Hydrogels represent a class of biomaterials that have great promise for the repair of tissues, particularly due to our ability to engineer their biophysical and biochemical properties. Hydrogels can provide instructive signals through material properties alone (e.g., mechanics, degradation, structure) or through the delivery of therapeutics that can influence tissue morphogenesis and repair. Here, I will give examples of the design of hydrogels based on hyaluronic acid (HA) for use as injectable therapeutics, where local and sustained delivery overcomes many of the challenges (e.g., off-target complications) of systemic delivery. Towards cardiac repair, my laboratory is interested in designing materials that can influence the left ventricular remodeling process that occurs after myocardial infarction. To permit percutaneous delivery of hydrogels (e.g., via catheters), we are developing classes of shear-thinning and self-healing hydrogels that can be used for the delivery of therapeutics. These hydrogels assemble based on either dynamic covalent crosslinks (e.g., hydrazone bonds) or via guest-host (e.g., adamantane/cyclodextrin) interactions, where shear during injection permits the material to flow and rapid healing occurs upon reaching the injection site. There are numerous therapeutic molecules that are useful for delivery to the heart, including protease inhibitors that limit matrix remodeling and microRNA that can stimulate cardiomyocyte proliferation. Hydrogels are being designed to degrade in response to matrix metalloproteinases (MMPs) to release therapeutics “on-demand” or to bind directly to drugs to sustain their release. Recently, and to increase the complexity of possible therapeutic release profiles, we are designing granular hydrogel systems where multiple microgels with independent degradation and release behavior can be combined to deliver multiple therapeutic molecules. Microfluidic devices are used to fabricate the microgels using photoinitated thiol-ene reactions for intraparticle crosslinking where crosslinkers can be stable or responsive to local proteases and microgel assembly occurs through interparticle crosslinking. These efforts in engineered hydrogels will advance our abilities to treat tissue after myocardial infarction.

Shear-thinning and self-healing hydrogels for therapeutic delivery

255th National Meeting (2018)

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