Cell Adhesion by Design: Engineering Tissue Culture Scaffolds With Adhesion Cues

ABSTRACT In scaffold‐based tissue engineering, the matrix should provide adequate adhesion cues for cell attachment, spreading, and function. Given the multitude of adhesion receptors and the diversity of scaffolds, there are many approaches to render scaffolds adhesive, even though they are not all equivalent. The objective of this Perspective is to provide the rationale underlying scaffold design strategies, emphasizing how the adhesive cues and their presentation can be matched with cell functionality as well as with the level of complexity of engineered tissues. We focus on engineering 3D scaffolds and how the distribution of adhesive cues can be integrated in the scaffold fabrication process. We compare the use of full‐length ECM proteins and synthetic peptides, self‐assembled fibrillar networks, as well as cell‐deposited ECM. Finally, we describe the supramolecular and biochemical tools that enable adhesive ligand presentation on polymer backbones and how these approaches can be leveraged to rationally design adhesion in increasingly complex tissue constructs.