Cardiac amyloidosis (CA), once thought to be a rare disease, is increasingly recognized due to enhanced clinical awareness and better diagnostic imaging. CA is becoming of heightened interest to the cardiology community given more effective treatment strategies for light chain amyloidosis (AL), as well as emerging therapies for transthyretin amyloidosis (ATTR). Furthermore, reversing amyloid deposition in affected organs using monoclonal antibodies is actively being tested in clinical trials. A high index of suspicion and a systematic approach to the diagnosis of CA can lead to referral to a center of expertise for timely treatment.

During tissue morphogenesis and homeostasis, cells experience various signals in their environments, including gradients of physical and chemical cues. Spatial and temporal gradients regulate various cell behaviours such as proliferation, migration, and differentiation during development, inflammation, wound healing, and cancer. One of the goals of functional tissue engineering is to create microenvironments that mimic the cellular and tissue complexity found in vivo by incorporating physical, chemical, temporal, and spatial gradients within engineered three-dimensional (3D) scaffolds. Hydrogels are ideal materials for 3D tissue scaffolds that mimic the extracellular matrix (ECM). Various techniques from material science, microscale engineering, and microfluidics are used to synthesise biomimetic hydrogels with encapsulated cells and tailored microenvironments. In particular, a host of methods exist to incorporate micrometer to centimetre scale chemical and physical gradients within hydrogels to mimic the cellular cues found in vivo. In this review, we draw on specific biological examples to motivate hydrogel gradients as tools for studying cell–material interactions. We provide a brief overview of techniques to generate gradient hydrogels and showcase their use to study particular cell behaviours in two-dimensional (2D) and 3D environments. We conclude by summarizing the current and future trends in gradient hydrogels and cell–material interactions in context with the long-term goals of tissue engineering.