ACS Applied Bio Materials最新文献

Polyphenols, natural compounds abundant in phenolic structures, have received widespread attention due to their antioxidant, anti-inflammatory, antibacterial, and anticancer properties, making them valuable for biomedical applications. However, the green synthesis of polyphenol-based materials with economical and environmentally friendly strategies is of great significance. In this study, a multifunctional wound dressing was achieved by introducing polyphenol-based materials of copper phosphate-tannic acid with a flower-like structure (Cu-TA NFs), which show the reactive oxygen species scavenging performance. This strategy endowed the electrospun wound dressing, composed of poly(caprolactone)-coated gum arabic-poly(vinyl alcohol) nanofibers (GPP), with the antibacterial and antibiofilm properties. Our research demonstrates that GPP/Cu-TA NFs are effective against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. Furthermore, the developed GPP/Cu-TA NFs showed excellent hemocompatibility and biocompatibility. These results suggest that the synergistic properties of this multifunctional polyphenol platform (GPP/Cu-TA NFs) make it a promising candidate for the further development of wound dressing materials.

Pain and inflammation are common symptoms of a majority of the diseases. Chronic pain and inflammation, as well as related dreadful disorders, remain difficult to control due to a lack of safe and effective medications. In this work, biocompatible platinum nanoparticles with significant analgesic and anti-inflammatory action were synthesized through a wet chemical method using polyethylene glycol-400 as a capping agent and sodium borohydride as a reducing agent. The average particle size of these Pt nanospheres was determined to be 3.26 nm using TEM analysis, and X-ray diffraction confirmed their face-centered cubic crystalline structure. Fourier transform infrared and UV-visible spectroscopy confirm that Pt-NPs are coated with the PEG-400 molecule. The significantly negative zeta potential value (-26.8 mV) indicates the stability of the produced nanoparticles. In vitro cytotoxicity studies on normal cell lines show nontoxic behavior with over 96% cell viability at 100 μg/mL of the test sample. In vitro assays of inhibition of protein denaturation and DPPH free radical scavenging elucidated the anti-inflammatory and antioxidant properties of PEGylated Pt NPs with promising EC₅₀ values 57.99 and 9.324 μg/mL, respectively. In vivo animal trials confirmed that PEG-capped Pt-NPs are more effective than conventional medicines. The in vivo hot plate assay for the analgesic study shows a maximum response time of 14.5 ± 1.22 s (92.54% analgesia) at a dosage of 50 mg/kg and 13.8 ± 0.71 s (86.05% analgesia) at a dosage of 25 mg/kg after 180 and 240 min of administration, respectively. In the rat paw edema model for anti-inflammatory activity, the PEG-capped Pt NPs exhibit significant inhibitory action, with the maximum percentage of edema inhibition at a dosage of 50 mg/kg identical to that of the aspirin-based standard medication administered at a higher dosage of 100 mg/kg, resulting in 42% inhibition, suggesting a versatile solution for inflammation and persistent pain.

Bone is a dynamic tissue that serves several purposes in the human body, including storing calcium, forming blood cells, and protecting and supporting the body's organs. Alkaline phosphatase (ALP) is secreted into the circulation by osteoblasts, the cells responsible for making bone. It attaches to the surface of osteoblast cells or matrix vesicles. Accordingly, ALP is present in serum and is a popular biomarker for the evaluation of bone disease and other disorders in clinical evaluations. In this study, a composite probe made of bioactive glass (BG) and multiwalled carbon nanotubes (MWCNT) was used to detect ALP through electrochemical impedance spectroscopy (EIS) without the need for labels. By combination of physical methods with electrochemical analysis, the biosensor probe was characterized. The analytical performance of the biosensor was evaluated using EIS, and the results revealed that it has a limit of detection (LOD) of 2.29 ± 0.35 U/L and a linear dynamic range (LDR) of 25-600 U/L; both of which are within the acceptable range for ALP detection in clinics. When tested against serum interfering chemicals, the biosensor probe that was designed shows a strong selectivity for ALP (K_sel < 0.06). In addition, human serum and fetal bovine serum were used to test the system's ability to detect ALP in biological samples.

Using a laser-scribed (direct printing) technique, we have fabricated an enzymeless, mediatorless, and paper-interfaced electrochemical device (P-LSG) for uric acid detection on a flexible polyimide sheet. Various paper substrates were investigated, and it was found that Whatman filter paper-1 is promising to obtain the best electrochemical signals at the small volume of electrolyte, i.e., 20 μL. Furthermore, the Whatman filter paper-1 was modified with gold nanoparticles (AuNPs) to improve the electrocatalytic activity of the P-LSG device. The fabricated AuNP-modified P-LSG biosensor exhibited excellent electrocatalytic activity for the detection of uric acid over a wide range of 10 to 750 μM, with sensitivity of ∼0.214 μA μM^-1 cm^-2, and a limit of detection of ∼1.4 μM. The sensor was further validated by using the UHPLC-ESI-MS/MS technique, and the observed percentage recovery was less than 10%. This work opens the window to modified paper substrates with various nanomaterials to improve the sensing parameters. The electrolyte storage capacity and rich chemistry of paper additionally provide an efficient immobilization platform for biorecognition elements to diagnose other metabolites. Furthermore, it has the potential to analyze the volume of small samples (like sweat, tears, urine, etc.) using paper to develop noninvasive wearable biosensors.

Tuberculosis (TB) triggers a robust immune response, which leads to significant destruction of the lung tissue at the site of infection, aiding in the transmission of Mycobacterium tuberculosis (Mtb) to the hosts. The excessive inflammatory response contributes heavily to extracellular matrix (ECM) damage, which is linked to high mortality rates among TB patients. Matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, are pivotal in the breakdown of the ECM, worsening tissue destruction. In the context of host-directed therapy (HDT), a strategy aimed at modulating the immune response rather than directly targeting the pathogen, we evaluated the potential of lovastatin (LOV). LOV has shown promise in reducing MMP activity and inflammation, which could alleviate the immune-mediated pathology in TB. However, its clinical use has been limited due to poor solubility and biocompatibility, reducing its therapeutic efficacy. To overcome these limitations, we designed inhalable gelatin microspheres (GA-MS) loaded with LOV using the spray-drying technology. This approach improved the solubility and allowed for the controlled release of the drug. The resulting LOV-loaded gelatin microspheres (LOV/GA-MS) had an optimal particle size of 2.395 ± 0.67 μm, facilitating macrophage uptake due to their aerodynamic properties. In in vitro studies using Mtb-infected macrophages, LOV/GA-MS effectively suppressed MMP expression and reduced levels of pro-inflammatory cytokines at a concentration of 20 μg/mL, demonstrating substantial anti-inflammatory potential. Moreover, these microspheres showed a synergistic effect when combined with standard anti-TB drugs, enhancing the overall therapeutic efficacy in in vitro experiments. The findings suggest that inhalable LOV/GA-MS microspheres represent a promising adjunctive host-directed therapy for TB. By modulating the host's immune response and targeting key inflammatory mediators such as MMPs, this approach could mitigate lung tissue damage, improve clinical outcomes, and provide a more holistic treatment option for TB.

A series of tripodal (three-arm) lysine-based peptides were designed and synthesized and their self-assembly properties in aqueous solution and antimicrobial activity were investigated. We compare the behaviors of homochiral tripodal peptides (KKY)₃K and a homologue containing the bulky aromatic fluorenylmethoxycarbonyl (Fmoc) group Fmoc-(KKY)₃K, and heterochiral analogues containing k (d-Lys), (kkY)₃K and Fmoc-(kkY)₃K. The molecular conformation and self-assembly in aqueous solutions were probed using various spectroscopic techniques, along with small-angle X-ray scattering (SAXS) and cryogenic-transmission electron microscopy (cryo-TEM). In cell viability assays using fibroblast cell lines, the tripodal peptides without Fmoc were observed to be noncytotoxic over the concentration range studied, and the Fmoc functionalized tripodal peptides were only cytotoxic at the highest concentrations (above the critical aggregation concentration of the lipopeptides). The molecules also show good hemocompatibility at sufficiently low concentration, and antimicrobial activity was assessed via MIC (minimum inhibitory concentration) and MBC (minimum bactericidal concentration) assays. These revealed that the Fmoc-functionalized tripodal peptides had significant activity against both Gram-negative and Gram-positive bacteria, and in the case of Gram-positive Staphylococcus aureus, the antimicrobial activity for Fmoc-(kkY)₃K was improved compared to polymyxin B. The mechanism of the antimicrobial assay was found to involve rupture of the bacterial membrane as evident from fluorescence microscopy live/dead cell assays, and scanning electron microscopy images.

Moth-eye nanostructures, known for their biological antireflective properties, are formed by a self-assembly mechanism. Understanding and replicating this mechanism on artificial surfaces open avenues for the engineering of bioinspired multifunctional nanomaterials. Analysis of corneal nanocoatings from butterflies of the genus Papilio reveals a variety of nanostructures with uniformly strong antiwetting properties accompanied by varying antireflective functionalities. Interestingly, while the structural features of the nanocoatings determine the antireflective functionality, the antiwetting is controlled by their chemical composition, an unusual trait among insects. The availability of whole-genome sequences for several Papilio species allowed us to identify the corneal proteome, including the protein responsible for the nanocoating assembly, CPR67A. The high hydrophobicity of this protein, coupled with its capacity to mediate self-assembly, underlies the formation of unique multifunctional Papilio nanostructures and permits the development of bioinspired artificial nanocoatings. Our findings pave the way for biomimetic nanomaterials and guide the engineering of nanostructures with predefined functionalities.

The present study aims to formulate a stimuli-responsive in situ hydrogel system to codeliver acacia honey and glycyrrhizic acid for topical application that will aid in absorbing wound exudates, control microbial infestation, and produce angiogenic and antioxidant effects to accelerate wound healing. Therefore, both the natural active constituents were incorporated within an in situ hydrogel composed of poloxamer and hydroxypropyl methylcellulose (HPMC), where the concentrations of the polymers were optimized using Design-Expert software considering optimum values of the dependent variables, gelation temperature (34-37 °C), gelation time (<10 min), and the viscosity (2000-3500 cPs). The optimized formulation showed improved physicochemical properties such as mucoadhesiveness, porosity, swelling, and spreadability, which makes it suitable for wound application. Additionally, the in situ hydrogel exhibited potent in vitro and ex vivo antioxidant effects, in vitro antimicrobial activities, and ex ovo angiogenic effects. Furthermore, the optimized formulation was found to be nontoxic while tested in the HaCaT cell line and acute dermal irritation and corrosion study. The findings of the in vivo wound-healing studies in experimental animal models showed complete wound closure within 15 days of treatment and accelerated development of the extracellular matrix. In addition, the antioxidant, antimicrobial, angiogenic, and wound-healing properties of acacia honey and glycyrrhizic acid coloaded in situ hydrogel were also found to be promising when compared to the standard treatments. Overall, it can be concluded that the optimized stimuli-responsive in situ hydrogel containing two natural compounds could be an alternative to existing topical formulations for acute wounds.

Transarterial embolization (TAE) is an image-guided, minimally invasive procedure for treating various clinical conditions by delivering embolic agents to occlude diseased arteries. Conventional embolic agents focus on vessel occlusion but can cause unintended long-term inflammation and ischemia in healthy tissues. Next-generation embolic agents must exhibit biocompatibility, biodegradability, and effective drug delivery, yet some degradable microspheres degrade too quickly, leading to the potential migration of fragments into distal blood vessels causing off-target embolization. This study presents the development of whey protein hydrogel microspheres (WPHMS) made from methacrylated whey protein, which successfully withstood terminal sterilization by autoclaving. In vitro characterization revealed that sterile WPHMS are suspensible in iodine-containing contrast agents, injectable through standard catheters and microcatheters, and can be temporarily compressed by at least 12.8% without permanent deformation. Cytocompatibility was confirmed using NIH/3T3 cells, while enzymatic degradation was assessed with proteinase K. Preliminary drug loading and release studies demonstrated the potential for doxorubicin hydrochloride (Dox-HCl) as a model drug. In vivo assessments in rabbit renal models showed that WPHMS successfully occluded the renal arteries in the acute study and remained in the renal arteries for up to 3 weeks in the chronic study, with signs of early degradation. Fibrous tissue anchored the degraded residues, minimizing the risk of migration. These findings indicate that WPHMS holds significant promise as endovascular embolization agents for minimally invasive therapies.

Dye-contaminated wastewater poses serious environmental risks to ecosystems and human health. Diatoms, algae with nanoporous frustules (cell walls), offer promising potential for wastewater remediation due to their high surface area and adsorption properties. While dead diatom biomass is well-studied for biosorption, research on living diatoms' bioaccumulation and biotransformation potential is limited, with gaps in kinetic and equilibrium modeling of dye adsorption. Here, we analyzed the adsorption of crystal violet (CV) dye onto living Phaeodactylum tricornutum (P-cell) and Navicula cryptocephala var. veneta (N-cell) diatoms by characterizing the physiochemical properties of the species' outer surfaces and monitoring the adsorption of CV using surface-specific second harmonic scattering (SHS) spectroscopy. Direct monitoring of dye adsorption, rather than its removal from the solution, enables a more accurate investigation of adsorption kinetics and thermodynamics, revealing strong correlations with the cell surface structure and composition. We found that the N-cell has a greater adsorption capacity for CV than the P-cell, though with slightly less favorable adsorption free energy. Ionic strength could impact uptake capacities, likely due to competition between metal cations and the dye cation as well as surface screening. SHS experiments revealed a simple adsorption process for N-cells, while P-cells exhibited a multistep process involving CV transport through thinner, nonporous cell walls to the plasmic membrane, contributing to favorable adsorption free energy. The thicker, porous walls of N-cells provided more surface sites, increasing the capacity, while P-cells facilitated deeper uptake. Ionic strength had only a significant effect on adsorption capacity, not adsorption free energy, reflecting the intricacies that govern adsorption and uptake by living organisms. The comprehensive analysis presented herein demonstrates great potential for diatoms to be used as biosorbents in dye remediation and provides systematic relationships between the structure and function of diatom cell walls, which will inform the use of tailored species for more efficient remediation.