Alkaline Microenvironment Research Articles

Borosilicate bioactive glass synergizing low-dose antibiotic loaded implants to combat bacteria through ATP disruption and oxidative stress to sequentially achieve osseointegration

Bone infection is a catastrophe in clinical orthopedics. Despite being the standard therapy for osteomyelitis, antibiotic-loaded polymethyl methacrylate (PMMA) cement has low efficiency against bacteria in biofilms. Furthermore, high-dose antibiotic-loaded implants carry risks of bacterial resistance, tissue toxicity, and impairment of local tissue healing. By incorporating borosilicate bioactive glass (BSG) into low-dose gentamicin sulfate (GS)-loaded PMMA cement, an intelligent strategy that synergistically eradicates bacteria and sequentially promotes osseointegration, was devised. Results showed that BSG did not compromises the handling properties of the cement, but actually endowed it with an ionic and alkaline microenvironment, thereby damaging the integrity of bacterial cell walls and membranes, inhibiting ATP synthesis by disrupting the respiratory chain in cell membranes and glycogen metabolism, and elevating reactive oxygen species (ROS) levels by weakening antioxidant components (peroxisomes and carotenoids). These antibacterial characteristics of BSG synergistically reinforced the effectiveness of GS, which was far below the actual clinical dosage, achieving efficient bacterial killing and biofilm clearance by binding to the 30S subunit of ribosomes. Furthermore, the released GS and the ionic and alkaline microenvironment from the implants fostered the osteogenic activity of hBMSCs in vitro and coordinately enhanced osseointegration in vivo. Collectively, this study underscores that BSG incorporation offers a promising strategy for reducing antibiotic dosage while simultaneously enhancing the antibacterial activity and osteogenesis of implants. This approach holds potential for resolving the conflict between bacterial resistance and bone infection.

Double Enzyme Active Hydrogel Program Regulates the Microenvironment of Staphylococcus aureus-Infected Pressure Ulcers.

The treatment of infected pressure ulcers (IUPs) requires addressing diverse microenvironments. A pressing challenge is to effectively enhance the regenerative microenvironment at different stages of the healing process, tailoring interventions as needed. Here, a dual enzyme mimetic and bacterial responsive self-activating antimicrobial hydrogel designed to enhance IPUs healing is introduced. This hydrogel incorporates pH-responsive dual enzyme-active nanoplatforms (HNTs-Fe-Ag) encapsulated within a methacrylate-modified silk fibroin (SFMA) and dopamine methacrylamide (DMA) matrix. This composite hydrogel exhibits adaptive microenvironment regulation capabilities. Under the low pH microenvironment of bacterial infection, it has excellent antimicrobial activity by self-activating the •OH generation in conjunction with photothermal effects. Under the neutral and alkaline microenvironment of chronic inflammation, it catalyzes the decomposition of hydrogen peroxide (H2O2) to produce oxygen (O2), thereby alleviating hypoxia and scavenging reactive oxygen species (ROS), which in turn remodulates the phenotype of macrophages. The composite hydrogel demonstrates on-demand therapeutic effects in the microenvironment of infected wounds, significantly enhancing the regenerative microenvironment of IUPs by promoting wound closure, inflammation regulation, and collagen deposition through self-activated antimicrobial action during infection and adaptive hypoxia relief during recovery. This approach offers a novel strategy for developing smart wound dressings.

Microenvironment regulation for high-performance acidic CO2 electroreduction on Poly(ionic liquid)-modified Cu surface

Electrocatalytic reduction of CO2 (CO2RR) under acidic conditions provides a feasible way for converting CO2 to multi-carbon products (C2+) with high feedstock conversion and high energetic efficiency (EE). In this work, poly(ionic liquid) (PIL)-Cu hybrids were employed as excellent acidic CO2RR electrocatalysts. A high faradaic efficiency towards C2+ products (FEC2+) of more than 61.0 % was achieved within a wide pH range from 2 to 14 at –700 mA cm–2. The optimum FEC2+ of 83.1 % was obtained at –700 mA cm–2 and pH = 2, corresponding to an EEC2+ of 37.6 %. By reducing the inlet CO2 flow rate to 1.59 mL min–1, a very high CO2 single-pass conversion of 98.7 % was achieved at –300 mA cm–2. The confinement of PIL layer caused by the semi-rigid abundant porous structure and dense cationic-anionic network enables the maintenance of a moderate local alkaline microenvironment and enrichment of K+ cations at the active sites. These effects jointly promote the C–C coupling at the Cu-PIL interface under acidic conditions. Remarkably, the CO2RR pathway can be regulated by functionality and morphology of the PIL layer.

Anionic Ionomer: Released Surface-Immobilized Cations and an Established Hydrophobic Microenvironment for Efficient and Durable CO2-to-Ethylene Electrosynthesis at High Current over One Month.

Electrosynthesis of multicarbon products, such as C2H4, from CO2 reduction on copper (Cu) catalysts holds promise for achieving carbon neutrality. However, maintaining a steady high current-level C2H4 electrosynthesis still encounters challenges, arising from unstable alkalinity and carbonate precipitation caused by undesired ion migration at the cathode under a repulsive electric field. To address these issues, we propose a universal "charge release" concept by incorporating tiny amounts of an oppositely charged anionic ionomer (e.g., perfluorinated sulfonic acid, PFSA) into a cationic covalent organic framework on the Cu surface (cCOF/PFSA). This strategy effectively releases the hidden positive charge within the cCOF, enhancing surface immobilization of cations to impede both outward migration of generated OH- and inward migration of cations, inhibiting carbonate precipitation and creating a strong alkaline microenvironment. Meanwhile, the ionomer's hydrophobic chains create a hydrophobic environment within the cCOF, facilitating efficient gas transport. In situ characterizations and theoretical calculations demonstrate that the cCOF/PFSA catalyst establishes a hydrophobic strong alkaline microenvironment, optimizing the adsorption strength and configuration of *CO intermediates to promote the C2H4 formation. The optimized catalyst achieves a 70.5% Faradaic efficiency for C2H4 with a partial current density over 470 mA cm-2. Notably, it delivers a high single-pass carbon efficiency of 96.5% for CO2RR and sustains an exceptional stability over 760 h. When implemented in a large-area MEA electrolyzer and a 5-cell MEA stack, the system achieves an industrial current of 15 A and continuous C2H4 production exceeding 19 mL min-1, marking a significant step toward industrial feasibility in CO2RR-to-C2H4 conversion.

Constructing alkaline microenvironment on catalyst surface for enhanced electrocatalytic synthesis of hydrogen peroxide in a neutral electrolyte

The direct electrochemical synthesis of H2O2 via a two-electron oxygen reduction reaction (2e− ORR) offers a feasible alternative to the energy-intensive anthraquinone oxidation process. Compared to alkaline electrolytes, challenges remain in achieving high 2e− ORR selectivity and activity for electrosynthesis of H2O2 in neutral electrolytes due to the low concentration of OH−, which hinders the effective binding of key intermediate OOH*. Here, we introduced Lewis acid TiO2 to modify carbon black catalyst for adsorbing in-situ generated OH− and created a local alkaline microenvironment for enhancing the 2e− ORR activity and selectivity in neutral electrolytes. H2O2 productivity of TiO2 modified carbon black catalyst (52.5 mmol L−1 h−1) in a neutral electrolyte (0.5 M Na2SO4) at 0.2 V vs. RHE was 1.6 times as much as that of pristine carbon black (33 mmol L−1 h−1), which was similar with that of pristine carbon black (58.4 mmol L−1 h−1) in an alkaline electrolyte (0.1 M KOH). The finite-element method simulations and experiments indicated that TiO2 could enhance local alkalinity to increase the current density for facilitating 2e− ORR. The density functional theory calculations indicated that the introducing of TiO2 into the CB structure could promote the adsorption of O2, facilitate the adsorption of *OOH and reduce the overpotential, resulting in high activity towards 2e− ORR to H2O2. This work proposes a new strategy for optimizing electrode–electrolyte interface to enhance 2e− ORR performance in neutral electrolytes.

Promoting the transformation of green rust for As immobilization with Acidovorax sp. strain BoFeN1

Microbially mediated Fe(II) oxidation has a great potential for attenuating arsenic (As) mobility in an anoxic groundwaters. Green rust (GR), a common Fe(II)-bearing phase in such environments, could be easily oxidized into Fe (oxyhydr)oxides through microbial activity. This study focused on Acidovorax sp. strain BoFeN1, an anaerobic nitrate-reducing Fe(II)-oxidizing (NRFO) bacterium, to promote the transformation of GR. In biotic GR transformation experiments, magnetite formation occurred at [As]ini = 5 mg/L while lepidocrocite and goethite were formed at [As]ini = 10 mg/L. In the absence of bacterium, the GR persisted throughout the 120-h experiment. Meanwhile, with the addition of strain BoFeN1, the final aqueous As concentration significantly decreased from 0.237 to 0.004 mg/L (C0 = 5 mg/L) and from 1.457 to 0.096 mg/L (C0 = 10 mg/L) at 120 h. It was indicated that strain BoFeN1 played a crucial role in promoting the GR transformation and enhancing As immobilization. Further investigations revealed that the role of strain BoFeN1 extended beyond Fe-oxidation. With nitrite (the intermediate of nitrate bioreduction) as oxidizer, lepidocrocite/goethite were formed in the chemical-oxidation system, excluding magnetite. In the Bio - [As]ini = 5 mg/L, the occurrence of lepidocrocite via the bio-oxidation of Fe(II) in GR at 24 h, along with the metabolism of strain BoFeN1 reducing nitrate accompanied with H+ consumption, it should be reasonably deduced that the alkaline micro-environment of periplasm induced by strain BoFeN1 were vital for the transformation of lepidocrocite to magnetite triggered by trace Fe(II). However, in the Bio - [As]ini = 10 mg/L, more As adsorbed on GR inhibiting the adsorption of bacterium, so the alkaline micro-environment had no obvious effect on such transformation. This study helps to understand the interdependence between GR and anaerobic NRFO bacterium, and provides a new perspective for more effective As remediation strategies in anoxic groundwaters.

Interlayer-confined strategy to modulate alkaline reaction microenvironment for in-situ degradation of ofloxacin

In advanced oxidation processes designed for the mineralization of organic contaminants, the acidic microenvironment in the peroxymonosulfate (PMS) activation system poses a major threat to the stability of active species. In this study, we developed a low-cost Co-Mg–layered double hydroxide (LDH) structure with an OH−-enriched, interlayer-confined alkaline microenvironment around Co sites. This structure exhibited enhanced surface availability and a short reactant diffusion path, which accelerated proton migration and regulated local pH at the slipping plane. Theoretical calculations revealed that CoMg-LDH exhibited high catalytic activity for PMS cleavage and generated high-valence Co-oxo (Co(IV)=O) species in this specific microenvironment. At a natural pH, the optimized system achieved 100 % removal efficiency of the target pollutant (ofloxacin), with negligible Co leaching. It also demonstrated stability in long-term experiments and effectively purified hospital wastewater. Overall, this study provides valuable insights into the in-situ degradation of contaminants through self-regulating catalytic systems.

Enhanced osteogenesis and physicochemical properties of PMMA bone cement with SrBG/HA porous core-shell microspheres

Artificial bone graft with osteoconductivity, angiogenesis, and immunomodulation is promising clinical therapeutics for the reluctant healing process of bone defects. Among various osteogenic substitutes, polymethyl methacrylate (PMMA) bone cement is a quit competitive platform due to its easy deployment to the bone defects with irregular shape and biomimetic mechanical properties. However, the biologically inert essence of PMMA is reliant on the passive osseointegration and cannot provide sufficient biologic cues to induce fast bone repair. Bioactive glass could serve as an efficient platform for the active osteogenesis of PMMA via ionic therapy and construction of alkaline microenvironment. However, the direct of deployment of bioactive glass into PMMA may trigger additional cytotoxicity and hinder cell growth on its surface. Hence we incorporated ionic therapy as osteogenic cue into the PMMA to enhance the biomedical properties. Specifically, we synthesized core-shell microspheres with a strontium-doped bioactive glass (SrBG) core and hydroxyapatite (HA) shell, and then composited them with PMMA to introduce multifunctional effects of HA incorporation, alkaline microenvironment construction, and functional ion release by adding microsphere. We prepared xSrBG@HA/PMMA cements (x = 30, 40, 50) with varied microsphere content and evaluated impacts on mechanical/handling properties, ion release, and investigated the impacts of different composite cements on proliferation, osteogenic differentiation, angiogenic potential, and macrophage polarization. These findings provide new perspectives and methodologies for developing advanced bone biomaterials to promote tissue regeneration.

A Composite Hydrogel Functionalized by Borosilicate Bioactive Glasses and VEGF for Critical-Size Bone Regeneration.

Critical-size bone defects pose a formidable challenge in clinical treatment, prompting extensive research efforts to address this problem. In this study, an inorganic-organic multifunctional composite hydrogel denoted as PLG-g-TA/VEGF/Sr-BGNPs is developed, engineered for the synergistic management of bone defects. The composite hydrogel demonstrated the capacity for mineralization, hydroxyapatite formation, and gradual release of essential functional ions and vascular endothelial growth factor (VEGF) and also maintained an alkaline microenvironment. The composite hydrogel promoted the proliferation and osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs), as indicated by increased expression of osteogenesis-related genes and proteins in vitro. Moreover, the composite hydrogel significantly enhanced the tube-forming capability of human umbilical vein endothelial cells (HUVECs) and effectively inhibited the process of osteoblastic differentiation of nuclear factor kappa-B ligand (RANKL)-induced Raw264.7 cells and osteoclast bone resorption. After the implantation of the composite hydrogel into rat cranial bone defects, the expression of osteogenic and angiogenic biomarkers increased, substantiating its efficacy in promoting bone defect repair in vivo. The commendable attributes of the multifunctional composite hydrogel underscore its pivotal role in expediting hydrogel-associated bone growth and repairing critical bone defects, positioning it as a promising adjuvant therapy candidate for large-segment bone defects.

Design of Multi-Functional Bio-Safe Dental Resin Composites with Mineralization and Anti-Biofilm Properties.

This study aims to develop multi-functional bio-safe dental resin composites with capabilities for mineralization, high in vitro biocompatibility, and anti-biofilm properties. To address this issue, experimental resin composites consisting of UDMA/TEGDMA-based dental resins and low quantities (1.9, 3.8, and 7.7 vol%) of 45S5 bioactive glass (BAG) particles were developed. To evaluate cellular responses of resin composites, MC3T3-E1 cells were (1) exposed to the original composites extracts, (2) cultured directly on the freshly cured resin composites, or (3) cultured on preconditioned composites that have been soaked in deionized water (DI water), a cell culture medium (MEM), or a simple HEPES-containing artificial remineralization promotion (SHARP) solution for 14 days. Cell adhesion, cell viability, and cell differentiation were, respectively, assessed. In addition, the anti-biofilm properties of BAG-loaded resin composites regarding bacterial viability, biofilm thickness, and biofilm morphology, were assessed for the first time. In vitro biological results demonstrated that cell metabolic activity and ALP expression were significantly diminished when subjected to composite extracts or direct contact with the resin composites containing BAG fillers. However, after the preconditioning treatments in MEM and SHARP solutions, the biomimetic calcium phosphate minerals on 7.7 vol% BAG-loaded composites revealed unimpaired or even better cellular processes, including cell adhesion, cell proliferation, and early cell differentiation. Furthermore, resin composites with 1.9, 3.8, and 7.7 vol% BAG could not only reduce cell viability in S. mutans biofilm on the composite surface but also reduce the biofilm thickness and bacterial aggregations. This phenomenon was more evident in BAG7.7 due to the high ionic osmotic pressure and alkaline microenvironment caused by BAG dissolution. This study concludes that multi-functional bio-safe resin composites with mineralization and anti-biofilm properties can be achieved by adding low quantities of BAG into the resin system, which offers promising abilities to mineralize as well as prevent caries without sacrificing biological activity.

Novel Tannic Acid-Modified Cobalt-Based Metal-Organic Framework: Synthesis, Characterization, and Antimicrobial Activity.

Metal-organic frameworks (MOFs) are a class of hybrid inorganic-organic materials with typical porous structures and a unique morphology. Due to their diversity, they are extensively used in a wide range of applications such as environmental, catalysis, biomedicine, etc. In this study, a novel cobalt-based MOF modified with tannic acid (Co-TPA/TA) (TPA: terephthalic acid; TA: tannic acid) as a promising material for antimicrobial agents was synthesized and characterized by X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy with energy-dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, inductively coupled plasma-optical emission spectrometry, and thermogravimetric analysis and compared with an as-synthesized cobalt-based framework. Co-TPA/TA demonstrated good antimicrobial efficiency under optimum conditions against yeast Candida albicans ATCC 10231, Gram-negative Escherichia coli ATCC 8739, and Gram-positive Staphylococcus aureus ATCC 6538 with an inhibition zone ranging from 14 to 20 mm. Reduced ATP levels, generation of reactive oxygen species, membrane damage from cobalt ion release, and development of an alkaline microenvironment could all be contributing factors to the possible antimicrobial pathways. The novel framework can be obtained using simple, affordable, and easily accessible commercial ligands and is considered to have the potential to be used as an antimicrobial material in the future.

Acidic solution irrigation as a novel approach for treating infected walled-off pancreatic necrosis

Walled-off pancreatic necrosis (WOPN) is a severe complication of acute pancreatitis arising from pancreatic or peripancreatic necrosis complicated by infection, leading to elevated mortality rates. Extravasation of pancreatic juice creates a weakly alkaline microenvironment favorable for the survivial of translocated intestinal bacteria and activated pancreatic enzyme-mediated autodigestion of pancreatic and peripancreatic tissues. Conventional treatments for WOPN involve invasive procedures with irrigation to mitigate postoperative infections. However, there remains a lack of a unified standard for lavage fluid. Herein, we raise the hypothesis that the utilization of acidic solution irrigation may serve as a promising strategy for preventing and treating infected WOPN. Acidic solutions create an unfavorable environment for translocated intestinal bacteria in WOPN cases. Additionally, the acidic microenvironment may alleviate self-digestion of pancreatic and peripancreatic tissues by inhibiting pancreatic enzyme activity. This innovative approach holds potential for enhancing the management and outcomes of infected WOPN.

Reactive Microneedle Patches with Antibacterial and Dead Bacteria-Trapping Abilities for Skin Infection Treatment.

Bacterial skin infections are highly prevalent and pose a significant public health threat. Current strategies are primarily focused on the inhibition of bacterial activation while disregarding the excessive inflammation induced by dead bacteria remaining in the body and the effect of the acidic microenvironment during therapy. In this study, a novel dual-functional MgB2 microparticles integrated microneedle (MgB2 MN) patch is presented to kill bacteria and eliminate dead bacteria for skin infection management. The MgB2 microparticles not only can produce a local alkaline microenvironment to promote the proliferation and migration of fibroblasts and keratinocytes, but also achieve >5 log bacterial inactivation. Besides, the MgB2 microparticles effectively mitigate dead bacteria-induced inflammation through interaction with lipopolysaccharide (LPS). With the incorporation of these MgB2 microparticles, the resultant MgB2 MN patches effectively kill bacteria and capture dead bacteria, thereby mitigating these bacteria-induced inflammation. Therefore, the MgB2 MN patches show good therapeutic efficacy in managing animal bacterial skin infections, including abscesses and wounds. These results indicate that reactive metal borides-integrated microneedle patches hold great promise for the treatment of clinical skin infections.

Modification of microenvironmental pH of nanoparticles for enhanced solubility and oral bioavailability of poorly water-soluble celecoxib

This study aimed to develop a novel pH-modified nanoparticle with improved solubility and oral bioavailability of poorly water-soluble celecoxib by modifying the microenvironmental pH. After assessing the impact of hydrophilic polymers, surfactants and alkaline pH modifiers on the drug solubility, copovidone, sodium lauryl sulfate (SLS) and meglumine were chosen. The optimal formulation of solvent-evaporated, surface-attached and pH-modified nanoparticles composed of celecoxib/copovidone/SLS/meglumine at weight ratios of 1:1:0.2:0, 1:0.375:1.125:0 and 1:1:1:0.2:0.02, respectively, were manufactured using spray drying technique. Their physicochemical characteristics, solubility, dissolution and pharmacokinetics in rats were evaluated compared to the celecoxib powder. The solvent-evaporated and pH-modified nanoparticles converted a crystalline to an amorphous drug, resulting in a spherical shape with a reduced particle size compared to celecoxib powder. However, the surface-attached nanoparticles with insignificant particle size exhibited the unchangeable crystalline drug. All of them gave significantly higher solubility, dissolution, and oral bioavailability than celecoxib powder. Among them, the pH-modified nanoparticles demonstrated the most significant improvement in solubility (approximately 1600-fold) and oral bioavailability (approximately 4-fold) compared to the drug powder owing to the alkaline microenvironment formation effect of meglumine and the conversion to the amorphous drug. Thus, the pH-modified nanoparticle system would be a promising strategy for improving the solubility and oral bioavailability of poorly water-soluble and weakly acidic celecoxib.

Unveiling pH-Dependent Adsorption Strength of *CO2 - Intermediate over High-Density Sn Single Atom Catalyst for Acidic CO2-to-HCOOH Electroreduction.

The acidic electrochemical CO2 reduction reaction (CO2RR) for direct formic acid (HCOOH) production holds promise in meeting the carbon-neutral target, yet its performance is hindered by the competing hydrogen evolution reaction (HER). Understanding the adsorption strength of the key intermediates in acidic electrolyte is indispensable to favor CO2RR over HER. In this work, high-density Sn single atom catalysts (SACs) were prepared and used as catalyst, to reveal the pH-dependent adsorption strength and coverage of *CO2 - intermediatethat enables enhanced acidic CO2RR towards direct HCOOH production. At pH=3, Sn SACs could deliver a high Faradaic efficiency (90.8 %) of HCOOH formation and a corresponding partial current density up to -178.5 mA cm-2. The detailed in situ attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopic studies reveal that a favorable alkaline microenvironment for CO2RR to HCOOH is formed near the surface of Sn SACs, even in the acidic electrolyte. More importantly, the pH-dependent adsorption strength of *CO2 - intermediate is unravelled over the Sn SACs, which in turn affects the competition between HER and CO2RR in acidic electrolyte.

Unveiling pH‐Dependent Adsorption Strength of *CO2− Intermediate over High‐Density Sn Single Atom Catalyst for Acidic CO2‐to‐HCOOH Electroreduction

AbstractThe acidic electrochemical CO2 reduction reaction (CO2RR) for direct formic acid (HCOOH) production holds promise in meeting the carbon‐neutral target, yet its performance is hindered by the competing hydrogen evolution reaction (HER). Understanding the adsorption strength of the key intermediates in acidic electrolyte is indispensable to favor CO2RR over HER. In this work, high‐density Sn single atom catalysts (SACs) were prepared and used as catalyst, to reveal the pH‐dependent adsorption strength and coverage of *CO2− intermediatethat enables enhanced acidic CO2RR towards direct HCOOH production. At pH=3, Sn SACs could deliver a high Faradaic efficiency (90.8 %) of HCOOH formation and a corresponding partial current density up to −178.5 mA cm−2. The detailed in situ attenuated total reflection Fourier transform infrared (ATR‐FTIR) spectroscopic studies reveal that a favorable alkaline microenvironment for CO2RR to HCOOH is formed near the surface of Sn SACs, even in the acidic electrolyte. More importantly, the pH‐dependent adsorption strength of *CO2− intermediate is unravelled over the Sn SACs, which in turn affects the competition between HER and CO2RR in acidic electrolyte.

Fabrication of a Nanoscale Magnesium/Copper Metal-Organic Framework on Zn-Based Guided Bone Generation Membranes for Enhancing Osteogenesis, Angiogenesis, and Bacteriostasis Properties.

Recently, zinc (Zn) and its alloys have demonstrated great potential as guided bone regeneration (GBR) membranes to treat the problems of insufficient alveolar bone volume and long-term osseointegration instability during dental implantology. However, bone regeneration is a complex process consisting of osteogenesis, angiogenesis, and antibacterial function. For now, the in vivo osteogenic performance and antibacterial activity of pure Zn are inadequate, and thus fabricating a platform to endow Zn membranes with multifunctions may be essential to address these issues. In this study, various bimetallic magnesium/copper metal-organic framework (Mg/Cu-MOF) coatings were fabricated and immobilized on pure Zn. The results indicated that the degradation rate and water stability of Mg/Cu-MOF coatings could be regulated by controlling the feeding ratio of Cu2+. As the coating and Zn substrate degraded, an alkaline microenvironment enriched with Zn2+, Mg2+, and Cu2+ was generated. It significantly improved calcium phosphate deposition, differentiation of osteoblasts, and vascularization of endothelial cells in the extracts. Among them, Mg/Cu1 showed the best comprehensive performance. The superior antibacterial activity of Mg/Cu1 was demonstrated in vitro and in vivo, which indicated significantly enhanced bacteriostatic activity against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli as compared to that of the bare sample. Bimetallic Mg/Cu-MOF coating could properly coordinate the multifunction on a Zn membrane and could be a promising platform for promoting its bone regeneration, which could pave the way for Zn-based materials to be used as barrier membranes in oral clinical trials.

PH-responsive, self-sculptured Mg/PLGA composite microfibers for accelerated revascularization and soft tissue regeneration

Biodegradable Mg/polymer composite fibers offer a promising therapeutic option for tissue injury because of bioactive Mg2+ and biomimetic microstructure. However, current studies are limited to the contribution of Mg2+ and the single microstructure. In this study, we designed Mg/poly (lactic-co-glycolic acid) (Mg/PLGA) composite microfibers that significantly enhanced angiogenesis and tissue regeneration synergistically by Mg2+ and self-sculptured microstructure, due to spontaneous in situ microphase separation in response to the weakly alkaline microenvironment. Our composite microfiber patch exhibited superior performance in the adhesion, spreading, and angiogenesis functions of human umbilical vein endothelial cells (HUVECs) due to the joint contribution of the hierarchically porous microstructure and Mg2+. Genomics and proteomics analyses revealed that the Mg/PLGA composite microfibers activated the cell focal adhesion and angiogenesis-related signaling pathways. Furthermore, the repair of typical soft tissue defects, including refractory urethral wounds and easily healed skin wounds, validated that our Mg/PLGA composite microfiber patch could provide favorable surface topography and ions microenvironment for tissue infiltration and accelerated revascularization. It could cause rapid urethral tissue regeneration and recovery of rabbit urethral function within 6 weeks and accelerate rat skin wound closure within 16 days. This work provides new insight into soft tissue regeneration through the bioactive alkaline substance/block copolymer composites interactions.

A MOF-doped molecularly imprinted polymer/MOF hybrid gel incorporating with pH-buffering sodium acrylate for practical detoxification of organophosphorus nerve agents

The fatal toxicity of organophosphorus nerve agents (ONAs) and the realistic condition of chemical attack occurring place trigger the urgent need to develop catalyst materials with degrading ability under the natural environment without bulk water and bases. Here, we strategically design a molecularly imprinted polymer (MIP)/MOF hybrid catalyst material by integrating enzyme-mimic MIP with Zr-MOF UiO-66-NH2 which demonstrate promising catalytic performance for degradation of ONAs. Furthermore, sodium acrylate functions as a hydrophilic and alkaline functional unit together with pyridine-amidoxime based functional monomers (PAAO) to copolymerize into molecularly imprinted polymeric network. The basic sodium carboxylate groups were installed near the active sites to provide appropriate alkaline microenvironment, non-bulk water and acid buffer capacity for the catalysis in pure water. The resultant MIP/MOF composite catalyst demonstrate outstanding catalytic activities in both liquid and solid phase hydrolysis of ONAs. Specifically, the half-life of liquid phase hydrolysis catalyzed by MIP/UiO-66-NH2-0.5 achieves 9.4 min for diethyl-4-nitrophenyl phosphate (DENP) and 10 min for dimethyl 4-nitrophenyl phosphate (DMNP), and solid-state hydrolysis present rapid degradation efficiency with a half-life of 28.6 min. In addition, composite catalyst MIP-Ag/UiO-66-NH2-0.5 that retains substrate selectivity of MIP, enables the simultaneous degradation of two types of organophosphorus substrates (phosphate and thiophosphate) by MIP and MOF in a synergistic way. Summarily, this work displays promising potential of MIP/MOF hybrid enzyme-like catalyst as effective and practical material for the practical protection and detoxification of organophosphorus nerve agents.

Boosting MRSA Infectious Osteoporosis Treatment: Mg‐Doped Nanofilm on Vacancy‐Enriched TiO2 Coating for Providing In Situ Sonodynamic Bacteria‐Killing and Osteogenic Alkaline Microenvironment

AbstractTo effectively combat infectious osteoporosis, Ti‐based implants with enhanced antibacterial and osseointegrative properties are urgently required. Herein, a one‐step method involving Mg thermal‐reduction is employed to modify a hydroxyapatite (HA) array on Ti, which comprises an inner TiO2 layer and an outer nanorod‐like HA layer. This process introduces oxygen vacancies (OVs) into the TiO2 layer and deposits a Mg─O‐contained amorphous nanolayer on each HA nanorod. The introduced OVs enhance reactive oxygen species (ROS) yield by the array during ultrasound treatment via narrowing TiO2 bandgap and improving H2O molecules absorption. The produced ROS, combined with a weak alkaline microenvironment created by the degraded Mg─O nanolayer, endows the array with potent bacterial‐killing and biofilm‐eradicating efficacies within a 5 min ultrasound treatment via the combination of proton‐consumption and cell envelop‐detriment effects. Moreover, due to the alkaline microenvironment and the released Mg2+, the array hinders osteoclastogenesis by activating the inflammation‐related FAK‐PI3K‐AKT signaling pathway in macrophages, as revealed by transcriptomic analysis, resulting in robust osseointegration in rat femoral shaft with concurrent bacterial‐infection and osteoporosis. This work paves a new way for simultaneously endowing a sonosensitive coating on Ti with sonodynamic treatment‐derived high antibacterial ability and alkaline microenvironment‐mediated strong osseointegration for infectious osteoporosis treatment.