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.

Matrigel 是一种从 Engelbreth-Holm-Swarm 小鼠肉瘤中提取的基底膜基质，四十多年来一直用于各种细胞培养应用。然而，由于其复杂、不明确且可变的成分，Matrigel 在细胞生物学、治疗细胞制造和药物发现中的适用性受到限制。单批次基质胶内以及批次之间的机械和生化特性的变化导致细胞培养实验的不确定性和重复性的缺乏。此外，基质胶不利于物理或生化操作，因此难以微调基质以促进预期的细胞行为并实现特定的生物学结果。合成支架的最新进展导致了无异种、化学成分明确、高度可调和可重复替代品的开发。在这篇综述中，我们评估了基质胶在细胞培养、再生医学和类器官组装中的应用，详细介绍了基质胶的局限性，并重点介绍了已显示出同等或更好结果的合成支架替代品。此外，我们还讨论了限制从基质胶全面过渡到合成支架的障碍，并对细胞培养应用合成支架的未来方向提供了简要的展望。