11.08.2016 // Lindsay Fitzpatrick, Queen's University, Department of Chemical Engineering

Macrophage activation and fusion on polymeric surfaces in the presence of damage-associated molecular patterns

Synthetic polymers have widespread use in current and emerging biomedical applications, as components of medical devices, tissue engineering scaffolds, drug delivery devices and sensors. However, the success of these applications is dependent on the cellular response to the implanted material. Essentially all materials elicit an inflammatory response following implantation that can have detrimental affects on the performance of the material, including material degradation leading to failure, chronic inflammation at the implant site and poor tissue integration at the material-tissue interface. Protein adsorption from the biomaterial’s local environment is considered a key factor in determining the cellular, and thus overall host response, to implanted materials. While effect of adsorbed proteins derived from blood has been investigated extensively, the role of endogenous danger signals in biomaterial-induced inflammatory responses is not well understood. These damage associated molecular patterns (DAMPs) are released upon tissue injury (e.g. during implant placement) and are known to induce inflammatory responses in macrophages, a key cell type of biomaterial host responses.
The work described here will focus on an in vitro model of macrophage-biomaterial interactions that investigates the adsorption of DAMPs, and subsequent macrophage activation, on polymer surfaces. Using cell lysate as a complex source of DAMPs, we have demonstrated that DAMP-adsorbed surfaces have increased Toll-like receptor (TLR)-2-mediated NF-kB activity and cytokine expression, compared to serum-adsorbed surfaces. Furthermore, we have observed rapid macrophage fusion to form multinucleated giant cells, independent of the addition of fusogenic factors interleukin (IL)-4, IL-13 and interferon (IFN)-g, suggesting the lysate-mediated fusion occurs through a novel fusion mechanism. The research aims to improve our understanding of in vivo material-cell interactions, which will guide the development of novel strategies to control biomaterial host responses current clinical materials and improve the lifespan of current medical implants.