IL-4 Release from a Biomimetic Scaffold for the Temporally Controlled Modulation of Macrophage Response

The interaction of immune cells with biomaterials has been identified as a possible predictor of either the success or the failure of the implant. Among immune cells, macrophages have been found to contribute to both of these possible scenarios, based on their polarization profile. This proof-of-concept study aimed to investigate if it was possible to affect the response of macrophages to biomaterials, by the release of anti-inflammatory mediators. Towards this end, a collagen scaffold, integrated with poly(lactic-co-glycolic acid)-multistage silicon particles (MSV) composite microspheres (PLGA-MSV) releasing IL-4 was developed (PLGA-MSV/IL-4). Macrophages' response to the scaffold was evaluated, both in vitro with rat bone-marrow derived macrophages, and in vivo in a rat subcutaneous pouch model. In vitro experiments revealed an overexpression of anti-inflammatory associated genes (Il-10, Mrc1, Arg1) at as soon as 48 h. The analysis of the cells that infiltrated the scaffold, revealed a prevalence of CD206(+) macrophages at 24 h. Our strategy demonstrated that it is possible to tune the in vivo early response to biomaterials by the release of an anti-inflammatory cytokine, and that could contribute to accelerate the resolution of the inflammatory phase, benefiting a vast range of tissue engineering applications.