Macroscale biomaterials strategies for local immunomodulation

The immune system plays key roles in tissue homeostatic and disease processes, and manipulation of innate and adaptive immune responses is of great promise for a wide array of human afflictions, including tissue repair and regeneration, cancer, autoimmune syndromes and chronic infections. Systemic approaches to immunomodulation can correct both hypoactive and hyperactive immunity; however, they typically interfere with the homeostatic role of the immune system at nontarget sites, are associated with lifelong comorbidities and potentially fatal side effects. To overcome these issues, macroscale delivery devices can be placed at sites of interest in the body and engineered to locally control the pharmacokinetics of immunomodulatory agents, including small molecules, macromolecules and cells. In this Review, we outline important cellular targets of immunotherapies in tissue repair and cancer and discuss how macroscale delivery devices can be designed to modulate the release of molecular factors to impact immune cell behaviour, control the fate of delivered therapeutic cells or directly recruit, house and modulate host cells for immunotherapy applications.