Beyond Matrigel: A novel hydrogel system designed to facilitate the transplantation of hPSC-derived cells and tissue

Matrigel is the most commonly used biomaterial for bioengineering tissues from hPSCs. However, its origins from mouse sarcoma come with significant drawbacks, including poor definability, batch-to-batch variability in composition, immunogenicity, and pathogen transmission, which hinder the clinical use of Matrigel and its derivatives in patients. Furthermore, there is a lack of clinically approved, synthetic alternatives. In addition, cross-linking reactions with synthetic reagents can be toxic in vivo and physically limit transferability into the patients.

The solution: The researchers performed a focused protein screen to identify key proteins found in the developing embryo. Having identified select laminins, they then biofabricated a hydrogel system based on human fibrin and human recombinant laminins (clinical grade is commercially available). The study reported that hPSC-derived cardiac, neural, and liver cells cultured in Alphagel (fibrin and Laminin 521) exhibited characteristics comparable to those cultured in Matrigel and, in some respects, better. The biocompatibility of Alphagel was validated in Black-6 immunocompetent mice. Importantly, when using the liver-optimised Hepatogel (composed of fibrin, Laminin 521, Laminin 411, and Laminin 111), researchers observed higher albumin secretion and improved retention of hPSC-derived hepatocytes at the site of transplantation compared with standard cell delivery. However, it was observed that the transplanted hPSC-derived hepatocytes were cleared after 1-2 weeks; this was attributed to residual immunity of the immunocompromised mouse model.

The future: Future research will focus on developing organ-optimized matrices to derive better end-target cells and tissues than generic matrices. The immunogenicity of hPSC-derived end-target cells and tissue remains a challenge for the field. However, with ongoing initiatives such as HLA biobanking and HLA suppression/silencing, clinically approved hPSCs can be used with this hydrogel system to bioengineer the desired cells and tissues needed for patients.

The impact: This work provides a novel hydrogel system that enables the bioengineering of tissues from clinically approved hPSCs for clinical use, overcoming the limitations of Matrigel and current synthetic matrices.

The research has been recently published in the online edition of Materials Futures, a prominent international journal in the field of interdisciplinary materials science research.

Reference: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 J. Rouhani, Yock Young Dan, Athina E. Markaki. A clinically defined and xeno-free hydrogel system for regenerative medicine[J]. Materials Futures. DOI: 10.1088/2752-5724/ae4e4d