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Synthetic alternatives to Matrigel

Abstract

Matrigel, a basement-membrane matrix extracted from Engelbreth–Holm–Swarm mouse sarcomas, has been used for more than four decades for a myriad of cell-culture applications. However, Matrigel is limited in its applicability to cellular biology, therapeutic-cell manufacturing and drug discovery, owing to its complex, ill-defined and variable composition. Variations in the mechanical and biochemical properties within a single batch of Matrigel — and between batches — have led to uncertainty in cell-culture experiments and a lack of reproducibility. Moreover, Matrigel is not conducive to physical or biochemical manipulation, making it difficult to fine-tune the matrix to promote intended cell behaviours and achieve specific biological outcomes. Recent advances in synthetic scaffolds have led to the development of xenogenic-free, chemically defined, highly tunable and reproducible alternatives. In this Review, we assess the applications of Matrigel in cell culture, regenerative medicine and organoid assembly, detailing the limitations of Matrigel and highlighting synthetic-scaffold alternatives that have shown equivalent or superior results. Additionally, we discuss the hurdles that are limiting a full transition from Matrigel to synthetic scaffolds and provide a brief perspective on the future directions of synthetic scaffolds for cell-culture applications.

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Fig. 1: Comparison of Matrigel and synthetic scaffolds.
Fig. 2: Advantages of synthetic scaffolds over Matrigel for cell culture, tissue engineering and organoid formation.
Fig. 3: Comparison of Matrigel and synthetic scaffolds for stem-cell differentiation and tissue engineering.
Fig. 4: Comparison of Matrigel and synthetic scaffolds for organoid assembly and preclinical tissue models.

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Acknowledgements

This research was funded by the US Environmental Protection Agency (STAR grant no. 83573701), the US National Institutes of Health (award nos. 1U01TR002383, R01HL093282 and 1R01NS109427) and the US National Science Foundation (award nos. EEC1648035 and DMR 170179). E.A.A. acknowledges funding by the US National Institutes of Health (T32HL110853).

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Aisenbrey, E.A., Murphy, W.L. Synthetic alternatives to Matrigel. Nat Rev Mater 5, 539–551 (2020). https://doi.org/10.1038/s41578-020-0199-8

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