Finding the sweet spot: a library of hydrogels with tunable degradation for tissue model development

In vitro models are valuable tools for applications including understanding cellular mechanisms and drug screening. Hydrogel biomaterials facilitate in vitro models by mimicking the extracellular matrix and in vivo microenvironment. However, it can be challenging for cells to form tissues in hydrogels that do not degrade. In contrast, if hydrogels degrade too much or too quickly, tissue models may be difficult to assess in a high throughput manner. In this paper, we present a poly(allylamine) (PAA) based synthetic hydrogel system which can be tuned to control the mechanical and chemical cues provided by the hydrogel scaffold. PAA is a polycation with several biomedical applications, including the delivery of small molecules, nucleic acids, and proteins. Based on PAA and poly(ethylene glycol) (PEG), we developed a synthetic non-degradable system with potential applications for long-term cultures. We then created a second set of gels that combined PAA with poly-l-lysine (PLL) to generate a library of semi-degradable gels with unique degradation kinetics. In this work, we present the hydrogel systems' synthesis, characterization, and degradation profiles along with cellular data demonstrating that a subset of gels supports the formation of endothelial cell cord-like structures.