A three-dimensional in vitro model to quantify inflammatory response to biomaterials

In vivo models are the gold standard for predicting the clinical biomaterial-host response due to the scarcity of in vitro model systems that recapitulate physiological settings. However, the simplicity, control and relatively lower cost of in vitro models make them more appropriate to quantify the contribution by each cell, material and molecule within the healing environment. In this study, human fibroblasts and monocytes are co-cultured in a three-dimensional (3-D) tissue model to study foreign body response by observing morphological changes and monitoring inflammatory cytokine production with multiplex quantitative protein analysis. While control monocultures of either cell type alone produced low levels of cytokines, their interactions in co-culture led to morphological changes and increased release of inflammatory cytokines. When challenged with a well-characterized biopolymer, poly(lactic-co-glycolic acid), the co-cultured human cells secreted elevated levels of IL-1β, IL-6, GM-CSF and TNF-α. This 3-D in vitro co-culture model may serve as a building block towards a versatile platform to study mechanisms of material-host interactions by co-culturing cells with engineered phenotypes and reporter systems, or predict patient-specific biocompatibility by using the individual patients' cells.