In vitro study of the host responses to model biomaterials via a fibroblast/macrophage co-culture system

Abstract

Surface properties are believed to play important roles in initial inflammatory and subsequent wound healing/fibrotic responses after implantation of biomaterials. To investigate the surface property effect in mediating these host responses, we used an in vitro fibroblast/macrophage co-culture model established with a cell migration chamber, and a series of self-assembling monolayers (SAMs) bearing different terminal groups as model surfaces to study the effect of surface properties on macrophage fusion, fibroblast attachment, spreading morphology, proliferation, outgrowth, as well as pro-(interleukin-6) and anti-(interleukin-10) inflammatory cytokine production, expression of ED-A fibronectin (FN) and alpha-smooth muscle actin (α-SMA). The obtained results show that the hydrophobic CH₃ surface caused high levels of inflammatory but low levels of wound healing/fibrotic responses, while the hydrophilic/anionic COOH surface resulted in both low levels of inflammatory and wound healing/fibrotic responses. Interestingly, the hydrophilic OH surface was found to possess a low potential of inducing inflammatory responses but high potential of inducing wound healing/fibrotic responses. These results reveal that the extent of inflammation and wound healing/fibrosis might not be always related in vitro. However, more important is the observation of the macrophage contributions in facilitating the wound healing and fibrotic responses by up-regulation of fibroblast outgrowth, cytokine production as well as ED-A FN and α-SMA expression. Overall, by linking the surface properties to cell activities with our established fibroblast/macrophage co-culture system, we could provide an useful model system for in vitro studies to design more biocompatible biomaterials for various biomedical and tissue engineering applications.