Prosthetic Joint Infections (PJIs) are increasing with the use of orthopedic devices on an ageing population. Cutibacterium acnes is a commensal organism that plays an important role in the ecosystem healthy human skin, yet this species is also recognized as a pathogen in foreign body infection: endocarditis, prostatitis and specifically in PJIs. C. acnes is able to escape the immune system. This phenomenon could reflect two bacterial behaviour: the bacterial internalization by host cells and the biofilm formation. In this study, we studied different clinical strains of C. acnes. We noticed that C. acnes isolated from PJIs form 2 fold-more biofilm than the strains isolated from a normal skin in two models (Crystal violet staining and fluorescent microscopy (p=0.04 and p=0.02, respectively, Mann-Whitney test). We did not observe any difference in the internalization rate of those strains by osteoblasts. However, the quantity of biofilm formed by C. acnes before and after the internalization was compared. A significant increase in biofilm formation was observed for the strains isolated from the skin (x2.3±0.07; p=0.008, Mann-Whitney test). However, the hydrophobicity of the skin strains is significantly less important than for the PJIs strains (24.8±13% vs 56.6±12% respectively; p=0.003, Mann-Whitney test) but this did not change after internalization suggesting that there is no cell wall evolution. In conclusion, we studied for the first time the impact of bacterial internalization by osteoblasts on the virulent behaviour of C. acnes, which could explain the hided pathogenicity of this commensal bacterium.

Mesenchymal stem cells (MSCs) are tissue-resident stroma cells capable of modulating immune cells through the secretion of paracrine factors. However, the comparison of MSCs potential, from different sources and submitted to hypoxia within a 3D scaffold, in secreting pro-healing factors has never been investigated. With a chemical composition similar to type I collagen, a major component of connective tissues retrieved in dental pulp, bone and umbilical cord, Hemocollagene® haemostatic foam presented porous and interconnected structure (> 90%) and a relative low elastic modulus of around 60 kPa. All these criteria meet basic requirements for tissue engineering based material. Herein, we assessed and compared the effect of hypoxia (3% O₂) on the regulation and release of pro-angiogenic factors (VEGF, b-FGF and IL-8) from bone marrow (BM), Wharton's jelly (WJ) and dental pulp (DP) derived MSCs cultured in Hemocollagene®. After 10 days of culture, qRT-PCR analysis showed an up-regulation of b-FGF and VEGF mRNA in BM- and WJ-derived MSCs, but not in DP-derived MSCs. Furthermore, hypoxia highly up-regulated IL-8 expression in WJ-derived MSCs and moderately in both BM and DP-derived MSCs. In contrast, ELISA analysis showed a higher amount of VEGF and IL-8 in supernatant provided from DP-derived MSCs culture compared to BM and WJ-derived MSCs. B-FGF was not detected whatever the experimental condition. In conclusion, MSCs derived from several tissues were able to release pro-angiogenic factors under hypoxic conditions. There was no clearly superior type of MSCs for therapeutic use, however DP-derived MSCs are likely to be more advantageous.