Bioactive Structures Research Articles

3D Printing‐Based Hydrogel Dressings for Wound Healing

AbstractSkin wounds have become an important issue that affects human health and burdens global medical care. Hydrogel materials similar to the natural extracellular matrix (ECM) are one of the best candidates for ideal wound dressings and the most feasible choices for printing inks. Distinct from hydrogels made by traditional technologies, which lack bionic and mechanical properties, 3D printing can promptly and accurately create hydrogels with complex bioactive structures and the potential to promote tissue regeneration and wound healing. Herein, a comprehensive review of multi‐functional 3D printing‐based hydrogel dressings for wound healing is presented. The review first summarizes the 3D printing techniques for wound hydrogel dressings, including photo‐curing, extrusion, inkjet, and laser‐assisted 3D printing. Then, the properties and design approaches of a series of bioinks composed of natural, synthetic, and composite polymers for 3D printing wound hydrogel dressings are described. Thereafter, the application of multi‐functional 3D printing‐based hydrogel dressings in a variety of wound environments is discussed in depth, including hemostasis, anti‐inflammation, antibacterial, skin appendage regeneration, intelligent monitoring, and machine learning‐assisted therapy. Finally, the challenges and prospects of 3D printing‐based hydrogel dressings for wound healing are presented.

Phenolic Components And Biological Activity Of Pomegranate.

Pomegranate (Punica granatum L.) have been subject of extensive studies for its abundance of phytochemicals and numerous biological and medicinal properties. It is a fruit-bearing tree, which is widely consumed as a nutraceutical source as well as functional food for putative health benefits. The phenolic components are the characteristic bioactive constitutes of pomegranate, including hydrolysable tannins, flavonoids, and phenolic acids. The whole plant of this tree has many medicinal folkloric uses and good therapeutic effect, such as anticancer, antioxidant, antibacterial, antiviral, hypoglycemic, lipid-lowering, cardioprotection and digestive system protection. Through comprehensive search of available literature, this narrative review can provide an up-to-date overview of the current knowledge of characteristic bioactive constituents's structure and potential health benefits of Pomegranate, which can be used as reference for the future clinical and basic research, and also helpful for the development of pomegranate into functional food and nutraceuticals.

Construction of Pickering emulsions stabilized by small molecular bioactive nanocrystals: Crosstalk between bioactive molecular structure and initial aqueous phase

Pickering emulsions stabilized with bioactive nanocrystals (BNC-PEs) have attracted increasing attentions in recent years. However, the mechanisms for the construction of stable BNC-PEs remain obscure. This study aimed to investigate the effects of the bioactive molecular structure and the initial pH of the aqueous phase on the fabrication and stability of BNC-PEs and the crosstalk between the two factors. Puerarin, tanshinone IIA and ferulic acid with unique structural characteristics were employed as model components to prepare BNC-PEs. Results showed that the initial pH of the aqueous phase significantly affected the stability of BNC-PEs through influencing the particle sizes and charges of nanocrystals, while the molecular structure of bioactive substances affected the three-phase contact angles or interfacial tensions. The construction and stability of the three kinds of BNC-PEs were all improved with increasing initial pH of the aqueous phase. Moreover, it was first found that the bioactive molecular structure strongly interfered with the influences of the initial pH of the aqueous phase on the stability of BNC-PEs. This study demonstrated for the first time that there might be a crosstalk between the bioactive molecular structure and the initial pH of the aqueous phase, and that the optimal pH of the aqueous phase might be intricately linked to the molecular structure of bioactive nanocrystals for BNC-PEs.

Compressive properties and biocompatibility of additively manufactured lattice structures by using bioactive materials

Porous bioactive materials were widely used in orthopedic implant fields because of their excellent mechanical properties and porous spaces. However, most porous types are predominantly stacked in two-dimensional configurations, which significantly limits their mechanical property range and adversely affects the modulus matching between the porous implants and surrounding bone tissues. Hence, various lattice structures were prepared using 3D printing technology with bioactive materials, and characterized by mechanical and biological tests. Numerical simulations were conducted to analyze the effect of relative density and geometric parameters on the equivalent compressive properties of the lattice structures. The results showed that the lattice structure exhibited a broad elastic modulus range, which can be adjusted to align with the mechanical properties of human cortical and cancellous bones, thereby helping to mitigate stress shielding in orthopedic implants. The biocompatibility of the 3D-printed solid materials was assessed in vitro using a cell counting assay kit-8 (CCK-8). The results indicated that poly-ether-ether-ketone (PEEK), carbon fiber reinforced PEEK (CFR/PEEK), nylon, and titanium (Ti) alloy all exhibited good biocompatibility, with no significant differences observed among the four materials. This study further enhances the understanding of bioactive lattice structures in the biomedical field and offers new possibilities for orthopedic repair.

Natural bioink of interpenetrating network hydrogels mimicking extracellular polymeric substances for microbial immobilization in water pollution control

Artificial biomanufacturing has been developed as a promising biotechnology for water pollution control. Effective bioimmobilization techniques are limited in application because of low productivity and the difficulty in achieving both mechanical strength and biocompatibility. Bioprinting technology, using biomaterials as bioink to enable the rapid on-demand production of bioactive structures, opens a new path for bioimmobilization. In this study, mimicking extracellular polysaccharide and protein of aerobic granular sludge (AGS), sodium alginate (SA) and silk fibroin methacryloyl (SilMA) were developed as the dual-component bioink with a suitable viscosity for bioprinting hydrogel. Interpenetrating network (IPN) hydrogel beads were manufactured using 1.5% (w/v) SA combined with 20% (w/v) SilMA through physical and covalent crosslinking, which exhibited excellent structural stability and bioactivity. The addition of SilMA provided a solution to the poor mechanical stability of SA-Ca hydrogels limited by Ca2+-Na+ ionic exchange. The unique structure of SilMA contributed to the reduction of hydrogel swelling as well as the prevention of SA loss. IPN hydrogels showed a swelling rate of less than 20% compared to the high swelling rate of more than 60% for SA hydrogels. On the other hand, SA controlled the hardening induced by excessive self-assembly of SilMA and improved mass transport in SilMA hydrogels. Compared to IPN hydrogels, SilMA hydrogels experienced a 15% volumetric shrinkage and exhibited a low water content of 92%. Sonication pretreatment of the dual-component bioink not only increased the intermolecular chain entanglement to form IPN, but also led to β-sheet content in SiMA reaching 46%–48%, which resulted in the formation of stable IPN hydrogels dominated entirely by physical crosslinking. Satisfactory proliferation and viability were achieved for the encapsulated bacteria in IPN hydrogels (μmax 1.49–2.18 d−1). Further, the IPN biohydrogels could maintain structural stability as well as achieve pollutant removal for treating synthetic wastewater with high Na+ concentration of 300 mg/L. The novel SA/SilMA hydrogel bioprinting strategy established in this study offers a new direction for bioimmobilization in water pollution control and other environmental applications.

Antibiotic intermediates and antibiotics synergistically promote the development of multiple antibiotic resistance in antibiotic production wastewater

Antibiotic resistance (AR) is a major public health concern. Antibiotic intermediates (AIs) used in the production of semisynthetic antibiotics have the same bioactive structure as parent antibiotics and synthetic antibiotic production wastewater usually contains high concentrations of residual AIs; however, the effects of AIs and their interactive effects with antibiotics on the emergence of AR are unknown. In this study, antibiotic-sensitive E. coli K12 was exposed to five types of β-lactam AIs and their parent antibiotic ampicillin to analyze their impact on the evolution of multiple AR. The results indicated that AI 6-APA inhibits bacterial growth and stimulates the production of reactive oxygen species, as well as induces AR and antibiotic persistence like the parent antibiotic AMP. Combined exposure to 6-APA and AMP synergistically stimulated the induction of multiple AR and antibiotic persistence. The resistance mutation frequency increased up to 6.1 × 106-fold under combined exposure and the combination index reached 1326.5, indicating a strong synergy of 6-APA and AMP. Phenotypic and genotypic analyses revealed that these effects were associated with the overproduction of reactive oxygen species, enhanced stress response signatures, and activation of efflux pumps. These findings provide evidence and mechanistic insights into AR induction by AIs in antibiotic production wastewater.

Cytotoxic and Anti-HSV-1 Effects of Caulerpin Derivatives.

Marine organisms represent a potential source of secondary metabolites with various therapeutic properties. However, the pharmaceutical industry still needs to explore the algological resource. The species Caulerpa lamouroux Forssk presents confirmed biological activities associated with its major compound caulerpin, such as antinociceptive, spasmolytic, antiviral, antimicrobial, insecticidal, and cytotoxic. Considering that caulerpin is still limited, such as low solubility or chemical instability, it was subjected to a structural modifications test to establish which molecular regions could accept structural modification and to elucidate the cytotoxic bioactive structure in Vero cells (African green monkey kidney cells, Cercopithecus aethiops; ATCC, Manassas, VA, USA) and antiviral to Herpes simplex virus type 1. Substitution reactions in the N-indolic position with mono- and di-substituted alkyl, benzyl, allyl, propargyl, and ethyl acetate groups were performed, in addition to conversion to their acidic derivatives. The obtained analogs were submitted to cytotoxicity and antiviral activity screening against Herpes simplex virus type 1 by the tetrazolium microculture method. From the semi-synthesis, 14 analogs were obtained, and 12 are new. The cytotoxicity assay showed that caulerpin acid and N-ethyl-substituted acid presented cytotoxic concentrations referring to 50% of the maximum effect of 1035.0 µM and 1004.0 µM, respectively, values significantly higher than caulerpin. The antiviral screening of the analogs revealed that the N-substituted acids with methyl and ethyl groups inhibited Herpes simplex virus type 1-induced cytotoxicity by levels similar to the positive control acyclovir.

Unveiling the governing role of ‘remodeling triangle area’ in soft-hard tissue interface equilibrium for metal implants advancement

Metal implants holds significant promise for diverse fixed prostheses. However, their long-term reliability and broader application are hindered by challenges related to the disequilibrium at the soft-hard tissue interface. By using anti-inflammatory (PDA/IL4) and pro-inflammatory (PDA/LPS/IFNγ) coatings to modulate distinct immune characteristics, we discovered a dynamic bioactive structure at the soft-hard tissue interface around metal implant, which we have named the 'Remodeling Triangle Area' (RTA). We further demonstrate that the RTA can be influenced by the PDA/IL4 coating to favor a phenotype that enhances both innate and adaptive immunity. This leads to stronger epithelial adhesion, the formation of dense connective tissue via IGF1 secretion, and a more balanced soft-hard tissue interface through the OPG/RANKL axis. Conversely, the PDA/LPS/IFNγ coating shifts the RTA towards a phenotype that activates the innate immune response. This results in a less cohesive tissue structure and bone resorption, characterized by reduced IGF1 secretion and an imbalanced OPG/RANKL axis. Over all, our study introduces the novel concept termed the 'Remodeling Triangle Area' (RTA), an immune-rich anatomical region located at the nexus of the implant interface, epithelial, connective, and bone tissue, which becomes highly interactive post-implantation to modulate the soft-hard tissue interface equilibrium. We believe that an RTA-centric, immunomodulatory approach has the potential to revolutionize the design of next-generation metal implants, providing unparalleled soft-hard tissue interface equilibrium properties.

Improvement of biological and corrosion behavior of plasma electrolytic oxidized Mg implant by 3D printed scaffold of amine-terminated PEG/PCL loaded with dexamethasone

Although magnesium-based implants have good biocompatibility and biodegradability, they suffer from rapid corrosion in the body environment, which limits their biomedical applications. This study represents an approach for designing a bioactive and anti-corrosive hybrid structure composed of an inorganic layer by plasma electrolytic oxidation process and an organic layer of 3D printed polycaprolactone and amine-terminated polyethylene glycol scaffold containing dexamethasone. The results indicated that the hybrid layer exhibited superior adhesion strength, high corrosion resistance, remarkable biocompatibility, cell attachment, and osteogenic differentiation. The dexamethasone released from the 3D printed scaffold revealed high osteogenic differentiation capability. Hence, the fabrication of plasma electrolytic oxidized interlayer with a 3D printed scaffold can be a novel platform to preserve the magnesium-based biological implants from corrosion and to regenerate bone along with the controlled release of osteogenic components.

Direct 3D printing of freeform anisotropic bioactive structure based on shear-oriented ink system

Various anisotropic tissue structures exist in organisms, including muscle tissue, skin tissue, and nerve tissue. Replicating anisotropic tissue structuresin vitrohas posed a significant challenge. Three-dimensional (3D) printing technology is often used to fabricate biomimetic structures due to its advantages in manufacturing principle. However, direct 3D printing of freeform anisotropic bioactive structures has not been reported. To tackle this challenge, we developed a ternary F/G/P ink system that integrates the printability of Pluronic F127 (F), the robust bioactivity and photocrosslinking properties of gelatin methacryloyl (G), and the shear-induced alignment functionality of high-molecular-weight polyethylene glycol (P). And through this strategic ternary system combination, freeform anisotropic tissue structures can be 3D printed directly. Moreover, these anisotropic structures exhibit excellent bioactivity, and promote orientational growth of different cells. This advancement holds promise for the repair and replacement of anisotropic tissues within the human body.

НЕОБЫЧНЫЕ ПРЕВРАЩЕНИЯ АДДУКТА МИХАЭЛЯ ЛЕВОГЛЮКОЗЕНОНА И ЦИКЛОГЕКСАНОНА

Academician Genrikh Alexandrovich Tolstikov is a unique personality, a world-class scientist. During the years of his work as director of Institute of Organic Chemistry of the USC RAS (now the Ufa Institute of Chemistry of the Ufa Federal Research Center, Russian Academy of Sciences), new scientific directions were opened that are relevant and continue to this day. Research using sugars and anhydrous sugars, in particular, levoglucosane in the synthesis of prostaglandins and other bioactive structures, originates in the laboratory for the synthesis of low molecular weight bioregulators under the direction of prof. M.S. Miftakhov. After the creation of the laboratory for the synthesis of secondary metabolites (now the laboratory of pharmacophore cyclic systems) under the guidance of prof. Valeev F.A. Since the 90 s to the present, scientific research has been successfully conducted on the use of levoglucosenone and its derivatives in the synthesis of natural biologically active compounds and their analogues. Levoglucosenone attracted the attention of researches due to its availability and reactive, chiral structure. Its solubility in all organic solvents, and even in water, makes it a unique starting compound for organic synthesis. When describing the chemical behavior of levoglucosenone, it is important to note that many of its transformations proceed in a nontrivial manner and lead to unexpected products, which makes levoglucosenone an even more interesting object for study. Moreover, it turned out that the chemical transformations of its derivatives, in particular the Michael adducts of levoglucosenone and cycloalkanones, turned out to be even more unpredictable. This article is devoted to consideration of aspects of these transformations. Thus, it was found that two keto groups in the Michael adduct of levoglucosenone and cyclohexanone are not equivalent, the keto group of the carbohydrate fragment is more reactive. At the same time, when searching for the possibility of implementing intramolecular aldol condensation, it was unexpectedly found that the keto group of the carbohydrate fragment remains inert. Intramolecular carbocyclization could only be carried out in the Michael adduct of levoglucosenone and cyclododecanone. Based on the Michael adduct of levoglucosenone and cyclohexanone, a ten-membered lactone annelated with a carbohydrate fragment was synthesized. The problem of introducing substituents into the lactone cycle and modifying the carbohydrate part of the resulting lactone has been solved. On the basis of this adduct, an analog of the natural lactone, foracantholide, was synthesized. All results presented in the article include research conducted in our laboratory from 2014 to the present day.

Strategies to Prepare Chitin and Chitosan-Based Bioactive Structures Aided by Deep Eutectic Solvents: A Review

Chitin and chitosan, abundant biopolymers derived from the shells of crustaceans and the cell walls of fungi, have garnered considerable attention in pharmaceutical circles due to their biocompatibility, biodegradability, and versatile properties. Deep eutectic solvents (DESs), emerging green solvents composed of eutectic mixtures of hydrogen bond acceptors and donors, offer promising avenues for enhancing the solubility and functionality of chitin and chitosan in pharmaceutical formulations. This review delves into the potential of utilizing DESs as solvents for chitin and chitosan, highlighting their efficiency in dissolving these polymers, which facilitates the production of novel drug delivery systems, wound dressings, tissue engineering scaffolds, and antimicrobial agents. The distinctive physicochemical properties of DESs, including low toxicity, low volatility, and adaptable solvation power, enable the customization of chitin and chitosan-based materials to meet specific pharmaceutical requirements. Moreover, the environmentally friendly nature of DESs aligns with the growing demand for sustainable and eco-friendly processes in pharmaceutical manufacturing. This revision underscores recent advances illustrating the promising role of DESs in evolving the pharmaceutical applications of chitin and chitosan, laying the groundwork for the development of innovative drug delivery systems and biomedical materials with enhanced efficacy and safety profiles.

Brønsted Acid‐Catalyzed Markovnikov Hydroarylation of Arylcyclobutene: A Route to gem‐Diaryl‐Substituted Cyclobutanes

AbstractA regioselective Markovnikov hydroarylation of arylcyclobutene has been developed using Brønsted acid catalysis through a protonation/Friedel‐Crafts sequence. The metal‐free catalytic reaction is operationally simple and feasible compared to previous reports that utilized elaborate arylcyclobutene and specific polyfluorinated reagents, affording a variety of gem‐diaryl‐ substituted arylcyclobutene in good yields. The possible mechanism of the reaction has been explored through step‐by‐step control experiments. This protocol involving indole in gem‐diaryl‐substituted cyclobutene scaffolds not only enriches the applications of Brønsted acid catalyzed hydroarylation, but also paves the way for a more extensive access to potential bioactive cyclobutanes structures.

Strategies for Accessing cis-1-Amino-2-Indanol.

cis-1-amino-2-indanol is an important building block in many areas of chemistry. Indeed, this molecule is currently used as skeleton in many ligands (BOX, PyBOX…), catalysts and chiral auxiliaries. Moreover, it has been incorporated in numerous bioactive structures. The major issues during its synthesis are the control of cis-selectivity, for which various strategies have been devised, and the enantioselectivity of the reaction. This review highlights the various methodologies implemented over the last few decades to access cis-1-amino-2-indanol in racemic and enantioselective manners. In addition, the various substitution patterns on the aromatic ring and their preparations are listed.

Computational Predictive and Electrochemical Detection of Metabolites (CP-EDM) of Piperine

In this article, we introduce a proof-of-concept strategy, Computational Predictive and Electrochemical Detection of Metabolites (CP-EDM), to expedite the discovery of drug metabolites. The use of a bioactive natural product, piperine, that has a well-curated metabolite profile but an unpredictable computational metabolism (Biotransformer v3.0) was selected. We developed an electrochemical reaction to oxidize piperine into a range of metabolites, which were detected by LC-MS. A series of chemically plausible metabolites were predicted based on ion fragmentation patterns. These metabolites were docked into the active site of CYP3A4 using Autodock4.2. From the clustered low-energy profile of piperine in the active site, it can be inferred that the most likely metabolic position of piperine (based on intermolecular distances to the Fe-oxo active site) is the benzo[d][1,3]dioxole motif. The metabolic profile was confirmed by comparison with the literature, and the electrochemical reaction delivered plausible metabolites, vide infra, thus, demonstrating the power of the hyphenated technique of tandem electrochemical detection and computational evaluation of binding poses. Taken together, we outline a novel approach where diverse data sources are combined to predict and confirm a metabolic outcome for a bioactive structure.

Therapeutic Effects of Essential Oils and Their Bioactive Compounds on Prostate Cancer Treatment.

Since prostate cancer (PCa) relies on limited therapies, more effective alternatives are required. Essential oils (EOs) and their bioactive compounds are natural products that have many properties including anticancer activity. This review covers studies published between 2000 and 2023 and discusses the anti-prostate cancer mechanisms of the EOs from several plant species and their main bioactive compounds. It also provides a critical perspective regarding the challenges to be overcome until they reach the market. EOs from chamomile, cinnamon, Citrus species, turmeric, Cymbopogon species, ginger, lavender, Mentha species, rosemary, Salvia species, thyme and other species have been tested in different PCa cell lines and have shown excellent results, including the inhibition of cell growth and migration, the induction of apoptosis, modulation in the expression of apoptotic and anti-apoptotic genes and the suppression of angiogenesis. The most challenging aspects of EOs, which limit their clinical uses, are their highly lipophilic nature, physicochemical instability, photosensitivity, high volatility and composition variability. The processing of EO-based products in the pharmaceutical field may be an interesting alternative to circumvent EOs' limitations, resulting in several benefits in their further clinical use. Identifying their bioactive compounds, therapeutic effects and chemical structures could open new perspectives for innovative developments in the field. Moreover, this could be helpful in obtaining versatile chemical synthesis routes and/or biotechnological drug production strategies, providing an accurate, safe and sustainable source of these bioactive compounds, while looking at their use as gold-standard therapy in the close future.

Structural characterization of strawberry pomace

Strawberries are a nutrient dense food rich in vitamins, minerals, non-nutrient antioxidant phenolics, and fibers. Strawberry fiber bioactive structures are not well characterized and limited information is available about the interaction between strawberry fiber and phenolics. Therefore, we analyzed commercial strawberry pomace in order to provide a detailed carbohydrate structural characterization, and to associate structures with functions. The pomace fraction, which remained after strawberry commercial juice extraction, contained mostly insoluble (49.1 % vs. 5.6 % soluble dietary fiber) dietary fiber, with pectin, xyloglucan, xylan, β-glucan and glucomannan polysaccharides; glucose, fructose, xylose, arabinose, galactose, fucose and galacturonic acid free carbohydrates; protein (15.6 %), fat (8.34 %), and pelargonidin 3-glucoside (562 μg/g). Oligosaccharides from fucogalacto-xyloglucan, methyl-esterified rhamnogalacturonan I with branched arabinogalacto-side chains, rhamnogalacturonan II, homogalacturonan and β-glucan were detected by MALDI-TOF MS, NMR and glycosyl-linkage analysis. Previous reports suggest that these oligosaccharide and polysaccharide structures have prebiotic, bacterial pathogen anti-adhesion, and cholesterol-lowering activity, while anthocyanins are well-known antioxidants. A strawberry pomace microwave acid-extracted (10 min, 80 °C) fraction had high molar mass (2376 kDa) and viscosity (3.75 dL/g), with an extended rod shape. A random coil shape, that was reported previously to bind to phenolic compounds, was observed for other strawberry microwave-extracted fractions. These strawberry fiber structural details suggest that they can thicken foods, while the polysaccharide and polyphenol interaction indicates great potential as a multiple-function bioactive food ingredient important for gut and metabolic health.

Recent Advances in the Bioactive Structure and Application of Single-atom Nanozymes

Recent Advances in the Bioactive Structure and Application of Single-atom Nanozymes

Bioactive Wound Healing 3D Structure Based on Chitosan Hydrogel Loaded with Naringin/Cyclodextrin Inclusion Nanocomplex.

The current assay aimed to fabricate and analyze a potent wound healing structure based on a naringin (Nar)/β-cyclodextrin (β-CD)-loaded chitosan hydrogel. Using the simulation studies, we assessed the interactions among the Nar, β-CD, and the formation of the inclusion complex. Then, the formation of the hydrogel nanocomplex was simulated and evaluated using the in silico methods. The results showed that after optimization of the structures by DMol3 based on DFT-D, the total energies of Nar, GP, CD, and β-CD were calculated at -2100.159, -912.192, -3778.370, and -4273.078 Ha, respectively. The encapsulation energy of Nar on β-CD in the solvent phase was calculated at -93.626 kcal/mol, and the Nar structure was located inside β-CD in solution. The negative interaction energy value for the encapsulation of Nar on β-CD suggests the exothermic adsorption process and a stable structure between Nar and β-CD. Monte Carlo method was applied to obtain adsorption of CS/GP on Nar/β-CD. Its value of the obtained interaction energy was calculated at -1.423 × 103 kcal/mol. The characterization confirmed the formation of a Nar/β-CD inclusion complex. The Zeta potential of the pristine β-CD changed from -4.60 ± 1.1 to -17.60 ± 2.34 mV after interaction with Nar, and the heightened surface negativity can be attributed to the existence of electron-rich naringin molecules, as well as the orientation of the hydroxyl (OH) group of the β-CD toward the surface in an aqueous solution. The porosity of the fabricated hydrogels was in the range of 70-90% and during 14 days around 47.0 ± 3.1% of the pure hydrogel and around 56.4 ± 5.1 of hydrogel nanocomposite was degraded. The MTT assay showed that the hydrogels were biocompatible, and the wound contraction measurement (in an animal model) showed that the closure of the induced wound in the hydrogel nanocomposite treatment was faster than that of the control group (wound without treatment). The results of this study indicate that the developed bioactive wound healing 3D structure, which is composed of a chitosan hydrogel containing a Nar/β-CD inclusion nanocomplex, has potential as an effective material for wound dressing applications.

Large extracellular vesicle (EV) and neutrophil extracellular trap (NET) interaction captured in vivo during systemic inflammation

Extracellular vesicles (EVs) and neutrophil extracellular traps (NETs) are pivotal bioactive structures involved in various processes including inflammation. Herein we report the interactions between EVs and NETs during murine endotoxemia studied in situ directly in the vasculature (cremaster muscle, liver sinusoids) using intravital microscopy (IVM). We captured NETs and EV release in real time by both non- and polarized neutrophils in liver but not in cremaster vasculature. When comparing numbers of circulating EVs of various origin (nanoparticle tracking analysis—NTA, flow cytometry) with those interacting with endothelium and NETs (IVM) we observed that whereas platelet and monocyte/macrophage-derived EVs dominate in blood and peritoneal lavage, respectively, mostly neutrophil-derived EVs interact with the vascular lining, NETs and leukocytes. Despite the interaction, NETs do not affect EV formation as NET release inhibition did not alter EV release. However, EVs inhibit NETs formation and in particular, erythrocyte-derived EVs downregulate NET release and this effect is mediated via Siglec-E-dependent interactions with neutrophils. Overall, we report that EVs are present in NETs in vivo and they do modulate their release but the process in not bidirectional. Moreover, EVs isolated from body fluids might not reflect their importance in direct endothelial- and leukocyte-related interactions.