Molecular and Cellular Dynamics of the Healing Response Associated with Implanted Expanded Polytetrafluoroethylene

Abstract

Implantation of biomaterials leads to the formation of an avascular, fibrotic capsule that isolates the implant from the surrounding tissue. Previous studies have demonstrated that ECM-modification of ePTFE promotes increased vascularity and decreased fibrosity in peri-implant tissue, two desired characteristics of engineered medical devices. However, little is known as to what is happening at the molecular level in tissue surrounding both ECM-modified and non-modified ePTFE during the healing process, or for that matter, what cellular pathway is responsible for the increased vascularity and improved healing response. Large-scale gene expression analysis using DNA microarrays was used to assemble gene expression patterns of peri-implant tissue. This data revealed that tissue surrounding ECM-modified ePTFE is more transcriptionally dynamic than tissue surrounding non-modified ePTFE. The microarray data also exposed a set of macrophage-relevant genes that directed investigation into how the ECM modification of ePTFE affected macrophage activation. It was demonstrated that ECM proteins secreted by the keratincocyte cell line HaCaT promoted fusion of macrophages to form multinucleated foreign body giant cells (FBGCs), as more FBGCs were seen at the material-tissue interface of the ECM modified ePTFE. The results of this work suggest a molecular mechanism through which ECM proteins induce FBGC formation. Taken together, this research advances the knowledge of material-associated healing which will lead to the improved biocompatibility of implanted medical devices.