Macrophage Immunomodulation Through New Polymers that Recapitulate Functional Effects of Itaconate as a Power House of Innate Immunity

Itaconate (ITA) is an emerging powerhouse of innate immunity with therapeutic potential that is limited in its ability to be administered in a soluble form. A library of polyester materials that incorporate ITA into polymer backbones resulting in materials with inherent immunoregulatory behavior is developed. Harnessing hydrolytic degradation release from polyester backbones, ITA polymers result in the mechanism specific immunoregulatory properties on macrophage polarization in vitro. In a functional assay, the polymer-released ITA inhibits bacterial growth on acetate. Translation to an in vivo model of biomaterial associated inflammation, intraperitoneal injection of ITA polymers demonstrate a rapid resolution of inflammation in comparison to a control polymer silicone, demonstrating the value of sustained biomimetic presentation of ITA.

Automated summary

ITA polymers, by leveraging hydrolytic degradation to release ITA, exhibit specific immunoregulatory properties on macrophage polarization in vitro and inhibit bacterial growth on acetate. In an in vivo model of biomaterial associated inflammation, intraperitoneal injection of ITA polymers leads to rapid resolution of inflammation compared to a control polymer silicone, highlighting the significance of sustained biomimetic presentation of ITA.