ABSTRACT
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.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
↵* denotes senior authorship.
1. Revision of all main figures and supplementary data. 2. Edits to the main text (all parts). 3. Inclusion of more data.