A Novel Wound Dressing Based on Ag/Graphene Polymer Hydrogel: Effectively Kill Bacteria and Accelerate Wound Healing

Avoiding wound infection and retaining an appropriate level of moisture around woundz are major challenges in wound care management. Therefore, designing hydrogels with desired antibacterial performance and good water‐maintaining ability is of particular significance to promote the development of wound dressing. Thus a series of hydrogels are prepared by crosslinking of Ag/graphene composites with acrylic acid and N,N′‐methylene bisacrylamide at different mass ratios. The antibacterial performance and accelerated wound‐healing ability of hydrogel are systematically evaluated with the aim of attaining a novel and effective wound dressing. The as‐prepared hydrogel with the optimal Ag to graphene mass ratio of 5:1 (Ag5G1) exhibits stronger antibacterial abilities than other hydrogels. Meanwhile, Ag5G1 hydrogel exhibits excellent biocompatibility, high swelling ratio, and good extensibility. More importantly, in vivo experiments indicate that Ag5G1 hydrogel can significantly accelerate the healing rate of artificial wounds in rats, and histological examination reveals that it helps to successfully reconstruct intact and thickened epidermis during 15 day of healing of impaired wounds. In one word, the present approach can shed new light on designing of antibacterial material like Ag/graphene composite hydrogel with promising applications in wound dressing.     

Silk-Inspired In Situ Hydrogel with Anti-Tumor Immunity Enhanced Photodynamic Therapy for Melanoma and Infected Wound Healing

Easy cancer recurrence and wound infections have been clinical challenges after surgical treatment of melanoma. Herein, a silk-inspired in situ gelation system containing methacrylated silk fibroin (SF) and chlorine e6 for improved cancer therapy with enhanced wound healing is developed. Favored by the macrophage recruitment capacity of the SF hydrogel, promising antitumor immune responses can be turned “on” via near infrared irradiation in a controllable manner to achieve combination therapy with photodynamic therapy to significantly suppress melanoma recurrence. Moreover, the effective photodynamic antibacterial activity of this bioactive system with the capacity of light-controllable modulating macrophage phenotype promotes remarkable tissue ingrowth with hair follicle regeneration for Staphylococcus aureus infected wound healing. Thus, this multifunctional silk-based hydrogel system, as a desirable wound dressing, provides a new platform for promising melanoma therapy and skin regeneration.     

Injectable Self‐Healing Antibacterial Bioactive Polypeptide‐Based Hybrid Nanosystems for Efficiently Treating Multidrug Resistant Infection,Skin‐Tumor Therapy,and Enhancing Wound Healing

The surgical procedure in skin‐tumor therapy usually results in cutaneous defects, and multidrug‐resistant bacterial infection could cause chronic wounds. Here, for the first time, an injectable self‐healing antibacterial bioactive polypeptide‐based hybrid nanosystem is developed for treating multidrug resistant infection, skin‐tumor therapy, and wound healing. The multifunctional hydrogel is successfully prepared through incorporating monodispersed polydopamine functionalized bioactive glass nanoparticles (BGN@PDA) into an antibacterial F127‐ε‐Poly‐L‐lysine hydrogel. The nanocomposites hydrogel displays excellent self‐healing and injectable ability, as well as robust antibacterial activity, especially against multidrug‐resistant bacteria in vitro and in vivo. The nanocomposites hydrogel also demonstrates outstanding photothermal performance with (near‐infrared laser irradiation) NIR irradiation, which could effectively kill the tumor cell (>90%) and inhibit tumor growth (inhibition rate up to 94%) in a subcutaneous skin‐tumor model. In addition, the nanocomposites hydrogel effectively accelerates wound healing in vivo. These results suggest that the BGN‐based nanocomposite hydrogel is a promising candidate for skin‐tumor therapy, wound healing, and anti‐infection. This work may offer a facile strategy to prepare multifunctional bioactive hydrogels for simultaneous tumor therapy, tissue regeneration, and anti‐infection.     

Physical Double‐Network Hydrogel Adhesives with Rapid Shape Adaptability,Fast Self‐Healing,Antioxidant and NIR/pH Stimulus‐Responsiveness for Multidrug‐Resistant Bacterial Infection and Removable Wound Dressing

Developing physical double‐network (DN) removable hydrogel adhesives with both high healing efficiency and photothermal antibacterial activities to cope with multidrug‐resistant bacterial infection, wound closure, and wound healing remains an ongoing challenge. An injectable physical DN self‐healing hydrogel adhesive under physiological conditions is designed to treat multidrug‐resistant bacteria infection and full‐thickness skin incision/defect repair. The hydrogel adhesive consists of catechol–Fe³⁺ coordination cross‐linked poly(glycerol sebacate)‐co‐poly(ethylene glycol)‐g‐catechol and quadruple hydrogen bonding cross‐linked ureido‐pyrimidinone modified gelatin. It possesses excellent anti‐oxidation, NIR/pH responsiveness, and shape adaptation. Additionally, the hydrogel presents rapid self‐healing, good tissue adhesion, degradability, photothermal antibacterial activity, and NIR irradiation and/or acidic solution washing‐assisted removability. In vivo experiments prove that the hydrogels have good hemostasis of skin trauma and high killing ratio for methicillin‐resistant staphylococcus aureus (MRSA) and achieve better wound closure and healing of skin incision than medical glue and surgical suture. In particular, they can significantly promote full‐thickness skin defect wound healing by regulating inflammation, accelerating collagen deposition, promoting granulation tissue formation, and vascularization. These on‐demand dissolvable and antioxidant physical double‐network hydrogel adhesives are excellent multifunctional dressings for treating in vivo MRSA infection, wound closure, and wound healing.     

Construction of Chitosan‐Based Hydrogel Incorporated with Antimonene Nanosheets for Rapid Capture and Elimination of Bacteria

To elaborately construct a novel and efficient photothermal antibacterial nanoplatform is a promising strategy for treating bacterial wound infections. In this work, a composite hydrogel (CS/AM NSs hydrogel) with outstanding antibacterial ability is constructed by incorporating antimonene nanosheets (AM NSs) with extraordinary photothermal properties into the network structure of chitosan (CS). When cultured with bacteria, the CS/AM NSs hydrogel can gather bacteria on the surface through the interaction of CS with the bacterial cell membrane. Subsequently, the intrinsic bactericidal property of CS will kill some of the bacteria. After the introduction of near‐infrared laser, the AM NSs effectively convert light energy into localized heat to eliminate residual bacteria. By virtue of the synergistic action between the capture effect of CS and the photothermal effect of AM NSs, the CS/AM NSs hydrogel shows predominant antibacterial behavior against Escherichia coli and Staphylococcus aureus. In vitro assay and in vivo tests of infected full‐thickness defect wound healing confirm the satisfactory biocompatibility and antibacterial ability. Overall, this work reveals that the CS/AM NSs hydrogel holds great potential as a broad‐spectrum antibacterial wound dressing for treating bacteria‐infected wounds. Additionally, this is the first report of the application of AM NSs in the field of antibacterial treatment.     

A Macroporous Hydrogel Dressing with Enhanced Antibacterial and Anti‐Inflammatory Capabilities for Accelerated Wound Healing

Here, a novel macroporous hydrogel dressing is presented that can accelerate wound healing and guard against bacteria‐associated wound infection. Carboxymethyl agarose (CMA) is successfully prepared from agarose. The CMA molecular chains are cross‐linked by hydrogen bonding to form a supramolecular hydrogel, and the hydroxy groups in the CMA molecules complex with Ag⁺ to promote hydrogel formation. This hydrogel composite exhibits pH‐responsiveness and temperature‐responsiveness and releases Ag⁺, an antibacterial agent, over a prolonged period of time. Moreover, this hydrogel exhibits outstanding cytocompatibility and hemocompatibility. In vitro and in vivo investigations demonstrate that the hydrogel has enhanced antibacterial and anti‐inflammatory capabilities and can significantly accelerate skin tissue regeneration and wound closure. Astonishingly, the hydrogel can cause the inflammation process to occur earlier and for a shorter amount of time than in a normal process. Given its excellent antibacterial, anti‐inflammatory, and physicochemical properties, the broad application of this hydrogel in bacteria‐associated wound management is anticipated.     

Mussel‐Inspired Contact‐Active Antibacterial Hydrogel with High Cell Affinity,Toughness, and Recoverability

Antibacterial hydrogel has received extensive attention in soft tissue repair, especially preventing infections those associated with impaired wound healing. However, it is challenging in developing an inherent antibacterial hydrogel integrating with excellent cell affinity and superior mechanical properties. Inspired by the mussel adhesion chemistry, a contact‐active antibacterial hydrogel is proposed by copolymerization of methacrylamide dopamine (MADA) and 2‐(dimethylamino)ethyl methacrylate and forming an interpenetrated network with quaternized chitosan. The reactive catechol groups of MADA endow the hydrogel with contact intensified bactericidal activity, because it increases the exposure of bacterial cells to the positively charged groups of the hydrogel and strengthens the bactericidal effect. MADA also maintains the good adhesion of fibroblasts to the hydrogel. Moreover, the hybrid chemical and physical cross‐links inner the hydrogel network makes the hydrogel strong and tough with good recoverability. In vitro and in vivo tests demonstrate that this tough and contact‐active antibacterial hydrogel is a promising material to fulfill the dual functions of promoting tissue regeneration and preventing bacterial infection for wound‐healing applications.     

A Multifunctional Pro‐Healing Zwitterionic Hydrogel for Simultaneous Optical Monitoring of pH and Glucose in Diabetic Wound Treatment

Diabetic ulcer is the most common kind of chronic wound worldwide. Though great efforts have been devoted, diabetic ulcer still remains as a challenge that requires constant monitoring and management. In this work, a multifunctional zwitterionic hydrogel is developed to simultaneously detect two fluctuant wound parameters, pH and glucose level, to monitor the diabetic wound status. A pH indicator dye (phenol red) and two glucose sensing enzymes, glucose oxidase (GOx) and horseradish peroxidase (HRP), are encapsulated in the anti‐biofouling and biocompatible zwitterionic poly‐carboxybetaine (PCB) hydrogel matrix. The visible images are collected by a smartphone and transformed into RGB signals to quantify the wound parameters. Results show that the activity and stability of both two enzymes are improved within PCB hydrogel, and the K_cat/K_m value of PCB‐HRP is ≈5.5 fold of free HRP in artificial wound exudate. This novel wound dressing can successfully monitor the pH range of 4–8 and glucose level of 0.1–10 × 10^?3 m . Meanwhile, it also provides a moist healing environment that can promote diabetic wound healing. This multifunctional wound dressing may open vistas in chronic wound management and guide the diabetes treatment in clinical applications.     

Bioinspired Intrinsic Versatile Hydrogel Fabricated by Amyloidal Toxin Simulant-Based Nanofibrous Assemblies for Accelerated Diabetic Wound Healing

Persistent microbial infection and decreased neovascularization are common issues associated with diabetic wound treatment. Hydrogel dressings that offer intrinsic antibacterial and angiogenesis-inducing may substantially avoid the use of antibiotics or angiogenic agents. Herein, a versatile hydrogel is fabricated using an amyloid-derived toxin simulant (Fmoc-LFKFFK-NH₂, FLN) as building blocks, inspired by the defense strategy of Staphylococcus aureus (S. aureus). The simulant assemblies of the hydrogel function as both matrix components and functional elements for diabetic wound treatment. The hydrogel undergoes quick assembly from random monomers to nanofibrils with abundant b-sheet driven by multiple non-covalent interactions. The developed hydrogel demonstrates excellent biocompatibility and accelerates angiogenesis via hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor A (VEGFA) signaling as a consequence of its amyloidal structure. The simulant-based nanofibrils endow the hydrogel with broad-spectrum antibacterial activity dominated by a membrane-disruption mechanism. In addition, the hydrogel exhibits excellent performance compared with the commercial hydrogel Prontosan in accelerating wound healing of diabetic mice infected with methicillin-resistant S. aureus (MRSA). This study highlights the fabrication of a single component and versatile hydrogel platform, thereby avoiding the drug-related side effects and complicated preparations and demonstrating its profound potential as a clinical dressing for the management of microbe-infected diabetic wounds.     

Rapid Sterilization and Accelerated Wound Healing Using Zn2+ and Graphene Oxide Modified g‐C3N4 under Dual Light Irradiation

Wound healing is affected by bacterial infection and related inflammation, cell proliferation and differentiation, and tissue remodeling. Current antibiotics therapy cannot promote wound healing and kill bacteria at the same time. Herein, hybrid nanosheets of g‐C₃N₄‐Zn²⁺@graphene oxide (SCN‐Zn²⁺@GO) are prepared by combining Zn²⁺ doped sheet‐like g‐C₃N₄ with graphene oxide via electrostatic bonding and π–π stacking interactions to assist wound healing and kill bacteria simultaneously by short‐time exposure to 660 and 808 nm light. The gene expressions of matrix metalloproteinase‐2, type I collagen, type III collagen, and interleukin β in fibroblasts are regulated by GO and released Zn²⁺, which can accelerate wound healing. Co‐irradiation produces an antibacterial ratio over 99.1% within a short time because of the synergistic effects of both photodynamic antibacterial and photothermal antibacterial treatments. The hyperthermia produced by 808 nm light illumination can weaken the bacterial activity. And these bacteria can be easily killed by membrane destruction, protein denaturation, and disruption of bacterial metabolic pathways due to reactive oxygen species produced under 660 nm light irradiation. This strategy of Zn²⁺ and GO modification can increase the antibacterial efficacy of SCN and accelerate wound healing at the same time, which makes this SCN‐Zn²⁺@GO be very promising in bacteria‐infected wound healing therapy.     

Liquid Bandage Harvests Robust Adhesive,Hemostatic, and Antibacterial Performances as a First‐Aid Tissue Adhesive

Massive bleeding and wound infection after tissue trauma are the major dangerous factors of casualties in disasters; hence, first‐aid supplies that can greatly achieve wound closure and effectively control the hemorrhage and infection are urgently needed. Although existing tissue adhesives can adhere to the tissue surfaces and achieve rapid wound closure, most of them have limited hemostatic and antibacterial capacities, making them unsuitable as the first‐aid tissue adhesives. In this study, inspired by the inherent hemostatic and antibacterial capacities of chitosan and the excellent tissue integration capacity originating from a Schiff base reaction, liquid bandage (LBA), an in situ imine crosslinking‐based photoresponsive chitosan hydrogel (NB‐CMC/CMC hydrogel), is developed for emergency wound management. Upon UV irradiation, o‐nitrobenzene in modified carboxymethyl chitosan (CMC) converts to o‐nitrosobenzaldehyde that subsequently crosslinks with amino groups on tissue surface, which endows the LBA with superior tissue adhesive performance. LBA's hemostatic and antibacterial properties can be tuned by the mass ratio of NB‐CMC/CMC. Moreover, it exhibits satisfactory biocompatibility, biodegradability, and the capability to enhance wound healing process. This study sheds new light on the development of a multifunctional hydrogel‐based first‐aid tissue adhesive that can achieve robust tissue adhesion, effectively control bleeding, prevent bacterial infection, and promote wound healing.     

Multifunctional Injectable Hydrogel Dressings for Effectively Accelerating Wound Healing: Enhancing Biomineralization Strategy

Bacterial infection can cause chronic nonhealing wounds, which may be a great threat to public health. It is highly desirable to develop an injectable wound dressing hydrogel with multifunctions including self-healing, remodeling, antibacterial, radical scavenging ability, and excellent photothermal properties to promote the regeneration of damaged tissues in clinical practice. In this work, dopamine-modified gelatin (Gel-DA) is employed for the first time as a biotemplate for enhancing the biomineralization ability of gelatin to synthesize dopamine-modified gelatin@Ag nanoparticles (Gel-DA@Ag NPs). Further, the prepared Gel-DA@Ag NPs with antioxidant activity and near-infrared (NIR) laser irradiation synergistic antibacterial behavior are fixed in the guar gum based hydrogels through the formation of borate/didiol bonds to possess remolding, injectable, and self-healing performance. In addition, the multifunctional hydrogels can completely cover the irregular wound shape to prevent secondary injury. More importantly, these hydrogel platforms under NIR can significantly accelerate wound healing with more skin appendages like hair follicles and blood vessels appearing. Therefore, it is expected that these hydrogels can serve as competitive multifunctional dressings in biomedical field, including bacteria-derived wound infection and other tissue repair related to reactive oxygen species overexpression.     

Multifunctional DNA Hydrogels with Hydrocolloid-Cotton Structure for Regeneration of Diabetic Infectious Wounds

Currently, diabetic infectious wound treatments remain a significant challenge for regenerative medicine due to the unicity of clinical dressings, which lack systemic multifunctional wound dressings with high absorbability, customizable shape, rapid self-healing, guiding tissue regeneration, and restoring physiological functions. Here, a multifunctional DNA hydrogel is conveniently obtained through grafting DNA units and polyethyleneimine dynamic cross-linking and doped heating function black phosphorus quantum dots. The obtained DNA hydrogel features excellent exudate absorption performance, adjustable heating ability, mechanical behavior, self-healing ability, writability, tissue adhesion, and antibacterial properties. The incorporation of procyanidin B2 (OPC B2) endows the DNA hydrogels with renowned scavenging free radicals and antioxidant properties. Furthermore, the DNA hydrogel dressing can promote the transformation of macrophages from pro-inflammatory M1 into repairing M2 phenotype, keeping the wound in a stable remodeled state. Astonishingly, the DNA hydrogel dressing can activate neurons to transform into a repair state, accelerating skin nerve regeneration and angiogenesis. Beyond that, it can recruit myeloid cells to activate the adaptive immune response, enhancing the ability of DNA hydrogel dressing to promote tissue regeneration, thereby promoting hair follicle and hair regeneration. Therefore, this advanced collaborative strategy provides an effective method for cascade management of clinical guided tissue regeneration.     

Engineering Bioactive M2 Macrophage-Polarized Anti-Inflammatory,Antioxidant, and Antibacterial Scaffolds for Rapid Angiogenesis and Diabetic Wound Repair

Diabetic wound healing still faces great challenges due to the excessive inflammation, easy infection, and impaired angiogenesis in wound beds. The immunoregulation of macrophages polarization toward M2 phenotype that facilitates the transition from inflammation to proliferation phase has been proved to be an effective way to improve diabetic wound healing. Herein, an M2 phenotype-enabled anti-inflammatory, antioxidant, and antibacterial conductive hydrogel scaffolds (GDFE) for producing rapid angiogenesis and diabetic wound repair are reported. The GDFE scaffolds are fabricated facilely through the dynamic crosslinking between polypeptide and polydopamine and graphene oxide. The GDFE scaffolds possess thermosensitivity, self-healing behavior, injectability, broad-spectrum antibacterial activity, antioxidant and anti-inflammatory ability, and electronic conductivity. GDFE effectively activates the polarization of macrophages toward M2 phenotype and significantly promotes the proliferation of dermal fibroblasts, the migration, and in vitro angiogenesis of endothelial cells through paracrine mechanisms. The in vivo results from a full-thickness diabetic wound model demonstrate that GDFE can rapidly promote the diabetic wound repair and skin regeneration, through fast anti-inflammation and angiogenesis and M2 macrophage polarization. This study provides highly efficient strategy for treating diabetic wound repair through designing the M2 polarization-enabled anti-inflammatory, antioxidant, and antibacterial bioactive materials.     

A Novel Double‐Crosslinking‐Double‐Network Design for Injectable Hydrogels with Enhanced Tissue Adhesion and Antibacterial Capability for Wound Treatment

Most photocrosslinkable hydrogels have inadequacy in either mechanical performance or biodegradability. This issue is addressed by adopting a novel hydrogel design by introducing two different chitosan chains (catechol‐modified methacryloyl chitosan, CMC; methacryloyl chitosan, MC) via the simultaneous crosslinking of carbon–carbon double bonds and catechol‐Fe³⁺ chelation. This leads to an interpenetrating network of two chitosan chains with high crosslinking‐network density, which enhances mechanical performance including high compressive modulus and high ductility. The chitosan polymers not only endow the hydrogels with good biodegradability and biocompatibility, they also offer intrinsic antibacterial capability. The quinone groups formed by Fe³⁺ oxidation and protonated amino groups of chitosan polymer further enhance antibacterial property of the hydrogels. Serving as one of the two types of crosslinking mechanisms, the catechol‐Fe³⁺ chelation can covalently link with amino, thiol, and imidazole groups, which substantially enhance the hydrogel's adhesion to biological tissues. The hydrogel's adhesion to porcine skin shows a lap shear strength of 18.1 kPa, which is 6‐time that of the clinically established Fibrin Glue's adhesion. The hydrogel also has a good hemostatic performance due to the superior tissue adhesion as demonstrated with a hemorrhaging liver model. Furthermore, the hydrogel can remarkably promote healing of bacteria‐infected wound.     

Construction of Nanozyme‐Hydrogel for Enhanced Capture and Elimination of Bacteria

The widespread multidrug resistance resulting from the abuse of antibiotics motivates researchers to explore alternative methods to treat bacterial infections. Recently, the emergence of nanozymes has provided a potential approach to combat bacteria. Such nanozymes can mimic the functions of natural enzymes to induce the production of highly toxic reactive oxygen species (ROS) as an antibacterial. However, the lack of effective interaction between nanozymes and bacteria, and the intrinsic short lifetime and diffusion distance of ROS greatly compromise their bactericidal activity. Furthermore, the dead bacteria left in the infected area can give rise to unexpected tissue inflammation. Herein, for the first time, a nanozyme‐hydrogel is constructed to realize reinforced antibacterials. The nanozyme‐hydrogel with the traits of positive charge and macropore can capture and restrict bacteria in the range of ROS destruction. Significantly, by combining the near‐infrared photothermal property of nanozymes, the nanozyme‐hydrogel can achieve a synergistic bactericidal effect. More importantly, the nanozyme‐hydrogel can eliminate bacteria and reduce the risk of inflammation. In consequence, the current work manifests an original strategy to improve the antibacterial performance of nanozymes, concurrently promote wound healing.     

Ag Nanoparticles Cluster with pH‐Triggered Reassembly in Targeting Antimicrobial Applications

Antibacterial efficiency can be effectively improved by applying targeting antibacterial materials and strategies. Herein, the successful synthesis of uniform pH‐responsive Ag nanoparticle clusters (AgNCs) is demonstrated, which can collapse and reassemble into nonuniform Ag NPs upon exposure to the acidic microenvironment of bacterial infections. This pH triggered reassembly contributes greatly to the improved antibacterial activities of AgNCs against both methicillin‐resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli). The minimum inhibitory concentration and minimum bactericidal concentration against MRSA are as low as 4 and 32 µg mL^?1 (which are 8 and 32 µg mL^?1 for E. coli), respectively. In vivo skin wound healing experiments confirm AgNCs can serve as an effective wound dressing to accelerate the healing of MRSA infection. The development of responsive AgNCs offers new materials and strategies in targeting antibacterial applications.     

Silver/Reduced Graphene Oxide Hydrogel as Novel Bactericidal Filter for Point‐of‐Use Water Disinfection

Nanomaterials open an alternative way for water disinfection. However, limitations such as aggregation, toxicity, and complex post‐treatment block their practical application. In this study, an antibacterial silver/reduced graphene oxide (Ag/rGO) hydrogel consisting of controlled porous rGO network and well‐dispersed Ag nanoparticle is synthesized by a facile hydrothermal reaction. Scanning electron microscopy, transmission electron microscope, X‐ray diffraction, mercury porosimetry, and Fourier transform IR spectroscopy are employed to characterize the Ag/rGO hydrogel. The 3D structure of the rGO network serves as an excellent support for Ag nanoparticles. Disinfection experiments show that the Ag/rGO hydrogel exhibits good efficacy against Escherichia coli when used as a bactericidal filter driven by gravity. The mechanistic study indicates that bacteria cells are inactivated due to cell membrane damage induced by silver nanoparticles and rGO nanosheets when they flow through Ag/rGO hydrogel. Moreover, due to the retaining of Ag by rGO, the leaching level of silver from Ag/rGO hydrogel is considerably lower than the drinking water standard. This study sheds new light on designing antibacterial materials for point‐of‐use water disinfection application.     

Multiple Stimuli-Responsive Nanozyme-Based Cryogels with Controlled NO Release as Self-Adaptive Wound Dressing for Infected Wound Healing

Wound with drug-resistant bacterial infections has become a serious challenge for the healthcare system, and designing wound dressing to self-adapt to the need of different stage of wound healing remains challenging. Herein, self-adaptive wound dressings with multiple stimuli-responsiveness and antibacterial activity are developed. Specifically, MoS₂ carrying a reactive oxygen species (ROS) responsive nitric oxide (NO) release precursor L-arginine (MSPA) is designed and incorporated into carboxymethyl chitosan/poly( N-isopropylacrylamide) based cryogels (CMCS/PNIPAM) with multiple responsiveness (pH, near infrared (NIR), and temperature) to form self-adaptive antibacterial cryogels that adapt to the therapeutic needs of different stages in infected wound healing. In response to the slightly acidic environment of bacterial infection, the cryogels assist the bacterial capture capacity through acid-triggered protonation behavior, and effectively enhance the photodynamic antibacterial efficiency. Controllable on-demand delivery of ROS, NO, and remote management of infected biofluid are achieved with NIR light as a trigger switch. The multiple stimuli-responsive nanozyme-based cryogels efficiently eliminate MRSA bacterial biofilm through NO assisted photodynamicand photothermal therapy (PDT&PTT). The multiple enzyme-like activities of the cryogels effectively relieved oxidative damage. Notably, these cryogels effectively reduce wound infection, alleviated oxidative stress, and accelerate collagen deposition and angiogenesis in infected wounds, indicating that multiple stimuli-responsive self-adaptive wound dressings provide new ideas for infected wound treatment.     

A Cooperative Copper Metal–Organic Framework‐Hydrogel System Improves Wound Healing in Diabetes

Chronic nonhealing wounds remain a major clinical challenge that would benefit from the development of advanced, regenerative dressings that promote wound closure within a clinically relevant time frame. The use of copper ions has shown promise in wound healing applications, possibly by promoting angiogenesis. However, reported treatments that use copper ions require multiple applications of copper salts or oxides to the wound bed, exposing the patient to potentially toxic levels of copper ions and resulting in variable outcomes. Herein the authors set out to assess whether copper metal organic framework nanoparticles (HKUST‐1 NPs) embedded within an antioxidant thermoresponsive citrate‐based hydrogel would decrease copper ion toxicity and accelerate wound healing in diabetic mice. HKUST‐1 and poly‐(polyethyleneglycol citrate‐co‐N‐isopropylacrylamide) (PPCN) are synthesized and characterized. HKUST‐1 NP stability in a protein solution with and without embedding them in PPCN hydrogel is determined. Copper ion release, cytotoxicity, apoptosis, and in vitro migration processes are measured. Wound closure rates and wound blood perfusion are assessed in vivo using the splinted excisional dermal wound diabetic mouse model. HKUST‐1 NPs disintegrated in protein solution while HKUST‐1 NPs embedded in PPCN (H‐HKUST‐1) are protected from degradation and copper ions are slowly released. Cytotoxicity and apoptosis due to copper ion release are significantly reduced while dermal cell migration in vitro and wound closure rates in vivo are significantly enhanced. In vivo, H‐HKUST‐1 induced angiogenesis, collagen deposition, and re‐epithelialization during wound healing in diabetic mice. These results suggest that a cooperatively stabilized, copper ion‐releasing H‐HKUST‐1 hydrogel is a promising innovative dressing for the treatment of chronic wounds.