Functionally graded biomaterials for use as model systems and replacement tissues.

The heterogeneity of native tissues requires complex materials to provide suitable substitutes for model systems and replacement tissues. Functionally graded materials have the potential to address this challenge by mimicking the gradients in heterogeneous tissues such as porosity, mineralization, and fiber alignment to influence strength, ductility, and cell signaling. Advancements in microfluidics, electrospinning, and 3D printing enable the creation of increasingly complex gradient materials that further our understanding of physiological gradients. The combination of these methods enables rapid prototyping of constructs with high spatial resolution. However, successful translation of these gradients requires both spatial and temporal presentation of cues to model the complexity of native tissues that few materials have demonstrated. This review highlights recent strategies to engineer functionally graded materials for the modeling and repair of heterogeneous tissues, together with a description of how cells interact with various gradients.