Silicon-dioxide−polyvinylpyrrolidone as a wound dressing for skin defects in a murine model  Ferenc Öri, Richard Dietrich, Cornelia Ganz, Michael Dau, Daniel Wolter, Annika Kasten, Thomas Gerber, Bernhard Frerich  Journal of Cranio-Maxillo-Facial Surgery  Volume 45, Issue 1, Pages 99-107 (January 2017) DOI: 10.1016/j.jcms.2016.10.002 Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery Terms and Conditions

Fig. 1 SiO2–PVP fleece (A) and SiO2–PVP gel (B) wound dressing. Journal of Cranio-Maxillo-Facial Surgery 2017 45, 99-107DOI: (10.1016/j.jcms.2016.10.002) Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery Terms and Conditions

Fig. 2 (A–D) Scanning electron microscopy photographs of the SiO2–PVP compound at different resolutions. The compound has a fiber-like structure. Journal of Cranio-Maxillo-Facial Surgery 2017 45, 99-107DOI: (10.1016/j.jcms.2016.10.002) Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery Terms and Conditions

Fig. 3 (A)Viscosity over SiO2 content within the solid content of the SiO2–PVP compound. Both the PVP solution and the SiO2 sol from which the compound is made have a very low viscosity. Adding SiO2 sol to the PVP solution results in an increase in the viscosity, which stabilizes at around 230 Pa*s for 33% SiO2 in the solid content. This is also the mixture from which the wound dressings are made. (B) Specific heat capacity over temperature measured with a differential scanning calorimetry for pure PVP and the compound from which the dressings are made. The diagram shows that the glass transition temperature of the compound (+) is higher than that from PVP (x). Also, the specific heat capacity step from the compound is smaller than that from PVP. This derives from the added SiO2 as well as that PVP forms a rigid amorphous fraction around the nanoparticles. Journal of Cranio-Maxillo-Facial Surgery 2017 45, 99-107DOI: (10.1016/j.jcms.2016.10.002) Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery Terms and Conditions

Fig. 4 Scanning electron microscopy (SEM) photographs and energy dispersive X-ray spectroscopy (EDX) investigations on sliced and dried SiO2–PVP fleece (A and B) and SiO2–PVP gel (C and D) wound dressings taken from the wound after 3 days. The three squares indicate the positions where the EDX investigations were made. The corresponding spectra are shown beneath the SEM photographs. Closer to the wound side of the dressings, the signal for silicon decreases, which might indicate a SiO2 diffusion out of the dressing into the wound. Journal of Cranio-Maxillo-Facial Surgery 2017 45, 99-107DOI: (10.1016/j.jcms.2016.10.002) Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery Terms and Conditions

Fig. 5 Viability/cytotoxicity assay of cells after stimulation with SiO2–PVP wound dressing supernatant. Murine fibroblasts were stimulated for 24 h with supernatant of three different batches (batches 1–3) of SiO2 wound dressings. (A–D) Viable cells and nuclei of apoptotic cells were stained in green and red, respectively. Counterstaining of cell nuclei is shown in blue. No cytotoxic effects were detected (Axio Observer, Carl Zeiss Microscopy GmbH; scale bars = 50 μm). (E) Metabolic activity of stimulated cells was not changed compared to that of control cells (n = 3, Boxplot, Kruskal-Wallis test: p = 0.558, no significant differences). Journal of Cranio-Maxillo-Facial Surgery 2017 45, 99-107DOI: (10.1016/j.jcms.2016.10.002) Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery Terms and Conditions

Fig. 6 (A) Macroscopic appearance of a 10 mm circular full-thickness skin defect in a skin regeneration murine model. Wound closure occurred mainly after 9 days in all groups. (B) Wound contraction was expressed as a mean ± SD percentage of the original wound size after 3, 6, and 9 days. After 3 days, wound contraction was significantly enhanced by treatment with SiO2–PVP gel, followed by SiO2–PVP fleece, compared to that in the control group (p < 0.05). Journal of Cranio-Maxillo-Facial Surgery 2017 45, 99-107DOI: (10.1016/j.jcms.2016.10.002) Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery Terms and Conditions

Fig. 7 (A) Histological overview of a hematoxylin-eosin section using the example of SiO2–PVP gel after 6 days. To determine the length of the newly formed epithelium (*), the entire wound size (gray bar) and residual defect (**) were histomorphometrically measured. (B) Histomorphometrical results of epithelialization after 3, 6, 9, and 12 days (mean ± SD). SiO2–PVP gel significantly reduced epithelialization after 3 days (p < 0.05) but increased and showed the most pronounced degree of epithelialization after 9 days. Journal of Cranio-Maxillo-Facial Surgery 2017 45, 99-107DOI: (10.1016/j.jcms.2016.10.002) Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery Terms and Conditions

Fig. 8 Histological evaluation of epithelium height after 15 days of (A) control (B) SiO2–PVP gel, and (C) SiO2–PVP fleece. The structure of the epidermis showed a more differentiated layer in the SiO2 groups compared to the control group. A well-differentiated stratum basale has been formed in the SiO2 gel. (D) Histomorphometric analyses after 15 days showed significantly (p < 0.05) higher values for SiO2–PVP gel and SiO2–PVP fleece compared to the control group. (E) Immunohistochemical studies of CD31 after 15 days as an indicator for neovascularization showed a higher degree of vascularization for SiO2 gel compared to that in the control group. Journal of Cranio-Maxillo-Facial Surgery 2017 45, 99-107DOI: (10.1016/j.jcms.2016.10.002) Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery Terms and Conditions