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      MMP-2 and TIMP-2 expression, quantitative analysis and biomechanical changes in scar hypertrophy after autologous free transplantation of rabbit oral mucosa and scrotal skin

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      Saudi Journal of Biological Sciences
      Elsevier
      Oral mucosa, Scar, Biomechanics

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          Abstract

          This study aimed to investigate the long-term scar hypertrophy in the rabbit transplanted oral mucosa and scrotal skin with changed matrix environment, as well as the scar location expression, quantitative analysis of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) and biomechanical changes in the transplanted tissues. The split-thickness skin grafts were collected from the oral mucosas and scrotal skins of 30 male rabbits, and prepared into reelpipes for autologous transplantation into the rabbit back muscular tissues. Samples were collected to carry out elastic tensile mechanical detection and histological observation. The maximum longitudinal tensile displacement of scrotal skin before 8 weeks of transplantation was greater than that after 8 weeks of transplantation (P < 0.05). The expression intensities of MMP-2 and TIMP-2 in the oral mucosa and in scrotal skin at 2 W time point were higher than those at T o time point (P < 0.05). The expression quantities of TIMP-2 in oral mucosa and scrotal skin during 8–24 W were higher than those of MMP-2 (P < 0.05). At 8 W time point, the TIMP-2/MMP-2 ratio in scrotal skin was higher than that in oral mucosa (P < 0.05). MMP-2 and TIMP-2 expression in normal oral mucosa and scrotal skin is weak, but their expression is remarkably up-regulated after 2 weeks of transplantation, revealing that scar formation was related to the high expression of MMP-2 and TIMP-2. At the 8th–24th weeks, the AOD values of TIMP-2 in oral mucosa and scrotal skin are apparently higher than those of MMP-2; moreover, the TIMP-2/MMP-2 ratio in scrotal skin at the 8th week was higher than that in oral mucosa, which can well explain the earlier scar formation in scrotal skin than in oral mucosa, and it also suggests that the different expression levels between TIMP-2 and MMP-2 may account for the important cause of scar formation.

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          Most cited references24

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          miR-155 promotes cutaneous wound healing through enhanced keratinocytes migration by MMP-2.

          Inflammation, re-epithelization and tissue remodeling are three essential steps during wound healing. The re-epithelization process plays the most important role which mainly involves keratinocyte proliferation and migration. miR-155 has been reported to participate in cell migration and transformation, however, its function in skin wound healing is largely unknown. Here we hypothesize that overexpression of miR-155 at wound edges could accelerate wound healing mediated by enhanced keratinocyte migration. To test this hypothesis, direct local injection of miR-155 expression plasmid to wound edges was conducted to overexpress miR-155 in vivo. Results shown that miR-155 significantly promoted wound healing and re-epithelization compared to control, while did not affect wound contraction. Also, miR-155 overexpression accelerated primarily cultured keratinocyte migration in vitro, but had no effect on cell proliferation. Importantly, western blot analysis shown that MMP-2 was significantly upregulated whiles its inhibitor TIMP-1 downregulated after miR-155 treatment. Moreover, the use of ARP-101, an MMP-2 inhibitor, effectively attenuated the accelerative effects on cell migration induced by miR-155. Taken together, our results suggest that miR-155 has the promote effect on wound healing that is probably mediated by accelerating keratinocyte migration via upregulated MMP-2 level. This study provides a rationale for the therapeutic effect of miR-155 on wound healing.
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            In vivo diabetic wound healing with nanofibrous scaffolds modified with gentamicin and recombinant human epidermal growth factor

            Diabetic wounds are susceptible to microbial infection. The treatment of these wounds requires a higher payload of growth factors. With this in mind, the strategy for this study was to utilize a novel payload comprising of Eudragit RL/RS 100 nanofibers carrying the bacterial inhibitor gentamicin sulfate (GS) in concert with recombinant human epidermal growth factor (rhEGF); an accelerator of wound healing. GS containing Eudragit was electrospun to yield nanofiber scaffolds, which were further modified by covalent immobilization of rhEGF to their surface. This novel fabricated nanoscaffold was characterized using scanning electron microscopy, Fourier transform infrared spectroscopy, and X-ray diffraction. The thermal behavior of the nanoscaffold was determined using thermogravimetric analysis and differential scanning calorimetry. In the in vitro antibacterial assays, the nanoscaffolds exhibited comparable antibacterial activity to pure gentemicin powder. In vivo work using female C57/BL6 mice, the nanoscaffolds induced faster wound healing activity in dorsal wounds compared to the control. The paradigm in this study presents a robust in vivo model to enhance the applicability of drug delivery systems in wound healing applications. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 641-651, 2018.
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              Substitution urethroplasty using oral mucosa graft for male anterior urethral stricture disease: Current topics and reviews.

              Male anterior urethral stricture is scarring of the subepithelial tissue of the corpus spongiosum that constricts the urethral lumen, decreasing the urinary stream. Its surgical management is a challenging problem, and has changed dramatically in the past several decades. Open surgical repair using grafts or flaps, called substitution urethroplasty, has become the gold standard procedure for anterior urethral strictures that are not amenable to excision and primary anastomosis. Oral mucosa harvested from the inner cheek (buccal mucosa) is an ideal material, and is most commonly used for substitution urethroplasty, and lingual mucosa harvested from the underside of the tongue has recently emerged as an alternative material with equivalent outcome. Onlay augmentation of oral mucosa graft on the ventral side (ventral onlay) or dorsal side (dorsal onlay, Barbagli procedure) has been widely used for bulbar urethral stricture with comparable success rates. In bulbar urethral strictures containing obliterative or nearly obliterative segments, either a two-sided dorsal plus ventral onlay (Palminteri technique) or a combination of excision and primary anastomosis and onlay augmentation (augmented anastomotic urethroplasty) are the procedures of choice. Most penile urethral strictures can be repaired in a one-stage procedure either by dorsal inlay with ventral sagittal urethrotomy (Asopa technique) or dorsolateral onlay with one-sided urethral dissection (Kulkarni technique); however, staged urethroplasty remains the procedure of choice for complex strictures, including strictures associated with genital lichen sclerosus or failed hypospadias. This article presents an overview of substitution urethroplasty using oral mucosa graft, and reviews current topics.
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                Author and article information

                Contributors
                Journal
                Saudi J Biol Sci
                Saudi J Biol Sci
                Saudi Journal of Biological Sciences
                Elsevier
                1319-562X
                2213-7106
                01 August 2020
                November 2020
                01 August 2020
                : 27
                : 11
                : 3046-3059
                Affiliations
                Department of Plastic Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, China
                Author notes
                [* ]Corresponding author at: The 2nd Department of Plastic Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 33, Ba-da-chu Road, Shijingshan District, Beijing 100144, China. liyangqun_doctor@ 123456126.com
                Article
                S1319-562X(20)30330-2
                10.1016/j.sjbs.2020.07.031
                7569130
                33100864
                5a76f40a-83a8-4d2a-b4a1-1bdfbaae9c7a
                © 2020 The Author(s)

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 10 April 2020
                : 15 July 2020
                : 25 July 2020
                Categories
                Original Article

                oral mucosa,scar,biomechanics
                oral mucosa, scar, biomechanics

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