Biomaterial surface chemistry as a cue for the modulation of macrophage polarisation

Increasing understanding of host responses towards biomaterials have led to the recognition of macrophages as crucial determinants of inflammatory outcomes following implantation. Macrophages perpetuate chronic inflammation or enhance tissue healing depending on the phenotype they adopt in response to biomaterials in vivo. In the context of tissue repair, timely shift in macrophage polarisation from an M1 phenotype (pro-inflammatory) to an M2 phenotype (anti-inflammatory) favours improved healing. Therefore, efforts to control host responses have focused on the development of materials that can direct macrophage polarisation away from an exaggerated M1 phenotype and towards a regulatory M2 phenotype. Biomaterial surface chemistry is known to influence functions of different cell types, including macrophages. Hence, the overall aim of this study was to discover new polymer chemistries that are able to modulate macrophage responses, including adhesion and polarisation. This study also sought to investigate possible molecular cues that could have contributed to polymer-induced macrophage polarisation. To investigate the effects of polymer chemistry on human monocyte-derived macrophages, a high-throughput screening of 283 acrylate and acrylamide polymers was performed. From this screen, polymers that influenced macrophage attachment and polarisation, determined by their surface phenotype, were identified. Polymers like, poly (propylene glycol) acrylate (pPGA), supported very high macrophage attachment, while others like, diacetone acrylamide (AAcAm), inhibited macrophage attachment. A selection of polymers that were identified to impact macrophage polarisation was scaled-up for further phenotypic and functional characterisation. Following polymer scale-up, macrophages grown on different polymers were seen to differentially express M1 and M2 associated cytokines and genes. Macrophages on 1,10-Decanediol dimethacrylate (DDDMA) expressed the highest levels of M1 cytokines (TNF-α, IL-6 and IL-1β); increased levels of regulatory cytokine, IL-10, was also seen on this polymer. Macrophages on glycerol propoxylate triacrylate (GPOTA) retained a less activated phenotype, expressing low levels of both M1 and M2 cytokines. Furthermore, polymers were seen to have varying effects on macrophage phagocytic ability; macrophages on tert-butyl methacrylate (tBMA) had the least phagocytic ability compared to those on DDDMA and GPOTA. To gain some insight into molecular cues that contributed to the observed polymer-induced macrophage responses, adsorption of proteins from serum-supplemented culture medium onto different ‘hit’ polymers was investigated. Quantitative evaluation of adsorbed proteins showed significantly increased protein over-layer thickness on DDDMA and tBMA compared to GPOTA. There seemed to be a relationship between macrophage activation and the thickness of protein over-layer on polymer surfaces. Moreover, different polymers with ability to support M1-like or M2-like phenotypes showed some differences in the molecular composition of adsorbed proteins. In summary, findings from this study show the potentials of a number of polymers to modulate macrophage behaviour. Also, the possible influence of differential protein adsorption on macrophage polarisation is highlighted. These observations could provide a framework for accelerated development of immune-modulatory materials, with potential application in medical devices and regenerative medicine.