Highly Efficient Hemostatic Cross-Linked Polyacrylate Polymer Dressings for Immediate Hemostasis.

A traumatic hemorrhage is fatal due to the great loss of blood in a short period of time; however, there are a few biomaterials that can stop the bleeding quickly due to the limited water absorption speed. Here, a highly absorbent polymer (HPA), polyacrylate, was prepared as it has the best structure-effectiveness relationship. Within a very short period of time (2 min), HPA continually absorbed water until it swelled up to its 600 times its weight; more importantly, the porous structure comprised the swollen dressing. This instantaneous swelling immediately led to rapid hemostasis in irregular wounds. We optimized the HPA preparation process to obtain a rapidly water-absorbent polymer (i.e., HPA-5). HPA-5 showed favorable adhesion and biocompatibility in vitro. A rat femoral arteriovenous complete shear model and a tail arteriovenous injury model were established. HPA exhibited excellent hemostatic capability with little blood loss and short hemostatic time compared with CeloxTM in both of the models. The hemostatic mechanisms of HPA consist of fast clotting by aggregating blood cells, activating platelets, and accelerating the coagulation pathway via water absorption and electrostatic interaction. HPA is a promising highly water-absorbent hemostatic dressing for rapid and extensive blood clotting after vessel injury.

Sequential administration of delta-tocotrienol ameliorates radiation-induced myelosuppression in mice and non-human primates through inducing G-CSF production.

To date only four recombinant growth factors, including Filgrastim (rhG-CSF), have been approved by FDA as radiomitigators to ameliorate hematopoietic acute radiation syndrome (H-ARS). These approved agents are not stable under room-temperature, needing to be stored at 2-8 °C, and would not be feasible in a mass casualty scenario where rapid and cost-effective intervention is crucial. Delta-tocotrienol (δ-T3H), the most potent G-CSF-inducing agent among vitamin E isoforms, exhibited efficiency and selectivity on G-CSF production in comparison with TLR and STING agonists in mice. Five-dose δ-T3H was utilized as the optimal therapeutic regimen due to long-term G-CSF production and the best peripheral blood (PB) recovery of irradiated mice. Comparable with rhG-CSF, sequential administration of δ-T3H post-irradiation improved hematologic recovery and accelerated the regeneration of hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) in the bone marrow (BM) and spleen of 6.5Gy irradiated mice; and consistently enhanced repopulation of BM-HSCs. In 4.0Gy irradiated nonhuman primates, δ-T3H exhibited comparable efficacy as rhG-CSF to promote PB recovery and colony-formation of BM-HPCs. Altogether, we demonstrated that sequential administration of delta-tocotrienol ameliorates radiation-induced myelosuppression in mice and non-human primates through inducing G-CSF production, indicated δ-T3H as a promising radiomitigator for the management of H-ARS, particularly in a mass casualty scenario.

Nanoengineered Red Blood Cells Loaded with TMPRSS2 and Cathepsin L Inhibitors Block SARS-CoV-2 Pseudovirus Entry into Lung ACE2+ Cells.

The enzymatic activities of Furin, Transmembrane serine proteinase 2 (TMPRSS2), Cathepsin L (CTSL), and Angiotensin-converting enzyme 2 (ACE2) receptor binding are necessary for the entry of coronaviruses into host cells. Precise inhibition of these key proteases in ACE2+ lung cells during a viral infection cycle shall prevent viral Spike (S) protein activation and its fusion with a host cell membrane, consequently averting virus entry to the cells. In this study, dual-drug-combined (TMPRSS2 inhibitor Camostat and CTSL inhibitor E-64d) nanocarriers (NCs) are constructed conjugated with an anti-human ACE2 (hACE2) antibody and employ Red Blood Cell (RBC)-hitchhiking, termed "Nanoengineered RBCs," for targeting lung cells. The significant therapeutic efficacy of the dual-drug-loaded nanoengineered RBCs in pseudovirus-infected K18-hACE2 transgenic mice is reported. Notably, the modular nanoengineered RBCs (anti-receptor antibody+NCs+RBCs) precisely target key proteases of host cells in the lungs to block the entry of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), regardless of virus variations. These findings are anticipated to benefit the development of a series of novel and safe host-cell-protecting antiviral therapies.

Cancer cell membrane-coated bacterial ghosts for highly efficient paclitaxel delivery against metastatic lung cancer.

Chemotherapy is one of the major approaches for the treatment of metastatic lung cancer, although it is limited by the low tumor delivery efficacy of anticancer drugs. Bacterial therapy is emerging for cancer treatment due to its high immune stimulation effect; however, excessively generated immunogenicity will cause serious inflammatory response syndrome. Here, we prepared cancer cell membrane-coated liposomal paclitaxel-loaded bacterial ghosts (LP@BG@CCM) by layer-by-layer encapsulation for the treatment of metastatic lung cancer. The preparation processes were simple, only involving film formation, electroporation, and pore extrusion. LP@BG@CCM owned much higher 4T1 cancer cell toxicity than LP@BG due to its faster fusion with cancer cells. In the 4T1 breast cancer metastatic lung cancer mouse models, the remarkably higher lung targeting of intravenously injected LP@BG@CCM was observed with the almost normalized lung appearance, the reduced lung weight, the clear lung tissue structure, and the enhanced cancer cell apoptosis compared to its precursors. Moreover, several major immune factors were improved after administration of LP@BG@CCM, including the CD4+/CD8a+ T cells in the spleen and the TNF-α, IFN-γ, and IL-4 in the lung. LP@BG@CCM exhibits the optimal synergistic chemo-immunotherapy, which is a promising medication for the treatment of metastatic lung cancer.

In situ forming hydrogel loaded with predatory bacteria treats drug-resistant corneal infection.

The development of potent bactericidal antibiotic alternatives is important to address the current antibiotic crisis. A representative example is the topical delivery of predatory Bdellovibrio bacteriovorus bacteria to treat ocular bacterial infection. However, the direct topical use of B. bacteriovorus suspensions has the problem of easy loss and inactivation. Here, a B. bacteriovorus in situ forming hydrogel (BIG) was constructed for the ocular delivery of B. bacteriovorus. BIGs, as a fluid in their primitive state, were temperature- and cation- dually sensitive, which was rapidly transformed into immobile gels in the ocular environment. BIGs not only kept the activity of B. bacteriovorus but also retained on the ocular surface for a long time. The biosafety of BIGs was good without HCEC cell toxicity and hemolysis. More importantly, BIGs highly inhibited the growth of drug-resistant Pseudomonas aeruginosa whether in vitro or in the infected rat eyes. The ocular infection was completely controlled by BIGs with no corneal ulcers and inflammations. This living bacteria gel is a promising medication for the local treatment of drug-resistant bacteria-induced ocular infection.

The effects of Lactobacillus reuteri microcapsules on radiation-induced brain injury by regulating the gut microenvironment.

A radiation-induced brain injury (RIBI) is a major adverse event following radiotherapy of malignant tumors. RIBI would affect cognitive function, leading to a series of complications and even death. However, the pathogenesis of RIBI is still unclear, and it still lacks specific therapeutic drugs. The gut-brain bidirectional communication may be mediated by various microbiota and metabolites in the gastrointestinal tract. Probiotics are closely related to physiological health. The theory of the gut-brain axis provides us with a new idea to improve the gut microenvironment by supplementing probiotics against RIBI. Here, Lactobacillus reuteri microcapsules (LMCs) were prepared, which were predominantly irregular spheres with a rough surface under a scanning electron microscope and a narrow size distribution ranging from 20 to 700 µm. The transmission electron microscopy images showed that the structure of microcapsules containing Lactobacillus reuteri (L. reuteri) was a core and shell structure. The survival of L. reuteri in microcapsules was significantly more than that of free L. reuteri in the simulated stomach environment of pH 1.2. 16S rDNA sequencing showed that LMCs observably increased the relative abundance of Lactobacillus in RIBI mice. More importantly, compared with the RIBI model mice, the behavior of RIBI mice treated with LMCs was significantly improved. In addition, LMCs greatly alleviated the pathological damage of the hippocampus and intestines in the mice after irradiation and reduced the level of TNF-α and IL-6 in vivo. Generally, LMCs are a promising oral preparation, which provide new ideas and methods for the treatment of RIBI.

Mesalazine hollow suppositories based on 3D printing for treatment of ulcerative colitis.

Mesalazine (MSZ) suppositories are a first-line medication for the localized treatment of ulcerative colitis (UC). However, the frequent defecation of patients with UC influences the retention of the suppository in the rectum and multiple doses have to be applied. Here, a mesalazine hollow suppository (MHS) is developed using three-dimensional (3D) printing. The MHS is composed of an inner supporting spring and an outer MSZ-loaded curved hollow shell. Springs were prepared using fused deposition modeling (FDM) 3D printing with thermoplastic urethane filaments, followed by splitting. The optimal parameters, including elasticity, filament diameter, spring inner diameter, and filament distance, were screened. The shell was prepared by FDM 3D printing utilizing MSZ, polyvinyl alcohol, and polyethylene glycol, which were assembled with springs to obtain FDM 3D-printed MHS (F-MHS); if 3D-printed metal molding was used in preparing shell, mold-formed MHS (M-MHS) was obtained. The F-MHS exhibited faster MSZ release than the M-MHS; therefore, the molding method is preferable. The inserted M-MHS was retained in the rat rectum for 5 h without affecting defecation. M-MHS alleviated tissue damage of UC rats and reduced inflammation with low levels of myeloperoxidase and proinflammatory cytokines. Personalized MHS is a promising medication for the localized treatment of UC.

Application of low-intensity ultrasound by opening blood-brain barrier for enhanced brain-targeted drug delivery.

Brain-targeted drug delivery has been a research hotspot, and substantial amount of related studies were already translated into standard therapy and put into clinical use. However, low effective rate retains a huge challenge for brain disease. Because, the blood-brain barrier (BBB) protects brain from pathogenic molecules and tightly controls the process of molecular transportation, which gives rise to poor-liposoluble drugs or molecules with high molecular weight cannot permeate the barrier to exert treating effect. There is an ongoing process to dig out more methods for efficient brain-targeted drug delivery. Besides modified chemical methods such as prodrugs design and brain-targeted nanotechnology, physical methods as a novel initiative could enhance the treatment effect for brain disease. In our study, the influence of low-intensity ultrasound on transient opening BBB and the related applications were explored. A medical ultrasound therapeutic device (1 MHz) was used on heads of mice at different intensities and for different treating time. Evans blue was used as a model to exhibit the permeability of the BBB after subcutaneous injection. Three types of intensities (0.6, 0.8, and 1.0 W/cm2) and duration times (1, 3, and 5 min) of ultrasound were respectively investigated. It was found that the combinations of 0.6 W/cm2/1 min, 0.6 W/cm2/3 min, 0.6 W/cm2/5 min, 0.8 W/cm2/1 min, and 1.0 W/cm2/1 min could open the BBB sufficiently with significant Evans blue staining in the brain. Brain pathological analysis showed structural change on moderate degree was found on cerebral cortex after ultrasound and could recovered rapidly. There are no obvious changes in the behavior of mice after ultrasound processing. More importantly, the BBB recovered quickly at 12 h after ultrasound application with complete BBB structure and unbroken tight junction, suggesting that ultrasound was safe to apply for brain-targeted drug delivery. Proper use of local ultrasound on the brain is a promising technique to open the BBB and enhance brain-targeted delivery.

Injectable multifunctional chitosan/dextran-based hydrogel accelerates wound healing in combined radiation and burn injury.

Clinical wound management of combined radiation and burn injury (CRBI) remains a huge challenge due to serious injuries induced by redundant reactive oxygen species (ROS), the accompanying hematopoietic, immunologic suppression and stem cell reduction. Herein, the injectable multifunctional Schiff base cross-linked with gallic acid modified chitosan (CSGA)/oxidized dextran (ODex) hydrogels were rationally designed to accelerate wound healing through elimination of ROS in CRBI. CSGA/ODex hydrogels, fabricated by mixing solutions of CSGA and Odex, displayed good self-healing ability, excellent injectability, strong antioxidant activity, and favorable biocompatibility. More importantly, CSGA/ODex hydrogels exhibited excellent antibacterial properties, which is facilitated for wound healing. Furthermore, CSGA/ODex hydrogels significantly suppressed the oxidative damage of L929 cells in an H2O2-induced ROS microenvironment. The recovery of mice with CRBI in mice demonstrated that CSGA/ODex hydrogels significantly reduced the hyperplasia of epithelial cells and the expression of proinflammatory cytokine, and accelerated wound healing which was superior to the treatment with commercial triethanolamine ointment. In conclusion, the CSGA/ODex hydrogels as a wound dressing could accelerate the wound healing and tissue regeneration of CRBI, which provides great potential in clinical treatment of CRBI.

Oral konjac glucomannan for prevention of ionizing radiation-induced injury by regulating gut microbiota and increasing short chain fatty acids.

Ionizing radiation-induced injury commonly happens in radiotherapy, leading to damages of the hematopoietic and gastrointestinal systems. Radioprotective medications are mainly applied in hospitals, although only injections are available and their gut protection is limited. Here, oral konjac glucomannan (KGM), a natural macromolecule and soluble dietary fiber, was used against ionizing radiation-induced injury. The mice were fed with KGM (0.4 g/kg) for 3 days or injected with a clinical medication amifostine before 6.5 Gy γ-ray whole body irradiation (WBI) or 13 Gy whole abdominal irradiation (WAI). In the WBI experiments, KGM improved blood cell recovery and bone marrow cell proliferation in the femur and spleen, though its effect was weaker than or similar to that of amifostine. In the WBI experiments, the gut protection of KGM was similar to or a little better than that of amifostine, involving regenerated crypts numbers, villus length, and gut permeability. Moreover, KGM remarkably enhanced the survival rates of WBI and WAI mice, consistent with amifostine. KGM, as a prebiotic, enhanced gut microbiota abundance, probiotic numbers, and short chain fatty acid production, maintaining gut homeostasis. Moreover, KGM inhibited the apoptosis of irradiated human intestinal epithelial cells. KGM is a promising natural macromolecule against ionizing radiation-induced injury.

Cannabidiol-loaded biomimetic macrophage membrane vesicles against post-traumatic stress disorder assisted by ultrasound.

Post-traumatic stress disorder (PTSD), which normally follows psychological trauma, has been increasingly studied as a brain disease. However, the blood-brain barrier (BBB) prevents conventional drugs for PTSD from entering the brain. Our previous studies proved the effectiveness of cannabidiol (CBD) against PTSD, but low water solubility, low brain targeting efficiency and poor bioavailability restricted its applications. Here, a bionic delivery system, camouflage CBD-loaded macrophage-membrane nanovesicles (CMNVs), was constructed via co-extrusion of CBD with macrophage membranes, which had inflammatory and immune escape properties. In vitro anti-inflammatory, cellular uptake and pharmacokinetic experiments respectively verified the anti-inflammatory, inflammatory targeting and immune escape properties of CMNVs. Brain targeting and excellent anti-PTSD effects of CMNVs had been validated in vivo by imaging and pharmacodynamics studies. In our study, the potential of ultrasound to open BBBs and improve the brain-targeted delivery of CBD was evaluated. In conclusion, this cell membrane bionic delivery system assisted with ultrasound had good therapeutic effect against PTSD mice, which is expected to help convey CBD to inflammatory areas within the brain and alleviate the symptoms of PTSD.

Preparation of informative wafers (info-wafers) by combination of 3D printing, code design and photopolymerization.

3D printing is used in manufacturing of personalized and customized medications. Moreover, information technology has been integrated with 3D printing, which builds the basis of informative medications. Here, clonidine hydrochloride (CH) was formulated in informative wafers (info-wafers) by combination of 3D printing, code design and photopolymerization. Braille code (recognized by blind persons), bar code, and quick response (QR) code were used for the design of info-wafers. A code positive mold was 3D-printed with rigid resins by stereolithography, which was transformed to the silicone negative mold by thermal polymerization. A homogeneous CH suspension in N-vinyl pyrrolidone was casted into the negative mold followed by photopolymerization to form CH info-wafers. The bulgy parts of info-wafers were painted with edible ink except for Braille code info-wafers. The CH in info-wafers maintained the amorphous state, which was demonstrated by X-ray diffraction. The amorphous CH had rapid dissolution. Bar code info-wafers were scanned by smartphone though only simple information was obtained. QR code info-wafers were smartphone-scanned to link a website that contained sufficient information such as the instruction of CH application and the collection of patient information. Info-wafers provide online drug information and use instructions for patients to make the treatment standardization and normalization.

Predatory bacterial hydrogels for topical treatment of infected wounds.

Wound infection is becoming a considerable healthcare crisis due to the abuse of antibiotics and the substantial production of multidrug-resistant bacteria. Seawater immersion wounds usually become a mortal trouble because of the infection of Vibrio vulnificus. Bdellovibrio bacteriovorus, one kind of natural predatory bacteria, is recognized as a promising biological therapy against intractable bacteria. Here, we prepared a B. bacteriovorus-loaded polyvinyl alcohol/alginate hydrogel for the topical treatment of the seawater immersion wounds infected by V. vulnificus. The B. bacteriovorus-loaded hydrogel (BG) owned highly microporous structures with the mean pore size of 90 µm, improving the rapid release of B. bacteriovorus from BG when contacting the aqueous surroundings. BG showed high biosafety with no L929 cell toxicity or hemolysis. More importantly, BG exhibited excellent in vitro anti-V. vulnificus effect. The highly effective infected wound treatment effect of BG was evaluated on mouse models, revealing significant reduction of local V. vulnificus, accelerated wound contraction, and alleviated inflammation. Besides the high bacterial inhibition of BG, BG remarkably reduced inflammatory response, promoted collagen deposition, neovascularization and re-epithelization, contributing to wound healing. BG is a promising topical biological formulation against infected wounds.

Potential applications of drug delivery technologies against radiation enteritis.

INTRODUCTION: The incidence of abdominal tumors, such as colorectal and prostate cancers, continually increases. Radiation therapy is widely applied in the clinical treatment of patients with abdominal/pelvic cancers, but it often unfortunately causes radiation enteritis (RE) involving the intestine, colon, and rectum. However, there is a lack of suitable treatment options for effective prevention and treatment of RE. AREAS COVERED: Conventional clinical drugs for preventing and treating RE are usually applied by enemas and oral administration. Innovative gut-targeted drug delivery systems including hydrogels, microspheres, and nanoparticles are proposed to improve the prevention and curation of RE. EXPERT OPINION: The prevention and treatment of RE have not attracted sufficient attention in the clinical practice, especially compared to the treatment of tumors, although RE takes patients great pains. Drug delivery to the pathological sites of RE is a huge challenge. The short retention and weak targeting of conventional drug delivery systems affect the therapeutic efficiency of anti-RE drugs. Novel drug delivery systems including hydrogels, microspheres, and nanoparticles can allow drugs long-term retention in the gut and targeting the inflammation sites to alleviate radiation-induced injury.

Advances in applications of head mounted devices (HMDs): Physical techniques for drug delivery and neuromodulation.

Head-mounted medical devices (HMDs) are disruptive inventions representing laboratories and clinical institutions worldwide are climbing the apexes of brain science. These complex devices are inextricably linked with a wide range knowledge containing the Physics, Imaging, Biomedical engineering, Biology and Pharmacology, particularly could be specifically designed for individuals, and finally exerting integrated bio-effect. The salient characteristics of them are non-invasive intervening in human brain's physiological structures, and alterating the biological process, such as thermal ablating the tumor, opening the BBB to deliver drugs and neuromodulating to enhance cognitive performance or manipulate prosthetic. The increasing demand and universally accepted of them have set off a dramatic upsurge in HMDs' studies, seminal applications of them span from clinical use to psychiatric disorders and neurological modulation. With subsequent pre-clinical studies and human trials emerging, the mechanisms of transcranial stimulation methods of them were widely studied, and could be basically came down to three notable approach: magnetic, electrical and ultrasonic stimulation. This review provides a comprehensive overviews of their stimulating mechanisms, and recent advances in clinic and military. We described the potential impact of HMDs on brain science, and current challenges to extensively adopt them as promising alternative treating tools.

Quercetin inclusion complex gels ameliorate radiation-induced brain injury by regulating gut microbiota.

Radiation-induced brain injury (RIBI) is a serious adverse effect of radiotherapy. RIBI has garnered considerable clinical attention owing to its powerful effects on brain function and cognition; however, no effective treatment is available. The microbiota-gut-brain axis theory is a novel concept of treating RIBI by regulating gut microbiota. Quercetin, a particularly common flavonoid compound, has a wide range of biological activities and can regulate gut microbiota; however, it has poor solubility and dispersibility. In the present study, oral gels of inclusion complex comprising quercetin and HP-ß-CD were prepared, which increased quercetin dispersion and extended its release time in the intestinal tract. First, the relative abundance and diversity of gut microbiota in RIBI mice changed after oral administration of quercetin inclusion complex gels (QICG). Second, the spontaneous activity behavior and short-term memory ability as well as anxiety level were improved. Third, changes in physical symptoms were observed, including a decrease in TNF-α and IL-6 levels. H&E staining revealed that gut epithelial injury and intestinal inflammation as well as hippocampal inflammation were ameliorated. Antibiotics treatment (Abx) mice were developed to disrupt the mice's original gut microbiota composition. No significant improvement was observed in behavior or histopathology after oral administration of QICG in Abx mice of RIBI, indicating that the effect of QICG on improving RIBI was regulated by intestinal microbiota. Finally, the QICG preparation is efficient, exerting a protective effect on RIBI by regulating gut microbiota via the microbiota-gut-brain axis, which provides a novel idea for RIBI treatment.

The Improved Brain-Targeted Drug Delivery of Edaravone Temperature-Sensitive Gels by Ultrasound for γ-ray Radiation-Induced Brain Injury.

Radiation-induced brain injury (RBI) is a common neurological disease caused by ionizing radiation (IR). Edaravone (EDA) is a free radical scavenger, has the potential to treat RBI. EDA loaded temperature-sensitive gels (TSGs) were prepared for subcutaneous injection to improve inconvenient administration of intravenous infusion. RBI mice model was established by irradiation of 60Co γ-ray on head. EDA TSGs could improve spontaneous behavior, learning and memory and anxiety of RBI mice by behavior tests, including the open field test, the novel object recognition test, the elevated plus maze test and the fear conditioning test. The therapeutic effects were enhanced with the assistance of ultrasound. Alleviative pathological changes, decreased the expression of Molondialdehyde (MDA) and Interleukin-6 (IL-6) in the hippocampus of brain, indicated reduced oxidative stress and inflammatory response with the treatment of EDA TSGs and ultrasound. Moreover, ultrasound was superior to the use of EDA TSGs. Safe and effective EDA TSGs were prepared for RBI, and the feasibility of brain-targeted drug delivery enhanced by ultrasound was preliminarily demonstrated in this study.

Cinnarizine dissolving microneedles against microwave-induced brain injury.

Microwave is commonly used in the life, manufacturing and military fields, which may induce body injuries. Brain is the major target organ of microwave radiation and microwave-induced brain injury (MIBI) can lead to insomnia, dreaminess, and a decline in learning and memory. However, there is no clinical medications are available currently. Calcium channel blockers may protect the brain tissue from microwave but most of them cannot enter the brain. Here, we selected a calcium channel blocker-cinnarizine to prepare its dissolving microneedles (MNs) for the therapy of MIBI. The cinnarizine MNs was composed of polyvinyl pyrrolidone (PVP) K90 as the tip, the photopolymerized PVP as the base and the drug, which owned high mechanical strength, leading to easily piecing the skin on the neck and high drug release in vivo. The cinnarizine MNs markedly improved the recovery of spatial memory and spontaneous exploratory behavior of the rats after microwave radiation by inhibiting the expression of calcineurin and calpain-1. The dissolving MN technique is a promising method to improve drugs into the body and perform the anti-microwave radiation action.

Light-triggered on-site rapid formation of antibacterial hydrogel dressings for accelerated healing of infected wounds.

An optimal wound dressing can seal variously shaped wounds and provide a complete barrier to resist bacterial invasion; more importantly, the dressing can be stretched or compressed when the wounds are subjected to external forces and quickly return to its original state after the forces are withdrawn. Here, we designed dressings with light-triggered on-site rapid formation of antibacterial hydrogel for the accelerated healing of infected wounds. The pro-hydrogel, composed of acrylamide (AM) and dopamine-hyaluronic acid-ε-poly-l-lysine (DA-HA-EPL), was filled into the Vibrio vulnificus-infected wound. A 405-nm blue light was exerted on the wound to rapidly photopolymerize AM to its polymer, i.e., polyacrylamide (PAM). A hydrogel network of PAM/DA-HA-EPL immediately formed on site within several seconds to insulate the wound. PAM/DA-HA-EPL possessed adhesion performance to adapt to changes in wound morphologies due to external forces. Moreover, it presented high antibacterial ability due to the presence of EPL, in vitro biocompatibility and the ability to promote cell migration. Vibrio vulnificus-infected wounds were established on full-thickness mouse skin, and the hydrogel dressing exhibited high healing efficiency in terms of skin tissue regeneration, collagen deposition, and angiogenesis. PAM/DA-HA-EPL is a promising hydrogel dressing for the accelerated healing of infected wounds.