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ACS Applied Materials & Interfaces · 2020 · IF 8.758

Injectable Adhesive Self-Healing Multicross-Linked Double-Network Hydrogel Facilitates Full-Thickness Skin Wound Healing

Bo Yang,Jiliang Song,Yuhang Jiang,Ming Li,Jingjing Wei,Jiajun Qin,Wanjia Peng,Fernando López Lasaosa,Yiyan He,Hongli Mao,Jun Yang,Zhongwei Gu

The development of natural polymer-based hydrogels, combining outstanding injectability, self-healing, and tissue adhesion, with mechanical performance, able to facilitate full-thickness skin wound healing, remains challenging. We have developed an injectable micellar hydrogel (AF127/HA-ADH/OHA-Dop) with outstanding adhesive and self-healing properties able to accelerate full-thickness skin wound healing. Dopamine-functionalized oxidized hyaluronic acid (OHA-Dop), adipic acid dihydrazide-modified HA (HA-ADH), and aldehyde-terminated Pluronic F127 (AF127) were employed as polymer backbones. They were cross-linked in situ using Schiff base dynamic covalent bonds (AF127 micelle/HA-ADH network and HA-ADH/OHA-Dop network), hydrogen bonding, and π–π stacking interactions. The resulting multicross-linked double-network design forms a micellar hydrogel. The unique multicross-linked double-network structure endows the hydrogel with both improved injection abilities and mechanical performance while self-healing faster than single-network hydrogels. Inspired by mussel foot adhesive protein, OHA-Dop mimics the catechol groups seen in mussel proteins, endowing hydrogels with robust adhesion properties. We also demonstrate the potential of our hydrogels to accelerate full-thickness cutaneous wound closure and improve skin regeneration with reduced scarring. We anticipate that our hydrogel platform based on a novel multicross-linked double-network design will transform the future development of multifunctional wound dressings.

研究领域: 生物材料学 · 再生医学 · 创伤修复
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Advanced Healthcare Materials · 2022 ·Vol. 11 ·期 15 ·2200902 · IF 11.092

Interpenetrating Polymer Network Hydrogels Formed Using Antibiotics as a Dynamic Crosslinker for Treatment of Infected Wounds

Mengjing Fu,Yingying Gan,Fenglin Jiang,Xue Lv,Nathanael Tan,Xiaomiao Zhao,Yi Yan Yang,Peiyan Yuan,Xin Ding

Antibacterial hydrogels, particularly antibiotic-loaded hydrogels, are promising wound dressing materials for treatment of bacteria-infected wound. However, it is challenging to achieve sustained release of antibiotics from hydrogels through physical encapsulation of the antibiotics. Herein, an interpenetrating polymer network P(AA- co -HEMA) Gen hydrogel is reported with double crosslinking formed by free radical polymerization of 2-hydroxyethyl methacrylate (HEMA) and acrylic acid (AA), while using the antibiotic gentamicin (Gen) as the dynamic physical crosslinker. Gentamicin is incorporated into the hydrogel networks via electrostatic interaction between the carboxyl groups of poly(acrylic acid) and the amino groups of gentamicin, which leads to pH-responsive drug release and a significant increase in mechanical strength (i.e., elastic modulus, viscous modulus, and compressive modulus). More importantly, the hydrogels with optimal compositions demonstrate long-lasting antibacterial activity against both Gram-positive bacteria ( Staphylococcus aureus ) and Gram-negative bacteria ( Escherichia coli ) over 28 d. The in vivo studies that are conducted in an S. aureus -infected full-thickness skin wound model demonstrate that the double crosslinking hydrogels loaded with gentamicin eliminate bacteria in the wounds more effectively and significantly accelerate wound healing as compared to 3M dressing and the control without any treatment. Taken together, this antibiotic-loaded interpenetrating polymer network hydrogel is potentially a promising wound dressing material for the treatment of bacteria-infected wound.

研究领域: 材料科学 · 生物医学工程 · 药剂学 · 伤口愈合 · 抗菌治疗
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Biomedical Materials · 2024 · IF 3.9

A low-swelling alginate hydrogel with antibacterial hemostatic and radical scavenging properties for open wound healing

Xuebin Ma,Xiao Fu,Jianwen Meng,Hongmei Li,Fang Wang,Huarong Shao,Yang Liu,Fei Liu,Daizhou Zhang,Bo Chi,Jinlai Miao

Development of a low-cost and biocompatible hydrogel dressing with antimicrobial, antioxidant, and low swelling properties is important for accelerating wound healing. Here, a multifunctional alginate hydrogel dressing was fabricated using the D-(+)-gluconic acid δ-lactone/CaCO3 system. The addition of hyaluronic acid and tannic acid (TA) provides the alginate hydrogel with anti-reactive oxygen species (ROS), hemostatic, and pro-wound healing properties. Notably, soaking the alginate hydrogel in a poly-ε-lysine (EPL) aqueous solution enables the alginate hydrogel to be di-crosslinked with EPL through electrostatic interactions, forming a dense network resembling "armor" on the surface. This simple one-step soaking strategy provides the alginate hydrogel with antibacterial and anti-swelling properties. Swelling tests demonstrated that the cross-sectional area of the fully swollen multifunctional alginate hydrogel was only 1.3 times its initial size, thus preventing excessive wound expansion caused by excessive swelling. After 5 hours of in vitro release, only 7% of TA was cumulatively released, indicating a distinctly slow-release behavior. Furthermore, as evidenced by the removal of 2,2-diphenyl-1-picrylhydrazyl free radicals, this integrated alginate hydrogel systems demonstrate a notable capacity to eliminate ROS. Full-thickness skin wound repair experiment and histological analysis of the healing site in mice demonstrate that the developed multifunctional alginate hydrogels have a prominent effect on extracellular matrix formation and promotion of wound closure. Overall, this study introduces a cost-effective and convenient multifunctional hydrogel dressing with high potential for clinical application in treating open wounds.

CAS / MDL: 28211-04-3
研究领域: 材料科学 · 生物材料 · 伤口愈合 · 生物医学工程 · 药剂学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2019 · IF 4.784

Effective wound dressing based on Poly (vinyl alcohol)/Dextran-aldehyde composite hydrogel

Ce Zheng,Chunyu Liu,Hailiang Chen,Ning Wang,Xia Liu,Guozhen Sun,Weihong Qiao

Wound dressing is of significant importance to promote cutaneous wound healing process. To develop an effective wound dressing, a PVA/DA hydrogel was prepared using a Poly (vinyl alcohol)/Dextran-aldehyde solution blend, followed by crosslinking via freeze-thaw method and freeze-drying. We characterized the hydrogel by infrared spectroscopy, mechanical property tests, swelling behavior test and biocompatibility test. Results showed that the PVA/DA hydrogels had a 3-dimensional, highly porous structure with uniformly distributed pores of 5–10 μm, strong tensile strength of 5.6 MPa, efficient ability to absorb fluid of 6 time its weight and suitable water vapor transmission rate of 2100 g m −2 day −1 to keep a moist environment and good biocompatibility shown by very low hemolysis and no cytotoxicity. In wound healing tests using a full-thickness skin wound model, macroscopic observations showed that the wound covered by the PVA/DA hydrogel almost reached complete healing faster by 10 days, while histological analysis indicated a faster regeneration of skin. Thus, the PVA/DA hydrogel was suitable for application as a wound dressing and may have potential for use in various biomedical applications.

CAS / MDL: 9048-71-9 9004-54-0
研究领域: 材料科学 · 生物医学工程 · 组织工程
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BIOMACROMOLECULES · 2023 · IF 6.2

Bioinspired Adhesive Antibacterial Hydrogel with Self-Healing and On-Demand Removability for Enhanced Full-Thickness Skin Wound Repair

Minwei Yang,Jing Tian,Kaiwen Zhang,Xu Fei,Fawen Yin,Longquan Xu,Yi Wang,Yao Li

Adhesive-caused injury is a great threat for extensive full-thickness skin trauma because extra-strong adhesion can incur unbearable pain and exacerbate trauma upon removal. Herein, inspired by the mussel, we designed and fabricated an adhesive antibacterial hydrogel dressing based on dynamic host–guest interaction that enabled on-demand stimuli-triggered removal to effectively care for wounds. In contrast with most hard-to-removable dressing, this adhesive antibacterial hydrogel exhibited strong adhesion property (85 kPa), which could achieve painless and noninvasive on-demand separation within 2 s through a host–guest competition mechanism (amantadine). At the same time, the hydrogel exhibited rapid self-healing properties, and the broken hydrogel could be completely repaired within 5 min. The hydrogel also had excellent protein adsorption properties, mechanical properties, antibacterial properties, and biocompatibility. This on-demand removal was facilitated by the introduction of amantadine as a competitive guest, without any significant adverse effects on cell activity (>90%) or wound healing (98.5%) in vitro. The full-thickness rat-skin defect model and histomorphological evaluation showed that the hydrogel could significantly promote wound healing and reduce scar formation by regulating inflammation, accelerating skin re-epithelialization, and promoting granulation tissue formation. These results indicate that the developed adhesive antibacterial hydrogel offers a promising therapeutic strategy for the healing of extensive full-layer skin injuries.

研究领域: 材料科学 · 生物医学工程 · 伤口愈合 · 组织工程 · 生物材料
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Biomedical Materials · 2023 ·Vol. 18 ·期 4 ·045007 · IF 4

Resveratrol loaded native silk fiber-sericin hydrogel double interpenetrating bioactive wound dressing facilitates full-thickness skin wound healing

Yanwei Li,Susu Wang,Yurong Li,Guozheng Zhang,Tangfeng Wu,Yongkang Wei,Xinyu Cao,Hui Yan,Peisheng Liang,Zihan Yan,Yanan Guo,Yeshun Zhang

Wound repair is challenging for traditional wound dressings. New bioactive dressings need to be developed urgently. Herein, we reported a highly bioactive silk protein wound dressing (SPD) with natural silk fiber-sericin hydrogel interpenetrating double network structure, which combines the dual characteristics of natural silk and sericin hydrogel. Silk fiber scaffolds were secreted directly from silkworms bred by regulating their spinning behaviors. Sericin in SPD is obtained by dissolving silkworm cocoons at high temperature and high pressure, while it remains intact activities to self-assemble a hydrogel. To explore the effect of SPD, we first systematically evaluated its physicochemical properties and biological activities in vitro. The SPD exhibits high porosity, prominent mechanical strength, pH-responsive degradability, and excellent anti-oxidation and cell compatibility. Besides, SPD can load and maintain long-term drug release. Based on the satisfactory performance of SPD in vitro, effective in vivo treatment was achieved in a mouse full-thickness wound model, as demonstrated by a significantly accelerated wound healing process, promote the regeneration of hair follicles and sebaceous glands, increased expression of vascular endothelial growth factor, and reduced inflammation. Further, resveratrol was loaded into SPD to enhance the effects of anti-oxidation and anti-inflammation for wound healing. Our investigation shows that SPD with excellent physicochemical and biological properties applied in a murine full-thickness skin wound model resulted in remarkable and efficient acceleration of healing process, which may inspire the design of new, effective, and safer medical materials for tissue regeneration.

CAS / MDL: 501-36-0
研究领域: 生物医学工程 · 材料科学 · 组织工程 · 药学 · 伤口护理
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2024 · IF 7.7

Hyaluronic acid hydrogels with excellent self-healing capacity and photo-enhanced mechanical properties for wound healing

Mengfan Zhang,Qi Dong,Kaidan Yang,Ruina Chen,Jing Zhang,Pu Xiao,Yingshan Zhou

A continuously stable moist healing environment is immensely beneficial for wound healing, which can be availably achieved by providing an in situ hydrogel with enough strength resembling skin tissue and self-healing ability. Herein, through a dual-crosslinking strategy, hyaluronic acid-based hydrogels with excellent self-healing capacity and enhanced mechanical properties are fabricated via the acylhydrazone linkages and subsequent photocrosslinking based on hydrazide-modified sodium hyaluronate and aldehyde-modified maleic sodium hyaluronate. The hydrogels demonstrate the fast gelation process (< 1 min), the controlled swelling behaviors, and the good biocompatibility. Notably, they possess enhanced mechanical strength similar to the human dermis (~ 2.2 kPa). Also, they can self-heal rapidly with a self-healing efficiency of ~90 % at 6 h. Based on this, the hyaluronic acid-based hydrogels, without any biological factors involved, can facilitate the full-thickness skin wound reconstruction process by accelerating the three phases of the wound repair, including reducing wound inflammation in the inflammatory phase, promoting angiogenesis in the proliferative phase, and promoting the deposition and reconstruction of collagen in the remodeling phase. The produced hyaluronic acid hydrogel can serve as an ideal candidate for wound healing.

CAS / MDL: 25952-53-8
研究领域: 材料科学 · 生物医学工程 · 伤口愈合
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Advanced Healthcare Materials · 2021 ·Vol. 11 ·期 4 ·2101808 · IF 9.933

One-Step Synthesis of Multifunctional Chitosan Hydrogel for Full-Thickness Wound Closure and Healing

Shen Guo,Minghao Yao,Dan Zhang,Yuanmeng He,Rong Chang,Yikun Ren,Fangxia Guan

Multifunctional hydrogel as a sealant or wound dressing with high adhesiveness and excellent antibacterial activity is highly desirable in clinical applications. In this contribution, one-step synthetic hydrogel based on quaternized chitosan (QCS), tannic acid (TA), and ferric iron (Fe(III)) is developed for skin incision closure and Staphylococcus aureus ( S. aureus )-infected wound healing. In this hydrogel system, the ionic bonds and hydrogen bonds between QCS and TA form the main backbone of hydrogel, the metal coordination bonds between TA and Fe(III) (catechol-Fe) endow hydrogel with excellent adhesiveness and (near-infrared light) NIR-responsive photothermal property, and these multiple dynamic physical crosslinks enable QCS/TA/Fe hydrogel with flexible self-healing ability and injectability. Moreover, QCS/TA/Fe hydrogel possesses superior antioxidant, anti-inflammatory, hemostasis, and biocompatibility. Also, it is safe for vital organs. The data from the mouse skin incision model and infected full-thickness skin wound model presented the high wound closure effectiveness and acceleration of the wound healing process by this multifunctional hydrogel, highlighting its great potential in wound management.

CAS / MDL: 1401-55-4
研究领域: 材料科学 · 生物医学工程 · 伤口愈合 · 药学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2024 · IF 7.7

Multifunctional fish-skin collagen-based hydrogel sealant with dual-dynamic-bond cross-linked for rapid hemostasis and accelerated wound healing

Pei-Fang Cai,Bing-De Zheng,Ya-Ling Xu,Bao-Xia Li,Zhi-Yu Liu,Ya-Yan Huang,Jing Ye,Mei-Tian Xiao

Collagen (COL) is the most widespread functional protein. Designing and developing dual-dynamic-bond cross-linked COL adhesive hydrogel sealants with multifunctional is highly advantageous for achieving a superior wound closure effect and hemostasis. In this study, we developed hybrid hydrogels consisting of fish-skin COL, oxidized sodium alginate (OSA), borax and polyvinyl alcohol (PVA) to enhance full-thickness wound healing. The hydrogels were furnished with first-rate self-healing capabilities through the dual-dynamic-bond cross-linking of dynamic Schiff base bonds (COL-OSA) and diol boric acid bonds (OSA-borax) with reversible breakage and re-formation. Moreover, the incorporation of PVA stimulated the formation of hydrogen bonds in the system, bolstering the stability of the hydrogel framework. The prepared hydrogel manifests self-healing, injectability, multifunctional adhesiveness and biodegradability. In vivo assessment of the hemostatic capacity of COSP 20 hydrogel was superior to gauze both in the mice liver injury model and mice tail amputation model. In addition, a full-thickness skin wound model in mice revealed that the COSP 20 hydrogel facilitated faster wound closure by accelerating reepithelialization, COL deposition and angiogenesis. These findings illustrate the potential of hybrid fish-skin COL-based hydrogels to enhance wound healing and promote rapid tissue repair, and provide new possibilities for the effective utilization of marine fishery resources.

CAS / MDL: 12650-88-3 9001-63-2
研究领域: 生物材料 · 伤口愈合 · 止血 · 生物医学工程 · 组织工程
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2024 · IF 7.7

Multi-dynamic-bond cross-linked antibacterial and adhesive hydrogel based on boronated chitosan derivative and loaded with peptides from Periplaneta americana with on-demand removability

Siwei Liang,Hangping Chen,Yu Chen,Ahamd Ali,Shun Yao

The design and development of a bio-adhesive hydrogel with on-demand removability and excellent antibacterial activities are meaningful to achieve high wound closure effectiveness and post-wound-closure care, which is desirable in clinical applications. In this work, a series of adhesive antioxidant antibacterial hydrogels containing peptides from Periplaneta americana (PAP) were prepared through multi-dynamic-bond cross-linking among 3,4-dihydroxybenzaldehyde (DBA) containing catechol and aldehyde groups and chitosan grafted with 3-carboxy-4-fluorophenylboronic acid (CS-FPBA) to enable the effective adhesion of skin tissues and prevention of bacterial infection of wound. PAP was derived from alcohol-extracted residues generated during the pharmaceutical process, aiming to minimize resource wastage and achieve the high-value development of such a medicinal insect. The hydrogel was prepared by freezing-thawing with no toxic crosslinkers. The multi-dynamic-bond cross-linking of dynamic borate ester bonds and dynamic Schiff base bonds can achieve reversible breakage and re-formation and the adhesive strength of CS-FPBA-DBA-P-gel treated with a 20 % glucose solution dramatically decreased from 3.79 kPa to 0.35 kPa within 10 s. Additionally, the newly developed hydrogel presents ideal biocompatibility, hemostasis and antibacterial activity against Staphylococcus aureus and Escherichia coli compared to commercial chitosan gel (approximately 50 % higher inhibition rate), demonstrating its great potential in dealing with infected full-thickness skin wounds.

研究领域: 生物材料 · 生物医学工程 · 药学 · 伤口愈合 · 组织工程
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Acta Biomaterialia · 2022 · IF 10.633

Dynamically evolving piezoelectric nanocomposites for antibacterial and repair-promoting applications in infected wound healing

Zixin Zhu,Xue Gou,Laiyi Liu,Tian Xia,Jiayi Wang,Yimeng Zhang,Chenjun Huang,Wei Zhi,Ran Wang,Xiaohong Li,Shengnian Luo

Wound healing from bacterial infections is one of the major challenges in the biomedical field. The traditional single administration methods are usually accompanied with side effects or unsatisfactory efficacy. Herein, we design dynamically evolving antibacterial and repair-promoting nanocomposites (NCs) by in situ self-assembling of zeolitic imidazolate framework-8 (ZIF-8) on the surface of barium titanate (BTO), and further loading with a small amount of ciprofloxacin (CIP). The new strategy of combining pH-stimulated drug delivery and ultrasound-controlled sonodyamics has the potential to dynamically evolve in infected wound sites, offering a multifunctional therapy. In vitro study demonstrates that the enhancement generation of reactive oxygen species through the sonodynamic process due to the heterostructures and a small amount of CIP released in an acidic environment are synergistically antibacterial, and the inhibition rate was >99.9%. In addition, reduced sonodynamic effect and Zn 2+ generated along with the gradual degradation of ZIF-8 simultanously promote cell migration and tissue regeneration . The in vivo study of full-thickness skin wounds in mouse models demonstrate a healing rate of 99.3% could be achieved under the treatment of [email protected] /CIP NCs. This work provides a useful improvement in rational design of multi-stimulus-responsive nanomaterials for wound healing. Statement of significance A novel piezoelectric nanocomposite was proposed to realize sonodynamic therapy and pH-stimulated drug releasing simultaneously in wound healing treatment. The dynamically evolving structure of the piezoelectric nanocomposite in acidic microenvironment has been theoretically and experimentally verified to contribute to a continuous variation of sonodymanic strength , which accompanied with the gradual releasing of drug and biocompatible Zn 2+ effectively balanced antibacterial and repair-promoting effects. Both of the in vitro and in vivo study demonstrated that the strategy could significantly accelerate wound healing, inspiring researchers to optimize the design of multi-stimulus-responsive nanomaterials for various applications in biomedical and biomaterial fields.

研究领域: 生物医学工程 · 纳米技术 · 伤口愈合 · 抗菌材料 · 组织工程
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CARBOHYDRATE POLYMERS · 2021 · IF 9.381

Chondroitin sulfate zinc with antibacterial properties and anti-inflammatory effects for skin wound healing

Guofeng Wu,Fenbo Ma,Yizhebang Xue,Ying Peng,Liqiu Hu,Xiaowo Kang,Qili Sun,Dong Fang Ouyang,Bin Tang,Lijun Lin

A chondroitin sulfate zinc (CSZn) complex was prepared by an ion-exchange method. The purified product was characterized by energy-dispersive X-ray spectroscopy, high-performance chromatography, elemental analysis , Fourier transform infrared spectroscopy , inductively coupled mass spectrometry , and nuclear magnetic resonance spectroscopy . The CSZn demonstrated antibacterial activity against Escherichia coli and Staphylococcus aureus and satisfied MTT cell viability (NIH3T3 fibroblasts) at ≤50 μg/mL. RT-PCR demonstrated significant promotion by CSZn of fibroblast growth factor beta (β-FGF), collagen III (COLIIIα1), vascular endothelial growth factor (VEGF) and reduction of cytokines IL-6, IL-1β & TNF-alpha. An in vivo rat full-thickness wound healing model demonstrated significant wound healing of CSZn relative to controls of saline treatment, zinc chloride treatment and chondroitin treatment. CSZn has demonstrated promising antibacterial and wound healing properties making it deserving of consideration for more advanced wound healing applications.

CAS / MDL: 9007-28-7
研究领域: 药学 · 伤口愈合 · 生物材料 · 生物医学工程 · 微生物学 · 细胞生物学
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