| The foreign body response (FBR) comprises a general, ubiquitous host tissue-based reaction to implanted materials, often resulting in device failure due to an aggressive host attack by immune cells, degrading materials, providing a toxic environment to nearby cells and stimulating a fibroproliferative response often resulting in subsequent encapsulation. The increasing use of implantable materials and devices necessitates an increased understanding of the body's response to implanted materials, and a better ability to screen the materials' behavior in vitro for predicting in vivo performance and designing more compatible materials. This work has focused on gaining a greater understanding of the in vitro behavior of both primary and secondary cells used to study the FBR and their respective ability to represent in vivo responses. We found that macrophages and fibroblasts in co-culture yielded more representative responses of in vivo signaling, than during mono-culture. We also identified fibroblasts that were capable of forming multinucleate giant cells in culture, and determined in vitro conditions in which macrophages senesce. Throughout these studies, we identified variations between primary- and secondary-derived macrophages and fibroblasts, and conclude that secondary cells in culture often have unrepresentative behavior of in vivo responses, and their use should be substantiated by primary-sourced cells. We further identified unique cell behavior in primary cultures that must be validated against in vivo cellular responses. |
