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      Metal nanoparticle hybrid hydrogels: the state-of-the-art of combining hard and soft materials to promote wound healing

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          Abstract

          Wounds represent a grave affliction that profoundly impacts human well-being. Establishing barriers, preventing infections, and providing a conducive microenvironment constitute the crux of wound therapy. Hydrogel, a polymer with an intricate three-dimensional lattice, serves as a potent tool in erecting physical barriers and nurturing an environment conducive to wound healing. This enables effective control over exudation, hemostasis, accelerated wound closure, and diminished scar formation. As a result, hydrogels have gained extensive traction in the realm of wound treatment. Metallic nanoparticle carriers, characterized by their multifaceted responses encompassing acoustics, optics, and electronics, have demonstrated efficacy in wound management. Nevertheless, these carriers encounter challenges associated with swift clearance and nonuniform effectiveness. The hybridization of metallic nanoparticle carriers with hydrogels overcomes the shortcomings inherent in metallic nanoparticle-based wound therapy. This amalgamation not only addresses the limitations but also augments the mechanical robustness of hydrogels. It confers upon them attributes such as environmental responsiveness and multifunctionality, thereby synergizing strengths and compensating for weaknesses. This integration culminates in the precise and intelligent management of wounds. This review encapsulates the structural classifications, design strategies, therapeutic applications, and underlying mechanisms of metal nanoparticle hybrid hydrogels in the context of acute and chronic wound treatment. The discourse delves into the generation of novel or enhanced attributes arising from hybridization and how the current paradigm of wound therapy leverages these attributes. Amidst this continually evolving frontier, the potential of metal nanoparticle hybrid hydrogels to revolutionize wound treatment is underscored.

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          Functional Hydrogels as Wound Dressing to Enhance Wound Healing

          Hydrogels, due to their excellent biochemical and mechnical property, have shown attractive advantages in the field of wound dressings. However, a comprehensive review of the functional hydrogel as a wound dressing is still lacking. This work first summarizes the skin wound healing process and relates evaluation parameters and then reviews the advanced functions of hydrogel dressings such as antimicrobial property, adhesion and hemostasis, anti-inflammatory and anti-oxidation, substance delivery, self-healing, stimulus response, conductivity, and the recently emerged wound monitoring feature, and the strategies adopted to achieve these functions are all classified and discussed. Furthermore, applications of hydrogel wound dressing for the treatment of different types of wounds such as incisional wound and the excisional wound are summarized. Chronic wounds are also mentioned, and the focus of attention on infected wounds, burn wounds, and diabetic wounds is discussed. Finally, the future directions of hydrogel wound dressings for wound healing are further proposed.
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            Antibacterial adhesive injectable hydrogels with rapid self-healing, extensibility and compressibility as wound dressing for joints skin wound healing

            Designing wound dressing materials with outstanding therapeutic effects, self-healing, adhesiveness and suitable mechanical property has great practical significance in healthcare, especially for joints skin wound healing. Here, we designed a kind of self-healing injectable micelle/hydrogel composites with multi-functions as wound dressing for joint skin damage. By combining the dynamic Schiff base and copolymer micelle cross-linking in one system, a series of hydrogels were prepared by mixing quaternized chitosan (QCS) and benzaldehyde-terminated Pluronic®F127 (PF127-CHO) under physiological conditions. The inherent antibacterial property, pH-dependent biodegradation and release behavior were investigated to confirm multi-functions of wound dressing. The hydrogel dressings showed suitable stretchable and compressive property, comparable modulus with human skin, good adhesiveness and fast self-healing ability to bear deformation. The hydrogels exhibited efficient hemostatic performance and biocompatibility. Moreover, the curcumin loaded hydrogel showed good antioxidant ability and pH responsive release profiles. In vivo experiments indicated that curcumin loaded hydrogels significantly accelerated wound healing rate with higher granulation tissue thickness and collagen disposition and upregulated vascular endothelial growth factor (VEGF) in a full-thickness skin defect model. Taken together, the antibacterial adhesive hydrogels with self-healing and good mechanical property offer significant promise as dressing materials for joints skin wound healing.
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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.

                Author and article information

                Journal
                Theranostics
                Theranostics
                thno
                Theranostics
                Ivyspring International Publisher (Sydney )
                1838-7640
                2024
                27 January 2024
                : 14
                : 4
                : 1534-1560
                Affiliations
                [1 ]Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai, 200433, People's Republic of China.
                [2 ]Changhai Clinical Research Unit, The First Affiliated Hospital of Naval Medical University, Shanghai, 200433, People's Republic of China.
                [3 ]Shanghai Key Laboratory of Nautical Medicine and Translation of Drugs and Medical Devices, Shanghai, 200433, People's Republic of China.
                Author notes
                ✉ Corresponding authors: Jie Gao: Tel.: +86 21 31166666; Fax: +86 21 31162332. Shichu Xiao: Tel.: +86 13166379405; Fax: +86 21 65589829. Shizhao Ji: Tel.: +86 18621583165; Fax: +86 21 65589829. Email addresses: ttddtds@ 123456163.com (Yuxiang Wang), yanzhenzhen_7@ 123456163.com (Zhenzhen Yan), zhangmengya0822@ 123456163.com (Mengya Zhang), shizhaoji2022@ 123456163.com (Shizhao Ji), huangzhuoxiao4@ 123456hotmail.com (Shichu Xiao), gaojiehighclea@ 123456smmu.edu.cn (Jie Gao).

                # These authors contributed equally to this work.

                Competing Interests: The authors have declared that no competing interest exists.

                Article
                thnov14p1534
                10.7150/thno.91829
                10879867
                38389845
                c713d32e-94e2-4616-b59f-7a82850938c7
                © The author(s)

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.

                History
                : 2 November 2023
                : 27 December 2023
                Categories
                Review

                Molecular medicine
                metal nanoparticles,hydrogels,wound healing,skin tissue engineering,biomaterials

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