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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.

SUBMITTER: Gammon JM

PROVIDER: S-EPMC6384133 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Engineering Immune Tolerance with Biomaterials.

Gammon Joshua M JM Jewell Christopher M CM

Advanced healthcare materials 20190103 4

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 duri ...[more]

PMID: 30605264

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Project description:Coronary artery disease is a severe ischemic condition characterized by the reduction of blood flow in the arteries of the heart that results in the dysfunction and death of cardiac tissue. Despite research over several decades on how to reduce long-term complications and promote angiogenesis in the infarct, the medical field has yet to define effective treatments for inducing revascularization in the ischemic tissue. With this work, we have developed functional biomaterials for the controlled release of immunomodulatory cytokines to direct immune cell fate for controlling wound healing in the ischemic myocardium. The reparative effects of colony-stimulating factor (CSF-1), and anti-inflammatory interleukins 4/6/13 (IL4/6/13) have been evaluated in vitro and in a predictive in vivo model of ischemia (the skin flap model) to optimize a new immunomodulatory biomaterial that we use for treating infarcted rat hearts. Alginate hydrogels have been produced by internal gelation with calcium carbonate (CaCO3) as carriers for the immunomodulatory cues, and their stability, degradation, rheological properties and release kinetics have been evaluated in vitro. CD14 positive human peripheral blood monocytes treated with the immunomodulatory biomaterials show polarization into pro-healing macrophage phenotypes. Unloaded and CSF-1/IL4 loaded alginate gel formulations have been implanted in skin flap ischemic wounds to test the safety and efficacy of the delivery system in vivo. Faster wound healing is observed with the new therapeutic treatment, compared to the wounds treated with the unloaded controls at day 14. The optimized therapy has been evaluated in a rat model of myocardial infarct (ischemia/reperfusion). Macrophage polarization toward healing phenotypes and global cardiac function measured with echocardiography and immunohistochemistry at 4 and 15 days demonstrate the therapeutic potential of the proposed immunomodulatory treatment in a clinically relevant infarct model.

Dataset Information

Engineering Immune Tolerance with Biomaterials.

Publications

Engineering Immune Tolerance with Biomaterials.

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