Spatially resolved molecular analysis of host response to medical device implantation using the 3D OrbiSIMS

A key goal for implanted medical devices is that they do not elicit a detrimental immune response. Macrophages play critical roles in modulation of the host immune response and are the cells responsible for persistent inflammatory reactions to implanted biomaterials. We investigate two novel immune-instructive polymers that stimulate pro- or anti-inflammatory responses from macrophages in vitro. These also modulate in vivo foreign body responses (FBR) when implanted subcutaneously in mice. Immunofluorescent staining of tissue abutting the polymer reveals responses consistent with pro- or anti-inflammatory responses previously described for these polymers. We apply 3DOrbiSIMS analysis to spatially characterise the metabolites in the tissue surrounding the implant, providing molecular histology insight into the metabolite response in the host. For the pro-inflammatory polymer, monoacylglycerols (MG) and diacylglycerols (DG) are observed at increased intensity, while for the anti-inflammatory coating the number of phospholipid species detected decrease and pyridine and pyrimidine levels were elevated. Small molecule signatures from single cell studies of M2 macrophages in vitro correlate with the in vivo observations, suggesting potential for prediction. Metabolite characterization by the 3DOrbiSIMS is shown to provide insight into the mechanism of bio-instructive materials as medical devices and to inform on the FBR to biomaterials. ### Competing Interest Statement The authors have declared no competing interest.