Hitchhiking Delivery Systems: Therapeutic Hydrogels as Advanced Tools for Immunomodulatory Applications

Recent conceptual and technological advances have underlined the importance of the human immune system in responding to dangerous threats, restoring tissue homeostasis, and mounting immunological memory. Our in-depth understanding of the immune system has also been driving the blossoming development of biocompatible macroscale biomaterials designed to prevent and treat various immune-related disorders. Hydrogels, a class of water-swollen networks with extracellular matrix-mimic characteristics, have served as promising biomaterials for guiding the immune system in biological milieus. The convergence of hydrogels and immunotherapy represents an interdisciplinary field that has driven significant advancements in both materials science and immunology. In this review, we first introduce the immune system to establish a fundamental understanding of its structure and function and then elaborate on the rational principles of hydrogel design, with a focus on passive and active mechanisms. Next, we explore a range of "hitchhiking" strategies employed to develop immunomodulatory hydrogels. State-of-the-art strategies regarding recent progress in immunomodulatory hydrogels for defense against pathological abnormalities are systematically summarized. Furthermore, the key scientific issues encountered and the hurdles faced in the development of immunomodulatory hydrogels are highlighted, aiming to show a full picture of immunomodulatory hydrogels for optimized therapeutic efficacy.