Monocyte/lymphocyte interactions and the foreign body response: In vitro effects of biomaterial surface chemistry

Abstract

To determine the effect of biomaterial surface chemistry on leukocyte interaction and activity at the material/tissue interface, human peripheral blood monocytes and lymphocytes were cultured on a series of poly(ethylene terephthalate) (PET)-based biomaterials. Both monocytes and lymphocytes were isolated from whole human blood and separated by a nonadherent density centrifugation method before being plated on PET disks, surface modified by photograft copolymerization to yield hydrophobic, hydrophilic, anionic, and cationic surface properties. Monocytes and lymphocytes were cultured separately, to elicit baseline levels of activity, in direct coculture, to promote direct cell surface interactions, or in an indirect coculture system with both cell types separated by a -0.02-microm Transwell apparatus, to promote indirect paracrine interactions. Monocyte adhesion, macrophage fusion, and lymphocyte proliferation were measured on days 3, 7, 10, and 14 of culture. Results demonstrated that the presence of monocytes increased the activity of cocultured lymphocytes at the biomaterial/tissue interface, while the corresponding presence of lymphocytes increased the activation and fusion of indirectly cocultured monocytes. Biomaterial surface chemistry was also found to have a significant effect on monocyte adhesion and activation, and lymphocyte activity. Hydrophilic surfaces significantly inhibited both initial and longterm monocyte adhesion, and inhibited lymphocyte proliferation at longer time points. Anionic and cationic surfaces both exhibited mild inhibition of monocyte adhesion at prolonged time points and increased levels of macrophage fusion, while cationic surfaces decreased levels of lymphocyte proliferation and inhibited monocyte activity. These results elucidate the complex role of juxtacrine and paracrine interactions between monocytes and lymphocytes in the foreign body response, as well as promote the consideration of hydrophilic surfaces in future designs of implantable biomedical devices and prostheses.