Hydrogels for Engineering the Immune System

Abstract

Human immune system has evolved as one of the most powerful defense systems to protect against invading pathogens and mutated cells. However, when persistent immune suppression or activation occurs, it can lead to adverse, chronic physiological effects including cancer and arthritis. Hydrogels are soft materials that can be engineered to modulate immune responses through controlled biomolecule release/adsorption, regeneration of lymphoid tissues, and enhanced antigen presentations. This is achieved by programming hydrogels to exhibit optimal properties such as porosity, biodegradability, and biocompatibility to interface seamlessly with the immune system. Herein, recent innovations and future challenges are described using programmable hydrogels to regenerate the lymphatic system, modulate inflammation, and enhance cancer immunotherapy. Key properties of hydrogels are also highlighted for engineering the immune system and techniques to characterize these properties.

Functional Hydrogels for Treatment of Chronic Wounds

“…For example, a high glucose level creates an acidic environment in diabetic foot ulcers. A hybrid hydrogel (Gel) composed of N-carboxyethyl CS (N-CS), HA-aldehyde (HA-ALD), and adipic acid dihydrazide (ADH) was developed by a pH-responsive bond between acylhydrazone and imine [ 130 ]. Insulin was incorporated into the Gel (Gel+In) to be released upon elevated acidity in the wound environment ( Figure 3 ).…”

Integrative lymph node-mimicking models created with biomaterials and computational tools to study the immune system

“…Another advantage of a biomaterial model is that, through tuning macromolecular chemical features and material physical properties, the matrix profile can be programmed to desired properties [ 155 , 156 ]. This is useful for experiments which require specific tissue features.…”

“…This findings suggest a possibility of connecting implanted or grafted lymphoid organs onto existing LV network as a form of therapy. Additionally, to realize regeneration of LNs and ambient LVs, some hydrogels have been developed to understand critical factors affecting LN regeneration and this has been reviewed elsewhere [ 156 ].…”

Intelligent hydrogels and their biomedical applications

“…161,162 Smart biomaterials are also engineered to modulate the host immune system to avoid negative responses. 161 In severe cases, the graft is rejected by producing inflammation and aggregation of collagen fibres over the implants causing inflammation by lowering the efficacy of the implants. 163 Vast knowledge of innate immunogenicity will help researchers figure out how to control and re-program immunity mechanisms, which is crucial for creating next-generation vaccines and immunotherapeutic materials.…”