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Background

Three-dimensional (3D) stem cell culture systems play an essential role in tissue engineering and regenerative medicine by recreating the cellular interactions and tissue architecture found in vivo. However, many existing culture systems rely on Matrigel, a mouse sarcoma-derived extracellular matrix that is poorly defined, exhibits batch-to-batch variability, and presents significant barriers to clinical translation. Although synthetic biomaterials have emerged as potential alternatives, many lack the biological signals required to effectively support human pluripotent stem cell (hPSC) culture and differentiation. Developing clinically defined extracellular matrices that combine physiological relevance with translational potential therefore remains a major challenge.

Biolaminin® contribution

To develop a clinically compatible alternative to conventional extracellular matrices, Ong et al. designed a modular hydrogel platform using physiologically relevant human proteins. Following a focused protein screen, Biolaminin 521 was identified as the most effective matrix protein for supporting long-term hPSC pluripotency. The researchers combined Biolaminin 521 with human fibrin to create Alphagel, a defined hydrogel designed to support 3D stem cell culture while mimicking key features of the embryonic extracellular matrix.

Alphagel supported long-term hPSC expansion while maintaining pluripotency and enabling directed differentiation into neural, cardiac, and hepatic tissues using established differentiation protocols. The hydrogel also demonstrated biocompatibility and biodegradability in vivo, supporting its potential as a clinically compatible biomaterial for regenerative medicine.

Building on this platform, the researchers developed an organ-specific hydrogel termed Hepatogel by incorporating additional liver-associated Biolaminin substrates, including Biolaminin 411 and Biolaminin 111, alongside Biolaminin 521. Compared with Matrigel, Hepatogel promoted more mature hepatic characteristics, including increased albumin secretion, enhanced CYP3A4 activity, and reduced expression of immature fetal liver markers. When transplanted into mouse livers, Hepatogel also significantly improved the retention of hPSC-derived hepatocytes compared with conventional aqueous cell delivery.

Future outlook

Rather than relying on generic extracellular matrices, this study highlights the potential of developing tissue-specific, clinically defined hydrogel systems using recombinant human extracellular matrix proteins. The modular approach allowed the researchers to support long-term stem cell culture and then adapt the extracellular environment toward a tissue-specific application. The authors suggest that customizable hydrogels such as Alphagel and Hepatogel could provide valuable platforms for regenerative medicine and support the clinical translation of stem cell-based therapies.

Cited study: Ong J, Gibbons G, Lim YS, et al. A clinically defined and xeno-free hydrogel system for regenerative medicine. Materials Futures. 2026;5(3):035401. https://doi.org/10.1088/2752-5724/ae4e4d

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