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openaire: EC/H2020/760921/EU//PANBioRA This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 760921 (“PANBioRA”; A.Z., M.G., N.E.V., J.B.) and from the “FUI-FASSIL” project (J.B., C.B.M., N.E.V.) Modern 3D printing of implantable devices provides an important opportunity for the development of personalized implants with good anatomical fit. Nevertheless, 3D printing of silicone has been challenging and the recent advances in technology are provided by the systems which can print medical grade silicone via extrusion. However, the potential impacts of the 3D printing process of silicone on its biomechanical properties has not been studied in sufficient detail. Therefore, the present study compares 3D printed and moulded silicone structures for their cytotoxicity, surface roughness, biomechanical properties, and in vivo tissue reaction. The 3D printing process creates increased nanoscale roughness and noticeably changes microscale topography. Neither the presence of these features nor the differences in processes were found to result in an increase in cytotoxicity or tissue reaction for 3D printed structures, exhibiting limited inflammatory reaction and cell viability above the threshold values. On the contrary, the biomechanical properties have demonstrated significant differences in static and dynamic conditions, and in thermal expansion. Our results demonstrate that 3D printing can be used for establishing a better biomechanical microenvironment for the surrounding tissue of the implant particularly for fragile soft tissue like epithelial mucosa without having any negative effect on the cytotoxicity or in vivo reaction to silicone. For engineering of the implants, however, one must consider the differences in mechanical properties to result in correct and personalized geometry and proper physical interaction with tissues.

Systemic sclerosis (SSc) is a systemic disease characterized by a great clinical and immunological heterogeneity whose pathophysiology is still being unraveled. Recently, innate immunity has been proposed to participate to the pathogenesis of SSc. In this study, we investigated the release of neutrophil extracellular traps (NETs) according to patient phenotype. Polymorphonuclear neutrophils (PMN) from 34 SSc patients and 26 healthy controls were stimulated by serum from SSc or healthy subject. NETs were visualized using epifluorescence microscope after DNA, myeloperoxidase, and Histone H3 tagging. Area of NETs were quantified using an original macro running in ImageJ&reg, software. PMN from SSc patients were significantly more prone to releasing NETs than control PMN after autologous stimulation. PMN from patients with severe vascular complications (pulmonary arterial hypertension, digital ulcers) produced more NETs than PMN from other SSc patients and their aberrant NET production appeared to be sustained over time. In patients with pulmonary interstitial disease or extensive cutaneous fibrosis, NET production was high at an early stage of the disease before progressively decreasing. Both serum factors and PMN activation status were involved in the enhanced production of NETs in SSc. Consequently, neutrophils and especially NETosis represent new physiopathological and therapeutic fields in SSc.