Engineering a Tolerogenic Immunomodulatory Hydrogel

Placental pregnancy is a biological scenario where tissue types bearing different antigen signatures co-exist within the same microenvironment without rejection. Placental trophoblast cells locally modulate the immune system in pregnancy, and one process through which this occurs is through the release of a class of nano-scaled extracellular vesicles called exosomes. The aim is to use these placental-derived immunomodulatory exosomes as a therapeutic and engineer a means to deliver these exosomes using a hydrogel vehicle. As such, two representative trophoblast cell lines, JAR and JEG-3, were used as exosome sources. First step involved the evaluation of the morphological and proteomic characterization of the isolated exosomes through dynamic light scattering (DLS) analysis, transmission electron microscopy (TEM) imaging, and mass spectrometry (MS) analysis. Following exosome characterization, incorporation of exosomes within hydrogel matrices like polyethylene glycol and alginate to determine their release profile over a timescale of 14 days was performed. Comparing the release between the two cell lines isolated exosomes, no discernible difference is observed in their release, and release appears complete within two days. Future studies will evaluate the impact of exosome loadings and hydrogel modification on exosome release profiles, as well as their influence on immune cells.