Surface Modification of Bioresorbable Phosphate Glasses for Controlled Protein Adsorption.

The traditional silicate bioactive glasses exhibit poor thermal processability, which inhibits fiber drawing or sintering into scaffolds. The composition of the silicate glasses has been modified to enable hot processing. However, the hot forming ability is generally at the expense of bioactivity. Metaphosphate glasses, on the other hand, possess excellent thermal processability, congruent dissolution, and a tailorable degradation rate. However, due to the layer-by-layer dissolution mechanism, cells do not attach to the material surface. Furthermore, the congruent dissolution leads to a low density of OH groups forming on the glass surface, limiting the adsorption of proteins. It is well regarded that the initial step of protein adsorption is critical as the cells interact with this protein layer, rather than the biomaterial itself. In this paper, we explore the possibility of improving protein adsorption on the surface of phosphate glasses through a variety of surface treatments, such as washing the glass surface in acidic (pH 5), neutral, and basic (pH 9) buffer solutions followed or not by a treatment with (3-aminopropyl)triethoxysilane (APTS). The impact of these surface treatments on the surface chemistry (contact angle, ζ-potential) and glass structure (FTIR) was assessed. In this manuscript, we demonstrate that understanding of the material surface chemistry enables to selectively improve the adsorption of albumin and fibronectin (used as model proteins). Furthermore, in this study, well-known silicate bioactive glasses (i.e., S53P4 and 13-93) were used as controls. While surface treatments clearly improved proteins adsorption on the surface of both silicate and phosphate glasses, it is of interest to note that protein adsorption on phosphate glasses was drastically improved to reach similar protein grafting ability to the silicate bioactive glasses. Overall, this study demonstrates that the limited cell/phosphate glass biological response can easily be overcome through deep understanding and control of the glass surface chemistry.

Priming of innate antimycobacterial immunity by heat-killed Listeria monocytogenes induces sterilizing response in the adult zebrafish tuberculosis model.

Mycobacterium tuberculosis remains one of the most problematic infectious agents, owing to its highly developed mechanisms to evade host immune responses combined with the increasing emergence of antibiotic resistance. Host-directed therapies aiming to optimize immune responses to improve bacterial eradication or to limit excessive inflammation are a new strategy for the treatment of tuberculosis. In this study, we have established a zebrafish-Mycobacterium marinum natural host-pathogen model system to study induced protective immune responses in mycobacterial infection. We show that priming adult zebrafish with heat-killed Listeria monocytogenes (HKLm) at 1 day prior to M. marinum infection leads to significantly decreased mycobacterial loads in the infected zebrafish. Using rag1-/- fish, we show that the protective immunity conferred by HKLm priming can be induced through innate immunity alone. At 24 h post-infection, HKLm priming leads to a significant increase in the expression levels of macrophage-expressed gene 1 (mpeg1), tumor necrosis factor α (tnfa) and nitric oxide synthase 2b (nos2b), whereas superoxide dismutase 2 (sod2) expression is downregulated, implying that HKLm priming increases the number of macrophages and boosts intracellular killing mechanisms. The protective effects of HKLm are abolished when the injected material is pretreated with nucleases or proteinase K. Importantly, HKLm priming significantly increases the frequency of clearance of M. marinum infection by evoking sterilizing immunity (25 vs 3.7%, P=0.0021). In this study, immune priming is successfully used to induce sterilizing immunity against mycobacterial infection. This model provides a promising new platform for elucidating the mechanisms underlying sterilizing immunity and to develop host-directed treatment or prevention strategies against tuberculosis.This article has an associated First Person interview with the first author of the paper.