Mechanically- Biologically-Tunable Polyethylene Glycol Hydrogels for Quantitative Neutrophil Migration Assays

摘要

Porated PEG gels can be used for modular, biomimetic, immunoassays to replicate the complexity and diversity of human ECM in vitro. Urea salt leached PEG gels serve as mechanistic models to explore chemotaxis in 3D ECM, such as interstitial tissue. Using these gels, we demonstrate that within a physiological range of soft tissues (<5 kPa), less stiff (lower Young's moduli), more locally elastic gels (higher PEG MW) are more supportive of PMN migration. Similarly, small pores and high pore densities further promote PMN chemotaxis in response to IL-8. We confirmed prior results showing that a dearth or an excess of cell binding sites reduces chemotaxis. We next presented thinner, porated gels that replicate specialized ECM, such as vascular BM. These gels offer mechanical and biological advantages to current models, i.e. TWs, while maintaining their thin structure. Overall, PEG gels improve in vitro ECM models and provide more relevant results of immune cell migration in mechanically and biologically complex settings.