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.     

Glycopeptide-Based Multifunctional Hydrogels Promote Diabetic Wound Healing through pH Regulation of Microenvironment

Excessive inflammation, bacterial infection, and blocked angiogenesis make diabetic wound healing challenging. Multifunctional wound dressings have several advantages in diabetic wound healing. In addition, the pH regulation of the microenvironment is shown to be a key factor that promotes skin regeneration through cellular immune regulation. However, few reports have focused on the development of functional dressings with the ability to regulate the pH microenvironment and promote diabetic wound healing. This study presents a novel approach for regulating the pH microenvironment of diabetic wound sites using a glycopeptide-based hydrogel consisting of modified hyaluronic acid and poly(6-aminocaproic acid). This hydrogel forms a network through Schiff base interactions and metal complexation, which suppresses inflammation and accelerates angiogenesis during wound healing. Hydrogels not only have adequate mechanical properties and self-healing ability but can also support tissue adhesion. They can also promote the secretion of inducible cAMP early repressor, which promotes the polarization of macrophages toward the M2 type. The in vivo results confirm that hydrogel promotes diabetic wound repair and skin regeneration by exerting rapid anti-inflammatory effects and promoting angiogenesis. Therefore, this hydrogel system represents an effective strategy for treating diabetic wounds.     

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.     

Omniphobic ZIF‐8@Hydrogel Membrane by Microfluidic‐Emulsion‐Templating Method for Wound Healing

Bacterial adhesion and colonization can result in chronic non‐healing wounds. Current hydrophilic wound dressings can release antibacterial agents into the wound exudate, but may result in overhydrated wounds, bacterial overgrowth, and even tissue maceration. Hydrophobic dressings are anti‐fouling, though ineffective to encapsulate and release bactericidal agents. Combining the advantages of hydrophilic and hydrophobic dressings seems difficult, until the development of superwettability surfaces offers an opportunity for omniphobic dressings from intrinsic hydrophilic polymers. Herein, omniphobic porous hydrogel wound dressings loaded with a zinc imidazolate framework 8 (ZIF‐8) are fabricated by a microfluidic‐emulsion‐templating method. The fabricated porous hydrogel membrane with its reentrant architecture is repellent to blood and body fluids, though intrinsically hydrophilic. This unique combination not only reduces the adhesion of harmful microbes, but also enables the encapsulation and release of antibacterial ingredients to wounded sites from hydrophilic polymer networks. As such, the omniphobic metal‐organic frameworks (MOFs)@hydrogel porous wound dressing can inhibit bacteria invasion and enable the controlled release of the bactericidal, anti‐inflammatory, and nontoxic zinc ions. Furthermore, in vivo study of infected full‐thickness skin defect models demonstrates that the dressing also accelerates wound closure by promoting angiogenesis and collagen deposition. Therefore, the omniphobic MOFs@hydrogel porous wound dressings are potentially useful for clinical application.     

Injectable Self-Healing Hydrogel Wound Dressing with Cysteine-Specific On-Demand Dissolution Property Based on Tandem Dynamic Covalent Bonds

Rapid gelation and on-demand dissolution are key characteristics governing the effectiveness of clinic hydrogel wound dressings. Here, an injectable self-healing hydrogel with rapid gelation and cysteine-specific on-demand dissolution is designed to be used as wound dressings. The hydrogel is prepared based on the formation of tandem dynamic covalent bonds comprised of CC double bonds produced through the catalysis-free Knoevenagel condensation reaction and boronate ester linkages. The prepared hydrogel displays excellent injectability and self-healing ability, showing rapid cysteine-triggered on-demand dissolution owing to the formation of the thiazolidino boronate complex. When used as dressings for healing full-thickness wounds, the hydrogel shows favorable biocompatibility, achieves rapid wound closure in seconds, and fast on-demand dissolution for dressing changes. These data highlight the utility of the designed tandem dynamic covalent bonds-based hydrogel dressings for promising wound healing applications.     

3D Printing Personalized,Photocrosslinkable Hydrogel Wound Dressings for the Treatment of Thermal Burns

Considering the variations in burns depending on the circumstances that caused them, the need for personalized medicine and care for burn victims is vital to ensure that optimal treatment is provided. With the level of accuracy and customization that 3D printing brings as a technology, there is potential in its use to fabricate wound dressings that can provide better treatment for burn patients, provided that the material of choice has good printability and can be customized while facilitating wound healing. In this study, the versatility of chitosan methacrylate as said material to be used to fabricate customizable wound dressings via 3D printing is investigated. Synthesized chitosan methacrylate is evaluated to be printable, biodegradable, and biocompatible during wound healing. Various drugs relevant to the treatment of burns are then loaded and different multimaterial wound dressing designs containing different dosages are fabricated via 3D printing. The incorporation of said drugs does not significantly affect the printability of chitosan methacrylate, and the incorporation of antimicrobial agents significantly improves its antimicrobial capabilities. Through in vivo models, these variations in wound dressing designs have good wound healing properties and do not cause any adverse effects in the process.     

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.     

Battery-Free and Wireless Smart Wound Dressing for Wound Infection Monitoring and Electrically Controlled On-Demand Drug Delivery

Real-time monitoring wound status and providing timely therapies with smart wound dressing is a promising way to treat wound infections and accelerate the healing process. Herein, to establish a closed-loop monitoring and treatment system, a fully integrated, battery-free, and wireless smart wound dressing for wound infection detection and on-demand drug delivery is developed using flexible electronics. The smart wound dressing integrated with the near field communication module can realize wireless power harvest and data transmission, on-site signal processing, and drug delivery control, through the miniaturized circuit and smartphone. The temperature, pH, and uric acid of the wound is detected simultaneously by the developed sensors to assess wound conditions. Meanwhile, the drug delivery electrode in the dressing is used to provide on-demand infection treatment by the electrically controlled antibiotics delivery. Through in vitro antibacterial experiments and in situ animal studies, it is shown that the dressing can effectively inhibit bacterial growth and accelerate wound healing, which fully validates its effectiveness in the wound treatment. Utilizing the advantages of near-field communication and flexible electronics, the battery-free and integrated design of sensing and treatment provides a promising solution for the development of a closed-loop biomedical system integrating monitoring, diagnosis, and therapy.     

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.     

Bioinspired Multifunctional Hybrid Hydrogel Promotes Wound Healing

Inspired by the coordinated multiple healing mechanism of the organism, a four‐armed benzaldehyde‐terminated polyethylene glycol and dodecyl‐modified chitosan hybrid hydrogel with vascular endothelial growth factor (VEGF) encapsulation are presented for efficient and versatile wound healing. The hybrid hydrogel is formed through the reversible Schiff base and possesses self‐healing capability. As the dodecyl tails can insert themselves into and be anchored onto the lipid bilayer of the cell membrane, the hybrid hydrogel has outstanding tissue adhesion, blood cell coagulation and hemostasis, anti‐infection, and cell recruitment functions. Moreover, by loading in and controllably releasing VEGF from the hybrid hydrogel, the processes of cell proliferation and tissue remodeling in the wound bed can be significantly improved. Based on an in vivo study of the multifunctional hybrid hydrogel, it is demonstrated that acute tissue injuries such as vessel bleeding and liver bleeding can be repaired immediately because of the outstanding adhesion and hemostasis features of the hydrogel. Moreover, the chronic wound‐healing process of an infectious full‐thickness skin defect model can also be significantly enhanced by promoting angiogenesis, collagen deposition, macrophage polarization, and granulation tissue formation. Thus, this multifunctional hybrid hydrogel is potentially valuable for clinical applications.     

Green Tea Derivative Driven Smart Hydrogels with Desired Functions for Chronic Diabetic Wound Treatment

Current treatments for chronic diabetic wounds remain unsatisfactory due to the lack of ideal wound dressings that can integrate matching mechanical strength, fast self-healability, facile dressing change, and multiple therapeutic effects into one system. In this work, benefiting from the catechol groups and therapeutic effect of epigallocatechin-3-gallate (EGCG, green tea derivative), a smart hydrogel dressing can be conveniently obtained through copolymerization of the complex formed by EGCG and 3-acrylamido phenylboronic acid (APBA) (the formation of boronate ester bond) and acrylamide. The resulting hydrogel features adequate mechanical properties, self-healing capability, and tissue adhesiveness. Otherwise, the substantial release of EGCG can not only realize anti-oxidation, antibacterial, anti-inflammatory and proangiogenic effect, and modulation of macrophage polarization to accelerate wound healing, but also facilitate easy dressing change. This advanced hydrogel provides a facile and effective way for diabetic chronic wound management and may be extended for the therapy of other complicated wound healings.     

Zinc Oxide Nanorod‐Based Piezoelectric Dermal Patch for Wound Healing

Current treatments for wound healing engage in passive healing processes and rarely participate in stimulating skin cell behaviors for active wound healing. Electric potential difference‐derived electrical fields (EFs) are known to modulate skin cell behaviors. Here, a piezoelectric dermal patch is developed that can be applied on skin wound site and EF is generated to promote wound healing. The one‐directionally aligned zinc oxide nanorod‐based piezoelectric patch generates piezoelectric potential upon mechanical deformations induced by animal motion, and induces EF at the wound bed. In vitro and in vivo data demonstrate that the piezoelectric patch promotes the wound healing process through enhanced cellular metabolism, migration, and protein synthesis. This modality may lead to a clinically relevant piezoelectric dermal patch therapy for active wound healing.     

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.     

Flexible Bicolorimetric Polyacrylamide/Chitosan Hydrogels for Smart Real-Time Monitoring and Promotion of Wound Healing

Real-time monitoring of wound healing remains a major challenge in clinical tissue regeneration, calling the need for the development of biomaterial-guided on-site monitoring wound healing technology. In this study, multifunctional double colorimetry-integrated polyacrylamide-quaternary ammonium chitosan-carbon quantum dots (CQDs)-phenol red hydrogels are presented, aiming to simultaneously detect the wound pH level, reduce bacterial infection, and promote wound healing. The hybridization of CQDs and pH indicator (phenol red) with the hydrogels enables their high responsiveness, reversibility, and accurate indication of pH variability to reflect the dynamic wound status in the context of both ultraviolet and visible light. Furthermore, these visual images can be collected by smartphones and converted into on-site wound pH signals, allowing for a real-time evaluation of the wound dynamic conditions in a remote approach. Notably, the hydrogels exhibit excellent hemostatic and adhesive properties, maintain sufficient wound moisture, and promote wound healing via their high antibacterial activity (against Staphylococcus Aureus, and Escherichia Coli) and skin repair function. Overall, the resulting hydrogels have high potential as a novel smart and flexible wound dressing platform for theranostic skin regeneration.     

Double Cross-Linked Biomimetic Hyaluronic Acid-Based Hydrogels with Thermo-Stimulated Self-Contraction and Tissue Adhesiveness for Accelerating Post-Wound Closure and Wound Healing

When skin trauma occurs, rapid achievement of the post-wound closure is required to prevent microbial invasion, inhibit scar formation and promote wound healing. To develop a wound dressing for accelerating post-wound-closure and wound healing, a thermo-responsive and tissue-adhesive hydrogel with interpenetrating polymer networks (IPN) is fabricated based on N-dimethylbisacrylamide (NIPAM) and glutaraldehyde (GTA) cross-linked hyaluronic acid (HA). Results not only confirm the thermo-stimulated self-contraction and tissue adhesiveness of the HA-based IPN (PNI-HA), which effectively aids wound closure via mechanical stretch, but also verify the hemocompatibility and cytocompatibility of PNI-HA that tend to accelerate wound healing. In vivo, a mouse model of total skin defect demonstrates that PNI-HA acting as hydrogel sealant significantly achieves the sutureless post-wound-closure at the early stage of wound healing, and then promotes wound healing by reducing inflammatory cells infiltration, promoting angiogenesis as well as reducing collagen deposition. These results indicate that the developed thermo-responsive and tissue-adhesive hydrogel dressing offers a candidate to serve as a tissue sealant for wound healing.     

The pH-Sensitive Optical Fiber Integrated CMCS-PA@Fe Hydrogels for Photothermal Therapy and Real-Time Monitoring of Infected Wounds

Bacterial infections are one of the biggest threats to wound healing. Despite significant efforts in wound condition monitoring and treatment, significant challenges remain in real-time wound monitoring and timely treatment. Herein, a kind of hydrogel with dual functions, which can not only quickly diagnose wound bacterial infection but also provide timely and effective treatment is developed. First, Carborxymethy chitosan (CMCS)-Protocatechualdehyde (PA)@Fe hydrogels with double dynamic bonds are prepared by chelating PA@Fe with CMCS. Second, the pH-sensitive Polydimethylsiloxane (PDMS) optical fibers are integrated into the CMCS-PA@Fe hydrogels to obtain the pH-sensitive optical fiber/CMCS-PA@Fe hydrogels that exhibit good real-time monitoring of the wound healing process. The tissue adhesion and self-healing properties of the pH-sensitive optical fiber/CMCS-PA@Fe hydrogels can adapt to the movement and stretching of the skin. Meanwhile, with the assistance of the photothermal effect, the hydrogels have a high antibacterial effect (>99.9%). In addition, the pH-sensitive optical fiber/CMCS-PA@Fe hydrogels also show an excellent therapeutic effect in the wound infection model. Moreover, reliable and timely wound pH information can be sent to intelligent devices through microcomputers to monitor the healing status. Overall, the pH-sensitive optical fiber/CMCS-PA@Fe hydrogels provide an entirely new platform for developing smart, real-time diagnostics and timely wound treatment.     

Ultrafast Self-Gelling and Wet Adhesive Powder for Acute Hemostasis and Wound Healing

Achieving rapid and effective hemostasis on irregularly shaped, non-compressible visceral, and high-pressure arterial bleeding wounds remains a critical clinical challenge. Herein, an ultrafast self-gelling and wet adhesive polyethyleneimine/polyacrylic acid/quaternized chitosan (PEI/PAA/QCS) powder is reported as the hemostatic material and wound dressing. PEI/PAA/QCS powder deposited on bleeding wounds can rapidly absorb a large amount of blood to concentrate coagulation factors. Meanwhile, the powder can form an adhesive hydrogel in situ within 4 s upon hydration to form a pressure-resistant physical barrier. Furthermore, PEI/PAA/QCS hydrogels can aggregate blood cells and platelets to enhance hemostasis. Depositing PEI/PAA/QCS powder on various bleeding wounds, including at the liver and heart, high-pressure femoral artery and tail vein of rats, arrests the bleeding around 10 s with no rebleeding after ten minutes. Excellent hemostasis of PEI/PAA/QCS powder is further demonstrated against massive hemorrhage in porcine spleen and liver in vivo, which are non-compressible organs with abundant blood supply. In addition, the powder can be used as a wound dressing to promote the healing of the full-thickness skin wounds. The advantages of PEI/PAA/QCS powder including rapid and effective hemostasis, effective wound healing, easy usage, low cost, and adaptability to fit complex target sites make it a promising biomaterial for surgical applications.     

Skin‐Inspired Antibacterial Conductive Hydrogels for Epidermal Sensors and Diabetic Foot Wound Dressings

Recently, artificial intelligence research has driven the development of stretchable and flexible electronic systems. Conductive hydrogels are a class of soft electronic materials that have emerging applications in wearable and implantable biomedical devices. However, current conductive hydrogels possess fundamental limitations in terms of their antibacterial performance and a mechanical mismatch with human tissues, which severely limits their applications in biological interfaces. Here, inspired by animal skin, a conductive hydrogel is fabricated from a supramolecular assembly of polydopamine decorated silver nanoparticles (PDA@Ag NPs), polyaniline, and polyvinyl alcohol, namely PDA@Ag NPs/CPHs. The resultant hydrogel has many desirable features, such as tunable mechanical and electrochemical properties, eye‐catching processability, good self‐healing ability as well as repeatable adhesiveness. Remarkably, PDA@Ag NPs/CPHs exhibit broad antibacterial activity against Gram‐negative and Gram‐positive bacteria. The potential application of this versatile hydrogel is demonstrated by monitoring large‐scale movements of the human body in real time. In addition, PDA@Ag NPs/CPHs have a significant therapeutic effect on diabetic foot wounds by promoting angiogenesis, accelerating collagen deposition, inhibiting bacterial growth, and controlling wound infection. To the best of the authors' knowledge, this is the first time that conductive hydrogels with antibacterial ability are developed for use as epidermal sensors and diabetic foot wound dressing.     

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.     

A Thermoresponsive Antimicrobial Wound Dressing Hydrogel Based on a Cationic Betaine Ester

This work reports a thermoresponsive multifunctional wound dressing hydrogel based on ABA triblock copolymers synthesized via reversible addition fragmentation chain transfer (RAFT) polymerization. The inner B block consists of a positively‐charged hydrolysable betaine ester loaded with an antimicrobial drug as its counter ion and the B block is flanked by two outer A blocks of thermoresponsive poly (N‐isopropylacrylamide) (PNIPAM). A solution containing the triblock copolymers can be applied to wound sites and immediately turns into a physical gel at the body temperature. This wound dressing can reduce the risk of wound infection by releasing small‐molecular‐weight antimicrobial drug and facilitate the attachment of mammalian cells during tissue regeneration through its positive surface charge. The cationic betaine ester can then hydrolyze at the wound site to its zwitterionic form, which is known to be biocompatible and nonsticky. The thermoresponsive in situ gelation feature along with controlled drug release, enhanced tissue–hydrogel interactions as well as long‐term biocompatibility make this hydrogel a very promising material for antimicrobial wound dressing applications.