The interaction between gut microbiota and host plays a central role in health. Dysbiosis, detrimental changes in gut microbiota and inflammation have been reported in non-communicable diseases. While diet has a profound impact on gut microbiota composition and function, the role of food additives such as titanium dioxide (TiO 2 ), prevalent in processed food, is less established. In this project, we investigated the impact of food grade TiO 2 on gut microbiota of mice when orally administered via drinking water. While TiO 2 had minimal impact on the composition of the microbiota in the small intestine and colon, we found that TiO 2 treatment could alter the release of bacterial metabolites in vivo and affect the spatial distribution of commensal bacteria in vitro by promoting biofilm formation. We also found reduced expression of the colonic mucin 2 gene, a key component of the intestinal mucus layer, and increased expression of the beta defensin gene, indicating that TiO 2 significantly impacts gut homeostasis. These changes were associated with colonic inflammation, as shown by decreased crypt length, infiltration of CD8 + T cells, increased macrophages as well as increased expression of inflammatory cytokines. These findings collectively show that TiO 2 is not inert, but rather impairs gut homeostasis which may in turn prime the host for disease development.

Extracellular vesicles (EVs) have been lauded as next-generation medicines, but very few EV-based therapeutics have progressed to clinical use. Limited clinical translation is largely due to technical barriers that hamper our ability to mass produce EVs, i.e., to isolate, purify, and characterize them effectively. Technical limitations in comprehensive characterization of EVs lead to unpredicted biological effects of EVs. Here, using a range of optical and non-optical techniques, we showed that the differences in molecular composition of EVs isolated using two isolation methods correlated with the differences in their biological function. Our results demonstrated that the isolation method determines the composition of isolated EVs at single and sub-population levels. Besides the composition, we measured for the first time the dry mass and predicted sedimentation of EVs. These parameters were likely to contribute to the biological and functional effects of EVs on single cell and cell cultures. We anticipate that our new multiscale characterization approach, which goes beyond traditional experimental methodology, will support fundamental understanding of EVs as well as elucidate the functional effects of EVs in in vitro and in vivo studies. Our findings and methodology will be pivotal for developing optimal isolation methods and establishing EVs as mainstream therapeutics and diagnostics. This innovative approach is applicable to a wide range of sectors including biopharma and biotechnology as well as to regulatory agencies.

Human hair keratins have proven to be a viable biomaterial for diverse regenerative applications. However, the most significant characteristic of this material has not been exploited, that is the ability to self-assemble into nanoscale intermediate filaments. Herein, we successfully demonstrated the induction of hair-extracted keratin self-assembly in vitro to form dense, homogenous and continuous nanofibrous networks. These networks remain hydrolytically stable in vitro for up to 5 days in complete cell culture media, and are compatible with primary human dermal fibroblasts and keratinocytes. These results enhance the versatility of human hair keratins for applications where structured assembly is of benefit.

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The leading reason for implant revision surgery globally is lack of implant integration with surrounding bone. A new titanium alloy GUMMETAL® (Ti59Nb36Ta2Zr3O0.3) is currently used in biomedical devices and has a Young’s modulus that is better matched to bone. The surface was subject to NaOH, CaCl2, heat and water treatment (BioGum) after which the surfaces were evaluated using atomic force microscope, scanning electron microscope, X-ray diffractometer and elemental analysis using energy dispersive X-ray. To demonstrate enhanced bone bonding ability and cytocompatibility, apatite formation in simulated body fluid and in vitro stem cell attachment, proliferation and cytoskeleton organisation were examined. The formation of a ~200 nm nanoscale needle-like calcium titanate network on the surface following treatment was revealed and upon soaking in simulated body fluid, the formation of a ~5 µm layer of apatite. Metabolic activity of rat bone marrow stem cells on BioGum was increased in comparison to control and the cell number appeared greater, with more elongated morphology as early as 2 h post-seeding. This positions the modification as a simple and potentially universal technology for the improvement of implant integration.