Biomaterials-mediated ligation of immune cell surface receptors for immunoengineering

A wide variety of cell surface receptors found on immune cells are essential to the body's immunological defense mechanisms. Cell surface receptors enable immune cells to sense extracellular stimuli and identify pathogens, transmitting activating or inhibitory signals that regulate the immune cell state and coordinate immunological responses. These receptors can dynamically aggregate or disperse due to the fluidity of the cell membrane, particularly during interactions between cells or between cells and pathogens. At the contact surface, cell surface receptors form microclusters, facilitating the recruitment and amplification of downstream signals. The strength of the immune signal is influenced by both the quantity and the specific types of participating receptors. Generally, receptor cross-linking, meaning multivalent ligation of receptors on one cell, leads to greater interface connectivity and more robust signaling. However, intercellular interactions are often spatially restricted by other cellular structures. Therefore, it is essential to comprehend these receptors' features for developing effective immunoengineering approaches. Biomaterials can stimulate and simulate interactions between immune cells and their targets. Biomaterials can activate immune cells to act against pathogenic organisms or cancer cells, thereby offering a valuable immunoengineering toolset for vaccination and immunotherapy. In this review, we systematically summarize biomaterial-based immunoengineering strategies that consider the biology of diverse immune cell surface receptors and the structural attributes of pathogens. By combining this knowledge, we aim to advance the development of rational and effective approaches for immune modulation and therapeutic interventions.