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Three-dimensional (3D) cell cultures offer an unparalleled platform to recreate spatial arrangements of cells  in vitro . 3D cell culture systems have gained increasing interest due to their evident advantages in providing more physiologically relevant information and more predictive data compared to their two-dimensional (2D) counterpart. Design and well-established fabrication of organoids (a particular type of 3D cell culture system) are nowadays considered a pivotal achievement for their ability to replicate  in vitro  cytoarchitecture and the functionalities of an organ. In this condition, pluripotent stem cells self-organize into 3D structures mimicking the  in vivo  microenvironments, architectures and multi-lineage differentiation. Scaffolds are key supporting elements in these 3D constructs, and Matrigel is the most commonly used matrix despite its relevant translation limitations including animal-derived sources, non-defined composition, batch-to-batch variability and poorly tailorable properties. Alternatively, 3D synthetic scaffolds, including self-assembling peptides, show promising biocompatibility and biomimetic properties, and can be tailored on specific target tissue/cells. In this review, we discuss the recent advances on 3D cell culture systems and organoids, promising tools for tissue engineering and regenerative medicine applications. For this purpose, we will describe the current state-of-the-art on 3D cell culture systems and organoids based on currently available synthetic-based biomaterials (including tailored self-assembling peptides) either tested in  in vivo  animal models or developed  in vitro  with potential application in the field of tissue engineering, with the aim to inspire researchers to take on such promising platforms for clinical applications in the near future.

Synthetic scaffolds for 3D cell cultures and organoids: applications in regenerative medicine