Modulation of macrophage polarization with surface immobilized bioactive molecules

Thesis (Ph.D.)--University of Washington, 2016-12Macrophages are widely recognized as a key cell type in modulating the foreign body response. The manner in which they affect the foreign body response largely depends on their activation state, often referred to as their polarization. The macrophage polarization state lies on a spectrum between two extremes, known as the M1 (inflammatory) polarization and M2 (anti-inflammatory, healing) polarization. It has been demonstrated throughout literature that the polarization state of macrophages depends on many different factors in the cell environment, including the presence of other cells, extra cellular matrix, and soluble factors such as cytokines. In this document, we demonstrate the ability of bioactive molecules that have been immobilized onto a biomaterial surface to modulate the macrophage response. In particular, we support the hypothesis that α-1 acid glycoprotein, as well as Collagen VI in conjunction with α-1 acid glycoprotein, can affect macrophages towards the M2 polarization state, even after immobilization onto a surface. This hypothesis is supported through in vitro analysis of cytokines released in macrophage culture media and RT-PCR analysis of genes correlating with M2 polarization. An in vivo pilot study of subcutaneous implants with immobilized bioactive molecules also supports our hypothesis through analysis of the foreign body capsule and immunohistochemical staining of macrophages at the implant surface. These data demonstrate that α-1 acid glycoprotein and Collagen VI could potentially be used as a surface coating of medical devices to reduce and modulate the foreign body response, as well as macrophage polarization