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

Biofabricated 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 and non-clinically approved synthetic biomaterials greatly hinder the translation of lab-grown therapies into clinical practice. Here, we describe a protein screen-based hydrogel system biofabricated from widely available clinical-grade human components. We show that “Alphagel”, a base hydrogel comprising human embryonic matrices, supports the trilineage differentiation of hPSCs into neural, cardiac, and liver tissue. Alphagel is also biocompatible and biodegradable in vivo . Further, by adding select proteins found in the maturing human foetal liver, the resulting hydrogel (termed “Hepatogel”) enhances the differentiation of hPSC-derived hepatocytes (H-iHeps) compared to Matrigel, a xenogenic and commonly used hydrogel that is prohibited in clinical use. Importantly, when injected into mice livers, Hepatogel significantly improves the engraftment rates of H-iHeps compared to standard cell injections. Altogether, our results provide proof of concept that this customisable hydrogel system is a useful tool for developing organ-specific and clinically translatable therapies for regenerative medicine and tissue engineering.