(9d) Understanding the Complex Rheology of Supramolecular Hydrogels for Designing Injectable Drug Delivery Materials

Supramolecular hydrogels have emerged as an exciting class of biomaterials for the development of injectable therapeutic strategies and extrudable materials for 3D printing. They are comprised of physically associated and dynamic crosslinking motifs that imbue them with complex rheological behaviors (e.g. yield stress, shear-thinning, thixotropy). Most notably, supramolecular hydrogels may demonstrate solid-like behaviors at rest and liquid-like behaviors in response to shear, allowing for both injection and printing processes. Emerging advances in the formulations of supramolecular hydrogels for a broad range of applications has resulted in a pressing need to better elucidate key property–function relationships between rheological properties and extrudability. However, defining extrudability for a broad range of design constraints (e.g. needle vs. catheter) a priori remains an important challenge in the field.

Herein, I present a model for the extrusion of supramolecular hydrogels through high gauge needles to predict and validate corresponding injection pressures. A generalizable engineering design strategy is shown for defining target flow properties. The complex rheological behavior of supramolecular hydrogels at the shear rates relevant for injection will be presented, highlighting the need for comprehensive rheological characterization up to shear rates in the range of 10³ – 10⁶ s^-1. I will discuss resulting strategies for tuning the solid-like properties of supramolecular hydrogels without compromising their injectability or printability. I show that increasing the concentration and altering the composition of the supramolecular crosslinker has a large impact on the hydrogel’s properties at rest while having minimal impact on the flow properties at shear rates operative during printing and injection. Through the discovery of design rules for supramolecular hydrogels and development of property-function relationships, I hope to create engineering design strategies to accelerate the materials discovery and design process for the next generation of biomaterials for injectable drug delivery and 3D printing.