(725a) Injectable Hydrogels with Secondary Reinforcement for Regenerative Medicine | AIChE

(725a) Injectable Hydrogels with Secondary Reinforcement for Regenerative Medicine


Heilshorn, S. C. - Presenter, Stanford University

While injectable hydrogels are able to be surgically implanted in a minimally invasive way, they typically rely either on polymerization in situ, which is difficult to control in a surgical setting, or are designed to be shear-thinning, which results in mechanically weak gels with fast erosion rates. To address these limitations, we have designed several injectable double-network hydrogels that undergo two stages of crosslinking: the first stage provides cell protection during injection and rapid hydrogel self-healing, while the second stage reinforces the hydrogel in situ to minimize erosion and to provide a dynamic range of tunable mechanical properties. Several different types of crosslinking strategies and engineered biopolymers have been employed in these designs, which allows for customization for a variety of clinical regenerative medicine applications. In this talk, two newly designed double-network hydrogels will be discussed to demonstrate the range of design variables that can be used in these formulations. In the first formulation, the hydrogel undergoes ex situ chemical crosslinking through the formation of dynamic covalent hydrazone bonds by mixing two components together:  hydrazine-modified elastin-like polypeptide (ELP) and aldehyde-modified hyaluronic acid (HA). In situ at physiological temperature, secondary physical crosslinking occurs via thermoresponsive aggregation of ELP to reinforce the network, resulting in a hydrogel with viscoelastic, stress-relaxation behavior. In the second formulation, the hydrogel undergoes ex situ physical crosslinking through peptide-based molecular-recognition by mixing two components together: peptide-modified alginate and a protein-engineered, block-copolymer. In situ at physiological salinity, secondary crosslinking occurs via electrostatic interactions with divalent calcium ions. In both formulations, the injectable, shear-thinning networks provide encapsulated cells with mechanical protection during injection and significantly decreases membrane damage during transplantation by direct injection. These novel, double-network hydrogels combine the advantages of traditional physical and covalent crosslinking and have a wide tuning range of storage moduli (~ 50 to 5,000 Pa below 5 wt% polymer). These dynamically adaptable hydrogels will be useful in fundamental studies of cell mechanotransduction in response to viscoelastic, stress-relaxation properties and for injectable, minimally invasive, regenerative medicine applications.