The role of xenogenic and autologous serum proteins and protein derivatives in mediating monocyte/macrophage adhesion and inflammatory responses on a variety of modified and unmodified biomaterial substrates.

摘要

Monocytes and monocyte-derived macrophages play a distinctly pivotal role in directing the host response to an implanted biomaterial and can be stimulated to have multiple roles in the body, potentially acting in an inflammatory or anti-inflammatory manner and acting to destroy or regenerate tissue. Due to this central role in the determination of the efficacy of a biomaterial, the development of a better understanding of monocyte/macrophage interactions with biomaterials may lead to the design of biomaterials with improved biocompatibility. Consequently, macrophages are studied extensively in biomaterials research. In vivo, both resident mature tissue macrophages with multiple phenotypes and monocyte-derived macrophages that migrate to the site of injury interact with an implanted biomaterial or wound and orchestrate the host response. As with all cells, monocyte interaction with a biomaterial is through the identity and conformation of proteins adsorbed to the biomaterial surface. Therefore, developing a greater understanding of macrophage interactions with proteins adsorbed to biomaterials both in vivo and in vitro will lead to improved biomaterial efficacy. Of particular interest in biomaterials research is the extra-cellular matrix (ECM) protein fibronectin. This protein has been demonstrated to enhance cell adhesion to biomaterials and additionally to stimulate the release of numerous cytokines from macrophages including the broadly-acting and potent cytokine interleukin-1beta (IL-1beta). Macrophage responses to biomaterial surfaces grafted with peptides simulating this synergistic region were explored as was macrophage fibronectin-binding integrin upregulation in response to IL-1beta. To further explore this relationship in mature macrophages, monocytes were matured into biomaterial-specific phenotypes. However, as is ubiquitous in cell culture, in the field of biomaterials primary monocytes are typically supplemented with fetal bovine serum, in contrast to our research where autologous human serum is used. A differential effect of these sera was observed for maturing primary monocytes and this research was expanded greatly. The role of serum in determining monocyte phenotype was extensively explored on various biomaterial surfaces and protein release was found to be modulated by a combination of both the serum type and the biomaterial surface, however all macrophages displayed at least some properties similar to a classically activated macrophage.