In vitro characterization of sonothrombolysis and echocontrast agents to treat ischemic stroke

The development of adjuvant techniques to improve thrombolytic efficacy is important for advancing ischemic stroke therapy. We characterized octafluoropropane and recombinant tissue plasminogen activator (rt-PA)-loaded echogenic liposomes (OFP t-ELIP) using differential interference and fluorescence microscopy, attenuation spectroscopy, and electrozone sensing. The loading of rt-PA in OFP t-ELIP was assessed using spectrophotometry. Further, it was tested whether the agent shields rt-PA against degradation by plasminogen activator inhibitor-1 (PAI-1). An in vitro system was used to assess whether ultrasound (US) combined with either Definity or OFP t-ELIP enhances rt-PA thrombolysis. Human whole blood clots were mounted in a flow system and visualized using an inverted microscope. The perfusate consisted of either (1) plasma alone, (2) rt-PA, (3) OFP t-ELIP, (4) rt-PA and US, (5) OFP t-ELIP and US, (6) Definity and US, or (7) rt-PA, Definity, and US (n = 16 clots per group). An intermittent US insonation scheme was employed (220 kHz frequency, and 0.44 MPa peak-to-peak pressures) for 30 min. Microscopic imaging revealed that OFP t-ELIP included a variety of structures such as liposomes (with and without gas) and lipid-shelled microbubbles. OFP t-ELIP preserved up to 76% of rt-PA activity in the presence of PAI-1, whereas only 24% activity was preserved for unencapsulated rt-PA. The use of US with rt-PA and Definity enhanced lytic efficacy (p \u3c 0.05) relative to rt-PA alone. US combined with OFP t-ELIP enhanced lysis over OFP t-ELIP alone (p \u3c 0.01). These results demonstrate that ultrasound combined with Definity or OFP t-ELIP can enhance the lytic activity relative to rt-PA or OFP t-ELIP alone, respectively

<i>Terminalia arjuna</i>, a Cardioprotective Herbal Medicine–Relevancy in the Modern Era of Pharmaceuticals and Green Nanomedicine—A Review

Herbal medicines were the main source of therapeutic agents in the ancestral era. Terminalia arjuna (TA) is one such medicinal plant widely known for its several medicinal properties, especially its cardiovascular properties. They have several phytochemicals, such as flavonoids, polyphenols, triterpenoids, tannins, glycosides, and several minerals, proteins, and others that are responsible for the above-mentioned medicinal properties. In this review, we have first elaborated on the various processes and their parameters for the efficient extraction of relevant phytochemicals from TA extracts. Secondly, the mechanisms behind the various medicinal properties of TA extracts are explained. We have also highlighted the role of TA extracts on the green synthesis of metallic nanoparticles, especially silver and gold nanoparticles, with an elucidation on the mechanisms behind the synthesis of nanoparticles. Finally, TA extracts-based polymeric formulations are discussed with limitations and future perspectives. We believe that this review could help researchers understand the importance of a well-known cardioprotective medicinal plant, TA, and its biomedical properties, as well as their role in green nanotechnology and various formulations explored for encapsulating them. This review will help researchers design better and greener nanomedicines as well as better formulations to improve the stability and bioavailability of TA extracts

Evaluation of non-cross linked xeno-free hyaluronic acid solutions as visco elastic biomaterials

Background: Hyaluronic acid (HA) is a naturally occurring biodegradable, high molecular weight, non-sulfated glycosaminoglycan (GAG) polymer known for its excellent biocompatibility. HA-based products are widely used as viscosupplements, dermal fillers, and ophthalmic lubricants in clinical settings. Although animal and bacterial-derived HA are commonly reported, plant-sourced HA is not frequently reported. In this study, we have evaluated various viscoelastic properties of one such plant-based HA solution and propose them as an alternative to existing animal/bacteria-sourced HA. Materials and Methods: The viscoelastic properties of plant-sourced HA solution of various concentrations (0.1%, 0.5%, 1%, and 2% in PBS) were studied using a rheometer at 37°C. Flow curves, amplitude sweep studies, and frequency sweep studies were performed and compared for all HA solutions. Results: The HA solutions displayed shear-thinning behavior, which is an important characteristic of an injectable biomaterial. The 0.1 and 0.5% HA were found to have viscoelastic properties appropriate for eye lubricants, while 1 and 2% HA solutions showed properties suitable for soft tissue fillers. Frequency sweep studies indicated that all the samples are typically viscoelastic liquids with a loss modulus (G″) higher than the storage modulus (G′). This indicated that the samples needed further processing like crosslinking of HA or using higher molecular weight HA to be suitable as viscosupplements. However, the frequency sweep studies also indicated that these solutions can be used as soft tissue fillers of any type based on the G′ and tan δ values. Conclusion: The plant-sourced HA solutions are found to exhibit good shear-thinning properties with viscoelastic properties suitable for eye lubricants and soft tissue fillers. However, to be used as viscosupplements, the viscoelastic properties of HA solutions have to be further modified through non-toxic crosslinking strategies, and hydrophobic derivatives as well as by using high molecular weight HAs

ZigBee enabled IoT based intelligent lane control system for autonomous agricultural electric vehicle application

The paper develops an investigative ZigBee IoT based intelligent lane control mechanism for India’s first field ready electric tractors, Sonalika Tiger Electric to operate with the chosen constraints. It employs the state-of-the-art Microcontroller based embedded system to govern the comprehensive requirements in accordance with the changes that the vehicle either experiences or becomes necessary for it to negotiate. The design involves the bounding of the parameters that include the vehicle speed, engine speed, battery SoC (State of Charge), battery SoH (State of Health), a real time GPS navigator along with Edge/ Boundary Detection Algorithm which enters the system using ZigBee enabled wireless sensors and IoT based maps to incorporate the lane control system. It primarily ensures a close monitoring methodology to develop a sequence of steps that allow the system to remain in operation over scheduled durations. The procedure involves a simulation process carried out using embedded-c firmware code to epitomize the virtues of the proposed scheme and elicit the performance of the chosen vehicle in terms of its ability to operate at the predefined constraints

Recent Advances in Two-Dimensional MXene-Based Electrochemical Biosensors for Sweat Analysis

Sweat, a biofluid secreted naturally from the eccrine glands of the human body, is rich in several electrolytes, metabolites, biomolecules, and even xenobiotics that enter the body through other means. Recent studies indicate a high correlation between the analytes’ concentrations in the sweat and the blood, opening up sweat as a medium for disease diagnosis and other general health monitoring applications. However, low concentration of analytes in sweat is a significant limitation, requiring high-performing sensors for this application. Electrochemical sensors, due to their high sensitivity, low cost, and miniaturization, play a crucial role in realizing the potential of sweat as a key sensing medium. MXenes, recently developed anisotropic two-dimensional atomic-layered nanomaterials composed of early transition metal carbides or nitrides, are currently being explored as a material of choice for electrochemical sensors. Their large surface area, tunable electrical properties, excellent mechanical strength, good dispersibility, and biocompatibility make them attractive for bio-electrochemical sensing platforms. This review presents the recent progress made in MXene-based bio-electrochemical sensors such as wearable, implantable, and microfluidic sensors and their applications in disease diagnosis and developing point-of-care sensing platforms. Finally, the paper discusses the challenges and limitations of MXenes as a material of choice in bio-electrochemical sensors and future perspectives on this exciting material for sweat-sensing applications

Efficient photocatalytic degradation of textile dye pollutants using thermally exfoliated graphitic carbon nitride (TE–g–C3N4)

Abstract Graphitic carbon nitride (g–C3N4), an organic photocatalyst was reported to have beneficial properties to be used in wastewater treatment applications. However, g–C3N4, in its bulk form was found to have poor photocatalytic degradation efficiency due to its inherent limitations such as poor specific surface area and fast electron–hole pair recombination rate. In this study, we have tuned the physiochemical properties of bulk g–C3N4 by direct thermal exfoliation (TE–g–C3N4) and examined their photocatalytic degradation efficiency against abundant textile dyes such as methylene blue (MB), methyl orange (MO), and rhodamine B (RhB). The degradation efficiencies for MB, MO, and RhB dyes are 92 ± 0.18%, 93 ± 0.31%, and 95 ± 0.4% respectively in 60 min of UV light irradiation. The degradation efficiency increased with an increase in the exfoliation temperature. The prepared catalysts were characterized using FTIR, XRD, FE-SEM, EDAX, BET, and UV-DRS. In BET analysis, TE–g–C3N4 samples showed improved surface area (48.20 m2/g) when compared to the bulk g–C3N4 (5.03 m2/g). Further, the TE–g–C3N4 had 2.98 times higher adsorption efficiency than the bulk ones. The free radicals scavenging studies revealed that the superoxide radicals played an important role in the photodegradation for dyes, when compared to the hydroxyl radical (.OH) and the photo-induced holes (h+), Photoluminescence (PL) emission and electrochemical impedance spectroscopy (EIS) spectra of TE–g–C3N4 indicated a lowered electron–hole pairs’ recombination rate and an increased photo-induced charge transfer respectively. Further, the TE–g–C3N4 were found to have excellent stability for up to 5 cycles with only a minor decrease in the activity from 92% to 86.2%. These findings proved that TE–g–C3N4 was an excellent photocatalyst for the removal and degradation of textile dyes from wastewater

Fabrication and Characterization Techniques of In Vitro 3D Tissue Models

The culturing of cells in the laboratory under controlled conditions has always been crucial for the advancement of scientific research. Cell-based assays have played an important role in providing simple, fast, accurate, and cost-effective methods in drug discovery, disease modeling, and tissue engineering while mitigating reliance on cost-intensive and ethically challenging animal studies. The techniques involved in culturing cells are critical as results are based on cellular response to drugs, cellular cues, external stimuli, and human physiology. In order to establish in vitro cultures, cells are either isolated from normal or diseased tissue and allowed to grow in two or three dimensions. Two-dimensional (2D) cell culture methods involve the proliferation of cells on flat rigid surfaces resulting in a monolayer culture, while in three-dimensional (3D) cell cultures, the additional dimension provides a more accurate representation of the tissue milieu. In this review, we discuss the various methods involved in the development of 3D cell culture systems emphasizing the differences between 2D and 3D systems and methods involved in the recapitulation of the organ-specific 3D microenvironment. In addition, we discuss the latest developments in 3D tissue model fabrication techniques, microfluidics-based organ-on-a-chip, and imaging as a characterization technique for 3D tissue models

Chitosan as Functional Biomaterial for Designing Delivery Systems in Cardiac Therapies

Cardiovascular diseases are a leading cause of mortality across the globe, and transplant surgeries are not always successful since it is not always possible to replace most of the damaged heart tissues, for example in myocardial infarction. Chitosan, a natural polysaccharide, is an important biomaterial for many biomedical and pharmaceutical industries. Based on the origin, degree of deacetylation, structure, and biological functions, chitosan has emerged for vital tissue engineering applications. Recent studies reported that chitosan coupled with innovative technologies helped to load or deliver drugs or stem cells to repair the damaged heart tissue not just in a myocardial infarction but even in other cardiac therapies. Herein, we outlined the latest advances in cardiac tissue engineering mediated by chitosan overcoming the barriers in cardiac diseases. We reviewed in vitro and in vivo data reported dealing with drug delivery systems, scaffolds, or carriers fabricated using chitosan for stem cell therapy essential in cardiac tissue engineering. This comprehensive review also summarizes the properties of chitosan as a biomaterial substrate having sufficient mechanical stability that can stimulate the native collagen fibril structure for differentiating pluripotent stem cells and mesenchymal stem cells into cardiomyocytes for cardiac tissue engineering

In vitro cytotoxicity evaluation of flowable hyaluronic acid–acellular stromal vascular fraction (HA–aSVF) mixture for tissue engineering applications

Background: The stromal vascular fraction (SVF) is an aqueous fraction isolated from the adipose tissue that constitutes different kinds of cells and extracellular matrix components. Hyaluronic acid (HA) is a linear polysaccharide in vertebrate tissues and is considered a potential tissue engineering scaffold due to its biocompatible nature. In this study, we have evaluated the cytotoxicity of xenofree HA in combination with an acellular component of adipose SVF (HA–aSVF) to propose it as a candidate biomaterial for future applications. Materials and Methods: 3-(4,5-dimethyl thiazolyl-2)-2,5-diphenyltetrazolium bromide assay of L-929 cells treated with HA–aSVF was used in our study. Data were normalized to cell control (untreated) and extracts of copper and ultra-high molecular weight polyethylene were used as positive (PC) and negative controls (NC). Results: Fibroblast cells retained the morphology after 24 h of treatment with HA–aSVF mixture and exhibited a similar percentage of cell activity compared to NC. PC showed a positive cytotoxic response as expected. The cells incubated with HA–aSVF showed a linear increase in cell activity indicating proliferation. Conclusion: The mixture of HA and acellular SVF in its flowable form is non-cytotoxic and showed improved cell proliferation. Hence the mixture can be proposed as a biomaterial and can be further explored for specific tissue engineering applications