A chemically defined and xeno-free hydrogel system for regenerative medicine

Abstract

ABSTRACTBio-fabricated scaffolds facilitate bona fide cellular interactions, cell-type specification, and the formation of three-dimensional tissue architecture from human pluripotent stem cells (hPSCs). However, poorly defined xenogenic and non-clinically approved synthetic biomaterials greatly hinder translation into clinical therapy. Here we describe a protein screen-based hydrogel system made from widely available clinical-grade components. We show that Alphagel, a base hydrogel synthesized from human embryonic matrices, supported trilineage hPSC differentiation and was biocompatiblein vivo. Further, by adding select proteins found in the maturing foetal liver, the resulting hydrogel (Hepatogel) enhanced the differentiation of hPSC-derived hepatocytes (H-iHeps) compared to Matrigel, a generic hydrogel. Importantly, when H-iHeps and Hepatogel were injected into the liver of immunocompromised mice, cell engraftment rates were significantly improved. Altogether, our customisable and clinically translatable hydrogel system provides a useful tool for developing organ-specific and effective therapies for regenerative medicine.