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February 6, 2020 – Supramolecular (Bio)materials: From Fundamentals to Advanced Healthcare Solutions

3d molecular model of a double helix dna structure.

Supramolecular biomaterials exploit rationally-designed non-covalent interactions to enable innovative approaches to drug formulation and delivery. For example, supramolecular interactions can be used to dynamically cross-link polymer networks, yielding shear-thinning and self-healing hydrogels that allow for minimally invasive implantation in vivo though direct injection or catheter delivery to tissues. Alternatively, rationally designed high-affinity interactions can be used to non-covalently modify therapeutic proteins, endowing them with prosthetic function such as enhanced stability in formulation or extended activity in vivo. In this talk, we will discuss the investigation of a hydrogel platform exploiting dynamic multivalent interactions between biopolymers and nanoparticles. These materials exhibit viscous flow under shear stress (shear-thinning) and rapid recovery of mechanical properties when the applied stress is relaxed (self-healing), afford minimally invasive implantation in vivo though direct injection. The hierarchical construction of these biphasic hydrogels allows for multiple therapeutic compounds to be entrapped simultaneously and delivered with identical release profiles, regardless of their chemical make-up, over user-defined timeframes ranging from days to months. These materials enable novel approaches to immunomodulatory therapies such as vaccines and cancer immunotherapies that rely on precise and sustained release of complex mixtures of compounds. We demonstrate that these unique characteristics enable the development of vaccines that greatly enhance the magnitude, quality, and durability of the humoral immune response.

DNA Nanotechnology.png

Further, we will discuss the use of supramolecular interactions to append functionality to therapeutic proteins to enhance their stability in formulation and therapeutic function. This non-covalent approach to modification of authentic proteins is highly modular and allows for formulation of historically incompatible proteins. Overall, this presentation will demonstrate the utility of a supramolecular approach to the design of biomaterials affording unique opportunities in the formulation and controlled release of therapeutics.

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Eric A. Appel is an Assistant Professor of Materials Science & Engineering at Stanford University. He received his BS in Chemistry and MS in Polymer Science from California Polytechnic in San Luis Obispo, CA. Eric performed his MS thesis research with Robert D. Miller and James L. Hedrick at the IBM Almaden Research Center in San Jose, CA. He then obtained his PhD in Chemistry with Prof. Oren A. Scherman in the Melville Laboratory for Polymer Synthesis at the University of Cambridge. His PhD research focused on the preparation of dynamic and stimuli-responsive supramolecular polymeric materials. For his PhD work, Eric was the recipient of the Jon Weaver PhD prize from the Royal Society of Chemistry and a Graduate Student Award from the Materials Research Society. Upon graduating from Cambridge in 2012, he was awarded a Ruth L. Kirschstein National Research Service Award from the NIH (NIBIB) and a Wellcome Trust Postdoctoral Fellowship to work with Prof. Robert Langer at MIT on the development of supramolecular biomaterials for drug delivery and tissue engineering. During his post-doctoral work, he received a Margaret A. Cunningham Immune Mechanisms in Cancer Research Award. His work at Stanford focuses on the development of biomimetic polymeric materials that can be used as tools to better understand fundamental biological processes and to engineer advanced healthcare solutions. He has recently been awarded a Hellman Faculty Scholarship, a Junior Faculty Development Award through the American Diabetes Association, a Research Scholar Grant from the PhRMA Foundation, a Research Scholar Grant from the American Cancer Society, a Research Starter Fellowship from the PhRMA Foundation, and a Young Investigator Award from the Polymeric Materials Science & Engineering division of the American Chemical Society.