Material surface chemistry influences the differentiation of human macrophages and their degradative and inflammatory response

Numerous medical devices are comprised partially or completely of polyurethane (PU) materials, used as a result of their flexible, segmented structure, tensile strength and relative biocompatibility. The polycarbonate-based PU (PCNU), has been incorporated in the use of many devices as a result of their enhanced resistance to oxidative and hydrolytic degradation. Although relatively biocompatible, these materials still are sensitive to hydrolytic degradation and attachment of inflammatory cell types. Monocyte-derived macrophages (MDM) have been found as the primary cell type to adhere and remain at the cell-material interface of long-term implant devices. Although efforts are continually targeting the modification and design of improved PCNUs, cellular responses and MDM-mediated degradation of PCNU materials are not completely understood. The participation of inflammatory phospholipase A2 (PLA2) pathways were investigated for their participation in mechanisms leading to PCNU degradation by macrophages. Moreover, the influence of these materials on the stimulation of PLA2 pathways and the hydrolysis product, arachidonic acid, was further explored. Fully differentiated human MDM have been typically used for subsequent studies evaluating PCNU degradation, however, studies here were the first to examine the morphology and function of monocytes differentiating along the macrophage lineage under the influence of altered material surface chemistry. Finally, the tools of proteomics were employed here for the first time in the investigation of material surface influence on both the differentiation of MDM and in assessments of degradative capacity of MDM adherent to PCNU. The results presented here in this collection of manuscripts has provided evidence that PCNU materials induce changes in expression and activation of PLA2 enzymes, that in turn may have indirect participation in the mechanisms of degradation. In addition, the material surface upon which MDM differentiate, greatly influences not only cellular morphology but also function in terms of degradative capacity and cytoskeletal protein expression and rearrangement of actin-based structures. Proteomics techniques have identified proteins that may link contributors to the multi-factorial foreign body response to PCNU materials in vitro, involving PLA2 and the structural proteins actin, vinculin and vimentin that would ultimately lead to the release of hydrolytic enzymes that contribute to material breakdown. The understanding of these cellular responses and mechanisms of material destruction is an essential base of knowledge required for efficient design of medical implant materials for their intended use.