Microencapsulation of Bifidobacterium lactis and Lactobacillus plantarum within a Novel Polysaccharide-Based Core-Shell Formulation: Improving Probiotic Viability and Mucoadhesion.

Probiotics health benefits are hampered by long-term storage, gastrointestinal transit, and lack of adequate colonization within the colon. To this end, we have designed a core-shell structure that features an acid resistant core formulation with low water activity composed of alginate, hydroxypropyl methyl cellulose, and gellan gum (AHG) and a mucoadhesive shell made from chemically modified carboxymethyl chitosan with polyethylenimine (PEI-CMC). The structure of the core-shell microparticles was examined using scanning electron microscopy, and rheological measurements confirmed the improved ionic interactions between the core and the shell using the PEI-modified CMC. Simulated release from core-shell microparticles using polystyrene beads showed preferential release under intestinal conditions. PEI-CMC coating yielded improvements in mucoadhesion that was consistent with a positive shift in surface charge of the particles. Ex vivo studies using Bifidobacterium lactis probiotic bacteria demonstrated a 1.1 × 105-fold improvement in bacterial viability with encapsulation under storage conditions of high humidity and temperature (30 °C). When exposed to simulated gastric fluid, encapsulation increased the probiotic viability by 3.0 × 102-fold. In vivo studies utilizing bioluminescent Lactobacillus plantarum in mice revealed that encapsulation extended the duration of the signal within the gut and resulted in higher plate counts in suspensions isolated from the cecum. Conversely, we observed an abrupt loss of signal in the gut of the free probiotic. In conclusion, this core-shell system is suitable for improving probiotic shelf life and maximizing delivery to and retention by the colon.

Thread-Based Bienzymatic Biosensor for Linoleic Acid Detection.

The concentration of nonesterified fatty acids (NEFAs) in biological media is associated with metabolic and cardiovascular disorders (e.g., diabetes, cancer, and cystic fibrosis) and in food products is indicative of their quality. Therefore, the early identification of NEFAs is crucial for both medical diagnosis and food quality assessment. However, the development of a portable and scalable sensor capable of detecting these compounds at a low cost presents challenges due to their considerable chemical and physical stability. This research endeavors to illustrate the viability of detecting linoleic acid using a chemiresistive bienzymatic sensor constructed with cotton thread. The sensor's design incorporates the conductive polymer poly(3,4-ethylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS) within the thread, alongside the enzymes horseradish peroxidase (HRP) and lipoxygenase (LOX). By implementing this technology, a sensitive detection range spanning from 161 nM to 16.1 µM is achieved when the PEDOT:PSS/HRP/LOX system is integrated into a single thread. The sensor exhibits exceptional selectivity toward linoleic acid, owing to the specific enzymatic reaction between LOX and linoleic acid. This selectivity is upheld even in the presence of other unsaturated fatty acids. This system can be used for future designs with the capability to detect polyunsaturated fatty acids and other intricate biomolecules.

Developing a Chemiresistive Gas Sensor Array for Simultaneous Detection of Ammonia and Carbon Dioxide Gases.

Chemiresistive polymer-based sensors are promising platforms for monitoring various gases and volatile organic compounds. While they offer appealing attributes, such as ease of fabrication, flexibility, and cost-effectiveness, most of these sensors have a nearly identical response to cross-reactive gases, such as ammonia (NH3) and carbon dioxide (CO2). Aiming to address the shortcomings of chemiresistive polymer-based sensors in selectivity and simultaneous measurements of cross-reactive gases, a chemiresistive sensor array was developed consisting of components sensitive to carbon dioxide and ammonia as well as a control segment to provide the baseline. The designed system demonstrated a wide detection range for both ammonia (ranging from 0.05 to 1000 ppm) and carbon dioxide (ranging from 103 to 106 ppm) at both room and low temperatures (e.g., 4 °C). Our results also demonstrate the ability of this sensor array for the simultaneous detection of carbon dioxide and ammonia selectively in the presence of other gases and volatile organic compounds. Finally, the array was used to monitor CO2/NH3 in real food samples to demonstrate the potential for real-world applications.

Chemiresistive Sensor for Enhanced CO2 Gas Monitoring.

Carbon dioxide (CO2) gas sensing and monitoring have gained prominence for applications such as smart food packaging, environmental monitoring of greenhouse gases, and medical diagnostic tests. Although CO2 sensors based on metal oxide semiconductors are readily available, they often suffer from limitations such as high operating temperatures (>250 °C), limited response at elevated humidity levels (>60% RH), bulkiness, and limited selectivity. In this study, we designed a chemiresistive sensor for CO2 detection to overcome these problems. The sensing material of this sensor consists of a CO2 switchable polymer based on N-3-(dimethylamino)propyl methacrylamide (DMAPMAm) and methoxyethyl methacrylate (MEMA) [P(D-co-M)], and diethylamine. The designed sensor has a detection range for CO2 between 103 and 106 ppm even at high humidity levels (>80% RH), and it is capable of differentiating ammonia at low concentrations (0.1-5 ppm) from CO2. The addition of diethylamine improved sensor performance such as selectivity, response/recovery time, and long-term stability. These data demonstrate the potential of using this sensor for the detection of food spoilage.

Ammonia detection: A pathway towards potential point-of-care diagnostics.

Invasive methods such as blood collection and biopsy are commonly used for testing liver and kidney function, which are painful, time-consuming, require trained personnel, and may not be easily accessible to people for their routine checkup. Early diagnosis of liver and kidney diseases can prevent severe symptoms and ensure better management of these patients. Emerging approaches such as breath and sweat analysis have shown potential as non-invasive methods for disease diagnosis. Among the many markers, ammonia is often used as a biomarker for the monitoring of liver and kidney functions. In this review we provide an insight into the production and expulsion of ammonia gas in the human body, the different diseases that could potentially use ammonia as biomarker and analytical devices such as chemiresistive gas sensors for non-invasive monitoring of this gas. The review also provides an understanding into the different materials, doping agents and substrates used to develop such multifunctional sensors. Finally, the current challenges and the possible future trends have been discussed.

Evolution of CRISPR-enabled biosensors for amplification-free nucleic acid detection.

CRISPR biosensors enable rapid and accurate detection of nucleic acids without resorting to target amplification. Specifically, these systems facilitate the simultaneous detection of multiple nucleic acid targets with single-base specificity. This is an invaluable asset that can ultimately facilitate accurate diagnoses of biologically complex diseases.

Bioinspired polymeric heart valves: A combined in vitro and in silico approach.

Background: Polymeric heart valves (PHVs) may address the limitations of mechanical and tissue valves in the treatment of valvular heart disease. In this study, a bioinspired valve was designed, assessed in silico, and validated by an in vitro model to develop a valve with optimum function for pediatric applications. Methods: A bioinspired heart valve was created computationally with leaflet curvature derived from native valve anatomies. A valve diameter of 18 mm was chosen to approach sizes suitable for younger patients. Valves of different thicknesses were fabricated via dip-coating with siloxane-based polyurethane and tested in a pulse duplicator for their hydrodynamic function. The same valves were tested computationally using an arbitrary Lagrangian-Eulerian plus immersed solid approach, in which the fluid-structure interaction between the valves and fluid passing through them was studied and compared with experimental data. Results: Computational analysis showed that valves of 110 to 200 µm thickness had effective orifice areas (EOAs) of 1.20 to 1.30 cm2, with thinner valves exhibiting larger openings. In vitro tests demonstrated that PHVs of similar thickness had EOAs of 1.05 to 1.35 cm2 and regurgitant fractions (RFs) <7%. Valves with thinner leaflets exhibited optimal systolic performance, whereas thicker valves had lower RFs. Conclusions: Bioinspired PHVs demonstrated good hydrodynamic performance that exceeded ISO 5840-2 standards. Both methods of analysis showed similar correlations between leaflet thickness and valve systolic function. Further development of this PHV may lead to enhanced durability and thus a more reliable heart valve replacement than contemporary options.

Strategies for senolytic drug discovery.

Senolytics are a category of drugs that reduce the impact of cellular senescence, an effect associated with a range of chronic and age-related diseases. Since the discovery of the first senolytics in 2015, the number of known senolytic agents has grown dramatically. This review discusses the broad categories of known senolytics-kinase inhibitors, Bcl-2 family protein inhibitors, naturally occurring polyphenols, heat shock protein inhibitors, BET family protein inhibitors, P53 stabilizers, repurposed anti-cancer drugs, cardiac steroids, PPAR-alpha agonists, and antibiotics. The approaches used to screen for new senolytics are articulated including a range of methods to induce senescence, different target cell types, various senolytic assays, and markers. The choice of methods can greatly influence the outcomes of a screen, with high-quality screens featuring robust systems, adequate controls, and extensive validation in alternate assays. Recent advances in single-cell analysis and computational methods for senolytic identification are also discussed. There is significant potential for further drug discovery, but this will require additional research into drug targets and mechanisms of actions and their subsequent rigorous evaluation in pre-clinical models and human trials.

Synthesis and Evaluation of Functionalized Polyurethanes for pH-Responsive Delivery of Compounds in Chronic Wounds.

Chronic wounds, depending on the bacteria that caused the infection, can be associated with an extreme acidic or basic pH. Therefore, the application of pH-responsive hydrogels has been instigated for the delivery of therapeutics to chronic wounds. Herein, with the aim of developing a flexible pH-responsive hydrogel, we functionalized hydrophilic polyurethanes with either cationic (polyethylene imine) or anionic (succinic anhydride) moieties. A comprehensive physicochemical characterization of corresponding polymers was carried out. Particularly, when tested in aqueous buffers, the surface charge of hydrogel films was closely correlated with the pH of the buffers. The loading of the cationic and anionic hydrogel films with various compound models (bromophenol blue; negatively charged or Pyronin Y; positively charged) showed that the electrostatic forces between the polymeric backbone and the compound model will determine the ultimate release rate at any given pH. The potential application of these films for chronic wound drug delivery was assessed by loading them with an antibiotic (ciprofloxacin). In vitro bacterial culturing was performed using Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Results showed that at the same drug dosage, different release profiles achievable from cationic and anionic polyurethanes can yield different degrees of an antibacterial effect. Overall, our results suggest the potential application of cationic and anionic hydrophilic polyurethanes as flexible pH-responsive materials for the delivery of therapeutics to chronic wounds.

Pediatric pulmonary valve replacements: Clinical challenges and emerging technologies.

Congenital heart diseases (CHDs) frequently impact the right ventricular outflow tract, resulting in a significant incidence of pulmonary valve replacement in the pediatric population. While contemporary pediatric pulmonary valve replacements (PPVRs) allow satisfactory patient survival, their biocompatibility and durability remain suboptimal and repeat operations are commonplace, especially for very young patients. This places enormous physical, financial, and psychological burdens on patients and their parents, highlighting an urgent clinical need for better PPVRs. An important reason for the clinical failure of PPVRs is biofouling, which instigates various adverse biological responses such as thrombosis and infection, promoting research into various antifouling chemistries that may find utility in PPVR materials. Another significant contributor is the inevitability of somatic growth in pediatric patients, causing structural discrepancies between the patient and PPVR, stimulating the development of various growth-accommodating heart valve prototypes. This review offers an interdisciplinary perspective on these challenges by exploring clinical experiences, physiological understandings, and bioengineering technologies that may contribute to device development. It thus aims to provide an insight into the design requirements of next-generation PPVRs to advance clinical outcomes and promote patient quality of life.

In vitro and in vivo applications of a universal and synthetic thermo-responsive drug delivery hydrogel platform.

A synthetic and thermo-responsive polymer, poly(N-isopropylacrylamide)-co-(polylactide/2-hydroxy methacrylate)-co-(oligo (ethylene glycol)), is used to formulate a universal carrier platform for sustained drug release. The enabling carrier, denoted as TP, is prepared by dissolving the polymer in an aqueous solution at a relatively neutral pH. A wide range of therapeutic moieties can be incorporated without the need for the addition of surfactants, organic solvents, and other reagents to the carrier system. The resulting solution is flowable through fine gauge needle, allowing accurate administration of TP to the target site. After injection, TP carrier undergoes a coil to globe phase transition to form a hydrogel matrix at the site. The benign nature of the polymer carrier and its physical gelation process are essential to preserve the biological activity of the encapsulated compounds while the adhesive hydrogel nature of the matrix allows sustained elusion and controlled delivery of the incorporated therapeutics. The TP carrier system has been shown to be non-toxic and elicits a minimal inflammatory response in multiple in vitro studies. These findings suggest the suitability of TP as an enabling carrier of therapeutics for localized and sustained drug delivery. To confirm this hypothesis, the capabilities of TP to encapsulate and effectively deliver multiple therapeutics of different physicochemical characteristics was evaluated. Specifically, a broad range of compounds were tested, including ciprofloxacin HCl, tumor necrosis factor-alpha (TNF-α), transforming growth factor beta 1 (TGF-ß1), and recombinant human bone morphogenetic protein 2 (BMP2). In vitro studies confirmed that TP carrier is able to control the release of the encapsulated drugs over an extended period of time and mitigate their burst release regardless of the compounds' physiochemical properties for the majority of the loaded therapeutics. Importantly, in vitro and in vivo animal studies showed that the released drugs from the TP hydrogel matrix remained potent and bioactive, confirming the high potential of the TP polymer system as an enabling carrier.

Biopolymeric Coatings for Local Release of Therapeutics from Biomedical Implants.

The deployment of structures that enable localized release of bioactive molecules can result in more efficacious treatment of disease and better integration of implantable bionic devices. The strategic design of a biopolymeric coating can be used to engineer the optimal release profile depending on the task at hand. As illustrative examples, here advances in delivery of drugs from bone, brain, ocular, and cardiovascular implants are reviewed. These areas are focused to highlight that both hard and soft tissue implants can benefit from controlled localized delivery. The composition of biopolymers used to achieve appropriate delivery to the selected tissue types, and their corresponding outcomes are brought to the fore. To conclude, key factors in designing drug-loaded biopolymeric coatings for biomedical implants are highlighted.

From Scan to Simulation-A Novel Workflow for Developing Bioinspired Heart Valves.

Current heart valve replacements lack durability and prolonged performance, especially in pediatric patients. In part, these problems may be attributed to the materials chosen for these constructs, but another important contributing factor is the design of the valve, as this dictates hemodynamic performance and impacts leaflet stresses which may accelerate structural valve deterioration. Most current era bioprosthetic valves adhere to a fundamental design where flat leaflets are supported by commissural posts, secured to a sewing ring. This overall design strategy is effective, but functionality and durability can be improved by incorporating features of the native valve geometry. This paper presents a novel workflow for developing and analyzing bio-inspired valve designs computationally. The leaflet curvature was defined using a mathematical equation whose parameters were derived from the three-dimensional model of a native sheep pulmonary valve obtained via microcomputed tomography. Finite element analysis was used to screen the various valve designs proposed in this study by assessing the effect of leaflet thickness, Young's modulus, and height/curvature on snap-through (where leaflets bend against their original curvature), geometric orifice area (GOA) and the stress in the leaflets. This workflow demonstrated benefits for valve designs with leaflet thicknesses between 0.1 and 0.3 mm, Young's moduli less than 50 MPa, and elongated leaflets with higher curvatures. The proposed workflow brings substantial efficiency gains at the design stage, minimizing manufacturing and animal testing during iterative improvements, and offers a bridge between in vitro and more complex in silico studies in the future.

Carbon dots: a novel platform for biomedical applications.

Carbon dots (CDs) are a recently synthesised class of carbon-based nanostructures known as zero-dimensional (0D) nanomaterials, which have drawn a great deal of attention owing to their distinctive features, which encompass optical properties (e.g., photoluminescence), ease of passivation, low cost, simple synthetic route, accessibility of precursors and other properties. These newly synthesised nano-sized materials can replace traditional semiconductor quantum dots, which exhibit significant toxicity drawbacks and higher cost. It is demonstrated that their involvement in diverse areas of chemical and bio-sensing, bio-imaging, drug delivery, photocatalysis, electrocatalysis and light-emitting devices consider them as flawless and potential candidates for biomedical application. In this review, we provide a classification of CDs within their extended families, an overview of the different methods of CDs preparation, especially from natural sources, i.e., environmentally friendly and their unique photoluminescence properties, thoroughly describing the peculiar aspects of their applications in the biomedical field, where we think they will thrive as the next generation of quantum emitters. We believe that this review covers a niche that was not reviewed by other similar publications.

Thermoresponsive and Injectable Hydrogel for Tissue Agnostic Regeneration.

Injectable hydrogels can support the body's innate healing capability by providing a temporary matrix for host cell ingrowth and neovascularization. The clinical adoption of current injectable systems remains low due to their cumbersome preparation requirements, device malfunction, product dislodgment during administration, and uncontrolled biological responses at the treatment site. To address these challenges, a fully synthetic and ready-to-use injectable biomaterial is engineered that forms an adhesive hydrogel that remains at the administration site regardless of defect anatomy. The product elicits a negligible local inflammatory response and fully resorbs into nontoxic components with minimal impact on internal organs. Preclinical animal studies confirm that the engineered hydrogel upregulates the regeneration of both soft and hard tissues by providing a temporary matrix to support host cell ingrowth and neovascularization. In a pilot clinical trial, the engineered hydrogel is successfully administered to a socket site post tooth extraction and forms adhesive hydrogel that stabilizes blood clot and supports soft and hard tissue regeneration. Accordingly, this injectable hydrogel exhibits high therapeutic potential and can be adopted to address multiple unmet needs in different clinical settings.

High throughput genome scale modeling predicts microbial vitamin requirements contribute to gut microbiome community structure.

Human gut microbiome structure and emergent metabolic outputs impact health outcomes. However, what drives such community characteristics remains underexplored. Here, we rely on high throughput genomic reconstruction modeling, to infer the metabolic attributes and nutritional requirements of 816 gut strains, via a framework termed GEMNAST. This has been performed in terms of a group of human vitamins to examine the role vitamin exchanges have at different levels of community organization. We find that only 91 strains can satisfy their vitamin requirements (prototrophs) while the rest show various degrees of auxotrophy/specialization, highlighting their dependence on external sources, such as other members of the microbial community. Further, 79% of the strains in our sample were mapped to 11 distinct vitamin requirement profiles with low phylogenetic consistency. Yet, we find that human gut microbial community enterotype indicators display marked metabolic differences. Prevotella strains display a metabolic profile that can be complemented by strains from other genera often associated with the Prevotella enterotype and agrarian diets, while Bacteroides strains occupy a prototrophic profile. Finally, we identify pre-defined interaction modules (IMs) of gut species from human and mice predicted to be driven by, or highly independent of vitamin exchanges. Our analysis provides mechanistic grounding to gut microbiome stability and to co-abundance-based observations, a fundamental step toward understanding emergent processes that influence health outcomes. Further, our work opens a path to future explorations in the field through applications of GEMNAST to additional nutritional dimensions.

Electrical Response of Poly(N-[3-(dimethylamino)Propyl] Methacrylamide) to CO2 at a Long Exposure Period.

Amine-functionalized polymers (AFPs) are able to react with carbon dioxide (CO2) and are therefore useful in CO2 capture and sensing. To develop AFP-based CO2 sensors, it is critical to examine their electrical responses to CO2 over long periods of time, so that the device can be used consistently for measuring CO2 concentration. To this end, we synthesized poly(N-[3-(dimethylamino)propyl] methacrylamide) (pDMAPMAm) by free radical polymerization and tested its ability to behave as a CO2-responsive polymer in a transducer. The electrical response of this polymer to CO2 upon long exposure times was measured in both the aqueous and solid phases. Direct current resistance measurement tests on pDMAPMAm films printed along with the silver electrodes in the presence of CO2 at various concentrations reveal a two-region electrical response. Upon continuous exposure to different CO2 flow rates (at a constant pressure of 0.2 MPa), the resistance first decreased over time, reaching a minimum, followed by a gradual increase with further exposure to CO2. A similar trend is observed when CO2 is introduced to an aqueous solution of pDMAPMAm. The in situ monitoring of pH suggests that the change in resistance of pDMAPMAm can be attributed to the protonation of tertiary amine groups in the presence of CO2. This two-region response of pDMAPMAm is based on a proton-hopping mechanism and a change in the number of free amines when pDMAPMAm is exposed to various levels of CO2.

Flexible Sensors for Hydrogen Peroxide Detection: A Critical Review.

Hydrogen peroxide (H2O2) is a common chemical used in many industries and can be found in various biological environments, water, and air. Yet, H2O2 in a certain range of concentrations can be hazardous and toxic. Therefore, it is crucial to determine its concentration at different conditions for safety and diagnostic purposes. This review provides an insight about different types of sensors that have been developed for detection of H2O2. Their flexibility, stability, cost, detection limit, manufacturing, and challenges in their applications have been compared. More specifically the advantages and disadvantages of various flexible substrates that have been utilized for the design of H2O2 sensors were discussed. These substrates include carbonaceous substrates (e.g., reduced graphene oxide films, carbon cloth, carbon, and graphene fibers), polymeric substrates, paper, thin glass, and silicon wafers. Many of these substrates are often decorated with nanostructures composed of Pt, Au, Ag, MnO2, Fe3O4, or a conductive polymer to enhance the performance of sensors. The impact of these nanostructures on the sensing performance of resulting flexible H2O2 sensors has been reviewed in detail. In summary, the detection limits of these sensors are within the range of 100 nM-1 mM, which makes them potentially, but not necessarily, suitable for applications in health, food, and environmental monitoring. However, the required sample volume, cost, ease of manufacturing, and stability are often neglected compared to other detection parameters, which hinders sensors' real-world application. Future perspectives on how to address some of the substrate limitations and examples of application-driven sensors are also discussed.

Identifying HSV-1 Inhibitors from Natural Compounds via Virtual Screening Targeting Surface Glycoprotein D.

Herpes simplex virus (HSV) infections are a worldwide health problem in need of new effective treatments. Of particular interest is the identification of antiviral agents that act via different mechanisms compared to current drugs, as these could interact synergistically with first-line antiherpetic agents to accelerate the resolution of HSV-1-associated lesions. For this study, we applied a structure-based molecular docking approach targeting the nectin-1 and herpesvirus entry mediator (HVEM) binding interfaces of the viral glycoprotein D (gD). More than 527,000 natural compounds were virtually screened using Autodock Vina and then filtered for favorable ADMET profiles. Eight top hits were evaluated experimentally in African green monkey kidney cell line (VERO) cells, which yielded two compounds with potential antiherpetic activity. One active compound (1-(1-benzofuran-2-yl)-2-[(5Z)-2H,6H,7H,8H-[1,3] dioxolo[4,5-g]isoquinoline-5-ylidene]ethenone) showed weak but significant antiviral activity. Although less potent than antiherpetic agents, such as acyclovir, it acted at the viral inactivation stage in a dose-dependent manner, suggesting a novel mode of action. These results highlight the feasibility of in silico approaches for identifying new antiviral compounds, which may be further optimized by medicinal chemistry approaches.

Biopolymer-Based Multilayer Microparticles for Probiotic Delivery to Colon.

The potential health benefits of probiotics may not be realized because of the substantial reduction in their viability during food storage and gastrointestinal transit. Microencapsulation has been successfully utilized to improve the resistance of probiotics to critical conditions. Owing to the unique properties of biopolymers, they have been prevalently used for microencapsulation of probiotics. However, majority of microencapsulated products only contain a single layer of protection around probiotics, which is likely to be inferior to more sophisticated approaches. This review discusses emerging methods for the multilayer encapsulation of probiotic using biopolymers. Correlations are drawn between fabrication techniques and the resultant microparticle properties. Subsequently, multilayer microparticles are categorized based on their layer designs. Recent reports of specific biopolymeric formulations are examined regarding their physical and biological properties. In particular, animal models of gastrointestinal transit and disease are highlighted, with respect to trials of multilayer microencapsulated probiotics. To conclude, novel materials and approaches for fabrication of multilayer structures are highlighted.