“Engineering granular hydrogels for biomedical applications”
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. In recent years, we have transitioned from traditional hydrogels to granular hydrogels that are comprised of smaller hydrogel units (i.e., microgels). Microgels can be readily fabricated through microfluidics, with variations in microgel size, shape, and throughput based on device design. Granular hydrogels are formed through the packing of microgels and can be designed to be injectable through shear-thinning behavior, heterogeneous through microgel mixing, and porous to support cell invasion. I will give examples of the design and use of granular hydrogels based on hyaluronic acid for use as injectable therapeutics for endogenous tissue repair or in 3D printing to fabricate hydrogel constructs. For cardiac therapeutics, we injected heterogeneous granular hydrogels into the myocardium and showed selective microgel degradation to release factors and introduce porosity for cellular ingrowth. In 3D printing, we jammed microgels to form shear-thinning and self-healing hydrogels that could be printed either onto surfaces or within other hydrogels. These could be cell-laden or stabilized where necessary with secondary crosslinking. As a last example, we have fabricated granular hydrogels from hydrogel fibers that assemble into structures that permit cell encapsulation and cell-mediated compaction, mimicking features of extracellular matrix. Overall, the design of granular hydrogels opens up new opportunities in the design of functional hydrogels for biomedical applications.