Rational design of hydrogels for immunomodulation

The immune system protects organisms against endogenous and exogenous harm and plays a key role in tissue development, repair and regeneration. Traditional immunomodulatory biologics exhibit limitations including degradation by enzymes, short half-life and lack of targeting ability. Encapsulating or binding these biologics within biomaterials is an effective way to address these problems. Hydrogels are promising immunomodulatory materials because of their prominent biocompatibility, tuneability and versatility. However, to take advantage of these opportunities and optimize material performance, it is important to more specifically elucidate, and leverage on, how hydrogels affect and control the immune response. Here, we summarize how key physical and chemical properties of hydrogels affect the immune response. We first provide an overview of underlying steps of the host immune response upon exposure to biomaterials. Then, we discuss recent advances in immunomodulatory strategies where hydrogels play a key role through (i) physical properties including dimensionality, stiffness, porosity and topography; (ii) chemical properties including wettability, electric property and molecular presentation;and (iii) the delivery of bioactive molecules via chemical or physical cues. Thus, this review aims to build a conceptual and practical toolkit for the design of immune-instructive hydrogels capable of modulating the host immune response.