Abstract
The immune system is the key target for vaccines and immunotherapeutic approaches aimed at blunting infectious diseases, cancer, autoimmunity, and implant rejection. However, systemwide immunomodulation is undesirable due to the severe side effects that typically accompany such strategies. In order to circumvent these undesired, harmful effects, scientists have turned to tailorable biomaterials that can achieve localized, potent release of immune-modulating agents. Specifically, "stimuli-responsive" biomaterials hold a strong promise for delivery of immunotherapeutic agents to the disease site or disease-relevant tissues with high spatial and temporal accuracy. This review provides an overview of stimuli-responsive biomaterials used for targeted immunomodulation. Stimuli-responsive or "environmentally responsive" materials are customized to specifically react to changes in pH, temperature, enzymes, redox environment, photo-stimulation, molecule-binding, magnetic fields, ultrasound-stimulation, and electric fields. Moreover, the latest generation of this class of materials incorporates elements that allow for response to multiple stimuli. These developments, and other stimuli-responsive materials that are on the horizon, are discussed in the context of controlling immune responses.