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Physical Contact-Triggered In Situ Reactivation of Antibacterial Hydrogels
Abstract
In situ reactivation of hydrogels remains a long-standing key challenge in chemistry and materials science. Herein, we first report an ultraconvenient in situ renewable antibacterial hydrogel prepared via a facile physical contact-triggered strategy based on an ultrafast chlorine transfer pathway. We discover that the as-proposed hydrogel with a programmable 3D network cross-linked by noncovalent bonds and physical interactions can serve as a smart platform for selective active chlorine transfer at the hydrogel/hydrogel interface. Systematic experiments and density functional theory prove that the N-halamine glycopolymers integrated into the hydrogel system work as a specific renewable biocide, permitting the final hydrogel to be recharged in situ within 1 min under ambient conditions. Due to its strength and durability, pathogen specificity, and biocompatibility, coupled with its rapid in situ reactivation, this antibacterial hydrogel holds great potential for in vivo biomedical use and circulating water disinfection. We envision this proposed strategy will pave a new avenue for the development of in situ renewable smart hydrogels for real-world applications.
The management of brain tumors presents numerous challenges, despite the employment of multimodal therapies including surgical intervention, radiotherapy, chemotherapy, and immunotherapy. Owing to the distinct location of brain tumors and the presence of the blood–brain barrier (BBB), these tumors exhibit considerable heterogeneity and invasiveness at the histological level. Recent advancements in hydrogel research for the local treatment of brain tumors have sought to overcome the primary challenge of delivering therapeutics past the BBB, thereby ensuring efficient accumulation within brain tumor tissues. This article elaborates on various hydrogel-based delivery vectors, examining their efficacy in the local treatment of brain tumors. Additionally, it reviews the fundamental principles involved in designing intelligent hydrogels that can circumvent the BBB and penetrate larger tumor areas, thereby facilitating precise, controlled drug release. Hydrogel-based drug delivery systems (DDSs) are posited to offer a groundbreaking approach to addressing the challenges and limitations inherent in traditional oncological therapies, which are significantly impeded by the unique structural and pathological characteristics of brain tumors.
Bio-inspiration and biomimetics offer guidance for designing and synthesizing advanced catalysts for oxygen reduction reaction (ORR) in microbial fuel cells (MFCs). Herein, chlorine-doped Fe2P supported by nitrogen-doped carbon (Cl-Fe2P/NC) catalysts...
Bacterial infection can impede the healing of chronic wounds, particularly diabetic wounds. The high‐sugar environment of diabetic wounds creates a favorable condition for bacterial growth, posing a challenge to wound healing. In clinical treatment, the irregular shape of the wound and the poor mechanical properties of traditional gel adjuvants make them susceptible to mechanical shear and compression, leading to morphological changes and fractures, and difficult to adapt to irregular wounds. Traditional gel adjuvants are prepared in advance, while in situ gel is formed at the site of administration after drug delivery in a liquid state, which can better fit the shape of the wound. Therefore, this study developed an in situ HA/GCA/Fe²⁺‐GOx gel using a photothermal‐enhanced Fenton reaction to promote the generation of hydroxyl radicals (·OH). The generation of ·OH has an antibacterial effect while promoting the formation of the gel, achieving a dual effect. The addition of double‐bonded adamantane (Ada) interacts with the host‐guest effect of graphene oxide and the double‐bond polymerization of HAMA gel, making the entire gel system more complete. At the same time, the storage modulus (G′) of the gel increased from 130 to 330 Pa, enhancing the mechanical properties of the gel. This enables the gel to have better injectability and self‐healing effects. The addition of GOx can consume glucose at the wound site, providing a good microenvironment for the repair of diabetic wounds. The gel has good biocompatibility and in a diabetic rat wound model infected with S. aureus, it can effectively kill bacteria at the wound site and promote wound repair. Meanwhile, the inflammation of wounds treated with HA/GCA/Fe²⁺‐GOx + NIR was lighter compared to untreated wounds. Therefore, this study provides a promising strategy for treating bacterial‐infected diabetic wounds.
Modern healthcare engineering requires a wound dressing solution supported by materials with outstanding features such as high biological compatibility, strong mechanical strength, and higher transparency with effective antibacterial properties. Here, we present a unique hydrogel technology consisting of two negatively charged biopolymers and a positively charged synthetic polymer. The interaction between charged polymers through hydrogen bonds has been created, which are revealed in the simulation by density functional theory and Fourier transform infrared spectra of individual polymers and the hydrogel film. The transparent hydrogel film dressings showed excellent stretchability, a higher water swelling ratio (60%), and strong mechanical strength (∼100 MPa) with self-healing abilities (85-90%). The fabricated hydrogel film showed stable blood clots (within 119 ± 15 s) with rapid hemostasis (<2%) properties and effective antibacterial studies against E. coli and S. aureus bacterial strains. In addition, the obtained hydrogel film also showed excellent cell viability on mouse fibroblast cells. With their enormous amenability to modification, these hydrogel films may serve as promising biomaterials for wound dressing applications.
The pandemic of the coronavirus disease 2019 (COVID-19) has become a global public health crisis. The symptoms of COVID-19 range from mild to severe, but the physiological changes associated with COVID-19 are barely understood. In this study, we performed targeted metabolomic and lipidomic analyses of plasma from a cohort of patients with COVID-19 who had experienced different symptoms. We found that metabolite and lipid alterations exhibit apparent correlation with the course of disease in these patients, indicating that the development of COVID-19 affected their whole-body metabolism. In particular, malic acid of the TCA cycle and carbamoyl phosphate of the urea cycle result in altered energy metabolism and hepatic dysfunction, respectively. It should be noted that carbamoyl phosphate is profoundly down-regulated in patients who died compared with patients with mild symptoms. And, more importantly, guanosine monophosphate (GMP), which is mediated not only by GMP synthase but also by CD39 and CD73, is significantly changed between healthy subjects and patients with COVID-19, as well as between the mild and fatal cases. In addition, dyslipidemia was observed in patients with COVID-19. Overall, the disturbed metabolic patterns have been found to align with the progress and severity of COVID-19. This work provides valuable knowledge about plasma biomarkers associated with COVID-19 and potential therapeutic targets, as well as an important resource for further studies of the pathogenesis of COVID-19.
Antibiotic resistance poses severe health threats throughout the world. Exploring new antibiotics is widely recognized as an effective strategy to counter antibiotic resistance, but new antibiotics will eventually lead to further antibiotic resistance when new drugs are misused or overused. An alternative tactic may be antibacterial regulation on demand. Here, we show experimentally and theoretically that unstable black phosphorus nanosheets (BPNs) can function as antibacterial agents without causing antibiotic resistance. This antibacterial strategy relies on an unprecedented synergism: The BPNs use reactive oxygen species, are not toxic towards nonbacterial cells within a wide range of BPN concentration (0.01–2.0 mg mL⁻¹), and are chemically degradable on demand. BPNs thus offer a promising approach to fighting bacterial infections without causing antibiotic resistance. We believe this proposed strategy offers new insights into instability‐guided antibacterial therapy in clinical applications and indicates a new direction for fighting antibiotic resistance.
Age-associated chronic inflammation (inflammageing) is a central hallmark of ageing¹, but its influence on specific cells remains largely unknown. Fibroblasts are present in most tissues and contribute to wound healing2,3. They are also the most widely used cell type for reprogramming to induced pluripotent stem (iPS) cells, a process that has implications for regenerative medicine and rejuvenation strategies⁴. Here we show that fibroblast cultures from old mice secrete inflammatory cytokines and exhibit increased variability in the efficiency of iPS cell reprogramming between mice. Variability between individuals is emerging as a feature of old age5–8, but the underlying mechanisms remain unknown. To identify drivers of this variability, we performed multi-omics profiling of fibroblast cultures from young and old mice that have different reprogramming efficiencies. This approach revealed that fibroblast cultures from old mice contain ‘activated fibroblasts’ that secrete inflammatory cytokines, and that the proportion of activated fibroblasts in a culture correlates with the reprogramming efficiency of that culture. Experiments in which conditioned medium was swapped between cultures showed that extrinsic factors secreted by activated fibroblasts underlie part of the variability between mice in reprogramming efficiency, and we have identified inflammatory cytokines, including TNF, as key contributors. Notably, old mice also exhibited variability in wound healing rate in vivo. Single-cell RNA-sequencing analysis identified distinct subpopulations of fibroblasts with different cytokine expression and signalling in the wounds of old mice with slow versus fast healing rates. Hence, a shift in fibroblast composition, and the ratio of inflammatory cytokines that they secrete, may drive the variability between mice in reprogramming in vitro and influence wound healing rate in vivo. This variability may reflect distinct stochastic ageing trajectories between individuals, and could help in developing personalized strategies to improve iPS cell generation and wound healing in elderly individuals.
A notable challenge for the design of engineered living materials (ELMs) is programming a cellular system to assimilate resources from its surroundings and convert them into macroscopic materials with specific functions. Here, an ELM that uses Escherichia coli as its cellular chassis and engineered curli nanofibers as its extracellular matrix component is demonstrated. Cell‐laden hydrogels are created by concentrating curli‐producing cultures. The rheological properties of the living hydrogels are modulated by genetically encoded factors and processing steps. The hydrogels have the ability to grow and self‐renew when placed under conditions that facilitate cell growth. Genetic programming enables the gels to be customized to interact with different tissues of the gastrointestinal tract selectively. This work lays a foundation for the application of ELMs with therapeutic functions and extended residence times in the gut. Biofabricated hydrogels have the ability to grow and self‐regenerate in the gastrointestinal tract. Genetic programming enables customization to interact with different tissues of the gastrointestinal tract selectively and to fabricate living hydrogel materials. This novel engineered living material lays a foundation for therapeutic applications in the gut, especially those that may benefit from a cohesive material with extended residence times.
Injectable hydrogels can fill irregular defects and promote in situ tissue regrowth and regeneration. The ability of directing stem cell differentiation in a three-dimensional microenvironment for bone regeneration remains a challenge. In this study, we successfully nanoengineer an interconnected microporous networked photocrosslinkable chitosan in situ-forming hydrogel by introducing two-dimensional nanoclay particles with intercalation chemistry. The presence of the nanosilicates increases the Young's modulus and stalls the degradation rate of the resulting hydrogels. We demonstrate that the reinforced hydrogels promote the proliferation as well as the attachment and induced the differentiation of encapsulated mesenchymal stem cells in vitro. Furthermore, we explore the effects of nanoengineered hydrogels in vivo with the critical-sized mouse calvarial defect model. Our results confirm that chitosan-montmorillonite hydrogels are able to recruit native cells and promote calvarial healing without delivery of additional therapeutic agents or stem cells, indicating their tissue engineering potential.
Inspired by embryonic wound closure, we present mechanically active dressings to accelerate wound healing. Conventional dressings passively aid healing by maintaining moisture at wound sites. Recent developments have focused on drug and cell delivery to drive a healing process, but these methods are often complicated by drug side effects, sophisticated fabrication, and high cost. Here, we present novel active adhesive dressings
consisting of thermoresponsive tough adhesive hydrogels that combine high stretchability, toughness, tissue adhesion, and antimicrobial function. They adhere strongly to the skin and actively contract wounds, in response to exposure to the skin temperature. In vitro and in vivo studies demonstrate their efficacy in accelerating and supporting skin wound healing. Finite element models validate and refine the wound contraction process enabled by these active adhesive dressings. This mechanobiological approach opens new avenues for wound management and may find broad utility in applications ranging from regenerative medicine to soft robotics.
The increasing number of infections caused by pathogenic bacteria has severely affected human society, for instance, numerous deaths are from Gram‐positive methicillin‐resistant Staphylococcus aureus (MRSA) each year. In this work, four biodegradable antibacterial polymer materials based on cationic polyaspartamide derivatives with different lengths of side chains are synthesized through the ring‐opening polymerization of β‐benzyl‐l‐aspartate N‐carboxy anhydride, followed by an aminolysis reaction and subsequent methylation reaction. The cationic quaternary ammonium groups contribute to the insertion of the catiomers into the negatively charged bacterial membranes, which leads to membranolysis, the leakage of bacterial content, and the death of pathogens. Except for wiping out MRSA readily, the biodegradable polymers possessing alterable antibacterial potency can minimize the possibility of microbial resistance and mitigate drug accumulation by virtue of their cleavable backbone. To manipulate the poor biocompatibility of these polycations, carboxylatopillar[5]arene (CP[5]A) is introduced to the polymeric antibacterial catiomers through the supramolecular host–guest approach to obtain novel antibacterial materials with pH‐sensitive characteristics (with CP[5]A departure from cationic quaternary ammonium compounds under acid conditions) and selective targeting of Gram‐positive bacteria. Finally, the facile and robust antibacterial system is successfully applied to in vivo MRSA‐infected wound healing, providing a significant reference for the construction of advanced antibacterial biomaterials.
Identifying probiotics and pathogens is of great interest to the health of human body. It is critical to develop microbiota-targeted therapies to have high specificity including strain specificity. In this study, we have utilized E.coli MG1655 bacteria as living templates to synthesize glycopolymers in situ with high selectivity. By this bacteria-sugar monomer-aptation-polymerization (BS-MAP) method, we have obtained glycopolymers from the surface of bacteria which can recognize template bacteria from two strains of E.coli and the specific bacteria-binding ability of glycolpolymers was confirmed by both bacterial aggregation experiment and QCM-D measurements. Furthermore, the synthesized glycopolymers have shown a powerful inhibitory ability which can prevent bacteria from harming cells in both anti-infection and co-culture tests.
Adhesive hydrogels have gained popularity in biomedical applications, however, traditional adhesive hydrogels often exhibit short-term adhesiveness, poor mechanical properties and lack of antibacterial ability. Here, a plant-inspired adhesive hydrogel has been developed based on Ag-Lignin nanoparticles (NPs)triggered dynamic redox catechol chemistry. Ag-Lignin NPs construct the dynamic catechol redox system, which creates long-lasting reductive-oxidative environment inner hydrogel networks. This redox system, generating catechol groups continuously, endows the hydrogel with long-term and repeatable adhesiveness. Furthermore, Ag-Lignin NPs generate free radicals and trigger self-gelation of the hydrogel under ambient environment. This hydrogel presents high toughness for the existence of covalent and non-covalent interaction in the hydrogel networks. The hydrogel also possesses good cell affinity and high antibacterial activity due to the catechol groups and bactericidal ability of Ag-Lignin NPs. This study proposes a strategy to design tough and adhesive hydrogels based on dynamic plant catechol chemistry.
Dissipative self-assembly is common in biological systems, where it serves to maintain a far-from-equilibrium functional state through fuel consumption. Synthetic dissipative systems have been prepared that can mimic some of the properties of biological systems, but they often show poor mechanical performance. Here, we report a shear-induced transient hydrogel that is highly stretchable. The system is constructed by adding Cu(ii) into the aqueous solution of a pseudopolyrotaxane, which is itself formed by threading molecular tubes on polyethylene glycol chains. Vigorous shaking transforms the solution into a gel, which gradually relaxes back to the sol state over time. This cycle can be repeated at least five times. A mechanism is proposed that relies on a shear-induced transition from intrachain to interchain coordination and subsequent thermal relaxation. The far-from-equilibrium hydrogel is highly stretchable, which is probably due to ‘frictional’ sliding of the molecular tubes on the polyethylene glycol chains. On shaking, the hydrogel undergoes fast self-healing.
The widespread multidrug resistance resulting from the abuse of antibiotics motivates researchers to explore alternative methods to treat bacterial infections. Recently, the emergence of nanozymes has provided a potential approach to combat bacteria. Such nanozymes can mimic the functions of natural enzymes to induce the production of highly toxic reactive oxygen species (ROS) as an antibacterial. However, the lack of effective interaction between nanozymes and bacteria, and the intrinsic short lifetime and diffusion distance of ROS greatly compromise their bactericidal activity. Furthermore, the dead bacteria left in the infected area can give rise to unexpected tissue inflammation. Herein, for the first time, a nanozyme‐hydrogel is constructed to realize reinforced antibacterials. The nanozyme‐hydrogel with the traits of positive charge and macropore can capture and restrict bacteria in the range of ROS destruction. Significantly, by combining the near‐infrared photothermal property of nanozymes, the nanozyme‐hydrogel can achieve a synergistic bactericidal effect. More importantly, the nanozyme‐hydrogel can eliminate bacteria and reduce the risk of inflammation. In consequence, the current work manifests an original strategy to improve the antibacterial performance of nanozymes, concurrently promote wound healing. To overcome the challenges that nanozymes face as an antibacterial, a nanozyme‐hydrogel is constructed to realize reinforced antibacterials. This nanozyme‐hydrogel with peroxidase‐like catalytic activity and near‐infrared photothermal properties can not only achieve an efficient synergistic bactericidal effect but also reduce the risk of inflammation induced by bacteria and promote wound healing.
Slippery and hydrophilic surfaces find critical applications in areas as diverse as biomedical devices, microfluidics, antifouling, and underwater robots. Existing methods to achieve such surfaces rely mostly on grafting hydrophilic polymer brushes or coating hydrogel layers, but these methods suffer from several limitations. Grafted polymer brushes are prone to damage and do not provide sufficient mechanical compliance due to their nanometer‐scale thickness. Hydrogel coatings are applicable only for relatively simple geometries, precluding their use for the surfaces with complex geometries and features. Here, a new method is proposed to interpenetrate hydrophilic polymers into the surface of diverse polymers with arbitrary shapes to form naturally integrated “hydrogel skins.” The hydrogel skins exhibit tissue‐like softness (Young's modulus ≈ 30 kPa), have uniform and tunable thickness in the range of 5–25 µm, and can withstand prolonged shearing forces with no measurable damage. The hydrogel skins also provide superior low‐friction, antifouling, and ionically conductive surfaces to the polymer substrates without compromising their original mechanical properties and geometry. Applications of the hydrogel skins on inner and outer surfaces of various practical polymer devices including medical tubing, Foley catheters, cardiac pacemaker leads, and soft robots on massive scales are further demonstrated. Multifunctional hydrogel skins are reported by interpenetrating hydrophilic polymers into the surfaces of diverse polymers with arbitrary shapes to provide soft, low‐friction, hydrophilic, antifouling, and ionically conductive surfaces. This new strategy not only addresses challenges for existing methods but also enables unprecedented applications including hydrogel‐coated complex medical devices and soft robots on massive scales.
The emergence and global spread of bacterial resistance to currently available antibiotics underscore the urgent need for new alternative antibacterial agents. Recent studies on the application of nanomaterials as antibacterial agents have demonstrated their great potential for management of infectious diseases. Among these antibacterial nanomaterials, carbon‐based nanomaterials (CNMs) have attracted much attention due to their unique physicochemical properties and relatively higher biosafety. Here, a comprehensive review of the recent research progress on antibacterial CNMs is provided, starting with a brief description of the different kinds of CNMs with respect to their physicochemical characteristics. Then, a detailed introduction to the various mechanisms underlying antibacterial activity in these materials is given, including physical/mechanical damage, oxidative stress, photothermal/photocatalytic effect, lipid extraction, inhibition of bacterial metabolism, isolation by wrapping, and the synergistic effect when CNMs are used in combination with other antibacterial materials, followed by a summary of the influence of the physicochemical properties of CNMs on their antibacterial activity. Finally, the current challenges and an outlook for the development of more effective and safer antibacterial CNMs are discussed.
The fabrication of highly biocompatible hydrogels with multiple unique healing abilities for the whole healing process, for example, multifunctional hydrogels with injectable, degradation, antibacterial, antihypoxic, and wound healing–promoting properties that match the dynamic healing process of skin flap regeneration, is currently a research challenge. Here, a multifunctional and dynamic coordinative polyethylene glycol (PEG) hydrogel with mangiferin liposomes (MF‐Lip@PEG) is developed for clinical applications through Ag–S coordination of four‐arm‐PEG‐SH and Ag+. Compared to MF‐PEG, MF‐Lip@PEG exhibits self‐healing properties, lower swelling percentages, and a longer endurance period. Moreover, the hydrogel exhibits excellent drug dispersibility and release characteristics for slow and persistent drug delivery. In vitro studies show that the hydrogel is biocompatible and nontoxic to cells, and exerts an outstanding neovascularization‐promoting effect. The MF‐Lip@PEG also exhibits a strong cytoprotective effect against hypoxia‐induced apoptosis through regulation of the Bax/Bcl‐2/caspase‐3 pathway. In a random skin flap animal model, the MF‐Lip@PEG is injectable and convenient to deliver into the skin flap, providing excellent anti‐inflammation, anti‐infection, and proneovascularization effects and significantly reducing the skin flap necrosis rate. In general, the MF‐Lip@PEG possesses outstanding multifunctionality for the dynamic healing process of skin flap regeneration.
Developing injectable antibacterial and conductive shape memory hemostatic with high blood absorption and fast recovery for irregularly shaped and noncompressible hemorrhage remains a challenge. Here we report injectable antibacterial conductive cryogels based on carbon nanotube (CNT) and glycidyl methacrylate functionalized quaternized chitosan for lethal noncompressible hemorrhage hemostasis and wound healing. These cryogels present robust mechanical strength, rapid blood-triggered shape recovery and absorption speed, and high blood uptake capacity. Moreover, cryogels show better blood-clotting ability, higher blood cell and platelet adhesion and activation than gelatin sponge and gauze. Cryogel with 4 mg/mL CNT (QCSG/CNT4) shows better hemostatic capability than gauze and gelatin hemostatic sponge in mouse-liver injury model and mouse-tail amputation model, and better wound healing performance than Tegaderm™ film. Importantly, QCSG/CNT4 presents excellent hemostatic performance in rabbit liver defect lethal noncompressible hemorrhage model and even better hemostatic ability than Combat Gauze in standardized circular liver bleeding model.
The past decade has seen a decided move from static and passive biomaterials to biodegradable, dynamic, and stimuli responsive materials in the laboratory and the clinic. Recent advances towards the rational design of synthetic cell-responsive hydrogels—biomaterials that respond locally to cells or tissues without the input of an artificial stimulus—have provided new strategies and insights on the use of artificial environments for tissue engineering and regenerative medicine. These materials can often approximate responsive functions of a cell's complex natural extracellular environment, and must respond to the small and specific stimuli provided within the vicinity of a cell or tissue. In the current literature, there are three main cell-based stimuli that can be harnessed to create responsive hydrogels: (1) enzymes (2) mechanical force and (3) metabolites/small molecules. Degradable bonds, dynamic covalent bonds, and non-covalent or supramolecular interactions are used to provide responsive architectures that enable features ranging from cell selective infiltration to control of stem-cell differentiation. The growing ability to spatio-temporally control the behavior of cells and tissue with rationally designed responsive materials has the ability to allow control and autonomy to future generations of materials for tissue regeneration, in addition to providing understanding and mimicry of the dynamic and complex cellular niche.
Microbial contamination arising from pathogens poses serious threats to human health and in recent decades has presented an unprecedented challenge to antibacterial research. Of the various antibacterial agents that effectively kill pathogens, halogen-based antibacterial compounds have been successful in eliminating harmful pathogen-associated diseases and are becoming the most popular disinfectants. As a significant subcategory of halogen antibacterial agents, N-halamines have drawn increasing research interest into their chemistry and practical applications. N-halamines have many advantages over other antibacterial agents, including effectiveness against a broad spectrum of microorganisms, long-term physicochemical stability, high structural durability, and the regenerability of their functional groups, with corresponding renewal of their antibacterial properties. This review examines recent progress and research trends in both theoretical and experimental studies of N-halamines, with the aim of providing a systematic and comprehensive survey and assessment of the significant advances in our understanding of antibacterial N-halamines. This review serves as a practical guide to developing N-halamines through both broad and in-depth basic research and offers suggestions for their potential future applications.
N-Halamine-based antibacterial materials play a significant role in controlling microbial contamination, but their practical applications are limited because of their complicated synthetic process and indistinct antibacterial actions. In this study, novel antibacterial N-halamine-containing polymer fibers were synthesized via an one-step electrospinning of N-halamine-containing polymers without any additives. By adjusting the concentration of precursor and the molecular weight of polymers, the morphology and size of the as-spun N-halamine-containing fibers can be regulated. The as-spun fibers showed antibacterial activity against both Gram-positive and Gram-negative bacteria. After an antibacterial assessment using different biochemical techniques, a combined mechanism of contact/release co-determined killing action was evidenced for the as-spun N-halamine-containing fibers. With the aid of contact action and/or release action, this combined mechanism can allow N-halamines to attack bacteria, making the as-spun fibers wide in the application of antibacterial fields, whatever it is in dry or wet environment. Also, a recycle antibacterial test demonstrated that the as-spun fibers can still offer antibacterial property after five recycle experiments.
Zinc oxides have gained exciting achievements in antimicrobial fields because of their advantageous properties, while their biological effects on bacteria are currently underexplored. In this study, biological effects of flower-shaped nano zinc oxides on bacteria were systematically investigated. Zinc oxide nanoflowers with controllable morphologies (viz., rod flowers, fusiform flowers, and petal flowers) were synthesized by modulating merely base type and concentration using the hydrothermal process. Their antibacterial power is in an order of petal flowers > fusiform flowers > rod flowers because of their differences in microscopic parameters such as specific surface area, pore size, and Zn-polar plane, ect. More importantly, the role of morphology in influencing biological effect on bacteria was examined, focusing on the morphology-induced effect on integrality of cell wall, permeability of cell membrane, DNA cleavage, etc. As for cytotoxicity, all petal flowers, fusiform flowers, and rod flowers show trivial cytotoxicity to the Hela cells. This work provides a guide for enhancing biological effect of the biocides on pathogenic bacteria by the morphological modulation.
The biocompatibility, processing ease, and mechanical properties of freeze-thawed poly(vinyl alcohol) (PVA)-based hydrogels have encouraged significant research toward developing this material for various biomedical applications. Crystallization that occurs during the freeze-thawing process is cited in the literature as the primary mechanism responsible for the resultant mechanical properties. Further analysis, however, shows the presence of two unique mechanisms that contribute to PVA's mechanical properties. During freeze–thaw cycling water freezes causing phase separation, which facilitates crystallization. The impact of phase separation during freeze–thaw cycling was investigated by comparing freeze-thawed and aged PVA hydrogels. Aged hydrogels were not prepared by freezing and, therefore, did not exhibit significant phase separation. The amount of phase separation was discerned using optical microscopy in the hydrated state. Crystallinity and mechanical properties were also evaluated as a function of the number of cycles (for freeze-thawed gels) and aging time (for aged gels). For freeze-thawed hydrogels, crystallinity deviated significantly from the trend observed in compressive modulus, indicating that crystallinity was not the only factor determining the hydrogel's mechanical properties. Phase separation was found to occur during freeze–thaw cycling independently of crystallization, especially at later freeze–thaw cycles (after the third). The trends observed for both crystallinity and modulus for aged hydrogels, however, were in better agreement with each other. Further evaluation of the mechanical properties of aged and freeze-thawed hydrogels with similar crystallinities indicated that freeze-thawed hydrogels have significantly higher modulus values (p < 0.05). As a result, phase separation, independently of crystallization, was determined to have a significant effect on gelation during freeze–thaw cycling. In particular, PVA-rich regions that are formed during phase separation, without additional cross-linking, are believed to have a significant effect on the resultant mechanical properties.
Peptides undergo a very fast halogenation reaction with aqueous halogens. The process takes place via aliphatic electrophilic substitution with bimolecular rate constants of ca. 10(7) M-1 s(-1). The products formed are N-halopeptides, ie., the halogenation process takes place on the nitrogen atom at the amino-terminal moiety of the amino acid residue. At ratios [halogenating agent]/[dipeptide] less than or equal to 1, no analytical or kinetic evidence has been found of halogenation on the peptide bond or on the oxygen atom of the carboxy-terminal residue. The intracellular oxidation of peptides to N-halo-peptides proceeds by an in vivo mechanism to reduce the oxidative stress caused by intracellular oxidants.
Supramolecular nanofunctional materials have attracted increasing attention from scientific researchers due to their advantages in biomedicine. Herein, we construct a nanosupramolecular cascade reactor through the cooperative interaction of multiple noncovalent bonds, which include chitosan, sulfobutylether-β-cyclodextrin, ferrous ions, and glucose oxidase. Under the activation of glucose, hydroxyl radicals generated from the nanoconfinement supramolecular cascade reaction process are able to initiate the radical polymerization process of vinyl monomers to form hydrogel network structures while inhibiting resistant bacterial infection. The results of the diabetic wound experiment confirmed the capacity of the glucose-activated nanoconfinement supramolecular cascade reaction in situ for potent antimicrobial efficacy and wound protection. This strategy of "two birds with one stone" provides a convenient method for the application of supramolecular nanomaterial in the field of biomedicine.
Real pyrolytic lignin (R-PLs) and pyrolytic products from model compounds (M-PL) were characterized by HPLC/Qtof-MS, GPC and 2D HSQC NMR to acquire molecular information. A huge amount of molecules were detected, analyzed and sorted into several categories according to their properties. Most compounds in R-PLs have complicated sidechains, with high molecular weight (MW) but moderate ring double bond equivalent (RDB), which might be derivatives of lignin fragments. The low MW fractions of R-PLs are considered as lignin simple monomers (LSM) and their derivatives, because the peaks of R-PLs and M-PL within low MW range of GPC are proximal. Molecules with medium MW but pretty high RDB, supposed to be coke/PAHs, were found more in M-PL than R-PLs, indicating that coke/PAHs primarily derive from LSM. Formation mechanisms of PL were proposed based on the differences between R-PLs and M-PL, which were supported by density functional theory (DFT) calculation. The results provide an in-depth understanding of pyrolytic lignin and inspire studies on high-value utilization of pyrolytic lignin.
As a promising functional material, hydrogels have attracted extensive attentions, especially in flexible wearable sensors fields, but it remains a great challenge to facilely integrate excellent mechanical properties, self-adhesion and strain sensitivity into a single hydrogel. In this work, we present a high strength, stretchable, conformable and self-adhesive chitosan/poly(acrylic acid) double-network nanocomposite hydrogels for application in epidermal strain sensor via in-situ polymerization of acrylic acid in chitosan acid aqueous solution with tannic acid coated cellulose nanocrystal (TA@CNC) acting as nanofillers to reinforce tensile properties, followed by a soaking process in saturated NaCl solution to crosslink chitosan chains. With addition of a small amount of TA@CNC, the double-network nanocomposite hydrogels became highly adhesive and mechanically compliant, which were critical factors for the development of conformable and resilient wearable epidermal sensors. The salt soaking process was applied to crosslink chitosan chains by shielded electrostatic repulsions between positively charged amino groups, drastically enhancing the mechanical properties of the hydrogels. The obtained double-network nanocomposite hydrogels exhibited excellent tunable mechanical properties that could be conveniently tailored with fracture stress and fracture strain ranging from 0.39 to 1.2 MPa and 370% to 800% respectively. Besides, the hydrogels could be tightly attached onto diverse substrates including wood, glass, plastic, polytetrafluoroethylene (PFTE), glass, metal and skin, demonstrating high adhesion strength and compliant adhesion behavior. In addition, benefiting from the abundant free ions from strong electrolytes, the flexible hydrogel sensors demonstrated stable conductivity and strain sensitivity, which could monitor both large human motions and subtle motions. Furthermore, the anti-bacterial property originating from chitosan made the hydrogels suitable for wearable epidermal sensors. The facile soaking strategy proposed in this work would be promising in fabricating high strength multifunctional conductive hydrogels used for wearable epidermal devices.
Natural livings normally have amazing control over the color, shape or morphology for camouflage, communication or even reproduction in response to interplay between several environmental stimuli. Such interesting phenomenon inspires scientists to develop smart soft actuators/robotics via integrating color‐changing functionality based on polymer films or elastomers. However, there is still no important progress with synergistic color‐changing and shape‐morphing capabilities in life‐like material system such as soft wet hydrogel. Herein, we reported a new class of bioinspired synergistic fluorescence‐color switchable polymeric hydrogel actuator based on supramolecular interaction of dynamic metal‐ligand coordination. Artificial hydrogel apricot flowers and chameleons are fabricated for the first time, in which simultaneous color‐changing and shape‐morphing behaviors are controlled by a subtle interplay between acidity/alkalinity, metal ions and temperature. This work has made color‐changeable soft machines accessible and is expected to hold wide potential applications in biomimetic soft robotics, biological sensors, and camouflage applications.
Smart hydrogels with multi-stimuli responsiveness have been increasingly exploited as soft matters for biomedical appli-cations in drug delivery, tissue engineering, and bioactuators. Whilst many of the effects have been well documented, the facile fabrication of multi-responsive hydrogels with specific functionality is met with profound challenges, particularly in the redundant synthesis of macromolecular building blocks and the integration of multiple dynamic linkages to construct hydrogel networks. To address this issue, herein we report a simple and rapid fabrication of smart hydrogels by direct gelation of all naturally occurring building blocks including aminoglycosides, protocatechualdehyde, and Fe(III) via two types of dynamic chemical bonds. The resulting smart hydrogels could perform excellent dynamic features and promis-ing multi-responsiveness to different stimuli including temperature, light, pH, redox, and electricity, and also exhibited high antibacterial activities. This study offers new opportunities in the facile preparation of smart hydrogels for a wide range of applications.
Endowing hydrogel with antibacterial capability is promising for tissue repair, but most strategies in the synthesis of antibacterial hydrogel is high-cost and low-yield, suffering from many tedious multi-step reaction procedures to obtain antibacterial function. Taking hyaluronic acid-based hydrogel as an example, we herein report a super-convenient and broad-spectrum effective strategy based on a simple N-halogenation reaction allowing a scalable production of N-halamine-based hydrogel capable of bacteria-killing for infected skin defect therapy. This N-halogenation-based strategy in building antibacterial hydrogel is available to most N–H bond-containing hydrogel, and the specific synthesis is regulatable on-demand by tuning N-halogenation conditions. After a biological systematic evaluation, the hydrogel shows good antibacterial function against bacteria, as well as a low toxicity. Meanwhile, in vivo wound healing test reveals that the hydrogel can resist wound bacterial infection, accelerate the healing process, and promote epithelial regeneration. This contribution demonstrates for the first time that benefiting from its integrated advantages of super-convenience, universality, and scalable producibility, the N-halamine-based hydrogel would be very promising in practical biomedical applications.
Biomaterial-associated infections caused by bacterial contamination and the subsequent formation of biofilms on the surfaces are challenging our healthcare system. In this work, povidone-iodine-functionalized fluorinated copolymers with stable antibacterial, antibiofilm, and antifouling activities were designed and prepared by a two-step synthesis. First, a series of poly(hexafluorobutyl methacrylate-co-N-vinyl-2-pyrrolidone), i.e., P(HFBMA-VP), were synthesized by radical copolymerization at different feed ratios to acquire water insoluble and antifouling copolymers. At the second step, the VP segments in the copolymer were complexed with iodine to obtain the objective antibacterial and antifouling copolymer P(HFBMA-VP)-I. The chemical and physical characteristics of the copolymers were investigated using 1H NMR, FTIR, XPS, EDX, UV-Vis, SEM, TEM, elemental analysis, and contact angle meter. P(HFBMA-VP)-I exhibited excellent antibacterial activity against both Gram-negative bacteria (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus), as well as good biocompatibility towards human hepatocyte cells (L02) and Caenorhabditis elegans. Using electrospinning or spraying technique, P(HFBMA-VP)-I was coated on polystyrene slides, medical stainless steel sheets, and cotton fabric, allowing the surfaces to have stable antibacterial and antibiofilm activities against pathogenic bacteria and antifouling capability against foulants and blood, and exhibit excellent self-cleaning property.
Sponges, Neofibularia nolitangere, can regenerate to its original appearance and recover functions spontaneously after being teased into countless pieces. Synthetic materials with such capability are highly desired but hardly achieved. Here, we present a sponges‐inspired self‐regenerative granular powders from double‐network (DN) tough hydrogel; these powders can regenerate into the original appearance of hydrogels with the mechanical properties largely preserved upon simple hydration. The powder‐to‐hydrogel transition can be repeated for multiple times, and vice versa. The regenerative capacity and the mechanical property still preserve for each regeneration, which is highly analogous to the regeneration of sponges. The straightforward strategy endows DN hydrogels with remarkable convenience of storage and shaping. This work may shed light on the development of regenerative materials for coatings and adhesives.
A craniotomy involves the removal of a skull fragment to access the brain, such as during tumor or epilepsy surgery, which is immediately replaced intra-operatively. The infection incidence after craniotomy ranges from 0.8-3%, with approximately half caused by Staphylococcus aureus ( S. aureus ). To mitigate infectious complications following craniotomy, we engineered a 3D bioprinted bone scaffold to harness the potent antibacterial activity of macrophages (MΦs) together with antibiotics using a mouse S. aureus craniotomy-associated biofilm model that establishes persistent infection on the bone flap, subcutaneous galea, and brain. The 3D scaffold contained rifampin and daptomycin printed in a composite slurry, with viable MΦs incorporated into a hydrogel-based bioink, which was assessed for both the treatment and prevention of craniotomy-associated infections in the mouse model. For the treatment paradigm, the bone flap was removed at day 7 post-infection after a mature biofilm had formed, and replaced with a 3D printed antibiotic scaffold, with or without MΦ incorporation. Bacterial burdens in the galea and brain were reduced by at least 100-fold at early time points, which was potentiated by bioprinting viable MΦs into the 3D antibiotic scaffold. We also examined a prevention paradigm, where scaffolds were placed at the time of surgery and challenged with S. aureus one day later at the surgical site. Interestingly, unlike the treatment paradigm, the incorporation of viable MΦs into the 3D antibiotic scaffold did not enhance bacterial clearance compared to antibiotic alone. With further refinement, our 3D bioprinted scaffold represents a potential treatment modality, since it delivers therapeutic antibiotic levels more rapidly than systemic administration, based on its proximity to the infection site. In addition, the incorporation of viable MΦs into the 3D scaffold is an important advance, which demonstrated improved therapeutic benefit for the treatment of established biofilms that represent the most clinically challenging scenario.
Antibacterial wound dressings play an important role in wound healing and infection treatment. However, traditional antibacterial wound dressings uncontrollably release antibiotics or silver ions through passive diffusion. The overuse of antibiotics and silver ions may cause drug resistance, side effects, and argyrism, thereby hindering the healing process and creating other health hazards. To overcome these shortcomings, this paper reports an easy approach to synthesize non-releasing antimicrobial Poly(ionic liquid)/PVA hydrogel dressing with high-strength through chemical polymerization and physical cross-linking. The hydrogel dressing exhibited effective antibacterial ability against bacteria (E. coli, S. aureus and B. subtilis), fungus (C. albicans), and mold (Asp. niger, Asp. oryzae, and Rhizopus). Furthermore, in a murine model, the hydrogel dressing efficiently accelerated cutaneous wound healing. After 15 days of healing process, histological tests indicated that this hydrogel dressing can promote the reconstruction of intact epidermis faster than the control. Therefore, this Poly(ionic liquid)/PVA hydrogel has potential as an antibacterial wound-healing dressing.
A series of secondary amine-modified cyclodextrin (CD) derivatives were synthesized with diverse exterior terminal groups (i.e., hydroxyl, methyl, methoxyl, and primary amine). Subsequent reaction with nitric oxide (NO) gas under alkaline condi-tions yielded N-diazeniumdiolate-modified CD derivatives. Adjustable NO payloads (0.6‒2.4 µmol/mg) and release half-lives (0.7‒4.2 h) were achieved by regulating both the amount of secondary amine precursors and the functional groups around the NO donor. The bactericidal action of these NO-releasing cyclodextrin derivatives was evaluated against Pseudo-monas aeruginosa, a Gram-negative pathogen with antibacterial activity proving dependent on both the NO payload and exterior modification. Materials containing a high density of NO donors or primary amines exhibited the greatest ability to eradicate P. aeruginosa. Of the materials prepared, only the primary amine-terminated hepta-substituted CD derivatives ex-hibited toxicity against mammalian L929 mouse fibroblast cells. The NO donor-modified CD was also capable of delivering promethazine, a hydrophobic drug, thus demonstrating potential as a dual-drug releasing therapeutic.
Conductive hydrogels are promising materials for soft electronic devices. To satisfy the diverse requirement of bioelectronic devices, especially those for human-machine interfaces, the hydrogels are required to be transparent, conductive, highly stretchable, and skin-adhesive. However, fabrication of a conductive-polymer-incorporated hydrogel with high-performance is a challenge because of the hydrophobic nature of conductive polymers making difficulties in processability. Here, we report a transparent, conductive, stretchable, and self-adhesive hydrogel by in situ formation of polydopamine-doped polypyrrole nanofibrils inner the polymer network. The in situ formed nanofibrils with good hydrophilicity were well integrated with the hydrophilic polymer phase and interwoven into a nanomesh, which created a complete conductive path and allowed visible light to pass through for transparency. Catechol groups from the PDA-PPy nanofibrils imparted the hydrogel with self-adhesiveness. The reinforcement by the nanofibrils made the hydrogel tough and stretchable. The proposed simple and smart strategy of in situ formation of conductive nanofillers opens a new route to incorporate hydrophobic and undissolvable conductive polymers into hydrogels. The fabricated multifunctional hydrogel shows promising in a range of applications, such as transparent electronic skins, wound dressings, and bioelectrodes for seeing-through body-adhered signal detection.
Developing highly specific and ultrasensitive techniques for monitoring hypochlorous acid (HOCl) in the environment and living systems is very important to guarantee its safe use and disclose its diverse biological functions. We herein presented a simple water-soluble lysosome-targeted fluorescent probe TCRH for the detection of HOCl. Probe TCRH could sensitively monitor HOCl at the nanomolar levels with the detection limit of 0.12 nM. Additionally, probe TCRH with the response unit of thiocarbamate could selectively detect HOCl over other various analytes. Furthermore, probe TCRH showed an ultrafast response for HOCl (<3 s), implying that it could offer a real-time analytical assay of HOCl. Finally, probe TCRH was used for monitoring the basal lysosomal HOCl levels without exogenous stimuli and tracking the fluctuations of endogenous/exogenous HOCl levels in the lysosomes of live RAW 264.7 macrophage cells.
Adaptable hydrogel networks with reversible connectivity have emerged as a promising platform for biomedical applications. Synthetic copolymers and Low-Molecular Weight Gelators (LMWG) have been shown to form reversible hydrogels through self-assembly of the molecules driven by self complementary hydrophobic interaction and hydrogen bonding. Here, inspired by the adhesive proteins secreted by mussels, we found that simply adding natural polyphenols, such as epigallocatechin gallate (EGCG) to amyloid fibrils present in the nematic phase, successfully drives the formation of hydrogels through self-assembly of the hybrid supramolecules. The hydrogels show birefringence under polarized light, indicating that the nematic orientation is preserved in the gel phase. Gel stiffness enhances with incubation time, increase of molecular ratios between polyphenol and fibrils, of fibril concentration, and pH. The hydrogels are shear thinning and thermostable from 25 to 90 0C without any phase transition. The integrity of the trihydroxyl groups, the gallate ester moiety in EGCG as well as the hydrophobicity of the polyphenols govern the interactions with the amyloid fibrils and thus the properties of the ensued hydrogels. The EGCG-binding amyloid fibrils, produced from lysozyme and peptidoglycans, retain the main binding functions of the enzyme, inducing bacterial agglomeration and immobilization on both Gram-positive and Gram-negative bacteria. Furthermore, the anti-bacteria mechanism of the lysozyme amyloid fibril hydrogels is initiated by membrane disintegration. In combination with the lack of cytotoxicity to human colonic epithelial cells demonstrated for these hybrid supramolecules, a potential role in combating multidrug-resistant bacteria in biomedical applications is suggested, such as in targeting diseases related to the infection of small intestine.
Development of bio-based hydrogels with good mechanical properties and high electrical conductivity is of great importance for their excellent biocompatibility and biodegradability. Novel electrically conducive and tough poly(vinyl alcohol)/sodium alginate (PVA/SA) composite hydrogel was obtained by a simple method in this paper. PVA and SA were firstly dissolved in distilled water to form the composite solution and the pure PVA/SA hydrogel was obtained through the freezing/thawing process. The pure PVA/SA hydrogels were subsequently immersed into the saturated NaCl aqueous solution to increase the gel strength and conductivity. The effect of the immersing time on the thermal and mechanical properties of PVA/SA hydrogel was studied. The swelling properties and the antiseptic properties of the obtained PVA/SA hydrogel were also studied. This paper provided a novel way for the preparation of tough hydrogel electrolyte.
Innate immune responses recognizing pathogen associated molecular patterns (PAMPs) play a crucial role in adaptive immunity. Toll-like receptors (TLRs) and C-type lectin receptors (CLRs) contribute to antigen capture, uptake, presentation and activation of immune responses. In this contribution, metal-free reversible addition–fragmentation chain transfer (RAFT) polymerization of N-3,4-dihydroxybenzenethyl methacrylamide (DMA) and 2-(methacrylamido) glucopyranose (MAG) under sunlight irradiation using 2-cyanoprop-2-yl-α-dithionaphthalate (CPDN) as iniferter agent, can be employed to fabricate the multivalent glycopolymer containing bioresponsive sugar group and multifunctional catechol functionalities. The polymerization behavior is investigated and it presents controlled features. Moreover, bioinspired dopamine chemistry can be successfully utilized to form in situ glycopolymer-coated gold nanoparticles (AuNPs) without the need of additional reducing reagent, design “pathogen-mimetic” glycoadjuvant recognized by both CLRs and TLRs. The synthetic glycoadjuvant is found to enhance the adjuvant activity as “infected signals” in vitro.
Hypochlorous acid (HOCl) acts as a weak acid distributed mainly in acidic organelle lysosomes of phagocytes and plays crucial roles in the immune defence. The elaborate interrelation between the variations of HOCl levels in lysosomes and dif-ferent physiological and pathological processes remains unclear. Thus, the accurate determination of lysosomal HOCl in living cells and in vivo is very important. Because of extremely low concentration and difficult to distinguish from OCl- under the physiological environment, it is still a great challenge to specifically monitor the intracellular intrinsic HOCl levels without exogenous stimulation, which impedes an exact understanding of its biological roles. In this paper, based on the electrophilic addition of Cl+ to sulfide moiety, we have developed a two-photon fluorescent probe O-(N-butyl-1,8-naphthalimide)-4-yl-N,N-dimethylthiocarbamate (NDMTC) for the specific determination of HOCl over OCl- and other bioactive molecules. Our results show that NDMTC possesses a detection limit of 7.6 pM, and is the first fluorescent probe for detecting HOCl at the picomolar level. Furthermore, by introducing an alkylmorpholine group to NDMTC framework, the lysosome-targetable derivative Lyso-NDMTC was obtained, and its ability to image HOCl in the lysosome organelles was clearly confirmed. Combined with two-photon fluorescence imaging of background suppression and deeper tissue penetration, NDMTC and Lyso-NDMTC were used to successfully visualize intracellular native HOCl and discern tumor tissues in mice. This study offers two perfect fluorescence imaging probes for further investigation of pathological roles of HOCl in various diseases.
A molecularly engineered dual-crosslinked hydrogel with extraordinary mechanical properties is reported. The hydrogel network is formed with both chemical crosslinking and acrylic-Fe(III) coordination; these, respectively, impart the elasticity and enhance the mechanical properties by effectively dissipating energy. The optimal hydrogel achieves a tensile stress of ca. 6 MPa at a large elongation ratio (>7 times), a toughness of 27 MJ m(-3) , and a stiffness of ca. 2 MPa, and has good self-recovery properties.
© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Increased resistance of bacteria to disinfection and antimicrobial treatment poses a serious public health threat worldwide. This has prompted the search for agents that can inhibit both bacterial growth and withstand harsh conditions (e.g., high organic loads). In the current study, N-halamine-derivatized cross-linked polymethacrylamide nanoparticles (NPs) were synthesized by co-polymerization of the monomer methacrylamide (MAA) and the cross-linker monomer N,N-methylenebisacrylamide (MBAA), and were subsequently loaded with oxidative chlorine, using sodium hypochlorite (NaOCl). The chlorinated NPs demonstrated remarkable stability and durability to organic reagents and to repetitive bacterial loading cycles as compared with the common disinfectant NaOCl (bleach), which was extremely labile under these conditions. The antibacterial mechanism of the cross-linked P(MAA-MBAA)-Cl NPs was found to involve generation of reactive oxygen species (ROS) only upon exposure to organic media. Importantly, ROS were not generated upon suspension in water, revealing that the mode of action is target-specific. Further, a unique and specific interaction of the chlorinated NPs with Staphylococcus aureus was discovered, whereby these microorganisms were all specifically targeted and marked for destruction. This bacterial encircling was achieved without using a targeting module (e.g., an antibody or a ligand) and represents a highly beneficial, natural property of the P(MAA-MBAA)-Cl nano-structures. In summary, our findings provide insights into the mechanism of action of P(MAA-MBAA)-Cl NPs and demonstrate the superior efficacy of the NPs over bleach (i.e. stability, specificity and targeting). This work underscores the potential of developing sustainable P(MAA-MBAA)-Cl NPs-based devices for inhibiting bacterial colonization and growth.
The antibacterial action of silver is utilized in numerous consumer products and medical devices. Metallic silver, silver salts, and also silver nanoparticles are used for this purpose. The state of research on the effect of silver on bacteria, cells, and higher organisms is summarized. It can be concluded that the therapeutic window for silver is narrower than often assumed. However, the risks for humans and the environment are probably limited. Silver shield: Silver is used in different forms as an antibacterial agent. Earlier, sparingly soluble silver salts were predominantly used, but today, silver nanoparticles (see picture for an SEM image of cubic silver nanoparticles) are gaining increasing importance. As silver is also toxic towards mammalian cells, there is the question of the therapeutic window in the cases of consumer products and medical devices.
A novel type of hydrophobic association hydrogels (HA-gels) was prepared through micellar copolymerization of acrylic acid (AA), acrylamide (AAm) as basic monomers and a small amount of octylphenol polyoxyethylene ether acrylate with seven ethoxyl units (OP7-AC) as hydrophobic association monomer. The HA-gels exhibited desirable mechanical property and stably reversible phase transition between opaque and transparency. The influences of adding urea and varying AA:AAm molar ratio on the phase transition behavior were discussed, which indicated that the phase transition was introduced by forming or dissociating of hydrogen bonding between amide and carboxyl groups. The introduction of hydrophobic units (OP7-AC) to poly(acrylic acid-co-acrylamide) (P(AA-AAm)) copolymer would result in the adulterating and cross-linking effects on the transition temperature. The former sharply reduced the transition temperature while the later gradually raised it. The transition temperature became linearly dropping with the increasing sodium dodecyl sulfate (SDS) content in the HA-gels. Therefore, the phase transition temperature can be finely adjusted by means of changing AA:AAm ratio, concentration, OP7-AC and/or SDS dosages in the synthesis of HA-gels.
Functionalization of polypropylene (PP) by radical graft polymerization with N-tert-butylacrylamide (NTBA) was successfully conducted during melt extrusion, and the grafted products were employed as precursors of biocidal N-halamine polymers. Graft polymerization conditions, including monomer and initiator concentrations, addition of a comonomer styrene (St), were studied. Fourier transformed spectroscopy (FTIR) results and nitrogen analysis confirmed the graft polymerization on PP backbone during the reactive extrusion. The results also indicated that increase in initiator concentration led to more PP chain scission and reduction in mixing torque or polymer chain length. As the monomer concentration rose, grafted monomer content in the products improved, revealing increased grafting copolymerization in the system. Addition of St as a comonomer adversely affected grafting of NTBA, but significantly prevented polymer chain scission. This may be due to lower tendency of NTBA for copolymerization. The halogenated products exhibited potent antimicrobial properties against Escherichia coli, and the antimicrobial properties were durable and regenerable. POLYM. ENG. SCI., 2009. © 2008 Society of Plastics Engineers
Orbitals and the non-interacting reference systemThe Kohn-Sham equationsDiscussion The Kohn-Sham potential is localThe exchange-correlation energy in the Kohn-Sham and Hartree-Fock schemesDo the Kohn-Sham orbitals mean anything?Is the Kohn-Sham approach a single determinant method?The unrestricted Kohn-Sham formalismOn degeneracy, ensembles and other odditiesExcited states and the multiplet problem The Kohn-Sham potential is localThe exchange-correlation energy in the Kohn-Sham and Hartree-Fock schemesDo the Kohn-Sham orbitals mean anything?Is the Kohn-Sham approach a single determinant method?The unrestricted Kohn-Sham formalismOn degeneracy, ensembles and other odditiesExcited states and the multiplet problem
Synthetic bioactive hydrogels have been widely recognized as key elements of emerging strategies to engineer tissues. However, the current shortage of highly specific and biocompatible methods to form and functionalize these materials hampers their wide pharmaceutical and medical use. In particular, enzymatic reactions are underexplored for the synthesis of bioactive hydrogels. Here, we present an approach by which phosphopantetheinyl transferase (PPTase), a small (16.2 kDa) enzyme that plays a key role in the biosynthesis of many natural products, was employed to catalyze covalent cross-linking of poly(ethylene glycol) (PEG)-based hydrogels. Gels were formed within minutes under physiological conditions by mixing two aqueous precursors containing multiarm PEG macromers end-functionalized with the PPTase substrate Coenzyme A (CoA) and a genetically engineered dimer of a carrier protein. The physicochemical properties of this new class of biomaterials were characterized. Bioactive hydrogels were produced by covalent incorporation of a CoA-functionalized cell adhesion peptide (RGDS), resulting in specific adhesion of primary fibroblasts on the hydrogel surfaces. 3D encapsulation of cells resulted in high cell viability (ca. 95%) and single cell migration over long distances within RGDS-modified gels.
In order to enhance the drug entrapment efficiency and improve the swelling behaviors of drug delivery system, Ca2+ crosslinking and freeze-thawing (FT) cycle techniques were used to prepare sodium alginate/poly(vinyl alcohol) (SA/PVA) hydrogel beads. The mixture solution of SA and PVA was firstly crosslinked with Ca2+ to form beads and then subjected to freezing-thawing cycles for further crosslinking. The crosslinking process was confirmed by Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). The swelling and pH-sensitive properties of the beads were investigated, and the drug loading and controlled release properties of the beads were also evaluated using diclofenac sodium as the model drug. Results indicate that the bead was formed well and the encapsulation efficiency was greatly improved when the ratio of PVA to SA is 3:1. The swelling and degradation of the developed beads was influenced by pH of the test medium and PVA content. FT process enhanced drug entrapment efficiency, improved swelling behaviors and slowed release of drug from the dual crosslinked beads compared with pure SA beads crosslinked with Ca2+ ion alone, which provide a facile and effective method to improve the drug delivery system.