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(chronic inflammation). The stromal spindle cells, interpreted as fibroblasts and endothelial cells, were densely dispersed throughout the wound area and arranged parallel to the wound surface. Most vessels were widely dilated and hyperemic. In GHP, the granulation tissue had more mature morphological features, such as reduction of the inflammatory response, higher content of hyperemic blood vessels, and more intense proliferation of fibroblast-like spindle cells. Nanomaterials 2020, 10, 390 11 of 16 On day 14, there was the persistence of vascular granulation tissue in GCTR, whereas GH and GHP presented a cellular fibrous scar. All groups exhibited full epithelization, but only GH and GHP showed epithelial buddings compatible with the neoformation of rudimentary cutaneous appendages. Also, epithelial buddings compatible with the neoformation of rudimentary cutaneous appendages. Also, suchbuddiingswerelliimiittedttotthesscarrredeedgeessiinGH butscatteredoverthewoundsurfaceiinGHP. H HP Figure 7. Photomicrographs of hematoxylin/eosin-stained histological sections representative of histological wound healing versus the time course of the experiment. Day 3: Wounds present intense edema (ed) and infiltration of polymorphonuclear neutrophils; note the lymphocyte-rich infiltrate (lym) and immature granulation tissue (igt) in the bottom of GH and GHP, respectively (100×). Polymorphonuclear neutrophil (small lobular nuclei) and lymphocytes (dark round nuclei) are highlighted in higher magnification (800×). Day 7: Thick strips of granulation tissue are observed in all groups (dashed arrows); irregular and slit-shaped capillary blood vessels concentrated in the edge are seen in GCTR (thin arrows), whereas dilated hyperemic vessels (thick arrows) are observed throughout the wound areas in GH and GHP (100×). Note the lower content of inflammatory cells in GHP. Stromal spindle cells (fibroblast and endothelial-like cells) are highlighted at higher magnification (800×). Day 14: Residual vascular granulation tissue (right) is observed in GCTR, but a cellular primary fibrous scar (cfb) is seen in GH and GHP. Epithelial buddings (compatible with rudimentary cutaneous appendages) (white arrows) are found in the edges of the wound area in GH but over the full epithelial surface in GHP (100×). Stromal spindle cells (fibroblast-like cells) are highlighted in higher magnification (800×). GCTR (Control Group), GH (Group with hydrogel sodium alginate/gelatin (80:20), and GHP (Group hydrogel with AgNP 4 mM AgNO3). The pathological findings observed in GCTR over the time-course of the experiment, expressed by acute inflammation, granulation tissue formation and primary scar development on day 3, 7 and 14, respectively, suggest that wound healing has occurred without intercurrences, which is also an indication that the control group can be used as an entirely acceptable parameter of normality of the pathophysiological steps of wound healing. The use of hydrogels containing AgNPs promoted histological changes in the healing tissue over the time course of wound healing, such as earlier development and maturation of granulationPDF Image | Wound Healing Silver Nanoparticles-Composing Hydrogel
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