Development of an injectable oxidized dextran/gelatin hydrogel capable of promoting the healing of alkali burn-associated corneal wounds.

The cornea serves as an essential shield that protects the underlying eye from external conditions, yet it remains highly vulnerable to injuries that could lead to blindness and scarring if not promptly and effectively treated. Excessive inflammatory response constitute the primary cause of pathological corneal injury. This study aimed to develop effective approaches for enabling the functional repair of corneal injuries by combining nanoparticles loaded with anti-inflammatory agents and an injectable oxidized dextran/gelatin/borax hydrogel. The injectability and self-healing properties of developed hydrogels based on borate ester bonds and dynamic Schiff base bonds were excellent, improving the retention of administered drugs on the ocular surface. In vitro cellular assays and in vivo animal studies collectively substantiated the proficiency of probucol nanoparticle-loaded hydrogels to readily suppress proinflammatory marker expression and to induce the upregulation of anti-inflammatory mediators, thereby supporting rapid repair of rat corneal tissue following alkali burn-induced injury. As such, probucol nanoparticle-loaded hydrogels represent a prospective avenue to developing long-acting and efficacious therapies for ophthalmic diseases.

Dual single atomic Ni sites constructing Janus hollow graphene for boosting electrochemical sensing of glucose.

Single atom catalysts (SACs) have attracted attention due to their excellent catalysis activity under specific reactions and conditions. However, the low density of SACs greatly limits catalytic performance. The three-dimensional graphene hollow nanospheres (GHSs) with very thin shell structure can be used as excellent carrier materials. Not only can its outer surface be used to anchor metal single atoms, but its inner surface can also provide rich sites. Here, a novel step-by-step assembly strategy is reported to anchor nickel single atoms (Ni SAs) on the inner and outer surfaces of GHSs (Ni SAs/GHSs/Ni SAs), which significantly increases the loading capacity of Ni SAs (4.8 wt%). Compared to conventional materials that only anchor Ni SAs to the outer surface of the carrier (Ni SAs/GHSs), Ni SAs/GHSs/Ni SAs exhibits significantly higher electrocatalytic activity toward glucose oxidation in alkaline media. The sensitivity of Ni SAs/GHSs/Ni SAs/GCE is nearly five times higher than that of Ni SAs/GHSs/GCE. Moreover, the sensor based on Ni SAs/GHSs/Ni SAs can detect glucose in a wide concentration range of 0.8 µM-1.1244 mM with a low detection limit of 0.19 µM (S/N = 3). This study not only provides an effective sensing material for glucose detection, but also opens a new avenue to construct high-density metal SACs.

Radical-Smiles Rearrangement by a Vitamin B2-Derived Photocatalyst in Water.

Herein, we report a catalytic radical-Smiles rearrangement system of arene migration from ether to carboxylic acid with riboflavin tetraacetate (RFT), a readily available ester of natural vitamin B2, as the photocatalyst and water as a green solvent, being free of external oxidant, base, metal, inert gas protection, and lengthy reaction time. Not only the known substituted 2-phenyloxybenzoic acids substrates but also a group of naphthalene- and heterocycle-based analogues was converted to the corresponding aryl salicylates for the first time. Mechanistic studies, especially a couple of kinetic isotope effect (KIE) experiments, suggested a sequential electron transfer-proton transfer processes enabled by the bifunctional flavin photocatalyst.

Hybrids of [FeFe]- and [NiFe]-H2ase Active Site Models.

Complexes of the type (diphosphine)Ni(µ-SR)2Fe(CO)3 are investigated with azadithiolate (adt, HN(CH2S-)2) as the dithiolate. The resulting complexes are hybrid models for the active sites of the [NiFe]- and [FeFe]-hydrogenases. The key complex (dppv)Ni(µ-adt)Fe(CO)3 (3) was prepared from the complex Ni[(SCH2)2NCbz](dppv), which contains a Cbz-protected adt ligand (Cbz = C(O)OCH2Ph, dppv = cis-1,2-(Ph2P)2C2H2). This complex combines with Fe2(CO)9 to give (dppv)Ni[(µ-SCH2)2NCbz]Fe(CO)3, which is readily deprotected to give 3. Complex 3 undergoes protonation at both Fe and N to give successively [(dppv)Ni(µ-adt)FeH(CO)3]+ ([H3]+) and [(dppv)Ni(µ-adtH)FeH(CO)3]2+ ([H3H]2+). The redox properties and dynamics of these complexes resemble previously reported analogues with propanedithiolate. Solutions of [H3]+ readily degrade to [(dppv)Ni[(µ-SCH2)2NCH2]Fe(CO)3]+ ([4]+), which features a methylene group linking N and Fe. Complex [4]+ can be made in high yield by reaction of [H3]+ with CH2O, and this conversion was also demonstrated with 13CH2O. Complex [4]+ undergoes hydrogenolysis by photochemical reaction with H2 to give [(dppv)Ni[(µ-SCH2)2NMe]FeH(CO)3]+, the N-methylated analogue of [H3]+. Upon treatment ith Me3O+, [4]+ undergoes quaternization, giving [(dppv)Ni[(µ-SCH2)2N(Me)CH2]Fe(CO)3]2+. In contrast with the lability of [H3]+, the phosphine-substituted derivative [(dppv)Ni(µ-adt)FeH(CO)2(PPh3)]+ did not degrade. Most complexes were characterized by X-ray crystallography.

Photo-Controlled Nano-Supramolecular Size and Reversible Luminescent Behaviors Based on Cucurbit[7]uril Cascaded Assembly.

Supramolecular luminescent material with switchable behavior and photo-induced aggregation with emission enhancement is a current research hot spot. Herein, a size-tunable nano-supramolecular assembly with reversible photoluminescent behavior was constructed by noncovalent polymerization of diarylethene-bridged bis(coumarin) derivative (DAE-CO), cucurbit[7]uril (CB[7]), and ß-cyclodextrin-grafted hyaluronic acid (HACD). Benefiting from the macrocyclic confinement effect, the guest molecule DAE-CO was included into the cavity of CB[7] to give enhanced fluorescence emission of the resulting DAE-CO⊂CB[7]2 with longer lifetime at 432 nm to 1.43 ns, thereby further enhancing fluorescence output and lifetime (1.46 ns) when further assembled with HACD, compared with the free DAE-CO (0.95 ns). In addition, DAE-CO, DAE-CO⊂CB[7]2, and DAE-CO⊂CB[7]2&HACD all possessed characteristics of aggregation-induced emission and reversible photo-switched structural interconversion, exhibiting an obvious photophysical activation phenomenon of self-aggregation into larger nanoparticles with increase in fluorescence emission intensity, lifetime, and size after irradiation, which could be increased step by step with the alternating irradiation of 254 nm (5 min) or >600 nm (30 s) repeated 7 times. These supramolecular assemblies were successfully used in the tumor cells' targeted imaging and anti-counterfeiting because of the capability of HACD for recognizing specific receptors overexpressed on the surface of tumor cells and the excellent photo-regulated switch ability of DAE-CO, providing an approach of constructing photo-induced emission-enhanced luminescent materials.

Alkyne Oxidation by a Vitamin B2-Based Photocatalytic System with Both H2O and O2 as the Oxygen Source.

The employment of readily available photocatalysts and green oxygen atom sources is recognized as a promising strategy to develop sustainable catalysis for oxidation reactions. We herein reported a sacrificial reagent-free system consisting of riboflavin tetraacetate (RFT), an ester of natural vitamin B2 as the photocatalyst, and Sc(OTf)3 and NaCl as the cocatalysts for alkyne oxidation under blue light or even sunlight irradiation to produce 1,2-diketone in which the oxygen atoms were from both water and molecular oxygen, respectively. A major Cl-/Cl• cycle was proposed to be involved and achieved by the excited [RFT-2Sc3+]* complex via single electron transfer for the first time, distinguished from the OCl- active species by a two-electron process in previous flavin-halide photo-oxidation systems.

Drug-Embedded Nanovesicles Assembled from Peptide-Decorated Hyaluronic Acid for Rheumatoid Arthritis Synergistic Therapy.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes endless pain and poor quality of life in patients. Usage of a lubricant combined with anti-inflammatory therapy is considered a reasonable and effective approach for the treatment of RA. Herein, inspired by glycopeptides, a peptide-decorated hyaluronic acid was synthesized, and the grafted Fmoc-phenylalanine-phenylalanine-COOH (FmocFF) peptide self-assembled with ß-sheet conformations could induce the folding of polymer molecular chains to form a vesicle structure in aqueous solution. The hydrophobic anti-inflammatory drug curcumin (Cur) could be embedded in the vesicle walls through π-π interactions with the FmocFF peptide. Furthermore, the inflammation suppression function of the Cur-loaded vesicles both in vitro and in vivo was demonstrated to be an effective treatment for RA therapy. This work proposes new insights into the folding and hierarchical assembly of glycopeptide mimics, providing an efficient approach for constructing intelligent platforms for drug delivery, disease therapy, and diagnostic applications.

Surface Engineering of Central Venous Catheters via Combination of Antibacterial Endothelium-Mimicking Function and Fibrinolytic Activity for Combating Blood Stream Infection and Thrombosis.

Long-term blood-contacting devices (e.g., central venous catheters, CVCs) still face the highest incidence of blood stream infection and thrombosis in clinical application. To effectively address these complications, this work reports a dual-functional surface engineering strategy for CVCs by organic integration of endothelium-mimicking and fibrinolytic functions. In this proposal, a lysine (Lys)/Cu2+ -incorporated zwitterionic polymer coating (defined as PDA/Lys/Cu-SB) is designed and robustly fabricated onto commercial CVCs using a facile two-step process. Initially, adhesive ene-functionalized dopamine is covalently reacted with Lys and simultaneously coordinated with bactericidal Cu2+ ions, leading to the deposition of a PDA/Lys/Cu coating on CVCs through mussel foot protein inspired surface chemistry. Next, zwitterionic poly(sulfobetaine methacrylate) (pSB) brushes are grafted onto the PDA/Lys/Cu coating to endow lubricant and antifouling properties. In the final PDA/Lys/Cu-SB coating, endothelium-mimicking function is achieved by combining the catalytic generation of nitric oxide from the chelated Cu2+ with antifouling pSB brushes, which led to significant prevention of thrombosis, and bacterial infection in vivo. Furthermore, the immobilized Lys with fibrinolytic activity show remarkably enhanced long-term anti-thrombogenic properties as evidenced in vivo by demonstrating the capability to lyse nascent clots. Therefore, this developed strategy provides a promising solution for long-term blood-contacting devices to combat thrombosis and infection.

Low-Valent Tungsten-Catalyzed Controllable Oxidative Dehydrogenative Coupling of Anilines.

Herein, we have developed an efficient tungsten-catalyzed homogeneous system for oxidative dehydrogenative coupling of anilines to selectively produce various azoaromatics and azoxyaromatics as well as 2-substituted indolone N-oxides by simply regulating the reaction solvent with peroxide as a terminal oxidant under additive-free conditions. These findings provide an experimental framework for exploring tungsten catalysis in organic synthesis and offer an efficient and convenient tactic for the selective oxidation of anilines.

A fully degradable transcatheter ventricular septal defect occluder: Towards rapid occlusion and post-regeneration absorption.

Degradable heart occluders are a promising replacement for currently clinically used non-degradable ones without concerns about the complications caused by the persistent residue of a foreign implant. However, the inherent mechanical properties of degradable occluders are poor and decline with material degradation, leading to a preference for a long degradation period upon designing a degradable heart occluder. This configuration can lower the risk of occluder dislodgement but reduce the benefits of degradable implants over their non-degradable counterparts due to a longer retention of foreign materials in the human body. Here, we fabricated a fully degradable ventricular septum defect (VSD) occluder consisting of polydioxanone (PDO) fiber and poly-L-lactic acid (PLLA) membrane featuring an auto-locking function. The degradable occluder showed an excellent shape recovery effect after transcatheter delivery and anchored securely to a heart defect as evidenced by in vitro and in vivo experiments. The degradable occluder could warrant robust fixation ability during the first 3-months of implantation within which tissue reconstruction was accomplished and be completely absorbed within 12 months. Benefitting from these merits, the degradable occluder displayed desired occlusion and no complications after being implanted in the VSD sites of canines during a 24-months follow-up. Compared with traditional non-degradable occluders, our degradable occluder could provide a potentially superior approach for rapidly repairing the congenital VSD without interfering with the normal development and physiological function of the heart.

Hemocompatibility Multi-in-One Hydrogel Coating with ROS-Triggered Inflammation Suppression and Anti-Infection Properties for Blood-Contacting Device.

In traditional blood-contacting medical devices, infection and thrombosis are easily formed on the surface of the materials. In addition, inflammation is also a clinical complication that cannot be ignored. More importantly, there is a mutually promoting relationship between the inflammatory response and the infection as well as thrombosis. In this work, we propose a self-adaptive anti-inflammatory coating strategy combined with anti-infection and anticoagulant capacity, which was accomplished based on nano-Ag particles and dexamethasone (Dex)-loaded hydrogel coating. The coating loaded with nano-Ag endows it with good bactericidal performance, including Gram-positive and Gram-negative bacteria. As an anti-inflammatory drug, Dex was grafted onto hydrogel coating by a reactive oxygen species (ROS)-cleavable thioketal (TK) bond and released upon the trigger of an inflammatory environment, blocking further inflammatory cascade, providing self-adaptive anti-inflammatory properties, and avoiding side effects of the drug. It was demonstrated that the coating worked as a precise strategy to resist coagulation, infection, and inflammation, provided a new perspective for designing clinical complication-conformable coatings, and had great application prospects on blood-contacting medical devices.

N-Arylimidazoliums as Highly Selective Biomimetic Antimicrobial Agents.

Antibiotic resistance has become one of the greatest health threats in the world. In this study, a charge-dispersed dimerization strategy is described for the antimicrobial peptide (AMP) mimics via a tunable cationic charge to improve the selectivity between prokaryotic microbes and eukaryotic cells. This strategy is demonstrated with a series of charge-dispersed AMP mimics based on N-arylimidazolium skeletons. These N-arylimidazolium AMP mimics show potent antibacterial activity against strains along with a low rate of drug resistance, good hemocompatibility, and low cytotoxicity. In addition to the elimination of planktonic bacteria, N-arylimidazolium AMP mimics can also inhibit biofilm formation and destroy the established biofilm. More importantly, methicillin-resistant Staphylococcus aureus (MRSA)-induced lung-infected mice can be effectively treated by the intravenous administration of N-arylimidazolium AMP mimic, which enable the design of N-arylimidazolium AMP mimics to offer an alternative avenue to eradicate drug-resistant bacterial infection.

Hydrophosphorylation of electron-deficient alkenes and alkynes mediated by convergent paired electrolysis.

A straightforward and practical strategy for hydrophosphorylation of electron-deficient alkenes and alkynes to access γ-ketophosphine oxides, enabled by a convergent paired electrolysis (CPE) in the absence of a metal, base, and redox reagent, has been described. Mechanistic studies have revealed that the diarylphosphane oxides play the dual role of a phosphorus radical precursor and hydrogen donor in this transformation.

Formation of Iridium(III) and Rhodium(III) Amine, Imine, and Amido Complexes Based on Pyridine-Amine Ligands: Structural Diversity Arising from Reaction Conditions, Substituent Variation, and Metal Centers.

Herein, we present the different coordination modes of half-sandwich iridium(III) and rhodium(III) complexes based on pyridine-amine ligands. The pyridyl-amine iridium(III) and rhodium(III) complexes, the corresponding oxidation pyridyl-imine products, and 16-electron pyridyl-amido complexes can be obtained through the change in reaction conditions (nitrogen/adventitious oxygen atmosphere, reaction time, and solvents) and structural variations in the metal and ligand. Overall, the reaction of pyridine-amine ligands with [(η5-C5(CH3)5)MCl2]2 (M = Ir or Rh) in the presence of adventitious oxygen afforded the oxidized pyridyl-imine complexes. The possible mechanism for the oxidation of iridium(III) and rhodium(III) amine complexes was confirmed by the detection of the byproduct hydrogen peroxide. Moreover, the formation of pyridyl-amine complexes was favored when nonpolar solvent CH2Cl2 was used instead of CH3OH. The rarely reported complex with [(η5-Cp*)IrCl3] anions can also be obtained without the addition of NH4PF6. The introduction of the sterically bulky i-Bu group on the bridge carbon of the ligand led to the formation of stable 16-electron pyridyl-amido complexes. The pyridyl-amine iridium(III) and rhodium(III) complexes were also synthesized under a N2 atmosphere, and no H2O2 was detected in the whole process. In particular, the aqueous solution stability and in vitro cytotoxicity toward A549 and HeLa human cancer cells of these complexes were also evaluated. No obvious selectivity was observed for cancer cells versus normal cells with these complexes. Notably, the represented complex 5a can promote an increase in the reactive oxygen species level and induce cell death via apoptosis.

A Uniform and Robust Bioinspired Zwitterion Coating for Use in Blood-Contacting Catheters with Improved Anti-Inflammatory and Antithrombotic Properties.

Inflammation and thrombosis are two major complications of blood-contacting catheters that are used as extracorporeal circuits for hemodialysis and life-support systems. In clinical applications, complications can lead to increased mortality and morbidity rates. In this work, a biomimetic erythrocyte membrane zwitterion coating based on poly(2-methacryloyloxyethyl phosphorylcholine-co-dopamine methacrylate) (pMPCDA) copolymers is uniformly and robustly modified onto a polyvinyl chloride (PVC) catheter via mussel-inspired surface chemistry. The zwitterionic pMPCDA coating exhibits excellent antifouling activity and resists bacterial adhesion, fibrinogen adsorption, and platelet adhesion/activation. The material also demonstrates great hemocompatibility, cytocompatibility, and anticoagulation properties in vitro. Additionally, this biocompatible pMPCDA coating reduces in vivo foreign-body reactions by mitigating inflammatory response and collagen capsule formation, due to its outstanding ability to resist nonspecific protein adsorption. More importantly, when compared with a bare PVC catheter, the pMPCDA coating exhibits outstanding antithrombotic properties when tested in an ex vivo rabbit perfusion model. Thus, it is envisioned that this biomimetic erythrocyte membrane surface strategy will provide a promising way to mitigate inflammation and thrombosis caused by the use of blood-contacting catheters.

Microneedle-mediated vascular endothelial growth factor delivery promotes angiogenesis and functional recovery after stroke.

Ischemic stroke is still the major cause of disability worldwide. Although vascular endothelial growth factor (VEGF) is able to promote both angiogenesis and functional recovery, its use is limited by needle-induced injury, nonhomogenous VEGF distribution, and limited VEGF retention in the brain after intracranial or intravenous injection. Here, we first present a gelatin methacryloyl (GelMA) microneedle (MN)-based platform for the sustained and controlled local delivery of an adeno-associated virus (AAV) expressing human VEGF (AAV-VEGF) that achieves homogenous distribution and high transfection efficiency in ischemic brains. An ischemic stroke model was established in adult rats, and MNs loaded with AAV-VEGF were epicortically inserted into both the ischemic core and penumbra of these rats one day after the onset of ischemia. One week later, the inflammatory response and microneedle biocompatibility were assessed by enzyme-linked immunosorbent assay (ELISA) and immunofluorescence. Eight weeks later, angiogenesis and neural stem cell proliferation and migration were assessed. GelMA MN implantation did not elicit an obvious inflammatory response and had good biocompatibility in the brain. AAV-green fluorescent protein (GFP)-loaded MNs could achieve successful transfection and homogeneous distribution in the brain cortex three weeks postoperatively. MNs loaded with AAV-VEGF increased VEGF expression and enhanced functional angiogenesis and neurogenesis. In summary, MNs might emerge as a promising platform for delivering various therapeutics to treat ischemic stroke and repair other neurologically diseased tissues.

Dressing Blood-Contacting Materials by a Stable Hydrogel Coating with Embedded Antimicrobial Peptides for Robust Antibacterial and Antithrombus Properties.

Although dressing blood-contacting devices with robust and synergistic antibacterial and antithrombus properties has been explored for several decades, it still remains a great challenge. In order to endow materials with remarkable antibacterial and antithrombus abilities, a stable and antifouling hydrogel coating was developed via surface-initiated polymerization of sulfobetaine methacrylate and acrylic acid on a polymeric substrate followed by embedding of antimicrobial peptides (AMPs), including WR (sequence: WRWRWR-NH2) or Bac2A (sequence: RLARIVVIRVAR-NH2) AMPs. The chemical composition of the AMP-embedded hydrogel coating was determined through XPS, zeta potential, and SEM-EDS measurements. The AMP-embedded antifouling hydrogel coating showed not only good hemocompatibility but also excellent bactericidal and antiadhesion properties against Gram-positive and Gram-negative bacteria. Moreover, the hydrogel coating could protect the AMPs with long-term bioactivity and cover the positive charge of the dotted distributed AMPs, which in turn well retained the hemocompatibility and antifouling capacity of the bulk hydrogels. Furthermore, the microbiological results of animal experiments also verified the anti-infection performance in vivo. Histological and immunological data further indicated that the hydrogel coating had an excellent anti-inflammatory function. Therefore, the present study might provide a promising approach to prevent bacterial infections and thrombosis in clinical applications of blood-contacting devices and related implants.

Surprising Condensation Reactions of the Azadithiolate Cofactor.

Azadithiolate, a cofactor found in all [FeFe]-hydrogenases, is shown to undergo acid-catalyzed rearrangement. Fe2 [(SCH2 )2 NH](CO)6 self-condenses to give Fe6 [(SCH2 )3 N]2 (CO)17 . The reaction, which is driven by loss of NH4+ , illustrates the exchange of the amine group. X-ray crystallography reveals that three Fe2 (SR)2 (CO)x butterfly subunits interconnected by the aminotrithiolate [N(CH2 S)3 ]3- . Mechanistic studies reveal that Fe2 [(SCH2 )2 NR](CO)6 participate in a range of amine exchange reactions, enabling new methodologies for modifying the adt cofactor. Ru2 [(SCH2 )2 NH](CO)6 also rearranges, but proceeds further to give derivatives with Ru-alkyl bonds Ru6 [(SCH2 )3 N][(SCH2 )2 NCH2 ]S(CO)17 and [Ru2 [(SCH2 )2 NCH2 ](CO)5 ]2 S.

CO substitution by PPh3 in Fe2S2(CO)6 proceeds via a novel Fe2S intermediate.

The reaction of Fe2S2(CO)6 and PPh3 affords Fe2S2(CO)4(PPh3)2 by an unprecedented mechanism involving the intermediacy of SPPh3 and Fe2S(CO)6(PPh3)2.

A conformally adapted all-in-one hydrogel coating: towards robust hemocompatibility and bactericidal activity.

Hospital-acquired infections and thrombosis caused by bacteria attached to the device surface, or fibrin crosslinking owing to platelet accumulation/activation, are major healthcare challenges that cause morbidity and mortality. To prevent these, surface coating technologies are considered an efficient tool that can combine hemocompatibility and bactericidal activity. In this study, surface-initiated polymerization was conducted to form an all-in-one hydrogel coating that could adapt to diverse medical devices. Different monomer ratios (acrylamide/acrylic acid) were used to adjust the antimicrobial agent loading capacity. The hydrogel coating obtained by a simple dip-absorbing method showed good hemocompatibility and maintained efficient bactericidal activity. We also explored the loading and release of antimicrobial agents with different molecular sizes, including nano-Ag particles, antibiotics, and antimicrobial peptides. The inhibition zone test and confocal laser scanning microscopy revealed that the hydrogel coating could maintain remarkable antimicrobial and antifouling properties for four weeks. Furthermore, the hydrogel coating decreased the platelet adhesion/activation without risk of hemolysis. The ex vivo blood circulation study confirmed the antithrombotic properties of the hydrogel coating. Such all-in-one hydrogel coatings that maintain high cell viability and exhibit both hemocompatibility and bactericidal activity possess the potential for applications in blood-contacting devices.