Wound Healing Infection Research Articles

Ultrafast enzyme-responsive hydrogel for real-time assessment and treatment optimization in infected wounds

Monitoring wound infection and providing appropriate treatment are crucial for achieving favorable outcomes. However, the time-consuming nature of laboratory culture tests may delay timely intervention. To tackle this challenge, a simple yet effective HDG hydrogel, composed of hydrogen peroxide (H₂O₂), dopamine, and GelMA polymer, is developed for the ultrafast detection and treatment of Staphylococcus aureus (SA) infections. The HDG hydrogel detects SA by exploiting its secreted catalase to catalyze H₂O₂, producing oxygen, which in turn accelerates the polymerization of colorless dopamine into deep brown polydopamine (PDA). The bacterial detection process takes only 10 min with high sensitivity, and the results can be readily recognized by the naked eye or quantified using a cell phone-based digital analysis. Moreover, the HDG hydrogel provides a dual antibacterial mechanism through chemical and photothermal therapies via the generated PDA, significantly improving bacterial clearance. In animal experiments, the HDG hydrogel demonstrated promising capabilities in monitoring and eliminating bacteria, enhancing collagen deposition, reducing inflammation, and promoting the healing of infected wounds. This multifunctional design offers an enzyme-responsive strategy for the rapid assessment and management of infections, simplifying infection evaluation and facilitating the development of advanced wound dressings.Graphical

Near-infrared/pH dual-responsive triggered on-demand release of curcumin from ammonium alginate/polyvinyl alcohol hydrogel for bacterial infected cutaneous wound healing

Near-infrared/pH dual-responsive triggered on-demand release of curcumin from ammonium alginate/polyvinyl alcohol hydrogel for bacterial infected cutaneous wound healing

ZnCur nanoparticle-enhanced multifunctional hydrogel platform: Synergistic antibacterial and immunoregulatory effects for infected diabetic wound healing

ZnCur nanoparticle-enhanced multifunctional hydrogel platform: Synergistic antibacterial and immunoregulatory effects for infected diabetic wound healing

Photodynamic hemostatic silk fibroin film with photo-controllable modulation of macrophages for bacteria-infected wound healing.

Massive hemorrhage and chronic wounds caused by bacterial infections after trauma are significant challenges in clinical practice. An ideal hemostatic wound dressing should simultaneously manage bleeding and prevent bacterial infections and also hold excellent biocompatibility and bioactivities to successfully modulate immune microenvironments to promote wound healing. In this study, a silk fibroin-based light-responsive film was demonstrated to possess effective capacity of light-induced non-compressible hemostasis on liver hemorrhage and tail bleeding in vivo by binding with blood platelets to promote the clotting cascade. The blood loss of the rats was significantly less after C-MASiF films were applied, which were 1223.33 ± 347.9 mg (liver trauma) and 363.33 ± 60.28 mg (tail trimming). Importantly, the films exhibited photo-controllable modulation activity on macrophages through repeated near-infrared irradiation to regulate the immune microenvironment to enhance photodynamic antibacterial therapy. Moreover, the light-responsive silk fibroin film effectively promoted Staphylococcus aureus infected burn wound healing in vivo. The quantity of residual bacteria in the wound sites of mice in the C-MASiF films group (0.05 ± 0.0047 × 108 CFU mL-1) was considerably less than that in the control group (3.18 ± 0.75 × 108 CFU mL-1), and the wound area in the C-MASiF group (78.03% ± 4.12%) was considerably smaller than that in the control group (60.33% ± 8.81%) after 14 days. Overall, this light-responsive silk fibroin film can provide a powerful strategy for wound healing of burns.

Silver functionalized chitosan composite hydrogel with sustained silver release and enhanced antibacterial properties promotes healing of infected wounds

Bacterial infections during wound healing often cause inflammation, which delays the healing process. Therefore, innovative wound dressings are urgently needed to inhibit bacterial infections and promote healing. This study proposes an Ag-functionalized chitosan hydrogel dressing, formed via a Schiff-base reaction between alkynyl Ag substituted chitosan (Ag-CS) and octafunctionalized polyhedral oligomeric silsesquioxane with benzaldehyde-terminated polyethylene glycol (POSS-PEG-CHO), to address the issue of bacterial infection in wounds. The hydrogel demonstrated excellent injectability and self-healing properties. AgNPs and alkynyl Ag, produced by the reducing effect of chitosan and the reversible reaction of alkynyl Ag, delay the release of Ag+. Furthermore, the hydrogel exhibits a broad-spectrum antibacterial effect and effectively inhibits bacterial biofilm formation. The release of Ag+ lasts for 7 days, ensuring sustainable antibacterial properties. In a mouse infected wound model, the composite hydrogel significantly accelerated wound healing. By the eighth day, the wound healing rate reached 99 %, whereas the control group achieved only 91 %. Histological and immunofluorescence staining results indicated that hydrogel-treated wounds had faster re-epithelialization, collagen deposition, and angiogenesis, with reduced inflammation. In conclusion, the Ag-functionalized chitosan hydrogel, with sustained Ag release and enhanced antibacterial properties, shows great potential as a wound dressing for promoting the healing of infected wounds.

Dual peptide-coordinated dynamic hydrogel with antibacterial and proangiogenic activities for infected skin wounds

Infected skin wounds represent a class of significant clinical challenges due to their complexity and the risk of delayed healing. Developing an effective wound dressing capable of promoting tissue regeneration while addressing infections is crucial. In this study, we designed a dual peptide-coordinated dynamic hydrogel with both antibacterial and proangiogenic properties, specifically tailored for treating infected skin wounds. The dynamic hydrogel was constructed using gelatin, a natural biomacromolecule with high biocompatibility, as the base material. Two functional peptides, the antibacterial melittin and angiogenic peptide, were incorporated to enhance both infection control and tissue repair. Hydrogelation was achieved through coordination interactions between gold (Au) ions and sulfhydryl groups, endowing the hydrogel with dynamic properties. The excellent biocompatibility, antibacterial efficacy and angiogenic capability of hydrogel allow it to provide structural support for wound healing while promoting cell proliferation and migration. By eradicating bacteria and stimulating new blood vessel formation, it accelerates the healing of infected wounds. Additionally, its injectability and self-healing properties make it suitable for treating irregularly shaped and deep wounds. This dual-functional hydrogel may offer a promising and minimally invasive treatment option for infected skin wounds, combining high biological safety with simplified surgical procedures.

A multifunctional hydrogel based on Sanghuang polysaccharides and MXene for infected wound healing

A multifunctional hydrogel based on Sanghuang polysaccharides and MXene for infected wound healing

A flash graphene composite hydrogel for the photothermal therapy of bacterial infected wound healing

A flash graphene composite hydrogel for the photothermal therapy of bacterial infected wound healing

Healing Potential of Chromolaena odorata Extract: Modulation of Neutrophil, Macrophage, and Lymphocyte Response in Infected Wounds of Mus musculus

Chromolaena odorata has been reported to possess antimicrobial, antibacterial, and anti-inflammatory properties that aid in wound healing. Previous studies demonstrated the significant effects of a 7.5% concentration of C. odorata extract on non-infected wounds. This study aims to investigate its impact on infected wound healing. An experimental study was conducted on 36 mice, divided into two groups. Partial-thickness wounds were created on the dorsal side of each mouse and contaminated with S. aureus (106 CFU/ml). Group 1 was treated with normal saline, while Group 2 was treated with C. odorata aqueous extract at 7.5%. Histopathological analysis was performed on days 3 and 5 to count neutrophils, macrophages, and lymphocytes. Results showed a significantly lower neutrophil, macrophage, and lymphocyte count in Group 2 compared to Group 1 (p < 0.05). On day 3 and 5, Group 2 had lower neutrophil counts (5.6 ± 1.8, 5.8 ± 0.6) compared to Group 1 (9.2 ± 5.2, 15.1 ± 3.9). Macrophage counts were also lower in Group 2 (6.9 ± 1.7, 1.9 ± 0.7) compared to Group 1 (3.7 ± 1.4, 4.3 ± 0.9). Lymphocyte counts followed a similar trend, with Group 2 having fewer lymphocytes on both days (p < 0.05). In conclusion, C. odorata aqueous extract at a 7.5% concentration demonstrates potential as a wound healing agent by reducing inflammatory cells in infected wounds.

Effects of GHK peptide and its structural analogues on dynamics of healing and bacterial contamination of infected wound

INTRODUCTION: Currently, a promising trend to accelerate wound process seems to be the use of NH2-Gly-L-His-L-Lys-COOH (GHK) tripeptide, which acts on the tissue regeneration, possesses antioxidant, immunotropic and anti-inflammatory effects. At the same time, the disadvantage of all peptides is their rapid degradation by proteolytic enzymes. One method to increase the stability of peptide molecules is the incorporation of D-isomers of amino acids in their structure. It was previously found by us that GHK-D-Ala produces a more marked effect on regenerative processes in the wound and facilitates increase in the number of fibroblast cells and macrophages in the wound with the underlying decrease in the number of granulocytes and lymphocytes; a significant effect of D-Ala-GHK and GHK-D-Ala on the parameters of the inborn immunity and lipid peroxidation was shown. AIM: To evaluate the healing dynamics and bacterial contamination of an infected wound when using Glycyl-Histidyl-Lysine (GHK) peptide and its structural modifications with D-alanine (D-Ala). MATERIALS AND METHODS: The experiments were conducted on Wistar rats. In the work, GHK peptide and its structural analogues D-Ala-GHK and GHK-D-Ala were used; they were administered intracutaneously around the wound at doses of 0.5 µg/kg and 1.5 µg/kg every 24 hours for 3rd, 7th and 10th days. The wound area with calculation of the relative wound healing coefficient (RWHC), the healing rate, the time of perifocal edema disappearance, wound cleansing, appearance of granulation and onset of marginal epithelialization were assessed. Bacterial contamination was determined by counting colonies on the nutrient media after inoculation of wound biopsy material on them. RESULTS: On day 3rd, RWHC increased 3.2–5.3 times (p 0.05–0.01) after the use of D-Ala-GHK and GHK-D-Ala peptides at both doses with no effect after the injection of GHK. On day 7th, the reduction of the wound area reached statistically significant differences in all experimental groups. By day 10th, the use of peptides resulted in decrease in the wound area most evident after the injection of GHK-D-Ala peptide (by 93%, p 0.001) in all groups. On days 7th–10th, GHK-D-Ala increased the healing rate 4.7–5.3 times (p 0.05-0.01) with no significant changes after the injection of GHK and D-Ala-GHK. Also, GHK-D-Ala at both doses resulted in the earliest disappearance of perifocal edema, wound cleansing, emergence of granulation and the onset of marginal epithelialization in all experimental groups. Significant reduction in bacterial contamination was observed after administration of all peptides on days 7th and 10th, being most pronounced after the use of GHK-D-Ala. CONCLUSION: The application of GHK peptide and its structural analogues D-Ala-GHK and GHK-D-Ala in infected skin wounds accelerated wound healing against the background reduction of bacterial contamination. The most pronounced changes of these parameters were observed after administration of GHK-D-Ala peptide, which indicates the importance of protecting GHK molecule against the impact of carboxypeptidases. A promising continuation of the research in this direction can be the development of local means with antibacterial effect for stimulation of the regeneration processes in the wound.

Hyperglycemia-responsive nitric oxide-releasing biohybrid cryogels with cascade enzyme catalysis for enhanced healing of infected diabetic wounds.

Diabetic wound infections are a frequent complication for diabetic patients, and conventional treatment for combating diabetic wound infections relies on antibiotics. However, the misuse and overuse of antibiotics have led to the emergence of drug-resistant bacteria, making these infections challenging to treat. Thus, there is an urgent need for alternative strategies to effectively manage diabetic wound infections. Herein, we have developed a hyperglycemia-responsive antibacterial cryogel system that can generate and release hydrogen peroxide (H2O2) and nitric oxide (NO). This system involves incorporating glucose oxidase (GO) and L-Arginine (L-Arg: A) into hyaluronic acid aldehyde methacryloyl (HAAMA: H) and gelatin methacryloyl (GelMA: G) hybrid cryogels (GOA@HG). HAAMA facilitated higher loading and longer stability of L-Arg and GO via a Schiff base reaction. In vitro studies demonstrate that GOA@HG cryogels exhibited outstanding breathability, effective exudate management, and excellent hemostasis capabilities. Moreover, this system could consume excess glucose in diabetic wounds and efficiently eliminate bacteria through the cascaded release of H2O2 and NO without causing antibiotic resistance. In vivo studies further reveal that GOA@HG cryogels significantly enhanced the healing of infected diabetic wounds by inhibiting bacterial growth, accelerating blood vessel formation, and promoting collagen deposition. Overall, GOA@HG cryogels displayed remarkable wound dressing properties and synergistic antimicrobial effects owing to glucose-responsive H2O2 and NO release, which could serve as a highly efficient therapeutic strategy for treating infected diabetic wounds.

A bacteria-responsive nanoplatform with biofilm dispersion and ROS scavenging for the healing of infected diabetic wounds.

Delayed wound healing in patients with diabetes remains a major health challenge worldwide. Uncontrolled bacterial infection leads to excessive production of reactive oxygen species (ROS) and persistent inflammatory responses, which seriously hinder conventional physiological healing processes after injury. Biofilms, as protective barriers for bacteria, pose a critical obstacle to effective bacterial eradication. Herein, an innovative therapeutic nanoplatform with in situ antibacterial and antioxidant properties is developed for enhancing infected diabetic wound healing. The enrichment of phenylboronic acid (PBA) moieties on the nanoplatform enhances biofilm penetration, actively anchors and aggregates the enclosed bacteria through the "multivalent effect", with an anchoring efficiency as high as 80%. Additionally, glycine moieties on the nanoplatform ensure spatial extensibility by charge repulsion, enabling targeted antibiotic release around bacteria. This precise antibacterial effect increases the bactericidal activities of the nanoplatform against S. aureus or P. aeruginosa by 25% and 22% respectively, effectively eliminating the bacteria and dispersing the biofilms. Furthermore, 3,4-dihydropyrimidin-2(1H)-one (DHPM) moieties act as ROS scavengers that alleviate oxidative stress and inflammatory responses, promoting tissue repair progression into the proliferative phase characterized by increased extracellular matrix deposition, angiogenesis, and granulation tissue formation, ultimately accelerating diabetic wound healing. Overall, this work presents an innovative bacterial response strategy for achieving in situ antibacterial and antioxidant effects in infected tissues and provides a promising therapeutic approach for treating infected diabetic wounds. STATEMENT OF SIGNIFICANCE: : Infected diabetic wound management remains a major world health issue. Severe bacterial infection leads to excessive oxidative stress and persistent inflammatory response, which seriously hinders the wound healing process. As a protective barrier for bacteria, biofilms are a key obstacle to effective bacterial clearance. This study provides a bacteria-responsive nanoplatform for the healing of infected diabetic wounds. The nanoplatform not only exhibits improved biofilm penetration but also actively anchors the enclosed bacteria and enables targeted antibiotic release to disperse the biofilm. The DHPM moieties of the nanoplatform act as ROS scavengers which could alleviate inflammatory responses, promote tissue repair progression into the proliferative phase, and ultimately accelerate diabetic wound repair.

Bioactive electrospun polylactic acid/chlorogenic acid-modified chitosan bilayer sponge for acute infection wound healing and rapid coagulation.

Acute severe trauma is often associated with rapid blood loss and a high risk of infection. Based on these concerns, this study successfully constructed a multifunctional dual-layer bioactive sponge PCCT with rapid hemostatic and infection-preventing ability. Its external surface is an electrospun poly(lactic acid) (PLA) nanofiber thin film layer, which ensures its high air permeability and effectively protects against external bacterial invasion. In vitro results showed that the film is effectively resistant to invasion by typical Gram-negative (E. coli) and Gram-positive (S. aureus) bacteria. The inner sponge layer was formed by chlorogenic acid (CGA) grafted with chitosan (CS) and loaded with tranexamic acid (TA). The abundant cationic groups on the sponge interacted with negatively charged erythrocytes and achieved rapid hemostasis at the wound site under the action of TA. In addition, the high porosity and bioactivity of the CS-CGA sponge scaffold endowed the hydrogel with good water absorption, antibacterial properties and anti-inflammatory activity, which effectively accelerated the healing of acute infected wounds in rats and demonstrated favorable biosafety.

Regulating the Atomic Active Center by Covalent Organic Framework-Derived Photothermal Nanozyme to Arm Self-Gelling Powder for Bacterial Wound Healing.

Creating simple methods to produce antioxidant nanozymes with clear structure-activity relationships, particularly aiming to improve disinfection and create practical drug formulations for bacterial wound healing, remains a crucial challenge. Herein, we synthesized iron-loaded covalent organic framework nanospheres, which were then controllably transformed into a carbon-based nanozyme with both iron single atoms and iron clusters through simple pyrolysis. We discovered that the gradual growth of iron clusters significantly boosted the nanozyme's adsorption onto the substrate and electron transfer, greatly influencing its activity. The nanozyme, optimized by the coexistence of single iron atoms and Fe4 clusters, exhibited the strongest catalase and superoxide dismutase enzyme activities as well as high photothermal efficiency. Under physiological conditions, its peroxidase and oxidase enzymatic activities, which stimulate oxidative stress, remained low. Furthermore, we created an antibacterial self-gelling powder capable of dispersing the nanozyme using polyacrylamide and poly(acrylic acid). The powder can rapidly gel and adhere to wet wound areas, synergistically sterilizing the wound through the combined actions of the gel's amino groups and the nanozyme's photothermal effect, while leveraging the antioxidant enzymatic effects to mitigate wound inflammation. These properties contribute to the fast healing of infectious wounds, thus promising a clear formulation and treatment.

A Portable, Sprayable, Highly Malleable, Elastic, and Hydrophobic Antibacterial Fibrous Wound Dressing for Infected Wound Healing

A Portable, Sprayable, Highly Malleable, Elastic, and Hydrophobic Antibacterial Fibrous Wound Dressing for Infected Wound Healing

Engineering Surface-Adaptive Metal-Organic Framework Armor to Promote Infected Wound Healing.

Metal-organic frameworks (MOFs) hold enormous promise for treating bacterial infections to circumvent the threat of antibiotic resistance. However, positioning MOFs on wound dressings is hindered and remains a significant challenge. Herein, a facile heterointerfacial engineering strategy was developed to tailor the "MOF armor" that adaptively weaponized the poly(ε-caprolactone) electrospun dressing with excellent bacteria-killing efficacy. Hydrophilic epitaxial crystallization to enhance the interfacial wettability is the key to induce the uniform seeding of Cu2+ and thus to generate a compact MOF layer on the electrospun dressing. The universality of the proposed strategy was demonstrated by the construction of different kinds of MOFs (HKUST-1, ZIF-8, and ZIF-67) on variously shaped substrates (nanofibers, pellets, plates, and 3D-printed porous scaffolds). By optimizing the Cu2+ loading, the Cu-MOF armor exhibited sustained ion release behavior, strong antibacterial activity, and good biocompatibility. In vivo rat model revealed that the Cu-MOF armor significantly promoted infected wound healing by inhibiting inflammatory factors, promoting collagen deposition, and angiogenesis. This unique MOF armor provides an appealing and effective solution for designing and fabricating advanced wound dressings.

Injectable and self-healing carboxymethyl chitosan/carboxymethyl cellulose/marine snail peptide hydrogel for infected wound healing.

Treatment of bacterial infected full-thickness wounds remains a great challenge in clinic. Herein, a HYP hydrogel was prepared using carboxymethyl chitosan, dialdehyde carboxymethyl cellulose, and marine snail peptide (Tyr-Ile-Ala-Glu-Asp-Ala-Glu-Arg) as starting materials. The marine snail peptide with good antioxidant activity could remove the reactive oxygen species in wound sites, thereby alleviating the excessive inflammatory response. The dynamic Schiff-base bonds endowed HYP with good injectable and self-healing abilities. HYP exhibited suitable gelation time, good rheological properties, and unique porosity structure, which were conducive to wound healing. In vitro biological studies indicated that HYP showed good biocompatibility, low hemolysis ratio, and improved antibacterial and antioxidant activities. In vivo study revealed that HYP could promote wound healing in a bacterial infected full-thickness skin defect rat model. The wound tissues showed reduced number of inflammatory cells, newly formed hair follicles, and obvious collagen deposition. The expression of inflammatory and angiogenesis related biomarkers (IL-6, IL-10, CD31, and α-SMA) significantly improved. Therefore, HYP hydrogel showed great application prospect as a wound dressing for bacterial infected wound.

Block cationic copolymer/quaternary ammonium chitosan-based composite antibacterial hydrogel dressings with NIR photothermal effects for bacteria-infected wound healing.

Wound infections caused by pathogenic bacteria can cause delayed wound healing and even threaten the life of patients. Drug resistance and effectiveness with regard to traditional wound dressings have become urgent issues which need to be addressed. The antibacterial effect of hydrogels, as novel wound dressings, is through contact-active antibacterial was limited by the contact area and time. In this paper, MXene (a 2D carbonitride) has been employed as the substrate and via the in-situ reduction of silver nanoparticles and the polymerization of dopamine on its surface the photothermal agent MXene-Ag-PDA was obtained. This was then introduced into the hydrogel matrix via the block cationic polymer (AM-VBIMBr-AAPBA), oxidized sodium alginate (OSA) and quaternary ammonium chitosan (HACC). Multifunctional composite hydrogels (PNVAO/M-A-P) possessing photo-thermal effects and inherent antibacterial activity were obtained after crosslinking, and were employed as medical materials to promote the healing of infected wounds. The cationic groups contained in the PNVAO/M-A-P were capable of capturing and killing bacteria by electrostatic interactions, and produced local heat killing adsorption and residual bacteria in the surrounding solution under NIR irradiation, thereby shortening the antibacterial cycle and improving the sterilization efficiency. Meanwhile, the introduction of glycerin in the hydrogel improved its anti-freezing and anti-drying properties, enabling the hydrogel to function stably under extreme environments. PNVAO/M-A-P composite hydrogels based on chemical and dynamic crosslinking exhibited the desired mechanical strength, and via their self-healing ability can adapt to dynamic wounds. The hydrogel dressing showed excellent anti-freezing and anti-drying properties, high bovine serum albumin (BSA) adsorption capacity (308.17mg·g-1), good biocompatibility (the cell viability exceeded 100% after 48h of incubation), antioxidant properties and excellent antibacterial activity (the sterilization rate can reach 99.9%). Furthermore, the hydrogel was applied to infected wound treatment and was able to control the wound infection, reduce pro-inflammatory factor production, promote collagen deposition and neovascularization formation, and thus promote wound healing. Therefore, multifunctional composite hydrogels with synergistic antibacterial effects can be used as an novel dressing for the treatment of bacterial infected wounds.

An Efficient Biosynthetic System for Developing Functional Silk Fibroin-Based Biomaterials.

Long historical evolution and domestication endow silkworms with the super ability to synthesize and secrete massive silk proteins using silk glands. The major component of this secretion consists of silk fibroin, considered a promising biomaterial for tissue repairs and engineering. To further expand the utility of this unique protein, there is a continuing need for silk fibroin functionalization. Here, a highly-efficient Fib-HEXP biosynthetic system is established to synthesize massive recombinant RFP in silk fibers using transgenic silkworms, which accounts for ≈7.86% of silk mass and achieves fabrication of fluorescent silk fibroin (SF) biomaterials. The universality of the Fib-HEXP system is validated by genetic engineering glucose oxidase (GOx) functionalized silk fibers for fabricating GOx-SF hydrogels with antimicrobial activity to promote healing of infected diabetic wounds in mouse through the enzyme-catalyzed reaction of glucose to gluconic acid and H2O2. These findings demonstrate that the Fib-HEXP system provides an opportunity for genetic functionalization of SF to broaden the utility of this biomaterial for a range of potential applications.

NIR-II Light-Driven Multifunctional Nanozymes PS@CS for Efficient Therapy against Melanoma and Post-tumor Surgery Infection.

Melanoma, the most prevalent form of skin cancer, is primarily treated with surgical intervention. However, complete tumor cell removal is challenging, and surgical wounds are prone to infection, complicating treatment and increasing costs. The successful treatment of melanoma generally requires multifunctional agents that are coordinated in tumor therapy and wound healing. In this study, we developed platinum (Pt)- and selenium (Se)-based nanozymes, Pt-Se@Chitosan (PS@CS), which exhibit synergistic antitumor and bactericidal efficacy attributed to their multienzyme activity and strong photothermal conversion efficiency. Furthermore, we engineered PS@CS hydrogels capable of inhibiting tumor regrowth postsurgery and accelerating healing of infected wounds. The PS@CS and PS@CS hydrogels presented herein incorporate characteristics including catalytic therapy, photothermal therapy, antibacterial properties, and skin damage healing, providing an innovative and comprehensive therapeutic approach for melanoma treatment.