Physiological Environment Research Articles

Investigating the Effect of Thickener Concentrations on the Corrosion Behavior of Pure Mg.

Magnesium (Mg) and its alloys are promising biodegradable implant materials due to their biocompatibility and ease of corrosion in physiological environment. In the tissue, diffusion of ions and gas released by Mg corrosion reaction will be interfered by extracellular matrix and cells, which may retard the corrosion reaction. Therefore, in the present study, we developed the in vitro model tissue with different diffusion rates to understand the effect of diffusion on the Mg corrosion. A thickener called gellan gum was added to the cell culture medium at appropriate concentrations to simulate tissues with different diffusion rates. The immersion study up to 28 days and the electrochemical studies were performed to evaluate the Mg corrosion behavior. The pure Mg specimens without thickener showed the highest corrosion rate in both immersion and electrochemical tests. The highest amount of insoluble salt layer with the lowest Mg and highest O concentrations were deposited on the specimen surface without thickener. The microfocus X-ray computed tomography (μCT) analysis confirmed these findings, showing the lowest remaining volume for specimens without thickener. There is an impediment of ion diffusion in the model tissue with increased thickener concentrations, thereby decreasing the corrosion rate. The corrosion rate for 0.2-0.3 wt. % thickener matched in the range of reported in vivo results. Hence, this model proves to be an effective tool for investigating biodegradation and understanding the mechanisms and controlling factors of this phenomenon.

Decreasing the aggregation of photosensitizers to facilitate energy transfer for improved photodynamic therapy.

The mode of energy transfer between photosensitizers and oxygen determines the yield of singlet oxygen (1O2), crucial for photodynamic therapy (PDT). However, the aggregation of photosensitizers promotes electron transfer while inhibiting pure energy transfer, resulting in the generation of the hypotoxic superoxide anion (O2-) and consumption of substantial oxygen. Herein, we achieve the reduction of the aggregation of photosensitizers to inhibit electron transfer through classical chemical crosslinking, thereby boosting the production of 1O2. Specifically, we constructed a cross-linked hydrogel-like nanophotosensitizer (HA-TPP NHs) via amidation reactions between hyaluronic acid (HA) and tetrakis(4-aminophenyl)porphyrin (TATPP). In HA-TPP NHs, porphyrin is anchored at the crosslinking sites, preventing their close proximity. Simultaneously, HA-TPP NHs swell in a physiological environment due to water absorption, further increasing the distance between porphyrin molecules to avoid their aggregation. Compared to porphyrin-hyaluronic acid assembling nanoparticles (HA-TPP NPs), we find that the 1O2 generation efficiency of HA-TPP NHs is elevated by over 80%. Furthermore, leveraging the targeting capabilities of hyaluronic acid, HA-TPP NHs demonstrate a remarkable anticancer effect in in vitro and in vivo experiments. This study offers a novel insight and method for improving the therapeutic efficacy of PDT.

Nanoization of Technical Pesticides: Facile and Smart Pesticide Nanocapsules Directly Encapsulated through "On Site" Metal-Polyphenol Coordination Assembly for Improved Efficacy and Biosafety.

Facile pesticide nanocapsules were successfully prepared by directly encapsulating the antisolvent precipitation of pesticides through instantaneous "on site" coordination assembly of tannic acid and Fe3+, avoiding tedious preparation, time consumption, and large amounts of organic solvents. The pesticide nanocapsules showed excellent resistance to ultraviolet photolysis and rainwater washing owing to the nanocapsule walls. The smart pesticide nanocapsules exhibited the controlled release of pesticides under multidimensional stimuli, such as acidic/alkaline pH, glutathione, H2O2, phytic acid, laccase, tannase, and sunlight, which were related to the physiological and natural environments of crops, pests, and pathogens. The tebuconazole nanocapsules not only enhanced the fungicidal activity against Fusarium graminearum and effective control efficacy in wheat powdery mildew through foliar spray and seed coating, but also improved the biosafety of target plant growth and nontarget organisms. The facile, smart, efficient, safe, and green pesticide nanocapsules using the universal strategy have broad application prospects in ecoagriculture.

Biomimetic Air-Lifted Organ Culture System with a Protective Coverage Membrane for Full-Thickness Corneal Preservation.

Effective storage and utilization of limited donor corneal resources are in high demand to alleviate the shortage of donor corneal tissue. Here, we designed a static air-lifted organ culture system equipped with a protective coverage membrane, namely, an air-lifted OC-P system, to provide a biomimetic physiological environment for full-thickness corneal preservation. The air-lifted OC-P system features a unique collagen-based protective coverage membrane that can offer a moist, oxygen-rich environment for corneal epithelium, produce an appropriate intraocular pressure onto the cornea by gravity, and facilitate the maintenance of the organ culture medium level for nutrient supply during corneal preservation. Compared with conventional submerged and air-lifted corneal preservation methods, the air-lifted OC-P system remarkably improved the overall quality of the preserved corneas. These preserved corneas not only exhibited superior controllability of corneal swelling and extraordinary maintenance of the morphology and viability of all three types of corneal cells (i.e., corneal epithelium, keratocytes, and endothelium) but also demonstrated optimal optical, thermal, and mechanical properties. This air-lifted OC-P system presents a biomimetic strategy that provides a static and efficient method to replicate the corneal natural conditions for corneal preservation effectively.

Targeted delivery of curcumin and CM11 peptide against hepatocellular carcinoma cells based on binding affinity of PreS1-coated chitosan nanoparticles to SB3 protein

In recent years, the use of cationic peptides as alternative drugs with anticancer activity has received attention. In this study, the targeted release of curcumin (Cur) and CM11 peptide alone and together against hepatocellular carcinoma (HCC) was evaluated using chitosan nanoparticles (CS NPs) coated with Pres1 that target the SB3 antigen of HCC cells (PreS1-Cur-CM11-CS NPs). SB3 protein is the specific antigen of HCC and the PreS1 peptide is a part of the hepatitis B antigen, which can specifically bind to the SB3 protein. Chitosan was used to prepare NPs. To Cur and CM11 loading, drugs were added to the CS solution in appropriate concentrations. Pres1 was coupled to the surface of the NPs using EDC catalyst to target NPs against HepG2 cells. SEM and DLS analysis confirmed that the PreS1-Cur-CM11-CS NPs had a size of about 132 nm, the ideal size for penetrating the cell membrane. The loading of Cur and CM11 was equal to 87% and 65%, respectively, which had a sustained and better release in the acidic environment than in the physiological environment. The MTT assay showed that PreS1-Cur-CM11-CS NPs act in a targeted and specific manner with the highest toxicity on the HepG2 cells compared to the control by a decrease in viability of about 26% after 48 h based on cell apoptosis. The results showed that PreS1-Cur-CM11-CS NPs are capable of targeted and specific drug release against HepG2 cancer cells and have significant potential to fight this cancer.Graphical abstract

Characterization of Additively Manufactured Titanium-Based Alloy with a Micro-Arc Oxidation Coating and Overlying Polyurethane Layer

Titanium alloys are widely used in the aerospace, automotive, chemical, and biomedical industries due to their excellent corrosion resistance, mechanical properties, and biocompatibility. However, the surface properties of titanium alloys are often insufficient to meet the increasingly complex requirements of certain applications. Therefore, enhancing the surface performance of titanium alloys in physiological environments has become a key focus of research. In this study, a porous oxide layer was generated on the surface of a titanium substrate through micro-arc oxidation (MAO). This layer served as an intermediate layer for a subsequently deposited polyurethane (PU) coating, providing a strong foundation for adhesion. The high porosity of the MAO layer not only facilitated the adhesion of the PU coating but also protected the titanium alloy, further enhancing its corrosion resistance. The surface microstructure after MAO treatment and the morphological changes after application of the PU coating were characterized using scanning electron microscopy. The PU layer uniformly covered the surface of the MAO layer, significantly improving the smoothness and uniformity of the surface. The increase in surface smoothness due to the PU coating on top of the MAO layer was verified through white light interferometry. Additionally, surface hydrophobicity was assessed through water contact angle measurements. The PU layer over the MAO coating significantly enhanced the hydrophobicity of the titanium alloy’s surface, which is crucial for reducing biofouling and improving the effectiveness of biomedical implants. Finally, electrochemical analysis was conducted to study the corrosion resistance of the titanium alloy after MAO and PU treatment. The titanium alloy with an MAO–PU composite coating exhibited the highest corrosion resistance. The findings revealed that the combination of the MAO layer and PU coating provides an excellent multifunctional protective layer for titanium alloys, not only enhancing their durability but also their ability to adapt to physiological and harsh environments.

Current advancements on magnesium alloy coatings for bioimplants: a closer look for biocompatibility and corrosion mitigation

Abstract The healthcare industry has closely considered magnesium (Mg) alloy because of its exceptional mechanical qualities, biological solid compatibility, and biodegradable properties. Since it has reactive chemistry of natural world, magnesium alloy typically exhibits excessive rate of deterioration in the physiological environment. Thus, surface modification research has become a hotspot for obtaining different potential abilities of magnesium alloy in medical applications. The coatings of magnesium alloy surfaces are discussed in this work based on their many types: metals (metal hydroxides and oxides), inorganic/nonmetallic, and natural/synthetic polymers. The metal oxide coating is loose and porous, and it is often used together with other types of coatings to form a composite coating. The metal hydroxide coating is easily damaged by Cl− ions in corrosive medium and cannot provide long-term effective protection to substrate. Inorganic nonmetallic coatings have more space defects and greater brittleness, which used in few bone implantation procedures. Polymer materials generally have better biocompatibility and biodegradability. However, polymer coatings have a weak binding force to the substrate and limited mechanical properties. The development prospects of magnesium alloy surface coatings for biomedical applications are forecasted together with the manufacturing techniques, resistance to corrosion, and compatibility for biological systems has been discussed.

Stability Study of Anticoagulant Hydrogel Coatings Toward Long-Term Cardiovascular Devices.

Implantable cardiovascular devices have revolutionized the treatment of cardiovascular diseases, yet their long-term functionality without causing thrombosis is a persistent challenge. Although the surface modification of anticoagulant coating has greatly improved the biocompatibility of the devices, its long-term stability in complex physiological environments still remains questionable. Herein, the stability of three anticoagulant hydrogel coatings, poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC), poly(sodium 2-acryloyl-2-methylpropanesulfonate) (PAMPS), and poly(4-styrenesulfonate sodium) (PSS), is studied. The fabrication of these coatings onto device surfaces is validated by using X-ray photoelectron spectroscopy (XPS) and attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy. In vitro anticoagulation assays confirm the coatings' significant anticoagulant effects. Among all three coatings, the PSS coating demonstrated superior chemical and mechanical stability in the comprehensive tests, showing great potential for improving the long-term anticoagulant performance of implantable cardiovascular devices.

P1312 Clickable nanozyme enhances colonization of Saccharomyces boulardii by spatiotemporal guidance for ameliorating inflammatory bowel disease

Abstract Background Compelling evidence indicates that dysregulated in the gut microbiota significantly contribute to the progression and pathogenesis of inflammatory bowel disease (IBD). Probiotic therapeutic interventions aimed at modulating the microbiota offer potential alternative approaches for treating IBD, but currently available probiotics often suffer from low intestinal colonization and limited targeting capability. Methods Here, we developed azido (N3)-modified Prussian blue nanozyme (PB@N3) spatio-temporal guidance enhances the targeted colonization of probiotics to alleviate intestinal inflammation. First, IVIS and Photoacoustic imaging demonstrated clickable PB@N3 targets intestinal inflammation, simultaneously, it scavenges reactive oxygen species (ROS). Subsequently, utilizing click chemistry “N3-DBCO” to spatio-temporally guide targeted colonization of dibenzocyclooctyne (DBCO)-modified Saccharomyces boulardii (S.Br@DBCO). The therapeutic effects of PB@N3 + S.Br@DBCO were verified by using the dextran sulfate sodium (DSS)-induced colitis mice model. Weight loss, fecal conditions, colon length and histopathological changes were monitored. Results PB@N3 targets and anchors to inflamed region. The "click" reaction between PB@N3 and S.Br@DBCO has excellent specificity and efficacy both in vivo and in vitro. Despite the complex physiological environment of IBD, "click" reaction can prolong the retention time of probiotics in the intestine. Dextran sulfate sodium (DSS)-induced colitis mice model, demonstrates that the combination of PB@N3 and S.Br@DBCO effectively enhances the colonization of probiotics, restores intestinal barrier function, and alleviates intestinal inflammation. Conclusion This is the first time that “click” chemistry was employed to combine fungal probiotics and nanozyme. PB@N3 spatio-temporal guidance enhances targeted colonization of S.Br@DBCO provides a promising medical treatment strategy for IBD.

Progress in degradable polyurethane scaffolds with variable degradation rates for tissue engineering applications

AbstractGlobal catastrophic consequences associated with wars, natural disasters, and accidents are increasing day by day. Tissue engineering (TE) regenerate damaged tissues by using growth factors, cells, or three‐dimensional support biomaterials, that is, scaffolds. Scaffolds should degrade into resorbable, noncytotoxic, and excretable products in the physiological environment, along with successfully regenerating the damaged tissues. However, the requirement for scaffold degradation rate varies from patient to patient, depending on the nature, size, and cause of injuries. Thus, the synthesis and development of degradable scaffolds with focus toward variable degradation rates has become an engrossed research area. In this regard, multifunctional polymers such as polyurethane (PU) are suitable candidates. The degradation rate of PUs can be changed with the variations in the PU scaffold composition, such as the selection of the isocyanate, polyol, or the chain extender. This review will fill the research gap by analyzing the state‐of‐the‐art expansions of the degradable PU scaffolds with variable degradation rates based primarily on the selection and composition of polyol, isocyanate, and CE. It aims to guide the development of patient‐specific/customized scaffolds with appropriate scaffold degradation and tissue regeneration rates, along with the recommendations for future work.Highlights The requirement for scaffold degradation rate varies from patient to patient. There is a need to synthesize scaffolds with variable/tunable degradation rates. Multifunctional polymers such as polyurethanes (PUs) are suitable candidates. PUs degradation rate can be tuned via isocyanates, polyols and chain extenders.

Intestine-Decipher Engineered Capsules Protect Against Sepsis-induced Intestinal Injury via Broad-spectrum Anti-inflammation and Parthanatos Inhibition.

Sepsis is a severe systemic inflammatory syndrome characterized by a dysregulated immune response to infection, often leading to high mortality rates. The intestine, owing to its distinct structure and physiological environment, plays a pivotal role in the pathophysiology of sepsis. It functions as the "central organ" or "engine" in the progression of sepsis, with intestinal injury exacerbating the condition. Despite the availability of current therapies that offer partial symptom relief, they fall short of adequately protecting the intestinal barrier. In this study, an advanced nanodrug formulation (OLA@MΦ NPs) is developed by coating macrophage membranes onto polymeric organic nanoparticles encapsulating olaparib. When loaded into pH-responsive capsules, an intestine-decipher engineered capsule (cp-OLA@MΦ NPs) is successfully formulated. Upon oral administration in septic mice, these capsules withstand gastric acid and release their contents in the intestine, specifically targeting injured tissues. The released OLA@MΦ NPs effectively neutralize pro-inflammatory cytokines via macrophage membrane receptors, while olaparib inhibits intestinal epithelial parthanatos (a form of programmed cell death) by suppressing poly(ADP-ribose) polymerase 1 (PARP1) activation. This strategy significantly reduces bacterial translocation, slows the progression of sepsis, and enhances survival in septic mice, thus presenting a promising therapeutic approach for sepsis in clinical applications.

Macrocyclic Peptide-Based Dual-Sensor Platform for Linkage-Specific Visualization of Ubiquitin Chain Assembling in Live Cells.

Intracellular monitoring of protein ubiquitination and differentiating polyubiquitin chain topology are crucial for understanding life processes and drug discovery, which is challenged by the high complexity of the ubiquitination process and a lack of molecular tools. Herein, a synthetic dual-sensor platform specific for K48-linked ubiquitin oligomers was tailored for in situ visualization of polyubiquitin chain assembling in live biosystems. This is achieved using macrocyclic peptides as recognition motifs and a tetraphenylethylene derivative as an activatable reporter. The efficient cell penetration, tight binding, and protection of polyubiquitin delivered a "freeze-and-image" approach, allowing fluorescent readout of polyubiquitin linkage type and chain elongation without perturbing the physiological environment. Motivated by these unique features, mapping of K48-ubiquitination dynamics during protein degradation was facilely achieved. Rapid, sensitive, and intracellular assessment of the mechanism of action and potency dependence for proteolysis-targeting chimeras (PROTACs) was demonstrated, presenting the sensors as promising molecular tools for PROTAC drug development.

Biofabricated tissue model for determining biocompatibility of metallic coatings.

Metallic biomaterials are extensively used in orthopedics and dentistry, either as implants or coatings. In both cases, metal ions come into contact with surrounding tissues causing a particular cell response. Here, we present a biofabricated in vitro tissue model, consisting of a hydrogel reinforced with a melt electrowritten mesh, to study the effects of bound and released metal ions on surrounding cells embedded in a hydrogel matrix. We evaluate the biocompatibility, bioactivity, and antibacterial properties of these metal coatings. Our approach involves integrating physical vapour deposition coating technology with 3D bioprinting methods. To produce tissue models, melt electrowritten (MEW) meshes composed of polycaprolactone (PCL) were printed and integrated into cell-laden methacrylated galatin (GelMa). The mouse embryonic fibroblast cell line (NIH3T3) was used. GelMa concentration and printing parameters for MEW were adjusted and mechanical analysis of the models was performed to find the optimal material composition. Optimized models were placed on the glass slide surfaces coated with typically non-toxic metals, i.e. titanium (Ti), tantalum (Ta), zirconium (Zr), silver (Ag), tungsten (W), and niobium (Nb). Except for W, all other coatings were stable in a physiological wet environment, as studied by SEM. The viability of the cells at different distances from the coated surface was analyzed. Antibacterial tests against pathogens Staphylococcus aureus and Escherichia coli were used to assess the models' resistance, important for infection control. While Ag coatings showed toxicity, Nb, Ta, Ti, and Zr coatings promoted fibroblast growth, with the highest cell viability after 14 days of culture revealed for Ta and Nb. The strongest antimicrobial effect against E. coli and S. aureus was observed for Ag and W, while Ta exhibited antibacterial activity only against S. aureus. From a broader perspective, our work offers an effective 3D in vitro model for an in-depth characterization of the biocompatibility of metals and metal coatings.

N-acetylcysteine and chitosan conjugate modified dexamethasone nanostructured lipid carriers: Enhanced permeability, precorneal retention and lower inflammation for the treatment of dry eye syndrome.

Dexamethasone (Dex) is a primary medication for treating dry eye syndrome, and tobramycin-dexamethasone eye drops are commercially available. However, the eye's complex physiological environment reduces its bioavailability, and repeated use can lead to significant systemic toxicity and side effects. This study introduces a novel conjugate of chitosan (CS) and N-acetylcysteine (NAC), a bioadhesive material, which was grafted onto the surface of a Dex-supported nanostructured lipid carrier (NLC) to develop an innovative nanoparticle lipid ocular drug delivery system (CS-NAC@Dex-NLC). The enhancements afforded by CS-NAC, such as adhesion, osmotic, and targeting properties, address the limitations of traditional eye drops. NMR characterization confirmed the successful synthesis of the copolymer (CS-NAC). Particle size (PS), zeta potential, and transmission electron microscopy (TEM) verified the proper formation of the CS-NAC@Dex-NLC system. Cytotoxicity tests confirmed its excellent biocompatibility and safety. Cellular uptake studies showed that CS-NAC@Dex-NLC achieved the highest efficiency. Pharmacokinetic assessments revealed a significant increase in Dex's bioavailability in tears and aqueous humor. In vitro corneal penetration and in vivo imaging experiments demonstrated effective corneal penetration and retention, enhancing the drug's duration on the ocular surface and overcoming the barrier effect. Pharmacodynamic studies in rabbits with dry eye syndrome indicated that CS-NAC@Dex-NLC effectively alleviates symptoms, repairs corneal damage, and stabilizes the tear film. ELISA results showed a reduction in inflammation caused by dry eye. These findings suggest that CS-NAC@Dex-NLC is a promising vector for dry eye treatment, offering significant clinical relevance.

Single-atom nanozymes with intelligent response to pathological microenvironments for bacterially infected wound healing.

Wound healing is a complex and dynamic process often accompanied by bacterial infection, inflammation, and excessive oxidative stress. Single-atom nanozymes with multi-enzymatic activities show significant potential for promoting the healing of infected wounds by modulating their antibacterial and anti-inflammatory properties in response to the wound's physiological environment. In this study, we synthesized MN4 single-atom nanozymes with multi-enzymatic activities that intelligently respond to pH value changes in the wound healing process. In vitro experiments confirm their effectiveness against Gram-negative bacteria, attributed to elevated reactive oxygen species (ROS) accumulation within the bacterial cells. Moreover, a full-thickness skin wound-infected model demonstrates that MN4 single-atom nanozymes accelerate wound repair and skin regeneration by suppressing the expression of tumor necrosis factor-alpha (TNF-α), promoting angiogenesis, and enhancing collagen deposition. In vivo biocompatibility experiments further demonstrate the favorable biocompatibility of these nanozymes, highlighting their potential for clinical applications in infected wound healing. These nanozymes respond intelligently to different microenvironments and may be suitable for addressing further complex and variable diseases.

Tumor microenvironment triggered iron-based metal organic frameworks for magnetic resonance imaging and photodynamic-enhanced ferroptosis therapy.

Photodynamic therapy (PDT) primarily relies on the generation of reactive oxygen species (ROS) to eliminate tumor cells. However, the elevated levels of glutathione (GSH) within tumor cells can limit the efficacy of PDT, posing a challenge to achieve complete tumor eradication. Herein, a porous iron-based metal-organic frameworks (PEG-Fe-MOFs) nanoplatform was developed for the combined application of PDT and ferroptosis in cancer treatment. The coordination between tetrakis (4-carboxyphenyl) porphyrin (TCPP) and ferric (Fe3+) enabled PEG-modified Fe-MOFs (PEG-Fe-MOFs) to deliver excellent T1-weighted magnetic resonance (MR) imaging performance in physiological environments. Within the tumor microenvironment (TME), PEG-Fe-MOFs gradually degraded to release TCPP, which could be utilized for fluorescence imaging. Moreover, Fe2+ enhanced intracellular ROS levels via the Fenton reaction, generating hydroxyl radicals that further amplified ROS production. This synergistic effect comprising increased ROS levels and GSH depletion augmented the efficacy of PDT while simultaneously inducing robust ferroptosis in tumor cells, thereby maximizing therapeutic outcomes. Both in vitro and in vivo experiments have demonstrated the superior T1 weighted MR and fluorescence imaging capabilities of PEG-Fe-MOFs, along with its potent synergistic therapeutic effects on tumors. These results highlighted the potential of this nanoplatform for combining PDT and ferroptosis in cancer treatment.

An Endothelium‐Mimicking, Healable Hydrogel Shield for Bioprosthetic Heart Valve with Enhanced Intravascular Biocompatibility

AbstractBioprosthetic heart valves (BHVs) for transcatheter replacement often face deterioration due to thrombosis, inflammation, and calcification, which are irreversible. Here, a multidimensional endothelium‐mimicking healable hydrogel shielded BHV that not only withstand the complex valvular physiological and hemodynamic environment but also able to reverse damage‐induced structural degeneration by in situ healing is proposed. Polydopamine/selenocystamine nanoparticles with photothermal effect are embedded to achieve light‐triggered healing and catalytic nitride oxide generation in polyvinyl alcohol hydrogel coating on BHV surface. Additionally, platelet inhibitor Tirofiban is encapsulated in the hydrogel shield to block acute coagulation cascade in early stage after implantation. A rodent intravascular leaflet‐like implantation model is developed to reveal the long‐term hemocompatibility of BHVs in abdominal aorta. The shielded BHVs exhibit enhanced antithrombotic properties, reduced inflammation, superior endothelialization, and improved vascular patency. Transcriptome analysis indicates better endothelial functions on shielded BHVs. Moreover, the endothelium‐mimicking hydrogel shield maintains both mechanical properties and biological functions after healing, facilitated great hemocompatibility and fast re‐endothelialization. Collectively, the multidimensional endothelium‐mimicking strategy provides new insight for preventing and reversing BHV damage instead of solely replacement.

Leveraging Metal Complexes for Microsecond Lifetime-Based Chloride Sensing.

Chloride is the most abundant anion in cells and plays many critical roles in maintaining cellular homeostasis. However, current chloride indicators are rare with inherent sensitivity in their emission properties, such as vulnerability to pH changes or short emission lifetimes. These limitations restrict their application in aqueous media and imaging. In this work, we employed a transition-metal complex bearing pyridinium as a recognition unit for chloride and studied the phosphorescence emission properties. Iridium(III) complex 1 was synthesized as an alternative chloride-sensitive luminophore. The conjugable design also allows customization for the desired applications. Complex 1 exhibited high sensitivity and selectivity in chloride sensing across different physiological environments, regardless of pH fluctuation and ionic strength. Additionally, complex 1 featured a microsecond emission lifetime. The chloride sensing ability of complex 1 can be measured through both the luminescence intensity and long-lived phosphorescent lifetime, providing an alternative potential route for chloride imaging. The analogue 1b was successfully applied in the imaging of Cl- in cellular environments and showed dose-dependent responses in both live and fixed cells.

A review of 3D bioprinting for organoids

Abstract Current two-dimensional (2D) cell models for effective drug screening suffer from significant limitations imposed by the lack of realism in the physiological environment. Three-dimensional (3D) organoids models hold immense potential in mimicking the key functions of human organs by overcoming the limitations of traditional 2D cell models. However, current techniques for preparation of 3D organoids models had limitations in reproducibility, scalability, and the ability to closely replicate the complex microenvironment found in vivo. Additionally, traditional 3D cell culture systems often involve lengthy and labor-intensive processes that hinder high-throughput applications necessary for a large-scale drug screening. Advancements in 3D bioprinting technologies offer promising solutions to these challenges by enabling precise spatial control over cell placement and material composition, thereby facilitating the creation of more physiologically relevant organoids than current techniques. This review provides a comprehensive summary of recent advances in 3D bioprinting technologies for creating organoids models, which begins with an introduction to different types of 3D bioprinting techniques (especially focus on volumetric bioprinting (VBP) technique), followed by an overview of bioinks utilized for organoids bioprinting. Moreover, we also introduce the applications of 3D bioprinting organoids in disease models, drug efficiency evaluation and regenerative medicine. Finally, the challenges and possible strategies for the development and clinical translation of 3D bioprinting organoids are concluded.

Synthesis and Evaluation of Cytotoxic Activity of RuCp(II) Complexes Bearing (Iso)nicotinic Acid Based Ligands.

Cancer remains one of the major challenges of our century. Organometallic ruthenium complexes are gaining recognition as a highly promising group of compounds in the development of cancer treatments. Building on the auspicious results obtained for [Ru(η5-C5H5)(PPh3)(bipy)][CF3SO3] (TM34), our focus has shifted to examining the effects of incorporating bioactive ligands into the TM34 framework, particularly within the cyclopentadienyl ring. In this study, we report the synthesis and characterization of two new ruthenium(II) complexes with the general formula [Ru(η5-C5H4CCH3=R)(PPh3)(bipy)][CF3SO3], where R represents a nicotinic acid derivative (NNHCO(py-3-yl)) (1) or an isoniazid derivative (NNHCO(py-4-yl)) (2). The complexes were fully characterized using a combination of spectroscopic techniques and computational analysis, revealing the presence of E/Z-hydrazone isomerism. Stability studies confirmed the robustness of both complexes in biological media, with compound 1 maintaining good stability in buffer solutions mimicking physiological (pH 7.4) and tumor-like (pH 6.8) environments. The cytotoxicity of the complexes was evaluated in vitro in several human cancer cell lines, namely melanoma (A375), alveolar adenocarcinoma (A549), epidermoid carcinoma (A431), and breast cancer (MDA-MB 231). Both compounds exhibited moderate to high cytotoxic activity, with complex 1 showing a greater propensity to induce cell death, particularly in the A431 and MDA-MB 231 cell lines.