Bioactive Materials Facilitating Targeted Local Modulation of Inflammation

• Electrospun polycaprolactone surfaces were immobilized with a monolayer of the cytokine interleukin-4 to create a “bioactive” immunomodulatory surface capable of influencing the phenotype of macrophages responding to the material surface in vivo. • Bioactive surfaces, evaluated in vitro by using macrophage culture, exhibited upregulation of anti-inflammatory M2 genes and facilitated morphological changes consistent with macrophage activation. • As a subcutaneous implant in a 14-day model of acute inflammation, bioactive surfaces polarized macrophages from their M1 pro-inflammatory to M2 anti-inflammatory phenotypes, leading to a significant reduction in the local immune-driven foreign body response. • As vascular grafts in a 28-day mouse carotid interposition model, bioactive grafts maintained their macrophage polarization and immunomodulatory effects, significantly reducing adventitial encapsulation and neointimal hyperplasia development. Cardiovascular disease is an inflammatory disorder that may benefit from appropriate modulation of inflammation. Systemic treatments lower cardiac events but have serious adverse effects. Localized modulation of inflammation in current standard treatments such as bypass grafting may more effectively treat CAD. The present study investigated a bioactive vascular graft coated with the macrophage polarizing cytokine interleukin-4. These grafts repolarize macrophages to anti-inflammatory phenotypes, leading to modulation of the pro-inflammatory microenvironment and ultimately to a reduction of foreign body encapsulation and inhibition of neointimal hyperplasia development. These resulting functional improvements have significant implications for the next generation of synthetic vascular grafts.