A clinically defined and xeno-free hydrogel system for regenerative medicine
Authors list
John Ong George Gibbons Yee Siang Lim Lei Zhou Junzhe Zhao Alexander W Justin Federico Cammarata Ravisankar Rajarethinam Colleen Limegrover Sanjay Sinha Andras Lakatos Foad Rouhani Yock Young Dan Athina E MarkakiAbstract
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, xenogenic biomaterials are poorly defined, and synthetic biomaterials remain underdeveloped and understudied, hindering regulatory approval for clinical use and preventing the translation of lab-grown therapies. Here, we describe a protein screen-based hydrogel system biofabricated from physiologically relevant 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 shown to be biocompatible and biodegradable in vivo. Further, upon adding select proteins from maturing human foetal liver to Alphagel, we show that the resulting hydrogel (termed ‘Hepatogel’) enhances the differentiation of hPSC-derived hepatocytes (H-iHeps) compared with Matrigel. Importantly, when injected into mice livers, Hepatogel significantly improves the retention of H-iHeps compared to standard aqueous cell injections. Altogether, our results provide proof of concept that customisable, organ-specific hydrogel systems are a valuable tool for developing clinically translatable therapies in regenerative medicine and tissue engineering.
Journal details
Journal
Materials Futures
Volume
5
Issue number
3
Pages
035401
Available online
Publication date
Full text links
Publisher website (DOI)
10.1088/2752-5724/ae4e4d
Europe PubMed Central
42089082
Pubmed
42089082
Keywords
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