Dynamic Covalent Hydrogels as Tissue Mimics

The tissues in our body are viscoelastic, yet many of the synthetic biomaterials used for cell culture and bioprinting technologies are elastomeric. Because a cell's behavior is directly influenced by the mechanics of its surrounding microenvironment, ideally each cell type would be cultured in its own customizable biomaterial. To fulfill this need, my lab designs bespoke dynamic covalent hydrogels that can be tailored to model different viscoelastic properties observed in real patient tissues. In one demonstration, I present a family of dynamic covalent biomaterials that support the growth of patient-derived organoids, i.e. three-dimensional cell aggregates that demonstrate emergent, tissue-like behavior. Our hydrogels are formulated with recombinant biopolymers that are fine-tuned to display a reproducible range of biochemical and biomechanical properties that mimic healthy tissue and cancerous tissue, enabling the study of tissue dynamics in pancreatic cancer. We then show that the free diffusion of small molecule competitors and catalysts within our hydrogel can transiently alter the number of crosslinks and the stability of crosslinks. Using a simple polymer physics model of percolation and reaction-diffusion equations, we can reliably predict how these small molecules transiently impact the viscoelastic properties of our materials. This results in a family of polymeric biomaterials that can be reversibly stiffened and weakened on demand, enabling applications in disease modeling and 3D bioprinting.