though direct injection or spraying approaches, making then well served for applications in biomedicine. Moreover, the hierarchical construction of these biphasic hydrogels enables innovative approaches to drug formulation and delivery as a diverse array of compounds to be entrapped and delivered over user-defined timeframes ranging from days to months. We demonstrate that these unique characteristics can be leveraged to generate vaccines exhibiting greatly enhanced magnitude, quality, and durability of humoral immune responses. Overall, this talk will illustrate our recent efforts exploiting dynamic and multivalent interactions between polymers and nanoparticles to generate hydrogel materials exhibiting properties not previously observed in biomaterials and affording unique opportunities in biomedicine.

Professor Eric Appel, Assistant Professor Department of Materials Science & Engineering, Stanford University