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The present work demonstrated an efficient cutaneous wound healing using Bixin-loaded polycaprolactone (PCL) nanofibers as a controlled delivery system. The influence of Bixin (Bix) content on PCL nanofiber, Bix-PCL1(2.5% w/w bix) and Bix-PCL2 (12.5% w/w bix) formation was investigated using electrical conductivity, attenuated total reflectance infrared spectroscopy, X-ray diffraction, thermal analysis, and scanning electronic microscopy. The results showed that a greater bixin concentration resulted in higher polymeric solution electrical conductivity. Moreover, higher polymeric solution electrical conductivity provides lower nanofibers in terms of average diameter than pure PCL nanofibers. In vitro release was largely governed by a diffusion-controlled mechanism. The initial Bixin release domain showed a burst release over the first 10 hours where approximately 30% and 40% of Bixin was released from Bix-PCL1 and Bix-PCL2 nanofibers, respectively. The second kinetic domain was comprised of a continuous and slow Bixin release that led to almost 100% of the Bixin being released within 14 days. The results on excisional wound model in induced diabetic mice indicated that the low concentration of Bixin released from loaded Bix-PCL nanofibers maintain the biological activity of Bixin and is efficient in accelerating the wound healing as well as in reducing the scar tissue area compared with pure PCL nanofibers. Therefore, soft material Bixin-loaded PCL nanofibers are a promising candidate for use in wound dressing. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1938-1949, 2017.

There is considerable interest in implantation techniques and scaffolds for tissue engineering and, for safety and biocompatibility reasons, inflammation, angiogenesis, and fibrosis need to be determined. The contribution of inducible nitric oxide synthase (iNOS) in the regulation of the foreign body reaction induced by subcutaneous implantation of a synthetic matrix was never investigated. Here, we examined the role of iNOS in angiogenesis, inflammation, and collagen deposition induced by polyether-polyurethane synthetic implants, using mice with targeted disruption of the iNOS gene (iNOS−/−) and wild-type (WT) mice. The hemoglobin content and number of vessels were decreased in the implants of iNOS−/− mice compared to WT mice 14 days after implantation. VEGF levels were also reduced in the implants of iNOS−/− mice. In contrast, the iNOS−/− implants exhibited an increased neutrophil and macrophage infiltration. However, no alterations were observed in levels of CXCL1 and CCL2, chemokines related to neutrophil and macrophage migration, respectively. Furthermore, the implants of iNOS−/− mice showed boosted collagen deposition. These data suggest that iNOS activity controls inflammation, angiogenesis, and fibrogenesis in polyether-polyurethane synthetic implants and that lack of iNOS expression increases foreign body reaction to implants in mice.

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Skin wound healing is a complex process involving different events such as blood coagulation, inflammation, new blood vessels formation, and extracellular matrix deposition. These events can be observed by using histology techniques. However, the lack of the standardization of such parameters impacts on the reproducibility of results. Here, we describe a protocol to perform macroscopic and microscopic analyses of the events that occur during skin wound healing using the experimental model of excisional wounds in rats.

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Schinus terebinthifolius Raddi (Aroeira) leaves oil attenuatesinflammatory responses in cutaneous wound healing in mice 1 AbstractPurpose: To investigated the inflammatory, angiogenic and fibrogenic activities of the Schinus terebinthifolius Raddi leaves oil (STRO) on wound healing. Methods:The excisional wound healing model was used to evaluate the effects of STRO. The mice were divided into two groups: Control, subjected to vehicle solution (ointment lanolin/ vaseline base), or STRO-treated group, administered topically once a day for 3, 7 and 14 days post-excision. We evaluated the macroscopic wound closure rate; the inflammation was evaluated by leukocytes accumulation and cytokine levels in the wounds. The accumulation of neutrophil and macrophages in the wounds were determined by assaying myeloperoxidase and N-acetyl-β-D-glucosaminidase activities. The levels of TNF-α, CXCL-1 and CCL-2 in wound were evaluated by ELISA assay. Angiogenesis and collagen fibers deposition were evaluated histologically. Results:We observed that macroscopic wound closure rate was improved in wounds from STRO-group than Control-group. The wounds treated with STRO promoted a reduction in leucocyte accumulation and in pro-inflammatory cytokine. Moreover, STRO treatment increased significantly the number of blood vessels and collagen fibers deposition, as compared to control group. Conclusion: Topical application of STRO display anti-inflammatory and angiogenic effects, as well as improvement in collagen replacement, suggesting a putative use of this herb for the development of phytomedicines to treat inflammatory diseases, including wound healing.

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