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      Bioinspired Andrias davidianus-Derived wound dressings for localized drug-elution

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          Abstract

          Local drug delivery has received increasing attention in recent years. However, the therapeutic efficacy of local delivery of drugs is still limited under certain scenarios, such as in the oral cavity or in wound beds after resection of tumors. In this study, we introduce a bioinspired adhesive hydrogel derived from the skin secretions of Andrias davidianus (SSAD) as a wound dressing for localized drug elution. The hydrogel was loaded with aminoguanidine or doxorubicin, and its controlled drug release and healing-promoting properties were verified in a diabetic rat palatal mucosal defect model and a C57BL/6 mouse melanoma-bearing model, respectively. The results showed that SSAD hydrogels with different pore sizes could release drugs in a controllable manner and accelerate wound healing. Transcriptome analyses of the palatal mucosa suggested that SSAD could significantly upregulate pathways linked to cell adhesion and extracellular matrix deposition and had the ability to recruit keratinocyte stem cells to defect sites. Taken together, these findings indicate that property-controllable SSAD hydrogels could be a promising biofunctional wound dressing for local drug delivery and promotion of wound healing.

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          Highlights

          • The SSAD is a biologically drawable source with facile production, cost-effective, and safe.

          • SSAD increases drug bioavailability with local application.

          • The drug release rate can be controlled by regulating SSAD particle size.

          • The SSAD-based wound dressing is adhesive.

          • SSAD can also promote wound healing.

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          Most cited references55

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          Antibacterial anti-oxidant electroactive injectable hydrogel as self-healing wound dressing with hemostasis and adhesiveness for cutaneous wound healing.

          Injectable self-healing hydrogel dressing with multifunctional properties including anti-infection, anti-oxidative and conductivity promoting wound healing process will be highly desired in wound healing application and its design is still a challenge. We developed a series of injectable conductive self-healed hydrogels based on quaternized chitosan-g-polyaniline (QCSP) and benzaldehyde group functionalized poly(ethylene glycol)-co-poly(glycerol sebacate) (PEGS-FA) as antibacterial, anti-oxidant and electroactive dressing for cutaneous wound healing. These hydrogels presented good self-healing, electroactivity, free radical scavenging capacity, antibacterial activity, adhesiveness, conductivity, swelling ratio, and biocompatibility. Interestingly, the hydrogel with an optimal crosslinker concentration of 1.5 wt% PEGS-FA showed excellent in vivo blood clotting capacity, and it significantly enhanced in vivo wound healing process in a full-thickness skin defect model than quaternized chitosan/PEGS-FA hydrogel and commercial dressing (Tegaderm™ film) by upregulating the gene expression of growth factors including VEGF, EGF and TGF-β and then promoting granulation tissue thickness and collagen deposition. Taken together, the antibacterial electroactive injectable hydrogel dressing prolonged the lifespan of dressing relying on self-healing ability and significantly promoted the in vivo wound healing process attributed to its multifunctional properties, meaning that they are excellent candidates for full-thickness skin wound healing.
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            Myofibroblasts and mechano-regulation of connective tissue remodelling.

            During the past 20 years, it has become generally accepted that the modulation of fibroblastic cells towards the myofibroblastic phenotype, with acquisition of specialized contractile features, is essential for connective-tissue remodelling during normal and pathological wound healing. Yet the myofibroblast still remains one of the most enigmatic of cells, not least owing to its transient appearance in association with connective-tissue injury and to the difficulties in establishing its role in the production of tissue contracture. It is clear that our understanding of the myofibroblast its origins, functions and molecular regulation will have a profound influence on the future effectiveness not only of tissue engineering but also of regenerative medicine generally.
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              Regulation of Wound Healing by Growth Factors and Cytokines

              Cutaneous wound healing is a complex process involving blood clotting, inflammation, new tissue formation, and finally tissue remodeling. It is well described at the histological level, but the genes that regulate skin repair have only partially been identified. Many experimental and clinical studies have demonstrated varied, but in most cases beneficial, effects of exogenous growth factors on the healing process. However, the roles played by endogenous growth factors have remained largely unclear. Initial approaches at addressing this question focused on the expression analysis of various growth factors, cytokines, and their receptors in different wound models, with first functional data being obtained by applying neutralizing antibodies to wounds. During the past few years, the availability of genetically modified mice has allowed elucidation of the function of various genes in the healing process, and these studies have shed light onto the role of growth factors, cytokines, and their downstream effectors in wound repair. This review summarizes the results of expression studies that have been performed in rodents, pigs, and humans to localize growth factors and their receptors in skin wounds. Most importantly, we also report on genetic studies addressing the functions of endogenous growth factors in the wound repair process.
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                Author and article information

                Contributors
                Journal
                Bioact Mater
                Bioact Mater
                Bioactive Materials
                KeAi Publishing
                2452-199X
                14 January 2022
                September 2022
                14 January 2022
                : 15
                : 482-494
                Affiliations
                [a ]Chongqing Key Laboratory of Oral Disease and Biomedical Sciences and Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education and Stomatological Hospital, Chongqing Medical University, Chongqing, 401174, China
                [b ]State Key Laboratory of Ultrasound in Medicine and Engineering and Chongqing Key Laboratory of Biomedical Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, China
                [c ]Department of Stomatology, The Third Affiliated Hospital, Chongqing Medical University, Chongqing, 401120, China
                [d ]Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhi Zao Ju Rd, Shanghai, 200011, China
                [e ]Department of Pharmacy, The 958th Hospital of PLA, Chongqing, 404100, China
                [f ]Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, 02139, USA
                [g ]Department of Plastic and reconstructive surgery, Hainan Western Central Hospital, HaiNan, 571700, China
                Author notes
                []Corresponding author. songjinlin@ 123456hospital.cqmu.edu.cn
                [∗∗ ]Corresponding author. yszhang@ 123456research.bwh.harvard.edu
                [∗∗∗ ]Corresponding author. zhangximu@ 123456hospital.cqmu.edu.cn
                [1]

                Co-first authors.

                Article
                S2452-199X(21)00572-7
                10.1016/j.bioactmat.2021.11.030
                8965088
                35386341
                87ad900a-efc8-4716-b705-5b12091473b2
                © 2021 The Authors

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

                History
                : 11 April 2021
                : 20 October 2021
                : 22 November 2021
                Categories
                Article

                andrias davidianus,hydrogel,drug loading,controlled drug delivery,stem cell recruitment,wound healing

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