The treatment of bacterial wound infection, particularly that caused by methicillin-resistant Staphylococcus aureus (MRSA), presents significant challenges owing to biofilm formation, multidrug resistance, and immune evasion. Here, we have rationally designed a multifunctional composite nanozyme (FTM) consisting of tannic acid (TA) and ferric ion (Fe3+) coordination compound loaded with antibiotic drug methicillin (Meth), which is capable of realizing pH-responsive self-adaptive regulation of oxidative stress for enhancing the treatment of MRSA-infected wound. During the early stages of wound infection (pH < 6.5), FTM demonstrates significant peroxidase-like activity for effectively catalyzing the conversion of endogenous H2O2 into highly toxic hydroxyl radical (center dot OH), which not only directly damages MRSA and eliminates its biofilm for chemodynamic therapy (CDT), but also disrupts the penicillin-binding protein 2a (PBP2a) to restore the sensitivity of MRSA to methicillin. Meanwhile, FTM exhibits strong near-infrared (NIR) absorption, achieving photothermal antibacterial therapy (PTT). While in the later stages (after complete elimination of MRSA), as the infectious microenvironment of wound becomes neutral (pH 7.4), FTM mainly reveals the superoxide dismutase (SOD)-like activity for scavenging excess reactive oxygen species (ROS), ultimately reducing oxidative stress and promoting tissue repair. In vitro and in vivo experiments show that the proposed FTM nanozyme with triple bactericidal modalities achieves satisfactory antibacterial and antibiofilm therapy and accelerates wound healing process. Consequently, by adapting to the dynamic changes of wound microenvironment, this multifunctional nanoplatform offers a promising strategy for treating drug-resistant wound infections.
Pathogen colonization causes tissue damage, chronic inflammation, and antimicrobial resistance, leading to nonhealing wounds. Moreover, bacteria-infected diabetic wounds are particularly difficult to heal owing to persistent hyperglycemia. Herein, a glucose (Glu)-responsive antibacterial nanogel (PAMGHM) consisting of polyacrylamide (PAM) loaded with glucose oxidase (GOx), horseradish peroxidase (HRP), and metronidazole (MTZ) is rationally constructed for combating the diabetic wound infections. This nanogel was fabricated via a reverse microemulsion polymerization approach, which enabled the co-encapsulation of GOx and HRP within nanoscale gel microspheres. Within PAMGHM, GOx first catalyzes the oxidation of Glu to produce H2O2, which is subsequently utilized by HRP to generate hydroxyl radicals (•OH). The close integration of cascade enzymes ensures rapid Glu consumption and •OH production, which not only directly kills bacteria but also establishes a localized hypoxic microenvironment through O2 depletion. The induced hypoxia promotes bacterial nitroreductase expression, thereby activating the antibacterial properties of MTZ. In vitro experiments reveal that PAMGHM exhibited a powerful killing effect against both Staphylococcus aureus and Escherichia coli, demonstrating synergistic chemodynamic/chemo dual-mode antibacterial therapy. Further in vivo assays exhibit that the proposed PAMGHM accelerates diabetic wound healing by killing bacteria and alleviating hyperglycemia-induced inflammation. This cascade enzyme-mediated antibiotic activation strategy offers a useful therapeutic approach to meet the requirements of efficient antibacterial therapy, hyperglycemia control, and anti-inflammation, showing great potential in the treatment of chronic diabetic wound infections.
Inducing compressive residual stress into surface layer is believed to enhance fatigue strength of materials. Water cavitation jet peening (WCJP) is recommended because of its high efficiency and uniform processing. This work proposes an enhanced WCJP technology by dissolving carbon dioxide (CO2). Mass loss, Vickers hardness, surface profile, residual stress, cavitation pit and grain size of the processed Aluminum were investigated. Results indicate that appropriate CO2 dissolution promotes cavitation peening with less surface distortion. The induced compressive residual stress is 28.6 % larger than pure waterjet peening. CO2 content of 200 mg/L is recommended to obtain a desired peening performance. (c) 2025 Society of Manufacturing Engineers (SME). Published by Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.
The treatment of diabetic wound infections remains a significant challenge. Nitric oxide (NO) generated by macrophage in body is essential for immune defense and wound healing, making it a promising therapeutic agent for wound infections. However, high glucose level in diabetic wound impairs macrophage function. Here, we construct a macrophage-mimetic living hydrogel microspheres capable of producing NO through a glucose-fueled cascade reaction for efficiently eliminating bacterial infection and accelerating the diabetic wound healing. In our design, glucose oxidase (GOx) and horseradish peroxidase (HRP) are covalently immobilized into the polyacrylamide (PAM) hydrogel microsphere containing poly-L-arginine (P-Arg), followed by encapsulating with M1 macrophage membrane (M) to yield PGHA@M with bacteria-targeting ability. In the presence of glucose, PGHA@M possesses remarkable capability to produce H₂O₂, which is subsequently catalyzed by HRP into hydroxyl radicals (OH). Meanwhile, the embedded P-Arg is oxidized by OH into NO. PGHA@M demonstrates satisfactory antibacterial and antibiofilm properties. Further in vivo experiments verify that PGHA@M can efficiently eliminate the biofilm bacteria and promote the diabetic wound healing. This study provides a potential strategy to simulate M1 macrophage functions via dual enzymatic cascade reactions, and offers a new perspective for the treatment of diabetic wound infections based on living hydrogel microspheres.
Enterotoxigenic Escherichia coli (ETEC) is a well-known strain associated with post-weaning diarrhea. Consequently, strategies to prevent and inhibit ETEC infections are critically important. Aptamers are single-stranded DNA or RNA sequences that exhibit high affinity and specificity for binding to target molecules. In this study, we used the intestinal porcine epithelial cell line IPEC-J2 as an in vitro model to demonstrate that two aptamers, K88-Apt A04 (a fimbrial-specific aptamer targeting ETEC K88) and K88-Apt 37 (a cell-specific aptamer targeting ETEC K88) effectively inhibited the adhesion of ETEC K88 to intestinal epithelial cells. We established an ETEC K88-IPEC-J2 interaction model by exposing the IPEC-J2 cell line to ETEC K88 at a multiplicity of infection of 10. Our findings revealed that the aptamers inhibited ETEC K88 adhesion to IPEC-J2 cells in a concentration-dependent manner, primarily through adherence inhibition and prevention. Furthermore, enzyme-linked immunosorbent assay and mRNA expression analyses indicated that the aptamers reduced the secretion of pro-inflammatory cytokines triggered by ETEC K88 infection. In conclusion the aptamers demonstrated the ability to reduce ETEC K88-induced cytotoxicity in IPEC-J2 cells in vitro.
Bacterial biofilm microenvironments including hypoxia, limited H2O2, and high glutathione (GSH) level seriously limit the bactericidal efficacy of reactive oxygen species (ROS)-based strategies. Alkyl radicals (center dot R) have gained much attention as hypoxia-irrelevant antibacterial agents. However, the controlled center dot R generation for specific bacterial biofilm elimination remains a great challenge. Here, we prepare a Zr-based metal-organic framework (ZrA) with valence-invariable chemodynamic property by using 2,2 '-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) as organic ligand, and load heat-sensitive azo initiators (Azo) on its surface to construct a H2O2-activatable cascade center dot R nanogenerator (ZrA-Azo) for programmed multi-mode precision therapy of biofilmassociated wound infections. In the wound infection sites or biofilm, endogenous H2O2 is converted by the ZrAmediated catalysis with invariable valence into highly toxic ROS for chemodynamic therapy. Immediately, ROS oxidizes colorless ABTS into blue-green ABTS center dot+ with strong near-infrared absorption for photothermal therapy. Local photonic hyperpyrexia also triggers the decomposition of azo initiators into center dot R for thermodynamic therapy. Significantly, center dot R not only promotes the generation of ABTS center dot+ and GSH depletion, but also improves H2O2 level in the infection sites by inhibiting the catalase activity for enhancing the H2O2-initiated cascade reactions. In vivo anti-infective experiments demonstrate that ZrA-Azo possesses satisfactory multi-mode antibiofilm performance and accelerates the healing of infected wound. This study provides an innovative hypoxia-irrelevant antibacterial strategy for precise biofilm elimination with high performance.
An ultrasmall bimetallic Au2Pd3 nanozyme with self-cascade enzyme-like activities and robust photothermal heating properties is synthesized and encapsulated into a poly(vinyl alcohol)/hyaluronic acid (PVA/HA) matrix via a repeated freezing and thawing process to yield a hydrogel microneedle patch (Au2Pd3@PH). This microneedle displays a good tissue-piercing capability and thermal-responsive melting behavior. Upon exposure to an 808 nm near-infrared laser, Au2Pd3@PH dissolves and releases Au2Pd3, which shows glucose oxidase (GOx)-like catalytic activity for the conversion of endogenous glucose into gluconic acid and hydrogen peroxide (H2O2), thereby reducing the glucose level and local pH at the wound site. The reduced pH induces the peroxidase-like activity of Au2Pd3 to further oxidize H2O2 into the hydroxyl radical (•OH). In vitro experiments reveal that Au2Pd3@PH exhibits antibacterial rates exceeding 99% against both Staphylococcus aureus and Salmonella typhimurium, showing a photothermal/chemodynamic dual-mode synergistic antibacterial effect. Further in vivo assays demonstrate that the Au2Pd3@PH treatment group achieves near-complete healing of infected diabetic wounds within 7 days, indicating an enhanced wound healing process. The treatment with Au2Pd3@PH effectively modulates inflammatory factor expression, including marked downregulation of TNF-α and IL-6, while simultaneously promoting collagen deposition and angiogenesis, with no adverse biological effects observed. Therefore, the proposed Au2Pd3@PH hydrogel microneedle provides a promising strategy for treating diabetic wound infections with a high performance.
Bacterial infections, particularly those caused by multidrug-resistant (MDR) bacteria, pose a serious global health threat. The limited efficacy of traditional antibiotic drugs against MDR strains and the slow development of antibiotics necessitate the exploration of alternative therapeutic strategies. Acid-degradable metallic peroxide has emerged as a promising solution, exhibiting broad-spectrum antimicrobial activity with a reduced risk of resistance development. In this study, we have constructed an acid-responsive bimetallic peroxide nanocomposite (ZCS@M@HA) for the treatment of wound infections involving methicillin-resistant Staphylococcus aureus (MRSA). In our design, the copper-doped zinc peroxide (ZC) nanoparticles are prepared and coated with mesoporous silica to obtain core-shell structured ZC@M, which is subsequently loaded with S-nitroso-N-acetylpenicillamine (SNAP) acting as a nitric oxide (NO) donor and capped with sodium hyaluronate (HA) to prevent premature SNAP release. In the acidic microenvironment of infectious sites, ZCS@M@HA releases Zn2+, Cu2+, and H2O2, and the former disrupts bacterial energy metabolism by impairing the electron transport chain. Meanwhile, self-supplied H2O2 and Cu2+ perform a Fenton-like reaction to generate highly toxic hydroxyl radicals (•OH) for damaging bacterial membranes. Moreover, Cu2+ depletes intracellular glutathione (GSH) to augment the oxidative stress. Furthermore, NO released from SNAP triggered by Cu2+ and GSH accelerates wound healing by promoting collagen deposition, tissue regeneration, and vascularization. In vivo assays demonstrate the high MRSA inhibition efficacy of ZCS@M@HA with optimal wound healing. The proposed acid-responsive ZCS@M@HA with multi-bactericidal modalities offers an effective approach to fight MDR bacteria and presents a promising strategy for treating wound infections.
Photosynthesis has garnered significant interest due to its potential for retrofitting and its intrinsic enzyme-mediated metabolic processes, which can convert carbon dioxide (CO2) into biomass powered by solar energy. However, natural photosynthesis is limited by factors such as low photosynthetic efficiency and constraints on the range of output products. To address these issues, researchers have developed various strategies for designing and engineering photosynthetic systems. These strategies include nanomaterial-assisted approaches to enhance light absorption and accelerate electron transfer, microfluidic technologies for precise manipulation of enzyme modules, synthetic biology techniques to optimize metabolic pathways, and photo-bioelectrochemical systems (PBESs) for efficient utilization of photosynthetic electrons. Inspired by these, numerous applications have emerged in the fields of artificial organelles, promotion of hypoxic tissue healing, bioproduction, and environmental production and sustainability. This review provides a comprehensive introduction to the principles of photosynthesis, encompassing light and carbon reactions. Additionally, it offers an overview of recent strategies for the design, structuring, and engineering of photosynthetic systems, while discussing several applications of photosynthesis. Finally, this review highlights the potential of engineered photosynthetic systems to address challenges in energy and matter conversion across various fields, offering insights into the future of sustainable, photosynthesis-based technologies.
Drug misdosing is a common cause of adverse effects. We first developed an aptamer target chain reaction (ATCR), which relies on a bivalent aptamer (HDTB-2) engineered with a sufficiently short spacer to continuously bind the target molecules, subsequently forming an aptamer target chain (ATC). ATCR is an universal, size-tunable, highly controllable, isothermal, self-assembly, and enzyme-free method for biomaterial formation. Through selecting aptamers with appropriate binding affinities, HDTB-2 inhibits target molecules only at the upregulated level and keeps it free at a healthy level to minimize the side effects due to misdosing. The design is applied as a smart anticoagulant, which exhibited stronger protection against misdosing and inhibition effects than commercial anticoagulants, due to the effective binding and enclosure of target molecules induced by the formation of bulky ATC. The efficacy and exceptional side effect management capability were further validated by a series of in vitro and in vivo experiments. To the best of our knowledge, this is the first report of a universal, non-covalently linked nucleic acid-biomolecule chain self-assembly method and a drug development technology that equips active pharmaceutical ingredients (API) with self-regulatory capability for smart management of the side effects.
High H2O2 levels are widely present at the infection sites or in the biofilm microenvironment. Herein, hemin with peroxidase-like catalytic activity and its substrate, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), are simultaneously introduced into a liposomal nanoparticle containing thermosensitive 2,2'-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIBI)-loaded bovine serum albumin (BAG), rationally constructing an H2O2-activatable liposomal nanobomb (Lipo@BHA) for combating biofilm-associated bacterial infections with high performance. In the presence of H2O2, hemin can catalyze the conversion of ABTS into its oxidized form (ABTS·+) with strong near-infrared (NIR) absorption, which produces photonic hyperpyrexia to cause the decomposition of AIBI into oxygen-independent alkyl radicals (·R) and nitrogen (N2) microbubbles. The former not only directly damage bacterial cells but also significantly accelerates the oxidization of ABTS to ABTS·+ for augmenting photothermal-triggered generation of ·R. Interestingly, the released N2 can induce transient cavitation to rupture lysosomal nanoparticle and improve the biofilm permeability, thereby enhancing the antibiofilm effect of Lipo@BHA. The proposed Lipo@BHA exhibits satisfactory multi-mode combination antibacterial properties. Through endogenous H2O2-activated cascade reaction, Lipo@BHA achieves remarkable hypoxia-irrelevant ·R therapy of biofilm-associated wound infections with low cytotoxicity and good in vivo biosafety. Therefore, this work presents a versatile H2O2-activatable cascade ·R generation strategy for biofilm-specific therapeutic applications.
Chemodynamic therapy (CDT) involving highly toxic hydroxyl radical (center dot OH) with no drug resistance has gained widespread attention for antibacterial applications. However, the CDT effect is seriously confined by overexpressed glutathione (GSH) and limited hydrogen peroxide (H2O2) in the infection sites. Here, we have constructed a cascade enzyme/nanozyme assembly (MCS/GO(x)) composing of a bimetallic sulfide MoCuSx (MCS) nanozyme loaded with natural glucose oxidase (GOx) for synergistic photothermal/photodynamic enhanced chemodynamic antimicrobial therapy with high performance. The loaded GOx can promote the peroxidase (POD)-like activity of MCS by providing an acidic microenvironment and self-supplying H2O2, achieving cascade generation of center dot OH for efficient CDT. The CDT effect can be further promoted by a co-catalysis mediated by the Mo4+/Mo6+ redox couple. Upon exposure to an 808 nm near-infrared laser, MCS/GOx provides hyperpyrexia for photothermal antibacterial therapy (PTT), and produce singlet oxygen (1O2) for photodynamic therapy (PDT). Moreover, MCS/GOx can significantly consume antioxidant glutathione via the Cu+/Cu2+ redox couple and PDTmediated O-1(2) production, thereby enhancing CDT antibacterial effect. In vitro experiments exhibit that MCS/GOx has combined antimicrobial effect against Staphylococcus aureus and Escherichia coli. Further in vivo studies demonstrate that MCS/GOx can efficiently eliminate bacterial cells in wound tissues and accelerate wound healing with low inflammatory response and good biosafety. Consequently, the proposed MCS/GOx with multiple bactericidal modalities shows a great potential in fighting wound infections.
Well-designed nanocatalysts capable of generating free radicals have recently shown promising potential for treating bacterial biofilm infections. However, the biofilm microenvironments such as hypoxia and over -expressed glutathione (GSH) seriously limit their biomedical applications. To address these issues, we herein construct a dual free radical nanogenerator (MnO2/GOx/AIBI) by loading glucose oxidase (GOx) and thermal -labile azo initiator (AIBI) onto the flower-like MnO2 with high loading capacity for the hypoxia-irrelevant treatment of biofilm-associated bacterial infections. On the one hand, MnO2/GOx/AIBI nanocomposites can generate hydroxyl radicals by glucose-fueled cascade catalytic reactions between GOx and MnO2 for efficient O2- and H2O2-self-supplying chemodynamic therapy (CDT). On the other hand, MnO2 can provide local photonic hyperpyrexia, which not only triggers the O2-independent generation of alkyl radicals for photothermal dynamic therapy (PTDT), but also enhances the CDT efficacy by accelerating the release of Fenton-type Mn2+. Besides, MnO2 can degrade GSH over-expressed in the infection sites, improving the synergistic CDT/PTDT therapeutic effectiveness by redox dyshomeobasis. The hybrid MnO2/GOx/AIBI nanocatalysts exhibit satisfactory in vitro and in vivo antibacterial and antibiofilm performances with minimal toxic side effects. Taken together, the developed hypoxia-irrelevant dual-mode synergistic antibacterial nanoplatform can effectively overcome the interferences of biofilm microenvironments, showing a promising potential for future biomedical applications.
Synthetic protocells are minimal systems that mimic certain properties of natural cells and are used to research the emergence of life from a nonliving chemical network. Currently, coacervate microdroplets, which are formed via liquid-liquid phase separation, are receiving wide attention in the context of cell biology and protocell research; these microdroplets are notable because they can provide liquid-like compartment structures for biochemical reactions by creating highly macromolecular crowded local environments. In this review, an overview of recent research on the formation of coacervate microdroplets through phase separation; the design of coacervate-based stimuli-responsive protocells, multichamber protocells, and membranized protocells; and their cell mimic behaviors, is provided. The simplified protocell models with precisely defined and tunable compositions advance the understanding of the requirements for cellular structure and function. Efforts are then discussed to establish signal communication systems in protocell and protocell consortia, as communication is a fundamental feature of life that coordinates matter exchanges and energy fluxes dynamically in space and time. Finally, some perspectives on the challenges and future developments of synthetic protocell research in biomimetic science and biomedical applications are provided.
Purpose:We aimed to develop an oxidative-stress-activated palladium-copper nanozyme to reduce bacterial's heat sensitivity by down-regulating heat shock proteins to overcome the shortcomings of conventional photothermal antimicrobial therapy and achieve mild photothermal bactericidal efficacy.Methods:We first synthesized palladium-copper nanozymes (PC-NPs) by hydration and used transmission electron microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy to demonstrate their successful preparation. Their photothermal therapy (PTT) and chemo-dynamic therapy (CDT) activities were then determined by a series of photothermal performance tests and peroxidase-like performance tests, and the destruction of heat shock proteins by reactive oxygen species (ROS) was verified at the protein level by Western Blotting tests, providing a basis for the effective bacteria-killing by the mild-temperature photothermal treatment subsequently applied. We also validated this promising programmed and controlled antimicrobial treatment with palladium-copper nanozymes by in vivo/in vitro antimicrobial assays. A hemolysis assay, MTT cytotoxicity test and histopathological analysis were also performed to assess the in vivo safety of PC-NPs.Results:In the micro-acidic environment of bacterial infection, PC-NPs showed peroxidase-like activity that broke down the H2O2 at the wound into hydroxyl radicals and down-regulated bacterial heat shock proteins. The application of PC-NPs increased bacteria's sensitivity to subsequent photothermal treatment, enabling the elimination of bacteria via mild photothermal treatment.Conclusion:The programmed synergistic catalytic enhancement of CDT and mild photothermal therapy achieves the most efficient killing of bacteria and their biofilms, which brings future thinking in the relationship between heat shock proteins and oxidative stress damage in bacteria.
Reactive oxygen species (ROS) such as hydroxyl radicals (center dot OH) and singlet oxygen (1O2) have emerged as promising therapeutic agents for combating biofilm-associated bacterial infections. However, the hypoxic mi-croenvironments in the biofilms severely hinder the ROS production. Herein, we have rationally integrated copper peroxide (CP) and indocyanine green (ICG) into a polydopamine (PDA) nanoparticle to construct a versatile hybrid nanoplatform (PDA/CP/ICG), which can enhance ROS generation for highly efficient biofilm elimination by relieving hypoxic microenvironment. When the PDA/CP/ICG accumulates at the infection site or biofilm, the acidic microenvironment triggers the co-release of Cu2+ and H2O2, and the former can catalyze the conversion of self-supplied H2O2 into center dot OH via a Fenton-like reaction and consume the overexpressed antioxidant glutathione (GSH) to further promote the oxidative stress. Moreover, with the help of an 808 nm laser, the hyperpyrexia caused by PDA induces the decomposition of CP into O2 that is immediately converted by ICG into 1O2. The PDA/CP/ICG shows satisfactory antibacterial and antibiofilm effect due to the self-amplified production of center dot OH and 1O2, and outstanding wound healing with good in vivo biosafety. Overall, this study provides a facile paradigm in ROS-based biofilm elimination, and the proposed hypoxia-irrelevant bactericidal nanoplatform has great potential for future biomedical applications.
Pathogenic bacterial infections of skin wounds have caused a significant threat to clinical treatment and human life safety. Here, we develop a bactericidal hydrogel dressing consisting of a polyacrylamide (PAM) hydrogel framework with in situ surface-deposition of iron-dopped polydopamine (FePDA). The prepared hydrogel dressing (FePDA-PAM) has a compact surface, good tensile strength, and excellent elastic recovery ability. The introduction of Fe3+ ions improve the photothermal therapy (PTT) efficiency of the PDA and endow the hydrogel dressing with chemodynamic therapy (CDT) properties. In vitro experiments show that the antibacterial effect of FePDA-PAM hydrogel on Staphylococcus aureus reach nearly 100% under the combined action of H2O2 and 808 nm near-infrared (NIR) laser, indicating an excellent combined antibacterial property of PTT and CDT. Furthermore, the FePDA-PAM + H2O2 + NIR treatment group in the in vivo antibacterial experiments displays lowest relative wound area and optimal wound healing within 5 days of treatment, thereby indicating the intensive skin wound disinfection. To summarize, the FePDA-PAM hydrogel has simple preparation and good biosafety. It may serve as a potential wound dressing for the combined PTT/CDT dual-mode antibacterial therapy.
Preventing bacterial infections and accelerating wound closure are essential in the process of wound healing. Current wound dressings lack enough mechanical properties, self healing ability, and tissue adhesiveness, and the bacterial killing also relies on the use of antibiotic drugs. Herein, a well-designed hybrid hydrogel dressing is constructed by simple copolymerization of acrylamide (AM), 3-acrylamido phenylboronic acid (AAPBA), chitosan (CS), and the nanoscale tannic acid (TA)/ferric ion (Fe3+) complex (TFe). The resulting hydrogel possesses lots of free catechol, phenylboronic acid, amine, and hydroxyl groups and contains many reversible and dynamic bonds such as multiple hydrogen bonds and boronate ester bonds, thereby showing satisfactory mechanical properties, fast self-healing ability, and desirable tissue-adhesive performance. Benefiting from the high photothermal conversion efficiency of the TFe, the hydrogel exhibits satisfactory antibacterial activity against both Gram-positive and Gram-negative bacteria. Moreover, the embedded TFe also endows the hydrogel with good antioxidant activity, antiinflammatory property, and cell proliferation to promote tissue regeneration. Remarkably, in vivo animal assays reveal that the hybrid hydrogel effectively eliminates biofilm bacteria in the wound sites and accelerates the healing process of infected wounds. Taken together, the developed versatile hydrogels overcome the shortcomings of traditional wound dressings and are expected to become potential antibacterial dressings for future biomedical applications.
Preventing bacterial infections and accelerating wound closure are essential in the process of wound healing. Current wound dressings lack enough mechanical properties, self-healing ability, and tissue adhesiveness, and the bacterial killing also relies on the use of antibiotic drugs. Herein, a well-designed hybrid hydrogel dressing is constructed by simple copolymerization of acrylamide (AM), 3-acrylamido phenylboronic acid (AAPBA), chitosan (CS), and the nanoscale tannic acid (TA)/ferric ion (Fe3+) complex (TFe). The resulting hydrogel possesses lots of free catechol, phenylboronic acid, amine, and hydroxyl groups and contains many reversible and dynamic bonds such as multiple hydrogen bonds and boronate ester bonds, thereby showing satisfactory mechanical properties, fast self-healing ability, and desirable tissue-adhesive performance. Benefiting from the high photothermal conversion efficiency of the TFe, the hydrogel exhibits satisfactory antibacterial activity against both Gram-positive and Gram-negative bacteria. Moreover, the embedded TFe also endows the hydrogel with good antioxidant activity, anti-inflammatory property, and cell proliferation to promote tissue regeneration. Remarkably, in vivo animal assays reveal that the hybrid hydrogel effectively eliminates biofilm bacteria in the wound sites and accelerates the healing process of infected wounds. Taken together, the developed versatile hydrogels overcome the shortcomings of traditional wound dressings and are expected to become potential antibacterial dressings for future biomedical applications.
Photothermal therapy (PTT) is a promising strategy for antimicrobial therapy. However, the application of PTT to treat bacterial infections remains a challenge as the high temperature required for bacterial elimination can partly damage healthy tissues. Selecting the appropriate treatment temperature is therefore a key factor for PTT. In this work, we designed a near-infrared/pH dual stimuli-responsive activated procedural antibacterial system based on zeolitic imidazolate framework-8 (ZIF-8), which was bottom-up synthesized and utilized to encapsulate both Pd-Cu nanoalloy (PC) and the antibiotic amoxicillin (AMO). This procedural antibacterial therapy comprises chemotherapy (CT) and PTT. The former disrupts the bacterial cell wall by releasing AMO in an acidic environment, which depends on the sensitive response of ZIF-8 to pH value change. With the progression in time, the AMO release rate decreased gradually. The latter can then significantly stimulate drug release and further complete the antibacterial effect. This impactful attack consisted of two waves that constitute the procedural therapy for bacterial infection. Accordingly, the treatment temperature required for antibacterial therapy can be significantly lowered under this mode of treatment. This antibacterial system has a significant therapeutic effect on planktonic bacteria (G(+)/G(-)) and their biofilms and also has good biocompatibility; thus, it provides a promising strategy to develop an effective and safe treatment against bacterial infections. Statement of Significance We have developed a near infrared/pH dual stimuli-responsive activated procedural antibacterial system that combines enhanced antibiotic delivery with photothermal therapy and has highly efficient antimicrobial activity. The antibacterial effect of this therapy was based on two mechanisms of action: chemotherapy, in which the bacterial cell wall was first destroyed, followed by photothermal therapy. After exposure to irradiation with an 808 nm laser, the inhibition rates were 99.8% and 99.1% for Staphylococcus aureus and Pseudomonas aeruginosa, respectively, and the clearance rates for their established biofilms were 75.3% and 74.8%, respectively. Thus, this procedural antibacterial therapy has shown great potentiality for use in the photothermal therapy of bacterial infectious diseases, including biofilm elimination. (C) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.