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

Bio-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 biocompatible in 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.