Strain-dependent modulation of macrophage polarization within scaffolds

Abstract

Implanted synthetic substrates for the regeneration of cardiovascular tissues are exposed to mechanical forces that induce local deformation. Circulating inflammatory cells, actively participating in the healing process, will be subjected to strain once recruited. We investigated the effect of deformation on human peripheral blood mononuclear cells (hPBMCs) adherent onto a scaffold, with respect to macrophage polarization towards an inflammatory (M1) and reparative (M2) phenotype and to early tissue formation. HPBMCs were seeded onto poly-ε-caprolactone bisurea strips and subjected to 0%, 7% and 12% cyclic strain for up to one week. After 1 day, cells subjected to 7% deformation showed upregulated expression of pro and anti-inflammatory chemokines, such as MCP-1 and IL10. Immunostaining revealed presence of inflammatory macrophages in all groups, while immunoregulatory macrophages were detected mainly in the 0 and 7% groups and increased significantly over time. Biochemical assays indicated deposition of sulphated glycosaminoglycans and collagen after 7 days in both strained and unstrained samples. These results suggest that 7% cyclic strain applied to hPBMCs adherent on a scaffold modulates their polarization towards reparative macrophages and allows for early synthesis of extracellular matrix components, required to promote further cell adhesion and proliferation and to bind immunoregulatory cytokines.