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International Journal of Biological... May 2024Alginate-based dressings have been shown to promote wound healing, leveraging the unique properties of alginate. This work aimed to develop and characterize flexible...
Alginate-based dressings have been shown to promote wound healing, leveraging the unique properties of alginate. This work aimed to develop and characterize flexible individual and bilayered films to deliver bacteriophages (phages) and ε-Poly-l-lysine (ε-PLL). Films varied in different properties. The moisture content, swelling and solubility increased with higher alginate concentrations. The water vapour permeability, crucial in biomedical films to balance moisture levels for effective wound healing, reached optimal levels in bilayer films, indicating these will be able to sustain an ideal moist environment. The bilayer films showed improved ductility (lower tensile strength and increased elongation at break) compared to individual films. The incorporated phages maintained viability for 12 weeks under vacuum and refrigerated conditions, and their release was sustained and gradual. Antibacterial immersion tests showed that films with phages and ε-PLL significantly inhibited Pseudomonas aeruginosa PAO1 growth (>3.1 Log CFU/cm). Particle release was influenced by the swelling degree and diffusional processes within the polymer network, providing insights into controlled release mechanisms for particles of varying size (50 nm to 6 μm) and charge. The films developed, demonstrated modulated release capabilities for active agents, and may show potential as controlled delivery systems for phages and wound healing adjuvants.
Topics: Polylysine; Pseudomonas aeruginosa; Bacteriophages; Wound Healing; Anti-Bacterial Agents; Alginates; Bandages; Steam; Permeability; Anti-Infective Agents
PubMed: 38688343
DOI: 10.1016/j.ijbiomac.2024.131963 -
Small (Weinheim An Der Bergstrasse,... Apr 2024Chronic wounds constitute an increasingly prevalent global healthcare issue, characterized by recurring bacterial infections, pronounced oxidative stress, compromised...
Chronic wounds constitute an increasingly prevalent global healthcare issue, characterized by recurring bacterial infections, pronounced oxidative stress, compromised functionality of immune cells, unrelenting inflammatory reactions, and deficits in angiogenesis. In response to these multifaceted challenges, the study introduced a stimulus-responsive glycopeptide hydrogel constructed by oxidized Bletilla striata polysaccharide (OBSP), gallic acid-grafted ε-Polylysine (PLY-GA), and paeoniflorin-loaded micelles (MIC@Pae), called OBPG&MP. The hydrogel emulates the structure of glycoprotein fibers of the extracellular matrix (ECM), exhibiting exceptional injectability, self-healing, and biocompatibility. It adapts responsively to the inflammatory microenvironment of chronic wounds, sequentially releasing therapeutic agents to eradicate bacterial infection, neutralize reactive oxygen species (ROS), modulate macrophage polarization, suppress inflammation, and encourage vascular regeneration and ECM remodeling, playing a critical role across the inflammatory, proliferative, and remodeling phases of wound healing. Both in vitro and in vivo studies confirmed the efficacy of OBPG&MP hydrogel in regulating the wound microenvironment and enhancing the regeneration and remodeling of chronic wound skin tissue. This research supports the vast potential for herb-derived multifunctional hydrogels in tissue engineering and regenerative medicine.
PubMed: 38686688
DOI: 10.1002/smll.202400516 -
Biomolecules Apr 2024In cancer therapy, photodynamic therapy (PDT) has attracted significant attention due to its high potential for tumor-selective treatment. However, PDT agents often...
In cancer therapy, photodynamic therapy (PDT) has attracted significant attention due to its high potential for tumor-selective treatment. However, PDT agents often exhibit poor physicochemical properties, including solubility, necessitating the development of nanoformulations. In this study, we developed two cationic peptide-based self-assembled nanomaterials by using a PDT agent, chlorin e6 (Ce6). To manufacture biocompatible nanoparticles based on peptides, we used the cationic poly-L-lysine peptide, which is rich in primary amines. We prepared low- and high-molecular-weight poly-L-lysine, and then evaluated the formation and performance of nanoparticles after chemical conjugation with Ce6. The results showed that both molecules formed self-assembled nanoparticles by themselves in saline. Interestingly, the high-molecular-weight poly-L-lysine and Ce6 conjugates (HPLCe6) exhibited better self-assembly and PDT performance than low-molecular-weight poly-L-lysine and Ce6 conjugates (LPLCe6). Moreover, the HPLCe6 conjugates showed superior cellular uptake and exhibited stronger cytotoxicity in cell toxicity experiments. Therefore, it is functionally beneficial to use high-molecular-weight poly-L-lysine in the manufacturing of poly-L-lysine-based self-assembling biocompatible PDT nanoconjugates.
Topics: Polylysine; Chlorophyllides; Porphyrins; Humans; Photochemotherapy; Nanoparticles; Photosensitizing Agents; Molecular Weight; Cell Survival
PubMed: 38672448
DOI: 10.3390/biom14040431 -
Nature Communications Apr 2024Biomolecular condensates play an important role in cellular organization. Coacervates are commonly used models that mimic the physicochemical properties of biomolecular...
Biomolecular condensates play an important role in cellular organization. Coacervates are commonly used models that mimic the physicochemical properties of biomolecular condensates. The surface of condensates plays a key role in governing molecular exchange between condensates, accumulation of species at the interface, and the stability of condensates against coalescence. However, most important surface properties, including the surface charge and zeta potential, remain poorly characterized and understood. The zeta potential of coacervates is often measured using laser doppler electrophoresis, which assumes a size-independent electrophoretic mobility. Here, we show that this assumption is incorrect for liquid-like condensates and present an alternative method to study the electrophoretic mobility of coacervates and in vitro condensate models by microelectrophoresis and single-particle tracking. Coacervates have a size-dependent electrophoretic mobility, originating from their fluid nature, from which a well-defined zeta potential is calculated. Interestingly, microelectrophoresis measurements reveal that polylysine chains are enriched at the surface of polylysine/polyaspartic acid complex coacervates, which causes the negatively charged protein ɑ-synuclein to adsorb and accumulate at the interface. Addition of ATP inverts the surface charge, displaces ɑ-synuclein from the surface and may help to suppress its interface-catalyzed aggregation. Together, these findings show how condensate surface charge can be measured and altered, making this microelectrophoresis platform combined with automated single-particle tracking a promising characterization technique for both biomolecular condensates and coacervate protocells.
Topics: Electrophoresis; Surface Properties; Biomolecular Condensates; alpha-Synuclein; Polylysine; Adenosine Triphosphate; Humans; Static Electricity
PubMed: 38670952
DOI: 10.1038/s41467-024-47885-2 -
Carbohydrate Polymers Jul 2024Skin wounds are susceptible to infection, leading to severe inflammatory reactions that can progress to chronic wounds, ultimately causing significant physical and...
Skin wounds are susceptible to infection, leading to severe inflammatory reactions that can progress to chronic wounds, ultimately causing significant physical and mental distress to the patient. In this study, we propose an injectable composite hydrogel achieved through one-pot gelation of oxidized xyloglucan (OXG), cationic polyamide ε-poly-l-lysine (EPL), and surface amino-rich silicon nanoparticles (SiNPs). OXG exhibits commendable anti-inflammatory properties and provides crosslinking sites. SiNPs serve as mechanically reinforced crosslinkers, facilitating the construction of a dynamic Schiff base network. SiNPs significantly reduced the gelation time to 3 s and tripled the storage modulus of the hydrogels. Additionally, the combination of EPL and SiNPs demonstrated synergistic antimicrobial activity against both S. aureus and E. coli. Notably, the hydrogel effectively halted liver bleeding within 30 s. The hydrogel demonstrated outstanding shear-thinning and self-healing properties, crucial considerations for the design of injectable hydrogels. Furthermore, its efficacy was evaluated as a wound dressing in a mouse model with S. aureus infection. The results indicated that, compared to commercial products, the hydrogel exhibited a shorter wound healing time, decreased inflammation, thinner epithelium, increased hair follicles, enhanced neovascularization, and more substantial collagen deposition. These findings strongly suggest the promising potential of the proposed hydrogel as an effective wound dressing for the treatment of infected wounds.
Topics: Glucans; Animals; Wound Healing; Xylans; Hydrogels; Polylysine; Mice; Nanoparticles; Escherichia coli; Staphylococcus aureus; Anti-Bacterial Agents; Staphylococcal Infections; Cross-Linking Reagents; Wound Infection; Male
PubMed: 38670773
DOI: 10.1016/j.carbpol.2024.122102 -
Journal of Colloid and Interface Science Aug 2024A key challenge to enhance the therapeutic outcome of photothermal therapy (PTT) is to improve the efficiency of passive targeted accumulation of photothermal agents at...
A key challenge to enhance the therapeutic outcome of photothermal therapy (PTT) is to improve the efficiency of passive targeted accumulation of photothermal agents at tumor sites. Carbon dots (CDs) are an ideal choice for application as photothermal agents because of their advantages such as adjustable fluorescence, high photothermal conversion efficiency, and excellent biocompatibility. Here, we synthesized polylysine-modified near-infrared (NIR)-emitting CDs assemblies (plys-CDs) through post-solvothermal reaction of NIR-emitting CDs with polylysine. The encapsulated structure of plys-CDs was confirmed by determining morphological, chemical, and luminescent properties. The particle size of CDs increased to approximately 40 ± 8 nm after polylysine modification and was within the size range appropriate for achieving superior enhanced permeability and retention effect. Plys-CDs maintained a high photothermal conversion efficiency of 54.9 %, coupled with increased tumor site accumulation, leading to a high efficacy in tumor PTT. Thus, plys-CDs have a great potential for application in photothermal ablation therapy of tumors.
Topics: Polylysine; Carbon; Photothermal Therapy; Animals; Quantum Dots; Mice; Infrared Rays; Particle Size; Humans; Mice, Inbred BALB C; Surface Properties; Female; Cell Survival; Neoplasms
PubMed: 38669991
DOI: 10.1016/j.jcis.2024.04.153 -
Analytical Methods : Advancing Methods... May 2024The presence of lead ions (Pb) in the environment not only leads to environmental contamination but also poses a significant risk to public health through their...
The presence of lead ions (Pb) in the environment not only leads to environmental contamination but also poses a significant risk to public health through their migration into food and drinking water. Therefore, the development of rapid and effective techniques for detection of trace amounts of Pb is crucial for safeguarding both the environment and biosafety. In this study, an aptamer-based electrochemical sensor was developed for specific detection of Pb by modifying a polylysine (PLL) coated silver-thiolated graphene (Ag-SH-G) nanocomposite (PLL/Ag-SH-G) on the surface of a glassy carbon electrode, which was further modified with gold nanoparticles (AuNPs) for attachment of aptamers (Apt) that specifically recognized Pb. The Ag-SH-G particles were synthesized using a one-step method, resulting in significantly enhanced electrochemical properties upon incorporating Ag nanoparticles into the PLL/Ag-SH-G composite. Coating of the covalently or no-covalently bonded Ag-SH-G particles with PLL provides an excellent supporting matrix, facilitating the assembly of AuNPs and a thiol-modified aptamer for Pb. Under optimized conditions, Apt/AuNPs/PLL/Ag-SH-G/GCE exhibited excellent sensing performance for Pb with a wide linear response range (10-1000 nM), a low detection limit (0.047 nM) and extraordinary selectivity. The sensor was employed and satisfactory results were obtained in river water, soil and vegetable samples for the detection of Pb.
Topics: Graphite; Lead; Aptamers, Nucleotide; Electrochemical Techniques; Silver; Metal Nanoparticles; Gold; Biosensing Techniques; Sulfhydryl Compounds; Limit of Detection; Water Pollutants, Chemical; Nanocomposites
PubMed: 38660709
DOI: 10.1039/d4ay00322e -
RSC Advances Apr 2024Human flavin-containing monooxygenase 3 (FMO3) is a drug-metabolizing enzyme (DME) which is known to be highly polymorphic. Some of its polymorphic variants are...
Human flavin-containing monooxygenase 3 (FMO3) is a drug-metabolizing enzyme (DME) which is known to be highly polymorphic. Some of its polymorphic variants are associated with inter-individual differences that contribute to drug response. In order to measure these differences, the implementation of a quick and efficient assay is highly desirable. To this end, in this work a microfluidic immobilized enzyme reactor (μ-IMER) was developed with four separate serpentines where FMO3 and its two common polymorphic variants (V257M and E158K) were covalently immobilized glutaraldehyde cross-linking in the presence of a polylysine coating. Computational fluid dynamics simulations were performed to calculate the selected substrate retention time in serpentines with different surface areas at various flow rates. The oxidation of tamoxifen, an anti-breast cancer drug, was used as a model reaction to characterize the new device in terms of available surface area for immobilization, channel coating, and applied flow rate. The highest amount of product was obtained when applying a 10 μL min flow rate on polylysine-coated serpentines with a surface area of 90 mm each. Moreover, these conditions were used to test the device as a multi-enzymatic platform by simultaneously assessing the conversion of tamoxifen by FMO3 and its two polymorphic variants immobilized on different serpentines of the same chip. The results obtained demonstrate that the differences observed in the conversion of tamoxifen within the chip are similar to those already published (E158K > WT > V257M). Therefore, this microfluidic platform provides a feasible option for fabricating devices for personalised medicine.
PubMed: 38655484
DOI: 10.1039/d4ra01516a -
Small (Weinheim An Der Bergstrasse,... Apr 2024The quest for efficient hemostatic agents in emergency medicine is critical, particularly for managing massive hemorrhages in dynamic and high-pressure wound...
The quest for efficient hemostatic agents in emergency medicine is critical, particularly for managing massive hemorrhages in dynamic and high-pressure wound environments. Traditional self-gelling powders, while beneficial due to their ease of application and rapid action, fall short in such challenging conditions. To bridge this gap, the research introduces a novel self-gelling powder that combines ultrafast covalent gelation and robust wet adhesion, presenting a significant advancement in acute hemorrhage control. This ternary system comprises ε-polylysine (ε-PLL) and 4-arm polyethylene glycol succinyl succinate (4-arm-PEG-NHS) forming the hydrogel framework. NaHPO functions as the "H sucker" to expedite the amidation reaction, slashing gelation time to under 10 s, crucial for immediate blood loss restriction. Moreover, PEG chains' hydrophilicity facilitates efficient absorption of interfacial blood, increasing the generated hydrogel's cross-linking density and strengthens its tissue bonding, thereby resulting in excellent mechanical and wet adhesion properties. In vitro experiments reveal the optimized formulation's exceptional tissue compliance, procoagulant activity, biocompatibility and antibacterial efficacy. In porcine models of heart injuries and arterial punctures, it outperforms commercial hemostatic agent Celox, confirming its rapid and effective hemostasis. Conclusively, this study presents a transformative approach to hemostasis, offering a reliable and potent solution for the emergency management of massive hemorrhage.
PubMed: 38643382
DOI: 10.1002/smll.202311859 -
ACS Biomaterials Science & Engineering May 2024Blood-contacting catheters play a pivotal role in contemporary medical treatments, particularly in the management of cardiovascular diseases. However, these catheters...
Blood-contacting catheters play a pivotal role in contemporary medical treatments, particularly in the management of cardiovascular diseases. However, these catheters exhibit inappropriate wettability and lack antimicrobial characteristics, which often lead to catheter-related infections and thrombosis. Therefore, there is an urgent need for blood contact catheters with antimicrobial and anticoagulant properties. In this study, we employed tannic acid (TA) and 3-aminopropyltriethoxysilane (APTES) to create a stable hydrophilic coating under mild conditions. Heparin (Hep) and poly(lysine) (PL) were then modified on the TA-APTES coating surface using the layer-by-layer (LBL) technique to create a superhydrophilic TA/APTES/(LBL) coating on silicone rubber (SR) catheters. Leveraging the superhydrophilic nature of this coating, it can be effectively applied to blood-contacting catheters to impart antibacterial, antiprotein adsorption, and anticoagulant properties. Due to Hep's anticoagulant attributes, the activated partial thromboplastin time and thrombin time tests conducted on SR/TA-APTES/(LBL) catheters revealed remarkable extensions of 276 and 103%, respectively, when compared to uncoated commercial SR catheters. Furthermore, the synergistic interaction between PL and TA serves to enhance the resistance of SR/TA-APTES/(LBL) catheters against bacterial adherence, reducing it by up to 99.9% compared to uncoated commercial SR catheters. Remarkably, the SR/TA-APTES/(LBL) catheter exhibits good biocompatibility with human umbilical vein endothelial cells in culture, positioning it as a promising solution to address the current challenges associated with blood-contact catheters.
Topics: Coated Materials, Biocompatible; Humans; Catheters; Polyphenols; Heparin; Tannins; Silanes; Anticoagulants; Propylamines; Amines; Anti-Bacterial Agents; Polylysine; Surface Properties; Hydrophobic and Hydrophilic Interactions; Human Umbilical Vein Endothelial Cells; Silicone Elastomers; Adsorption; Escherichia coli
PubMed: 38641433
DOI: 10.1021/acsbiomaterials.4c00578