Edible alginate-based films with anti-SARS-CoV-2 activity.

The viability of SARS-CoV-2 on food surfaces and its propagation through the food chain has been discussed by several stakeholders, as it may represent a serious public health problem, bringing new challenges to the food system. This work shows for the first time that edible films can be used against SARS-CoV-2. Sodium alginate-based films containing gallic acid, geraniol, and green tea extract were evaluated in terms of their antiviral activity against SARS-CoV-2. The results showed that all these films have strong in vitro antiviral activity against this virus. However, a higher concentration of the active compound (1.25%) is needed for the film containing gallic acid to achieve similar results to those obtained for lower concentrations of geraniol and green tea extract (0.313%). Furthermore, critical concentrations of the active compounds in the films were used to evaluate their stability during storage. Results showed that gallic acid-loaded films lose their activity from the second week of storage, while films with geraniol and green tea extract only show a drop in activity after four weeks. These results highlight the possibility of using edible films and coatings as antiviral materials on food surfaces or food contact materials, which may help to reduce the spreading of viruses through the food chain.

Inhibitory activities of alginate phosphate and sulfate derivatives against SARS-CoV-2 in vitro.

Alginate derivatives have been demonstrated remarkable antiviral activities. Here we firstly identified polymannuronate phosphate (PMP) as a highly potential anti-SARS-CoV-2 agent. The structure-activity relationship showed polymannuronate monophosphate (PMPD, Mw: 5.8 kDa, P%: 8.7 %) was the most effective component to block the interaction of spike to ACE2 with an IC50 of 85.5 nM. Surface plasmon resonance study indicated that PMPD could bind to spike receptor binding domain (RBD) with the KD value of 78.59 nM. Molecular docking further suggested that the probable binding site of PMPD to spike RBD protein is the interaction interface between spike and ACE2. PMPD has the potential to inhibit the SARS-CoV-2 infection in an independent manner of heparan sulfate proteoglycans. In addition, polyguluronate sulfate (PGS) and propylene glycol alginate sodium sulfate (PSS) unexpectedly showed 3CLpro inhibition with an IC50 of 1.20 µM and 1.42 µM respectively. The polyguluronate backbone and sulfate group played pivotal roles in the 3CLpro inhibition. Overall, this study revealed the potential of PMPD as a novel agent against SARS-CoV-2. It also provided a theoretical basis for further study on the role of PGS and PSS as 3CLpro inhibitors.

Microfluidic bioprinting of tough hydrogel-based vascular conduits for functional blood vessels.

Three-dimensional (3D) bioprinting of vascular tissues that are mechanically and functionally comparable to their native counterparts is an unmet challenge. Here, we developed a tough double-network hydrogel (bio)ink for microfluidic (bio)printing of mono- and dual-layered hollow conduits to recreate vein- and artery-like tissues, respectively. The tough hydrogel consisted of energy-dissipative ionically cross-linked alginate and elastic enzyme-cross-linked gelatin. The 3D bioprinted venous and arterial conduits exhibited key functionalities of respective vessels including relevant mechanical properties, perfusability, barrier performance, expressions of specific markers, and susceptibility to severe acute respiratory syndrome coronavirus 2 pseudo-viral infection. Notably, the arterial conduits revealed physiological vasoconstriction and vasodilatation responses. We further explored the feasibility of these conduits for vascular anastomosis. Together, our study presents biofabrication of mechanically and functionally relevant vascular conduits, showcasing their potentials as vascular models for disease studies in vitro and as grafts for vascular surgeries in vivo, possibly serving broad biomedical applications in the future.

Association of Midgut Bacteria and Their Metabolic Pathways with Zika Infection and Insecticide Resistance in Colombian Aedes aegypti Populations.

INTRODUCTION: Aedes aegypti is the vector of several arboviruses such as dengue, Zika, and chikungunya. In 2015-16, Zika virus (ZIKV) had an outbreak in South America associated with prenatal microcephaly and Guillain-Barré syndrome. This mosquito's viral transmission is influenced by microbiota abundance and diversity and its interactions with the vector. The conditions of cocirculation of these three arboviruses, failure in vector control due to insecticide resistance, limitations in dengue management during the COVID-19 pandemic, and lack of effective treatment or vaccines make it necessary to identify changes in mosquito midgut bacterial composition and predict its functions through the infection. Its study is fundamental because it generates knowledge for surveillance of transmission and the risk of outbreaks of these diseases at the local level. METHODS: Midgut bacterial compositions of females of Colombian Ae. aegypti populations were analyzed using DADA2 Pipeline, and their functions were predicted with PICRUSt2 analysis. These analyses were done under the condition of natural ZIKV infection and resistance to lambda-cyhalothrin, alone and in combination. One-step RT-PCR determined the percentage of ZIKV-infected females. We also measured the susceptibility to the pyrethroid lambda-cyhalothrin and evaluated the presence of the V1016I mutation in the sodium channel gene. RESULTS: We found high ZIKV infection rates in Ae. aegypti females from Colombian rural municipalities with deficient water supply, such as Honda with 63.6%. In the face of natural infection with an arbovirus such as Zika, the diversity between an infective and non-infective form was significantly different. Bacteria associated with a state of infection with ZIKV and lambda-cyhalothrin resistance were detected, such as the genus Bacteroides, which was related to functions of pathogenicity, antimicrobial resistance, and bioremediation of insecticides. We hypothesize that it is a vehicle for virus entry, as it is in human intestinal infections. On the other hand, Bello, the only mosquito population classified as susceptible to lambda-cyhalothrin, was associated with bacteria related to mucin degradation functions in the intestine, belonging to the Lachnospiraceae family, with the genus Dorea being increased in ZIKV-infected females. The Serratia genus presented significantly decreased functions related to phenazine production, potentially associated with infection control, and control mechanism functions for host defense and quorum sensing. Additionally, Pseudomonas was the genus principally associated with functions of the degradation of insecticides related to tryptophan metabolism, ABC transporters with a two-component system, efflux pumps, and alginate synthesis. CONCLUSIONS: Microbiota composition may be modulated by ZIKV infection and insecticide resistance in Ae. aegypti Colombian populations. The condition of resistance to lambda-cyhalothrin could be inducing a phenome of dysbiosis in field Ae. aegypti affecting the transmission of arboviruses.

Encapsulation of Bromelain in Combined Sodium Alginate and Amino Acid Carriers: Experimental Design of Simplex-Centroid Mixtures for Digestibility Evaluation.

Bromelain has potential as an analgesic, an anti-inflammatory, and in cancer treatments. Despite its therapeutic effects, this protein undergoes denaturation when administered orally. Microencapsulation processes have shown potential in protein protection and as controlled release systems. Thus, this paper aimed to develop encapsulating systems using sodium alginate as a carrier material and positively charged amino acids as stabilizing agents for the controlled release of bromelain in in vitro tests. The systems were produced from the experimental design of centroid simplex mixtures. Characterizations were performed by FTIR showing that bromelain was encapsulated in all systems. XRD analyses showed that the systems are semi-crystalline solids and through SEM analysis the morphology of the formed systems followed a pattern of rough microparticles. The application of statistical analysis showed that the systems presented behavior that can be evaluated by quadratic and special cubic models, with a p-value < 0.05. The interaction between amino acids and bromelain/alginate was evaluated, and free bromelain showed a reduction of 74.0% in protein content and 23.6% in enzymatic activity at the end of gastric digestion. Furthermore, a reduction of 91.6% of protein content and 65.9% of enzymatic activity was observed at the end of intestinal digestion. The Lis system showed better interaction due to the increased stability of bromelain in terms of the amount of proteins (above 63% until the end of the intestinal phase) and the enzymatic activity of 89.3%. Thus, this study proposes the development of pH-controlled release systems aiming at increasing the stability and bioavailability of bromelain in intestinal systems.

Effect of Hydrogel Contact Angle on Wall Thickness of Artificial Blood Vessel.

Vascular replacement is one of the most effective tools to solve cardiovascular diseases, but due to the limitations of autologous transplantation, size mismatch, etc., the blood vessels for replacement are often in short supply. The emergence of artificial blood vessels with 3D bioprinting has been expected to solve this problem. Blood vessel prosthesis plays an important role in the field of cardiovascular medical materials. However, a small-diameter blood vessel prosthesis (diameter < 6 mm) is still unable to achieve wide clinical application. In this paper, a response surface analysis was firstly utilized to obtain the relationship between the contact angle and the gelatin/sodium alginate mixed hydrogel solution at different temperatures and mass percentages. Then, the self-developed 3D bioprinter was used to obtain the optimal printing spacing under different conditions through row spacing, printing, and verifying the relationship between the contact angle and the printing thickness. Finally, the relationship between the blood vessel wall thickness and the contact angle was obtained by biofabrication with 3D bioprinting, which can also confirm the controllability of the vascular membrane thickness molding. It lays a foundation for the following study of the small caliber blood vessel printing molding experiment.

Biomaterials for Tissue Engineering Applications and Current Updates in the Field: A Comprehensive Review.

Tissue engineering has emerged as an interesting field nowadays; it focuses on accelerating the auto-healing mechanism of tissues rather than organ transplantation. It involves implanting an In Vitro cultured initiative tissue or a scaffold loaded with tissue regenerating ingredients at the damaged area. Both techniques are based on the use of biodegradable, biocompatible polymers as scaffolding materials which are either derived from natural (e.g. alginates, celluloses, and zein) or synthetic sources (e.g. PLGA, PCL, and PLA). This review discusses in detail the recent applications of different biomaterials in tissue engineering highlighting the targeted tissues besides the in vitro and in vivo key findings. As well, smart biomaterials (e.g. chitosan) are fascinating candidates in the field as they are capable of elucidating a chemical or physical transformation as response to external stimuli (e.g. temperature, pH, magnetic or electric fields). Recent trends in tissue engineering are summarized in this review highlighting the use of stem cells, 3D printing techniques, and the most recent 4D printing approach which relies on the use of smart biomaterials to produce a dynamic scaffold resembling the natural tissue. Furthermore, the application of advanced tissue engineering techniques provides hope for the researchers to recognize COVID-19/host interaction, also, it presents a promising solution to rejuvenate the destroyed lung tissues.

Engineering alginate hydrogel films with poly(3-hydroxybutyrate-co-3-valerate) and graphene nanoplatelets: Enhancement of antiviral activity, cell adhesion and electroactive properties.

A new biodegradable semi-interpenetrated polymer network (semi-IPN) of two US Food and Drug Administration approved materials, poly(3-hydroxybutyrate-co-3-valerate) (PHBV) and calcium alginate (CA) was engineered to provide an alternative strategy to enhance the poor adhesion properties of CA. The synthesis procedure allows the additional incorporation of 10 % w/w of graphene nanoplatelets (GNPs), which have no cytotoxic effect on human keratinocytes. This quantity of multilayer graphene provides superior antiviral activity to the novel semi-IPN against a surrogate virus of SARS-CoV-2. Adding GNPs hardly affects the water absorption or electrical conductivity of the pure components of CA and PHBV. However, the semi-IPN's electrical conductivity increases dramatically after adding GNP due to molecular rearrangements of the intertwined polymer chains that continuously distribute the GNP nanosheets, This new hydrophilic composite biomaterial film shows great promise for skin biomedical applications, especially those that require antiviral and/or biodegradable electroconductive materials.

A novel inhalable quercetin-alginate nanogel as a promising therapy for acute lung injury.

BACKGROUND: Acute lung injury (ALI), a severe health-threatening disease, has a risk of causing chronic pulmonary fibrosis. Informative and powerful evidence suggests that inflammation and oxidative stress play a central role in the pathogenesis of ALI. Quercetin is well recognized for its excellent antioxidant and anti-inflammatory properties, which showed great potential for ALI treatment. However, the application of quercetin is often hindered by its low solubility and bioavailability. Therefore, to overcome these challenges, an inhalable quercetin-alginate nanogel (QU-Nanogel) was fabricated, and by this special "material-drug" structure, the solubility and bioavailability of quercetin were significantly enhanced, which could further increase the activity of quercetin and provide a promising therapy for ALI. RESULTS: QU-Nanogel is a novel alginate and quercetin based "material-drug" structural inhalable nanogel, in which quercetin was stabilized by hydrogen bonding to obtain a "co-construct" water-soluble nanogel system, showing antioxidant and anti-inflammatory properties. QU-Nanogel has an even distribution in size of less than 100 nm and good biocompatibility, which shows a stronger protective and antioxidant effect in vitro. Tissue distribution results provided evidence that the QU-Nanogel by ultrasonic aerosol inhalation is a feasible approach to targeted pulmonary drug delivery. Moreover, QU-Nanogel was remarkably reversed ALI rats by relieving oxidative stress damage and acting the down-regulation effects of mRNA and protein expression of inflammation cytokines via ultrasonic aerosol inhalation administration. CONCLUSIONS: In the ALI rat model, this novel nanogel showed an excellent therapeutic effect by ultrasonic aerosol inhalation administration by protecting and reducing pulmonary inflammation, thereby preventing subsequent pulmonary fibrosis. This work demonstrates that this inhalable QU-Nanogel may function as a promising drug delivery strategy in treating ALI.

An ultrastretchable, high-performance, and crosstalk-free proximity and pressure bimodal sensor based on ionic hydrogel fibers for human-machine interfaces.

The traditional human-machine interaction mode of communicating solely with pressure sensors needs modification, especially at a time when COVID-19 is circulating globally. Here, a transparent, stretchable, resilient, and high-performance hydrogel fiber-based bimodal sensor is fabricated by using a polyacrylamide-alginate double network hydrogel, which features high sensitivity (3.17% cm-1), wide working range (18 cm), fast response/recovery speeds (90/90 ms) and good stability in proximity sensing, and impressive pressure sensing performance, including high sensitivity (0.91 kPa-1), short response/recovery time (40/40 ms), low detection limit (63 Pa) and good linearity. Moreover, the response switch between proximity/pressure modes is measured and non-interfering dual-mode detection is achieved. Notably, the stretchable bimodal sensor is capable of working under 100% tensile strain without degrading the sensing performance. Specifically, the proximity sensor shows good immunity to the strain, while the pressure sensitivity is even promoted. Furthermore, the sensor is tough enough to work normally after punctures from a knife and strikes from a wrench. Notably, the sensor can be used for gesture recognition and subtle pressure detection, such as small water droplets (10 mg), wrist pulse, etc. A 3 × 3 array is further shown for accurate spatial sensing and location identification, verifying the feasibility of its practical application.

3D culture of cancer cells in alginate hydrogel beads as an effective technique for emergency cell storage and transportation in the pandemic era.

Due to the restrictions in accessing research laboratories and the challenges in providing proper storage and transportation of cells during the COVID-19 pandemic, having an effective and feasible mean to solve these challenges would be of immense help. Therefore, we developed a 3D culture setting of cancer cells using alginate beads and tested its effectiveness in different storage and transportation conditions. The viability and proliferation of cancer cells were assessed using trypan blue staining and quantitative CCK-8 kit, respectively. The developed beads allowed cancer cells survival up to 4 weeks with less frequent maintenance measures such as change of the culture media or subculture of cells. In addition, the recovery of cancer cells and proliferation pattern were significantly faster with better outcomes in the developed 3D alginate beads compared to the standard cryopreservation of cells or the 2D culture conditions. The 3D alginate beads also supported the viability of cells while the shipment at room temperature for a duration of up to 5 days with no humidity or CO2  support. Therefore, 3D culture in alginate beads can be used to store or ship biological cells with ease at room temperature with minimal preparations.

Potential Antiviral Properties of Industrially Important Marine Algal Polysaccharides and Their Significance in Fighting a Future Viral Pandemic.

Over the decades, the world has witnessed diverse virus associated pandemics. The significant inhibitory effects of marine sulfated polysaccharides against SARS-CoV-2 shows its therapeutic potential in future biomedical applications and drug development. Algal polysaccharides exhibited significant role in antimicrobial, antitumor, antioxidative, antiviral, anticoagulant, antihepatotoxic and immunomodulating activities. Owing to their health benefits, the sulfated polysaccharides from marine algae are a great deal of interest globally. Algal polysaccharides such as agar, alginate, carrageenans, porphyran, fucoidan, laminaran and ulvans are investigated for their nutraceutical potential at different stages of infection processes, structural diversity, complexity and mechanism of action. In this review, we focus on the recent antiviral studies of the marine algae-based polysaccharides and their potential towards antiviral medicines.

Antiviral Properties of Alginate-Based Biomaterials: Promising Antiviral Agents against SARS-CoV-2.

The COVID-19 pandemic has made it essential to explore alternative antiviral materials. Alginate is a biodegradable, renewable, biocompatible, water-soluble and antiviral biopolymer with many potential biomedical applications. In this regard, this review shows 17 types of viruses that have been tested in contact with alginate and its related biomaterials. Most of these studies show that alginate-based materials possess little or no toxicity and are able to inhibit a wide variety of viruses affecting different organisms: in humans by the human immunodeficiency virus type 1, the hepatitis A, B, and C viruses, Sindbis virus, herpes simplex virus type 1 and 2, poliovirus type 1, rabies virus, rubella virus, and the influenza virus; in mice by the murine norovirus; in bacteria by the T4 coliphage, and in plants by the tobacco mosaic virus and the potato virus X. Many of these are enveloped positive-sense single-stranded RNA viruses, like SARS-CoV-2, which render alginate-based materials highly promising in the COVID-19 pandemic.

Chitosan, alginate, hyaluronic acid, gums, and ß-glucan as potent adjuvants and vaccine delivery systems for viral threats including SARS-CoV-2: A review.

Pathogen transmission is a widespread threat to global human health. Vaccines are very important during the outbreak of a pandemic. Destructive fractures caused by a sudden outbreak of COVID-19 have spurred vaccine production at an unprecedented rate. The strategy of an effective vaccine delivery system is opening up novel probabilities to make more immunization. Indeed, vaccination is the most successful way to prevent deaths from infectious diseases. In order to optimal immune response production or improvement in the effectiveness of vaccines, delivery systems or adjuvants are required. Natural polymers such as chitosan, alginate, hyaluronic acid, gums, and ß-glucan with antiviral activity have good potential as adjuvant or delivery systems for vaccine formulation development and design vaccine delivery devices. According to the antiviral performance and immunomodulation of these biopolymers, they will play significant characters in the anti-COVID-19 field. In this mini-review, the recent progress in vaccine development by using biopolymers is presented which, provides a reference for their research on anti-COVID-19 drugs and vaccines.

A novel capsule-based smell test fabricated via coaxial dripping.

In this paper, we demonstrate that aromatic oil capsules, produced by dripping droplets, can offer a simple, yet effective, testing tool to aid in the diagnosis of various diseases, in which the loss of smell is a key symptom. These include chronic neurological conditions such as Parkinson's and Alzheimer's diseases, and acute respiratory infections such as that caused by COVID-19. The capsules were fabricated by concentrically dripping oil/alginate droplets, from a coaxial nozzle, into an oppositely charged ionic liquid. This fabrication technique enables full control over the capsule size, the shell thickness and the volume of the encapsulated oil. After formation, liquid capsules were left to dry and form a solid crust surrounding the oil. The prototype test consists of placing a standardized number of capsules between adhesive strips that users crush and pull apart to release the smell. In addition to the fabrication method, a simple mathematical model was developed to predict the volume of encapsulated oil within the capsule in terms of the flow rate ratio and the nozzle size. Tensile tests show that capsule strength is inversely proportional to its size owing to an increase in the shell thickness. By increasing the alginate concentration, the load required to rupture the capsule increases, to the point where capsules are too stiff to be broken by a fingertip grip. Results from a preliminary screening test, within a group of patients with Parkinson's disease, found that smells were detectable using a 'forced choice' paradigm.

Persistent Bacterial Coinfection of a COVID-19 Patient Caused by a Genetically Adapted Pseudomonas aeruginosa Chronic Colonizer.

Pseudomonas aeruginosa is a biofilm-forming opportunistic pathogen which causes chronic infections in immunocompromised patients and leads to high mortality rate. It is identified as a common coinfecting pathogen in COVID-19 patients causing exacerbation of illness. In our hospital, P. aeruginosa is one of the top coinfecting bacteria identified among COVID-19 patients. We collected a strong biofilm-forming P. aeruginosa strain displaying small colony variant morphology from a severe COVID-19 patient. Genomic and transcriptomic sequencing analyses were performed with phenotypic validation to investigate its adaptation in SARS-CoV-2 infected environment. Genomic characterization predicted specific genomic islands highly associated with virulence, transcriptional regulation, and DNA restriction-modification systems. Epigenetic analysis revealed a specific N6-methyl adenine (m6A) methylating pattern including methylation of alginate, flagellar and quorum sensing associated genes. Differential gene expression analysis indicated that this isolate formed excessive biofilm by reducing flagellar formation (7.4 to 1,624.1 folds) and overproducing extracellular matrix components including CdrA (4.4 folds), alginate (5.2 to 29.1 folds) and Pel (4.8-5.5 folds). In summary, we demonstrated that P. aeuginosa clinical isolates with novel epigenetic markers could form excessive biofilm, which might enhance its antibiotic resistance and in vivo colonization in COVID-19 patients.

Use of Yoghurt Enhanced with Volatile Plant Oils Encapsulated in Sodium Alginate to Increase the Human Body's Immunity in the Present Fight Against Stress.

(1) Background: The COVID-19 pandemic and the imposition of strict but necessary measures to prevent the spread of the new coronavirus have been, and still are, major stress factors for adults, children, and adolescents. Stress harms human health as it creates free radicals in the human body. According to various recent studies, volatile oils from various aromatic plants have a high content of antioxidants and antimicrobial compounds. An external supply of antioxidants is required to destroy these free radicals. The main purpose of this paper is to create a yoghurt with high antioxidant capacity, using only raw materials from Romania; (2) Methods: The bioactive components used to enrich the cow milk yoghurt were extracted as volatile oils out of four aromatic plants: basil, mint, lavender and fennel. Initially, the compounds were extracted to determine the antioxidant capacity, and subsequently, the antioxidant activity of the yoghurt was determined. The 2,2-diphenyl-1-picrylhy-drazyl (DPPH) method was used to determine the antioxidant activity; (3) Results: The results show that cow milk yoghurt enhanced with volatile oils of basil, lavender, mint and fennel, encapsulated in sodium alginate has an antioxidant and antimicrobial effect as a staple food with multiple effects in increasing the body's immunity. The antioxidant activity proved to be considerably higher than the control sample. The highest antioxidant activity was obtained on the first day of the analysis, decreasing onwards to measurements taken on days 10 and 20. The cow milk yoghurt enriched with volatile basil oil obtained the best results; (4) Conclusions: The paper shows that yoghurts with a high antioxidant capacity were obtained, using only raw materials from Romania. A healthy diet, compliance with safety conditions and finding appropriate and safe methods to increase the body's immunity is a good alternative to a major transition through harder times, such as pandemics. The creation of food products that include natural antioxidant compounds combines both the current great possibility of developing food production in Romania and the prevention and reduction of the effects caused by pandemic stress in the human body.