Materials engineering for immunomodulation

Abstract

The engineering of materials that can modulate the immune system is an emerging field that is developing alongside immunology. For therapeutic ends such as vaccine development, materials are now being engineered to deliver antigens through specific intracellular pathways, allowing better control of the way in which antigens are presented to one of the key types of immune cell, T cells. Materials are also being designed as adjuvants, to mimic specific 'danger' signals in order to manipulate the resultant cytokine environment, which influences how antigens are interpreted by T cells. In addition to offering the potential for medical advances, immunomodulatory materials can form well-defined model systems, helping to provide new insight into basic immunobiology.The term 'immunobioengineering' is used to describe efforts by immunologists and engineers to design materials, delivery vehicles and molecules both to manipulate and to better understand the immune system. Examples are the engineering of material surfaces to induce or prevent complement activation, the engineering of adjuvants to activate the immune system, the engineering of antigen or adjuvant carriers for subunit vaccine delivery, and the engineering of microenvironments to determine the interaction kinetics of mature dendritic cells and naive T cells. These advances not only will contribute to prophylactic vaccine strategies for infectious diseases but also are likely to affect immunotherapeutics, particularly for cancer, and new approaches to prevent or treat allergies and autoimmune diseases. The field is rapidly evolving along with advances in our understanding of immunology and is also contributing to our knowledge of basic immunology.In this Review, we describe the current state of immunobioengineering as it intersects with the field of materials science, and we give a perspective on its current and future directions. We focus on materials for immunomodulation, particularly with respect to dendritic-cell modulation. We begin by providing a brief introduction to the targets for delivery: the types of cell that materials are being designed to target, the tissues in which those cells reside, the intracellular compartments within those cells, and the influence that delivery to those particular compartments has on immunological outcome. We then discuss the biomolecular payloads used to activate immune cells and the design of the materials used to deliver those 'danger' signals along with, in the context of vaccination, antigens. Finally, we highlight materials approaches that are being developed to explore basic immunological function, especially how dendritic cells and T cells interact. Tissue and cellular targetsAs the general goals of immunobioengineering are to probe and manipulate the immune system, we start with a general discussion of tissue, cellular and subcellular targets -what we want to target and why -to guide the design principles discussed below.The immune cells most frequently targeted include B cells, macrophages and dendritic cells, wh...

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