Engineering Immune Tolerance with Biomaterials

Abstract

Autoimmune diseases, rejection of transplanted organs and grafts, chronic inflammatory diseases, and immune‐mediated rejection of biologic drugs impact a large number of people across the globe. New understanding of immune function is revealing exciting opportunities to help tackle these challenges by harnessing—or correcting—the specificity of immune function. However, realizing this potential requires precision control over the interaction between regulatory immune cues, antigens attacked during inflammation, and the tissues where these processes occur. Engineered materials—such as polymeric and lipid particles, scaffolds, and inorganic materials—offer powerful features that can help to selectively regulate immune function during disease without compromising healthy immune functions. This review highlights some of the exciting developments to leverage biomaterials as carriers, depots, scaffolds—and even as agents with intrinsic immunomodulatory features—to promote immunological tolerance.

Role of lymph node stroma and microenvironment in T cell tolerance

“…Various engineered biomaterials are employed based on their material structures (Table 3), and several recent reviews discuss these approaches. [120][121][122][123] Many bioengineering approaches have been explored to create vaccines and induce positive immune responses against infectious or tumor antigens. The materials have been delivered systemically or locally, with the assumption they will be presented systemically or by local secondary lymphoid organs.…”

Biomaterials as Tools to Decode Immunity

“…These immune‐modifying therapies have dramatically improved outcomes for a subset of patients with certain types of cancer by limiting the ability of the cancer to suppress the immune response and by generating large numbers of T cells that can more specifically target cancerous cells. Even more broadly, increasing immunological knowledge has enabled new types of immunotherapies for diseases involving excess inflammation, such as allergies or autoimmunity . Autoimmune diseases occur when the body's immune system malfunctions and attacks self‐tissue, as occurs in multiple sclerosis (MS).…”

“…Some key examples include measuring specific immune functions, while using materials to vary the signals loaded in a material, the relative concentrations of these signals, the duration of signal presentation (e.g., through controlled release), or the direction of signals to specific immune cells or intracellular locations . The physicochemical properties of materials—such as size, shape, surface charge, hydrophobicity, and stiffness can also be used as levers to control the interactions just mentioned . Together, these opportunities can be exploited to decipher how multiple immune signals are integrated, to determine how the kinetic availability of immune signals impacts vaccines or immunotherapy outcomes, and to engineer systems to evaluate the mechanism of action of immune signals and cues.…”

“…In MS, for example, myelin lining the central nervous system is mistakenly attacked. Many materials‐based approaches have revealed nano‐ or microparticles containing myelin or other self‐antigens ameliorated disease symptoms in mouse models of MS, diabetes, or other diseases . These discoveries reveal self‐antigen alone can drive not only inflammation, but also tolerance to self‐antigens.…”

De novo design of functional zwitterionic biomimetic material for immunomodulation

“…There have been increasing interests in using biomaterials to actively regulate the immune system (13)(14)(15)(16). Currently, unwanted activation of the immune system represents a serious threat to human health as it causes various diseases (e.g., autoimmune diseases, allergies, and chronic inflammatory diseases) and compromises the safety and efficacy of implants and biopharmaceuticals (17,18).…”