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      Strontium nitrate-dopped zinc oxide-loaded alginate gels with gentamicin for improved wound healing

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          Abstract

          Wound dressing development is an area of active research. Traditional dressings lack antibacterial activity, biocompatibility, and tissue regeneration. Alginate is a heavily investigated polymer employed as wound dressings and can be combined with a wide range of additives. Herein, we report the preparation of alginate gel using the crosslinking technique as potential wound dressing, with insight investigation of the influence of employing single, two, or three cross-linkers: Strontium (Sr), zinc oxide (ZnO), and gentamicin sulfate. Rheology was used to confirm the gel’s preparation, where the samples’ viscosity curves show decreased viscosity with increased shear rate, indicating pseudoplastic flow. The linear viscoelastic region shows constant G’ and G” within the sample structure. In this study, we used three gels with different mixtures of ingredients: Gels A, B, and C contain sodium alginate (1% w/v) and 0.5 mL of Sr nitrate (4% w/v). However, Gels B and C contain 0.25 mL of ZnO (0.5% w/v). Gel C also includes 0.1 mL of gentamicin (1% w/v). The study examined the effectiveness of Gel A, B, and C on wound healing, calculating the reduction of wound area after seven, 14, and 20 days of a single topical treatment. Gel A, B, and C significantly reduced wound area, while Gel B and C showed a significant reduction. The zone of inhibition was used to detect the gels’ efficacy against microorganisms. The study found zinc deposition in the liver and bone, with Gel B and C showing higher levels. The study also found significant overexpression of MIP α and MIP β in tissues and downregulation of CCL2, IL8, and TGF β, explaining wound healing with minimal scar formation.

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          Critical Role of Transforming Growth Factor Beta in Different Phases of Wound Healing.

          This review highlights the critical role of transforming growth factor beta (TGF-β)1-3 within different phases of wound healing, in particular, late-stage wound healing. It is also very important to identify the TGF-β1-controlling factors involved in slowing down the healing process upon wound epithelialization. TGF-β1, as a growth factor, is a known proponent of dermal fibrosis. Several strategies to modulate or regulate TGF's actions have been thoroughly investigated in an effort to create successful therapies. This study reviews current discourse regarding the many roles of TGF-β1 in wound healing by modulating infiltrated immune cells and the extracellular matrix. It is well established that TGF-β1 functions as a wound-healing promoting factor, and thereby if in excess it may lead to overhealing outcomes, such as hypertrophic scarring and keloid. Thus, the regulation of TGF-β1 in the later stages of the healing process remains as critical issue of which to better understand. One hypothesis is that cell communication is the key to regulate later stages of wound healing. To elucidate the role of keratinocyte/fibroblast cross talk in controlling the later stages of wound healing we need to: (1) identify those keratinocyte-released factors which would function as wound-healing stop signals, (2) evaluate the functionality of these factors in controlling the outcome of the healing process, and (3) formulate topical vehicles for these antifibrogenic factors to improve or even prevent the development of hypertrophic scarring and keloids as a result of deep trauma, burn injuries, and any type of surgical incision.
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            Differential regulation of pro-inflammatory cytokines during wound healing in normal and glucocorticoid-treated mice.

            It has long been speculated that pro-inflammatory cytokines play an important role in wound repair. However, little is known about the temporal and spatial expression pattern of these cytokines during normal and impaired wound healing. In this study we show a strong and early induction of interleukins 1 alpha and beta (IL-alpha and beta) and of tumour necrosis factor alpha (TNF-alpha) expression after cutaneous injury. Highest levels of these cytokines were seen as early as 12-24 h after wounding. After completion of the proliferative phase of wound healing, mRNA levels of these cytokines returned to the basal level. During the early phase of wound repair, proinflammatory cytokines were predominantly expressed in polymorphonuclear leukocytes, suggesting a novel function of these cells in the initiation of wound healing. At later stages of the repair process, expression of IL-1 alpha, IL-1 beta and TNF-alpha was also seen in macrophages. Furthermore, TNF-alpha was detected in the hyperproliferative epithelium at the wound edge and IL-1 alpha was found in keratinocytes of the hair follicles. Induction of these cytokines after injury was significantly reduced during wound repair in healing-impaired glucocorticoid-treated mice. This finding demonstrates that wound healing defects are associated with impaired cytokine expression and suggests that the early induction of these genes is important for normal repair.
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              Pro-Inflammatory Chemokine CCL2 (MCP-1) Promotes Healing in Diabetic Wounds by Restoring the Macrophage Response

              Prior studies suggest that the impaired healing seen in diabetic wounds derives from a state of persistent hyper-inflammation characterized by harmful increases in inflammatory leukocytes including macrophages. However, such studies have focused on wounds at later time points (day 10 or older), and very little attention has been given to the dynamics of macrophage responses in diabetic wounds early after injury. Given the importance of macrophages for the process of healing, we studied the dynamics of macrophage response during early and late phases of healing in diabetic wounds. Here, we report that early after injury, the diabetic wound exhibits a significant delay in macrophage infiltration. The delay in the macrophage response in diabetic wounds results from reduced Chemokine (C-C motif) ligand 2 (CCL2) expression. Importantly, one-time treatment with chemoattractant CCL2 significantly stimulated healing in diabetic wounds by restoring the macrophage response. Our data demonstrate that, rather than a hyper-inflammatory state; the early diabetic wound exhibits a paradoxical and damaging decrease in essential macrophage response. Our studies suggest that the restoration of the proper kinetics of macrophage response may be able to jumpstart subsequent healing stages. CCL2 chemokine-based therapy may be an attractive strategy to promote healing in diabetic wounds.
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                Author and article information

                Contributors
                ola.tarawneh@zuj.edu.jo
                Journal
                J Mater Sci Mater Med
                J Mater Sci Mater Med
                Journal of Materials Science. Materials in Medicine
                Springer US (New York )
                0957-4530
                1573-4838
                7 January 2025
                7 January 2025
                2025
                : 36
                : 1
                : 2
                Affiliations
                [1 ]Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, ( https://ror.org/04a5b0p13) Amman, Jordan
                [2 ]Department of Basic Medical Sciences, Faculty of Medicine, Al-Balqa Applied University, ( https://ror.org/00qedmt22) Al-Salt, Jordan
                Author information
                http://orcid.org/0000-0001-5876-6939
                http://orcid.org/0000-0001-8164-5422
                http://orcid.org/0000-0003-4263-0134
                Article
                6836
                10.1007/s10856-024-06836-5
                11706890
                3400dafb-b35a-4df4-9466-687e00a6acab
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

                History
                : 29 March 2024
                : 9 October 2024
                Funding
                Funded by: FundRef https://doi.org/10.13039/, Ministry of Higher Education, Hashemite Kingdom of Jordan;
                Award ID: MPH/1/17/2018
                Award Recipient :
                Categories
                Biomaterials Synthesis and Characterization
                Custom metadata
                © Springer Science+Business Media, LLC, part of Springer Nature 2025

                Materials science
                Materials science

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