Bioinformatics-based selection of a model cell type for invitro biomaterial testing

Biomaterial properties can be tailored for specific applications via systematic and high-throughput screening of biomaterial-cell interactions. However, progress in material development is often hampered by the lack of adequate invitro testing methods, frequently due to incomplete understanding of involved invivo mechanisms. In line with drug discovery in pharmacology, a crucial step in assay development for biomaterial screening is the identification of a target to direct the screen against. Herein, the cell type to be used for screening is of essential importance and has to be carefully chosen. So far, few attention has been put on selecting a cell type specifically suitable for invitro testing of materials for predefined applications. In this manuscript, we describe an approach to define a suitable cell type for screening assays, for which biomaterials for bone regeneration served as example. Using a bioinformatics methodology, different cell lines are compared on three well-characterized model materials. The transcriptional profiles of MG63, iMSC, SV-HFO, hPPCT, hBPCT and SW480 cells are assessed on 3 calcium phosphate-based materials to evaluate their potential application in a screening assay. We show that MG63 is the most suitable cell line to evaluate biomaterials for bone regeneration applications, evidenced by their robust gene expression differences between the 3 model materials. The gene expression differences between the cell lines were assessed based on the overall gene expression profiles and specific subsets of genes and pathways related to osteogenesis and bone homeostasis in response to the 3 materials tested. In the next phase, this cell line will be used to identify a target correlating with invivo biomaterial performance and henceforth to develop an invitro screening system.