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Developing thermoelectric films without substrates—free-standing films—eliminates substrate-induced effects on performance and meets the flexibility requirements of emerging wearable thermoelectric applications. This study investigates Gallium-doped Zinc Oxide (GZO), composed of abundant and non-toxic elements, to fabricate a substrate-free GZO film via 3D printing and compares its structural, chemical, and thermoelectric properties with those of a substrate-constrained GZO film produced through chemical deposition. Both films exhibited uniform crystal structures and phase purity; however, the substrate-constrained film displayed additional diffraction peaks, suggesting potential substrate interactions. The 3D-printed free-standing film effectively eliminated the tensile stresses observed in the substrate-constrained film. FE-STEM analysis revealed nanostructures with homogeneous elemental distribution in both films, though the substrate-constrained film showed discontinuities, such as pores, likely caused by post-deposition annealing treatment. XPS analysis highlighted differences in chemical states and elemental compositions between the films, influenced by fabrication methods, substrate-induced stresses, and surface energy mismatches. The free-standing GZO film developed through 3D printing exhibited a more balanced incorporation of Zn and O, as it was not subject to substrate or post-deposition annealing constraints. Consequently, it demonstrated a 14 % increase in electrical conductivity and a 91 % improvement in the Seebeck coefficient compared to the substrate-constrained film, resulting in a higher room-temperature power factor of 261 nW/m·K2. These findings underscore the potential of 3D-printed free-standing GZO films to advance thermoelectric applications, offering a promising alternative to overcome the challenges of substrate-constrained films and further drive innovation in the field.

Hydrogels are three-dimensional structures that serve as substitutes for the extracellular matrix (ECM) and possess outstanding physicochemical and biochemical characteristics. They are gaining importance in regenerative medicine because of their similarity to the natural extracellular matrix in terms of moisture content and wound and tissue healing permeability. Tissue engineering advancements have resulted in the development of flexible hydrogels that mimic the dynamic characteristics of the ECM. Several approaches have been applied to produce hydrogels from biopolymers with enhanced functional and structural characteristics for different applications in tissue engineering and regenerative medicine (TERM). This review provides a comprehensive overview of hydrogel in wound healing, tissue engineering, and drug delivery systems. We outline different types of hydrogels based on the physical and chemical crosslinking, fundamental properties, and their applications in TERM. This review article provided the recent literature on hydrogels for tissue engineering and regenerative medicine within five years. Recent developments in biopolymer-based hydrogels for state-of-the-art tissue engineering and regenerative medicine have been discussed, emphasizing their significant challenges and future perspectives.

Abstract Diabetes Mellitus is a metabolic disease characterized by elevated blood sugar levels caused by inadequate insulin production, which subsequently leads to hyperglycemia. This study was aimed to investigate the antidiabetic potential of pyrazolobenzothiazine derivatives in silico, in vitro, and in vivo. Molecular docking of pyrazolobenzothiazine derivatives was performed against α-glucosidase and α-amylase and compounds were selected based on docking score, bonding interactions and low root mean square deviation (RMSD). Enzyme inhibition assay against α-glucosidase and α-amylase was performed in vitro using p-nitrophenyl-α-D-glucopyranoside (PNPG) and starch substrate. Synthetic compound pyrazolobenzothiazine (S1) exhibited minimal conformational changes during the 100 ns MD simulation run. S1 also revealed effective IC50 values for α-glucosidase (3.91 µM) and α-amylase (8.89 µM) and an enzyme kinetic study showed low ki (− 0.186 µM, − 1.267 µM) and ki′ (− 0.691 µM, − 1.78 µM) values with the competitive type of inhibition for both enzymes α-glucosidase and α-amylase, respectively. Moreover, studies were conducted to check the effect of the synthetic compound in a mouse model. A low necrosis rate was observed in the liver, kidney, and pancreas through histology analysis performed on mice. Compound S1 also exhibited a good biochemical profile with lower sugar level (110–115 mg/dL), increased insulin level (25–30 μM/L), and low level of cholesterol (85 mg/dL) and creatinine (0.6 mg/dL) in blood. The treated mice group also exhibited a low % of glycated haemoglobin (3%). This study concludes that S1 is a new antidiabetic-agent that helps lower blood glucose levels and minimizes the complications associated with type-II diabetes.

Computer-aided disease diagnosis and prognosis based on medical images is a rapidly emerging field. Many Convolutional Neural Network (CNN) architectures have been developed by researchers for disease classification and localization from chest X-ray images. It is known that different thoracic disease lesions are more likely to occur in specific anatomical regions compared to others. This article aims to incorporate this disease and region-dependent prior probability distribution within a deep learning framework. We present the ThoraX-PriorNet, a novel attention-based CNN model for thoracic disease classification. We first estimate a disease-dependent spatial probability, i.e., an anatomical prior, that indicates the probability of occurrence of a disease in a specific region in a chest X-ray image. Next, we develop a novel attention-based classification model that combines information from the estimated anatomical prior and automatically extracted chest region of interest (ROI) masks to provide attention to the feature maps generated from a deep convolution network. Unlike previous works that utilize various self-attention mechanisms, the proposed method leverages the extracted chest ROI masks along with the probabilistic anatomical prior information, which selects the region of interest for different diseases to provide attention. The proposed method shows superior performance in disease classification on the NIH ChestX-ray14 dataset compared to existing state-of-the-art methods while reaching an area under the ROC curve (%AUC) of 84.67. Regarding disease localization, the anatomy prior attention method shows competitive performance compared to state-of-the-art methods, achieving an accuracy of 0.80, 0.63, 0.49, 0.33, 0.28, 0.21, and 0.04 with an Intersection over Union (IoU) threshold of 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, and 0.7, respectively. The proposed ThoraX-PriorNet can be generalized to different medical image classification and localization tasks where the probability of occurrence of the lesion is dependent on specific anatomical sites.

Abstract Alzheimer’s disease (AD) is a chronic illness marked by increasing cognitive decline and nervous system deterioration. At this time, there is no known medication that will stop the course of Alzheimer’s disease; instead, most symptoms are treated. Clinical trial failure rates for new drugs remain high, highlighting the urgent need for improved AD modeling for improving understanding of the underlying pathophysiology of disease and improving drug development. The development of induced pluripotent stem cells (iPSCs) has made it possible to model neurological diseases like AD, giving access to an infinite number of patient-derived cells capable of differentiating neuronal fates. This advance will accelerate Alzheimer’s disease research and provide an opportunity to create more accurate patient-specific models of Alzheimer’s disease to support pathophysiological research, drug development, and the potential application of stem cell-based therapeutics. This review article provides a complete summary of research done to date on the potential use of iPSCs from AD patients for disease modeling, drug discovery, and cell-based therapeutics. Current technological developments in AD research including 3D modeling, genome editing, gene therapy for AD, and research on familial (FAD) and sporadic (SAD) forms of the disease are discussed. Finally, we outline the issues that need to be elucidated and future directions for iPSC modeling in AD.

Functional genomics is an emerging field focused on elucidating the functions of genes or proteins, which can help solve challenges related to reliable cancer therapy. One of the main challenges currently faced by cancer therapy is the variations in the number of mutations in patients, leading to drug resistance and cancer relapses. Drug intrinsic or acquired resistance, is generally associated with most cancer relapses. There are advanced tools that can help identify the mutant genes in cancer tissues causing cancer drug resistance (CDR). Such tools include but are not limited to DNA and RNA sequencing as well assynthetic lethality gene screen (CRISPR)-based diagnosis. This review discusses the role of functional genomics in understanding CDR and finding tools for discovering drug target genes for cancer therapy.

Abstract Cancer is still the leading cause of death globally. The approval of the therapeutic use of monoclonal antibodies against immune checkpoint molecules, notably those that target the proteins PD-1 and PD-L1, has changed the landscape of cancer treatment. In particular, first-line PD-1/PD-L1 inhibitor drugs are increasingly common for the treatment of metastatic cancer, significantly prolonging patient survival. Despite the benefits brought by immune checkpoint inhibitors (ICIs)-based therapy, the majority of patients had their diseases worsen following a promising initial response. To increase the effectiveness of ICIs and advance our understanding of the mechanisms causing cancer resistance, it is crucial to find new, effective, and tolerable combination treatments. In this article, we addressed the potential of ICIs for the treatment of solid tumors and offer some insight into the molecular pathways behind therapeutic resistance to ICIs. We also discuss cutting-edge therapeutic methods for reactivating T-cell responsiveness after resistance has been established.

Chronic wounds are among the major healthcare issues affecting millions of people worldwide with high rates of morbidity, losses of limbs and mortality. Microbial infection in wounds is a severe problem that can impede healing of chronic wounds. Accurate, timely and early detection of infections, and real time monitoring of various wound healing biomarkers related to infection can be significantly helpful in the treatment and care of chronic wounds. However, clinical methodologies of periodic assessment and care of wounds require physical visit to wound care clinics or hospitals and time-consuming frequent replacement of wound dressing patches, which also often adversely affect the healing process. Besides, frequent replacements of wound dressings are highly expensive, causing a huge amount of burden on the national health care systems. Smart bandages have emerged to provide in situ physiochemical surveillance in real time at the wound site. These bandages integrate smart sensors to detect the condition of wound infection based on various parameters, such as pH, temperature and oxygen level in the wound which reduces the frequency of changing the wound dressings and its associated complications. These devices can continually monitor the healing process, paving the way for tailored therapy and improved quality of patient's life. In this review, we present an overview of recent advances in biosensors for real time monitoring of pH, temperature, and oxygen in chronic wounds in order to assess infection status. We have elaborated the recent progress in quantitative monitoring of several biomarkers important for assessing wounds infection status and its detection using smart biosensors. The review shows that real-time monitoring of wound status by quantifying specific biomarkers, such as pH, temperature and tissue oxygenation to significantly aid the treatment and care of chronic infected wounds.

Impaired wound healing is a major healthcare problem in patients with diabetes often resulting in gangrene, microbial infection and amputation of affected limb. The delay or absence in healing process arises from several abnormalities, among them chronic hypoxia is a major concern due to its associated issues such as lack of collagen deposition, epithelization, fibroplasia, angiogenesis, and resistance to infections at the wound site. To address hypoxia, delivery of oxygen at the wound site through oxygen releasing agents have been proven to be effective therapeutics. Several oxygen releasing nanoparticles such as Sodium Percarbonate (SPC), Calcium Peroxide (CPO), Hydrogen Peroxide, Magnesium Peroxide (MPO) have been investigated in wound healing application. However, the uncontrolled/burst release of these nanotherapeutic agents and its accompanied cytotoxicity pose a barrier in expediting the healing process. In this study, a Chitosan-Polyvinyl alcohol (CS-PVA) based hydrogel containing oxygen releasing nanoparticle, calcium peroxide (CPO) was constructed to provide a slow and sustained delivery of oxygen for at least 5 days. In-vitro cell culture studies with this material using fibroblast and endothelial cell line exhibited improved biocompatibility, cell viability and enhanced proliferation in comparison with the control group. Additionally, cell migration study using scratch assay method showed superior cell migration ability of our proposed materials. Furthermore, In vivo study using diabetic rat model showed accelerated wound closure rate compared to untreated control wounds.

This study aimed to optimize the preparation parameters for air-jet spun blended poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and polycaprolactone (PCL) submicron fibrous scaffolds. Blends of PHBV and PCL were made using different weight ratios of polymers and examined for their mechanical, morphological, and biological properties. The 50/50 ratio PHBV/PCL blend scaffolds showed better overall mechanical properties compared to the scaffolds with higher PHBV content and provided better cell attachment and proliferation compared to PCL scaffolds. The incorporation of PCL improved the degree of crystallinity, thermal stability, and mechanical properties of PHBV/PCL blend scaffolds. In vivo subcutaneous implantation and subsequent histological analysis of the implanted scaffolds indicated that the scaffolds were compatible with animal tissues. The findings show that air-jet spun PHBV/PCL blended scaffolds in a 50/50 ratio can be employed in many tissue engineering applications.

The heart sound signals captured via a digital stethoscope are often distorted by environmental and physiological noise, altering their salient and critical properties. The problem is exacerbated in crowded low-resource hospital settings with high noise levels which degrades the diagnostic performance. In this study, we present a novel deep encoder-decoder-based denoising architecture (LU-Net) to suppress ambient and internal lung sound noises. Training is done using a large benchmark PCG dataset mixed with physiological noise, i.e., breathing sounds. Two different noisy datasets were prepared for experimental evaluation by mixing unseen lung sounds and hospital ambient noises with the clean heart sound recordings. We also used the inherently noisy portion of the PASCAL heart sound dataset for evaluation. The proposed framework showed effective suppression of background noises in both unseen real-world data and synthetically generated noisy heart sound recordings, improving the signal-to-noise ratio (SNR) level by 5.575 dB on an average using only 1.32 M parameters. The proposed model outperforms the current state-of-the-art U-Net model with an average SNR improvement of 5.613 dB and 5.537 dB in the presence of lung sound and unseen hospital noise, respectively. LU-Net also outperformed the state-of-the-art Fully Convolutional Network (FCN) by 1.750 dB and 1.748 dB for lung sound and unseen hospital noise conditions, respectively. In addition, the proposed denoising method model improves classification accuracy by 38.93% in the noisy portion of the PASCAL heart sound dataset. The results presented in the paper indicate that our proposed architecture demonstrated a robust denoising performance on different datasets with diverse levels and characteristics of noise. The proposed deep learning-based PCG denoising approach is a pioneering study that can significantly improve the accuracy of computer-aided auscultation systems for detecting cardiac diseases in noisy, low-resource hospitals and underserved communities.

Abstract The primary purpose of ADCs is to increase the efficacy of anticancer medications by minimizing systemic drug distribution and targeting specific cells. Antibody conjugates (ADCs) have changed the way cancer is treated. However, because only a tiny fraction of patients experienced long-term advantages, current cancer preclinical and clinical research has been focused on combination trials. The complex interaction of ADCs with the tumor and its microenvironment appear to be reliant on the efficacy of a certain ADC, all of which have significant therapeutic consequences. Several clinical trials in various tumor types are now underway to examine the potential ADC therapy, based on encouraging preclinical results. This review tackles the potential use of ADCs in cancer therapy, emphasizing the essential processes underlying their positive therapeutic impacts on solid and hematological malignancies. Additionally, opportunities are explored to understand the mechanisms of ADCs action, the mechanism of resistance against ADCs, and how to overcome potential resistance following ADCs administration. Recent clinical findings have aroused interest, leading to a large increase in the number of ADCs in clinical trials. The rationale behind ADCs, as well as their primary features and recent research breakthroughs, will be discussed. We then offer an approach for maximizing the potential value that ADCs can bring to cancer patients by highlighting key ideas and distinct strategies.

Abstract EV produced by tumour cells carry a diverse population of proteins, lipids, DNA, and RNA molecules throughout the body and appear to play an important role in the overall development of the disease state, according to growing data. Gliomas account for a sizable fraction of all primary brain tumours and the vast majority of brain malignancies. Glioblastoma multiforme (GBM) is a kind of grade IV glioma that has a very dismal prognosis despite advancements in diagnostic methods and therapeutic options. The authors discuss advances in understanding the function of extracellular vesicles (EVs), in overall glioma growth, as well as how recent research is uncovering the utility of EVs in glioma diagnostics, prognostic and therapeutics approaches.

Abstract Background Glioblastoma multiforme (GBM) is a heterogeneous CNS neoplasm which causes significant morbidity and mortality. One reason for the poor prognostic outcome of GBM is attributed to the presence of cancer stem cells (CSC) which confer resistance against standard chemo- and radiotherapeutics modalities. Two types of GBM-associated CSC were isolated from the same patient: tumor core- (c-CSC) and peritumor tissue-derived cancer stem cells (p-CSC). Our experiments are focused on glioblastoma–IDH-wild type, and no disease-defining alterations were present in histone, BRAF or other genes. Methods In the present study, potential differences in genetic variants between c-CSC versus p-CSC derived from four GBM patients were investigated with the aims of (1) comparing the exome sequences between all the c-CSC or p-CSC to identify the common variants; (2) identifying the variants affecting the function of genes known to be involved in cancer origin and development. Results By comparative analyses, we identified common gene single nucleotide variants (SNV) in all GBM c-CSC and p-CSC, a potentially deleterious variant was a frameshift deletion at Gln461fs in the MLLT1 gene, that was encountered only in p-CSC samples with different allelic frequency. Conclusions We discovered a potentially harmful frameshift deletion at Gln461fs in the MLLT1 gene. Further investigation is required to confirm the presence of the identified mutations in patient tissue samples, as well as the significance of the frameshift mutation in the MLLT1 gene on GBM biology and response to therapy based on genomic functional experiments.

Abstract The p53 protein is a transcription factor known as the "guardian of the genome" because of its critical function in preserving genomic integrity. The TP53 gene is mutated in approximately half of all human malignancies, including those of the breast, colon, lung, liver, prostate, bladder, and skin. When DNA damage occurs, the TP53 gene on human chromosome 17 stops the cell cycle. If p53 protein is mutated, the cell cycle is unrestricted and the damaged DNA is replicated, resulting in uncontrolled cell proliferation and cancer tumours. Tumor-associated p53 mutations are usually associated with phenotypes distinct from those caused by the loss of the tumor-suppressing function exerted by wild-type p53protein. Many of these mutant p53 proteins have oncogenic characteristics, and therefore modulate the ability of cancer cells to proliferate, escape apoptosis, invade and metastasize. Because p53 deficiency is so common in human cancer, this protein is an excellent option for cancer treatment. In this review, we will discuss some of the molecular pathways by which mutant p53 proteins might perform their oncogenic activities, as well as prospective treatment methods based on restoring tumor suppressive p53 functions.

Background: Because enzymes can control several metabolic pathways and regulate the production of free radicals, their simultaneous use with nanoplatforms showing protective and combinational properties is of great interest in the development of therapeutic nano-based platforms. However, enzyme immobilization on nanomaterials is not straightforward due to the toxic and unpredictable properties of nanoparticles in medical practice. Aim of review: In fact, because of the ability to load enzymes on nano-based supports and increase their renewability, scientific groups have been tempted to create potential therapeutic enzymes in this field. Therefore, this study not only pays attention to the therapeutic and diagnostic applications of diseases by enzyme–nanoparticle (NP) bio-conjugate (abbreviated as: ENB), but also considers the importance of nanoplatforms used based on their toxicity, ease of application and lack of significant adverse effects on loaded enzymes. In the following, based on the published reports, we explained that the immobilization of enzymes on polymers, inorganic metal oxide and hybrid compounds provide hopes for potential use of ENBs in medical activities. Then, the use of ENBs in bioassay activities such as paper-based or wearing biosensors and lab-on-chip/microfluidic biosensors were evaluated. Finally, this review addresses the current challenges and future perspective of ENBs in biomedical applications. Key scientific concepts of review: This literature may provide useful information regarding the application of ENBs in biosensing and therapeutic platforms.

Abstract Glioblastoma multiforme (GBM) is one of the deadliest brain tumors with an unfavorable prognosis and overall survival of approximately 20 months following diagnosis. The current treatment for GBM includes surgical resections and chemo‐ and radiotherapeutic modalities, which are not effective. CAR‐T immunotherapy has been proven effective for CD19‐positive blood malignancies, and the application of CAR‐T cell therapy for solid tumors including GBM offers great hope for this aggressive tumor which has a limited response to current treatments. CAR‐T technology depends on the use of patient‐specific T cells genetically engineered to express specific tumor‐associated antigens (TAAs). Interaction of CAR‐T cells with tumor cells triggers the destruction/elimination of these cells by the induction of cytotoxicity and the release of different cytokines. Despite the great promise of CAR‐T cell‐based therapy several challenges exist. These include the heterogeneity of GBM cancer cells, aberrant various signaling pathways involved in tumor progression, antigen escape, the hostile inhibitory GBM microenvironment, T cell dysfunction, blood‐brain barrier, and defective antigen presentation. All need to be addressed before full application at the clinical level can begin. Herein we provide a focused review of the rationale for the use of different types of CAR‐T cells (including FcγRs), the different GBM‐associated antigens, the challenges still facing CAR‐T‐based therapy, and means to overcome such challenges. Finally, we enumerate currently completed and ongoing clinical trials, highlighting the different ways such trials are designed to overcome specific problems. Exploitation of the full potential of CAR‐T cell therapy for GBM depends on their solution.

Background: Heterocyclic compounds have always been used as a core portion in the development of anticancer drugs. However, there is a pressing need for developing inexpensive and simple alternatives to high-cost and complex chemical agents-based catalysts for large-scale production of heterocyclic compounds. Also, development of some smart platforms for cancer treatment based on nanoparticles (NPs) which facilitate Fenton reaction have been widely explored by different scientists. Magnetic NPs not only can serve as catalysts in the synthesis of heterocyclic compounds with potential anticancer properties, but also are widely used as smart agents in targeting cancer cells and inducing Fenton reactions. Aim of Review: Therefore, in this review we aim to present an updated summary of the reports related to the main clinical or basic application and research progress of magnetic NPs in cancer as well as their application in the synthesis of heterocyclic compounds as potential anticancer drugs. Afterwards, specific tumor microenvironment (TME)-responsive magnetic nanocatalysts for cancer treatment through triggering Fenton-like reactions were surveyed. Finally, some ignored factors in the design of magnetic nanocatalysts- triggered Fenton-like reaction, challenges and future perspective of magnetic nanocatalysts-assisted synthesis of heterocyclic compounds and selective cancer therapy were discussed.Key Scientific Concepts of Review:This review may pave the way for well-organized translation of magnetic nanocatalysts in cancer therapy from the bench to the bedside.

Abstract In the present study, the effect of concentration of titanium carbide (TiC) particles on the structural, mechanical, and electrochemical properties of Ni–P composite coatings was investigated. Various amounts of TiC particles (0, 0.5, 1.0, 1.5, and 2.0 g L−1) were co-electrodeposited in the Ni–P matrix under optimized conditions and then characterized by employing various techniques. The structural analysis of prepared coatings indicates uniform, compact, and nodular structured coatings without any noticeable defects. Vickers microhardness and nanoindentation results demonstrate the increase in the hardness with an increasing amount of TiC particles attaining its terminal value (593HV100) at the concentration of 1.5 g L−1. Further increase in the concentration of TiC particles results in a decrease in hardness, which can be ascribed to their accumulation in the Ni–P matrix. The electrochemical results indicate the improvement in corrosion protection efficiency of coatings with an increasing amount of TiC particles reaching to ~ 92% at 2.0 g L−1, which can be ascribed to a reduction in the active area of the Ni–P matrix by the presence of inactive ceramic particles. The favorable structural, mechanical, and corrosion protection characteristics of Ni–P–TiC composite coatings suggest their potential applications in many industrial applications.

Magnetic resonance imaging (MRI) is commonly used in medical diagnosis and minimally invasive image-guided operations. During an MRI scan, the patient’s electrocardiogram (ECG) may be required for either gating or patient monitoring. However, the challenging environment of an MRI scanner, with its several types of magnetic fields, creates significant distortions of the collected ECG data due to the Magnetohydrodynamic (MHD) effect. These changes can be seen as irregular heartbeats. These distortions and abnormalities hamper the detection of QRS complexes, and a more in-depth diagnosis based on the ECG. This study aims to reliably detect R-peaks in the ECG waveforms in 3 Tesla (T) and 7T magnetic fields. A novel model, Self-Attention MHDNet, is proposed to detect R peaks from the MHD corrupted ECG signal through 1D-segmentation. The proposed model achieves a recall and precision of 99.83% and 99.68%, respectively, for the ECG data acquired in a 3T setting, while 99.87% and 99.78%, respectively, in a 7T setting. This model can thus be used in accurately gating the trigger pulse for the cardiovascular functional MRI.

Impaired diabetic wounds are serious pathophysiological complications associated with persistent microbial infections including failure in the closure of wounds, and the cause of a high frequency of lower limb amputations. The healing of diabetic wounds is attenuated due to the lack of secretion of growth factors, prolonged inflammation, and/or inhibition of angiogenic activity. Diabetic wound healing can be enhanced by supplying nitric oxide (NO) endogenously or exogenously. NO produced inside the cells by endothelial nitric oxide synthase (eNOS) naturally aids wound healing through its beneficial vasculogenic effects. However, during hyperglycemia, the activity of eNOS is affected, and thus there becomes an utmost need for the topical supply of NO from exogenous sources. Thus, NO-donors that can release NO are loaded into wound healing patches or wound coverage matrices to treat diabetic wounds. The burst release of NO from its donors is prevented by encapsulating them in polymeric hydrogels or nanoparticles for supplying NO for an extended duration of time to the diabetic wounds. In this article, we review the etiology of diabetic wounds, wound healing strategies, and the role of NO in the wound healing process. We further discuss the challenges faced in translating NO-donors as a clinically viable nanomedicine strategy for the treatment of diabetic wounds with a focus on the use of biomaterials for the encapsulation and in vivo controlled delivery of NO-donors.

Background: Microscopic patches as quite promising platforms in transdermal drug delivery suffer from conventional injections. In other hand, a wide range of pharmacokinetics, ranging from fast oral administration to sustained drug delivery, can be implemented with the help of microneedle arrays (MNAs). Aim of Review: Hence, in this paper, we overviewed different kinds of MNAs such as solid/coated, hollow, porous, hydrogel/swellable, and merged-tip geometry followed by introducing different types of material (silicon, glass, ceramics, dissolving and biodegradable polymers, and hydrogel) used for fabrication of MNAs. Afterwards, some conventional and brand-new simple and customizable MN mold fabrication techniques were surveyed. Polymeric MNAs have received a great deal of attention due to their potential biocompatibility and biodegradability in comparison to other materials. Therefore, we also covered different kinds of polymers such as hydrogel/swellable, dissolving and biodegradable analogues used for the development of MNAs as potential candidates in drug delivery systems (DDSs). Finally, we discussed different challenges and future perspectives in the aspect of MNAs-based drug delivery platforms. Key Scientific Concepts of Review: This review may provide guidelines for the rational design of polymeric MNAs-based DDSs for promising programmable drug release and enhanced therapeutic effect.

Podocyte damage is one of the hallmarks of diabetic nephropathy leading to proteinuria and kidney damage. The underlying mechanisms of podocyte injury are not well defined. Bradykinin (BK) was shown to contribute to diabetic kidney disease. Here, we evaluated the temporal changes in proteome profile and inflammatory signals of podocytes in response to BK (10−7M). Protein profile was evaluated by liquid chromatography mass Spectrometry (LC-MS/MS) analysis. Proteome profile analysis of podocytes treated with BK (10−7M) for 3 and 6 h, revealed 61 proteins that were differentially altered compared to unstimulated control podocytes. Pathway enrichment analysis suggested inhibition of cell death pathways, engagement of cytoskeletal elements and activation of inflammatory pathways. One of the inflammatory proteins that was identified to be induced by BK treatment is Prostaglandin (PG) H Synthase-2 (Cyclooxygenase-2, COX-2). In addition, BK significantly induced the production and release of PGE2 and this effect was inhibited by both COX-2 and MEK Kinase inhibitors, demonstrating that the production of PGE2 by BK is mediated via COX-2 and MAPK-dependent mechanisms. These findings provide a global understanding of the effector modulated proteome in response to BK and also reveal BK as an important modulator of inflammation and a potential player in podocyte injury.

The aim of this study was to investigate the mechanism of interaction between quercetin-3-O-sophoroside and different SARS-CoV-2’s proteins which can bring some useful details about the control of different variants of coronavirus including the recent case, Delta. The chemical structure of the quercetin-3-O-sophoroside was first optimized. Docking studies were performed by CoV disease-2019 (COVID-19) Docking Server. Afterwards, the molecular dynamic study was done using High Throughput Molecular Dynamics (HTMD) tool. The results showed a remarkable stability of the quercetin-3-O-sophoroside based on the calculated parameters. Docking outcomes revealed that the highest affinity of quercetin-3-O-sophoroside was related to the RdRp with RNA. Molecular dynamic studies showed that the target E protein tends to be destabilized in the presence of quercetin-3-O-sophoroside. Based on these results, quercetin-3-O-sophoroside can show promising inhibitory effects on the binding site of the different receptors and may be considered as effective inhibitor of the entry and proliferation of the SARS-CoV-2 and its different variants. Finally, it should be noted, although this paper does not directly deal with the exploring the interaction of main proteins of SARS-CoV-2 Delta variant with quercetin-3-O-sophoroside, at the time of writing, no direct theoretical investigation was reported on the interaction of ligands with the main proteins of Delta variant. Therefore, the present data may provide useful information for designing some theoretical studies in the future for studying the control of SARS-CoV-2 variants due to possible structural similarity between proteins of different variants.

Tumor treating fields (TTFields) are among clinically active anticancer modalities that utilize low‐intensity, intermediate frequency (IF), and alternating electric fields (AEFs) to selectively disrupt mitosis in cancerous cells. Application of TTFields in the range of 100–900 kHz in cancer therapy and its effect on normal and cancer cells have attracted a great deal of interest in recent years. TTFields affect solid tumors by introducing increased chromatid aberrations that reduce the capacity to repair DNA damage and chromosome segregation, resulting in autophagy and subsequent cell death. In this review, we present an overview of the applications of TTFields in the treatment of cancer. We discuss several practical applications of TTField frequencies combined with metallic nanoparticles (NPs) (magnetic or nonmagnetic NPs) for internalization into cancer cells. In addition, TTFields can be combined effectively with chemotherapy and radiotherapy.

Alzheimer's disease (AD) is the major cause of dementia worldwide. Early-onset familial AD accounts for about 0.5% of all AD and is caused by single major gene mutations and autosomal dominant inheritance. An N141I missense mutation is associated with a significant increase in basal cell death and apoptosis. In this work we generated hiPSC from skin fibroblasts obtained from an AD patient carrying a N141I missense mutation in PSEN2. The generated iPSC colonies grew and were characterized by pluripotency marker staining; the N141I missense mutation was corrected using genome editing technology.

Management of non-healing and slow to heal diabetic wounds is a major concern in healthcare across the world. Numerous techniques have been investigated to solve the issue of delayed wound healing, though, mostly unable to promote complete healing of diabetic wounds due to the lack of proper cell proliferation, poor cell-cell communication, and higher chances of wound infections. These challenges can be minimized by using hydrogel based wound healing patches loaded with bioactive agents. Gelatin methacrylate (GelMA) has been proven to be a highly cell friendly, cell adhesive, and inexpensive biopolymer for various tissue engineering and wound healing applications. In this study, S-Nitroso-N-acetylpenicillamine (SNAP), a nitric oxide (NO) donor, was incorporated in a highly porous GelMA hydrogel patch to improve cell proliferation, facilitate rapid cell migration, and enhance diabetic wound healing. We adopted a visible light crosslinking method to fabricate this highly porous biodegradable but relatively stable patch. Developed patches were characterized for morphology, NO release, cell proliferation and migration, and diabetic wound healing in a rat model. The obtained results indicate that SNAP loaded visible light crosslinked GelMA hydrogel patches can be highly effective in promoting diabetic wound healing.

Improving the intrinsic pharmacodynamics or pharmacokinetic of drugs is regarded as a crucial step in developing potential drug therapies. In this context, the development of nanostructured-based drug delivery systems (DDSs) responsive to exogenous or endogenous stimuli demonstrate an outstanding platform to clinical applications. Polymeric micelles (PM)-based DDSs are often modified with selective short peptides like cell penetrating peptides (CPPs) for highly efficient cellular internalization. In this review, we discussed recent achievements in the design and development of nanoscale pH-responsive micelles modified with CPPs to provide controlled drug release in the tumor cells. An overview on the application of micelles, especially PMs as promising engineered nanocarriers to combine pharmaceutical agents with CPPs are presented. Afterwards, the peptide-based transfection method as one of the promising approaches for drug delivery and therapeutic agents was explained. Subsequently, conjugation of pH-responsive micelles with CPPs as a novel DDS in cancer therapy was surveyed. Finally, the current challenges and future application of stimuli-sensitive nanoplatforms conjugated with CPP were discussed. In conclusion, the application of controlled delivery using pH-sensitive PMs-based DDSs conjugated with peptides can be considered as a potential approach to improve the therapeutic index of anticancer drugs.

Metastasis is the major reason for most brain tumors with up to a 50% chance of occurrence in patients with other types of malignancies. Brain metastasis occurs if cancer cells succeed to cross the ‘blood-brain barrier’ (BBB). Moreover, changes in the structure and function of BBB can lead to the onset and progression of diseases including neurological disorders and brain-metastases. Generating BBB models with structural and functional features of intact BBB is highly important to better understand the molecular mechanism of such ailments and finding novel therapeutic agents targeting them. Hence, researchers are developing novel in vitro BBB platforms that can recapitulate the structural and functional characteristics of BBB. Brain endothelial cells-based in vitro BBB models have thus been developed to investigate the mechanism of brain metastasis through BBB and facilitate the testing of brain targeted anticancer drugs. Bioengineered constructs integrated with microfluidic platforms are vital tools for recapitulating the features of BBB in vitro closely as possible. In this review, we outline the fundamentals of BBB biology, recent developments in the microfluidic BBB platforms, and provide a concise discussion of diverse types of bioengineered BBB models with an emphasis on the application of them in brain metastasis and cancer research in general. We also provide insights into the challenges and prospects of the current bioengineered microfluidic platforms in cancer research.

Cardiovascular disease is one of the leading causes of mortality worldwide. Cardiac tissue engineering strategies focusing on biomaterial scaffolds incorporating cells and growth factors are emerging as highly promising for cardiac repair and regeneration. The use of stem cells within cardiac microengineered tissue constructs present an inherent ability to differentiate into cell types of the human heart. Stem cells derived from various tissues including bone marrow, dental pulp, adipose tissue and umbilical cord can be used for this purpose. Approaches ranging from stem cell injections, stem cell spheroids, cell encapsulation in a suitable hydrogel, use of prefabricated scaffold and bioprinting technology are at the forefront in the field of cardiac tissue engineering. The stem cell microenvironment plays a key role in the maintenance of stemness and/or differentiation into cardiac specific lineages. This review provides a detailed overview of the recent advances in microengineering of autologous stem cell-based tissue engineering platforms for the repair of damaged cardiac tissue. A particular emphasis is given to the roles played by the extracellular matrix (ECM) in regulating the physiological response of stem cells within cardiac tissue engineering platforms.

Diabetes mellitus (DM) is one of the most prevalent diseases in the world, and is correlated to a high index of mortality. One of its major complications is diabetic foot, leading to plantar ulcers, amputation, and death. Several studies report that a thermogram helps to detect changes in the plantar temperature of the foot, which may lead to a higher risk of ulceration. However, in diabetic patients, the distribution of plantar temperature does not follow a standard pattern, thereby making it difficult to quantify the changes. The abnormal temperature distribution in infrared (IR) foot thermogram images can be used for the early detection of diabetic foot before ulceration to avoid complications. There is no machine learning-based technique reported in the literature to classify these thermograms based on the severity of diabetic foot complications. This paper uses an available labeled diabetic thermogram dataset and uses the k-mean clustering technique to cluster the severity risk of diabetic foot ulcers using an unsupervised approach. Using the plantar foot temperature, the new clustered dataset is verified by expert medical doctors in terms of risk for the development of foot ulcers. The newly labeled dataset is then investigated in terms of robustness to be classified by any machine learning network. Classical machine learning algorithms with feature engineering and a convolutional neural network (CNN) with image-enhancement techniques are investigated to provide the best-performing network in classifying thermograms based on severity. It is found that the popular VGG 19 CNN model shows an accuracy, precision, sensitivity, F1-score, and specificity of 95.08%, 95.08%, 95.09%, 95.08%, and 97.2%, respectively, in the stratification of severity. A stacking classifier is proposed using extracted features of the thermogram, which is created using the trained gradient boost classifier, XGBoost classifier, and random forest classifier. This provides a comparable performance of 94.47%, 94.45%, 94.47%, 94.43%, and 93.25% for accuracy, precision, sensitivity, F1-score, and specificity, respectively.

After cardiovascular disease, cancer is the leading cause of death worldwide with devastating health and economic consequences, particularly in developing countries. Inter-patient variations in anti-cancer drug responses further limit the success of therapeutic interventions. Therefore, personalized medicines approach is key for this patient group involving molecular and genetic screening and appropriate stratification of patients to treatment regimen that they will respond to. However, the knowledge related to adequate risk stratification methods identifying patients who will respond to specific anti-cancer agents is still lacking in many cancer types. Recent advancements in three-dimensional (3D) bioprinting technology, have been extensively used to generate representative bioengineered tumor in vitro models, which recapitulate the human tumor tissues and microenvironment for high-throughput drug screening. Bioprinting process involves the precise deposition of multiple layers of different cell types in combination with biomaterials capable of generating 3D bioengineered tissues based on a computer-aided design. Bioprinted cancer models containing patient-derived cancer and stromal cells together with genetic material, extracellular matrix proteins and growth factors, represent a promising approach for personalized cancer therapy screening. Both natural and synthetic biopolymers have been utilized to support the proliferation of cells and biological material within the personalized tumor models/implants. These models can provide a physiologically pertinent cell–cell and cell–matrix interactions by mimicking the 3D heterogeneity of real tumors. Here, we reviewed the potential applications of 3D bioprinted tumor constructs as personalized in vitro models in anticancer drug screening and in the establishment of precision treatment regimens.

The interaction of nanoparticles with biological systems can provide useful information about their therapeutic applications. The aluminum nanoparticles (Al2O3 NPs) were synthesized by laser ablation technique and well-characterized by different methods. Fluorescence spectroscopy, circular dichroism (CD) spectroscopy, and molecular docking studies were employed to evaluate the effect of Al2O3 NPs on the protein structure. Growth inhibitory and apoptotic effects of the Al2O3 NPs against K562 cancer cells and lymphocyte cells were assessed using [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT), flow cytometry, and real time polymerase chain reaction (PCR) assays. The antipathogenic activity of Al2O3 NPs against a diverse range of Gram-negative and Gram-positive pathogens was explored through a disk diffusion method. The characterization techniques determined that the Al2O3 NPs were successfully synthesized in the nanoscales. Intrinsic, 1-anilino-8-naphthalenesulfonate (ANS) and acrylamide fluorescence spectroscopy studies disclosed that Al2O3 NPs can partially change the tertiary structure of human serum albumin (HSA), whereas CD spectroscopy investigation depicted that the secondary structure of HSA remained intact. Molecular docking investigation also manifest that the Al2O3 nano-clusters preferably bind to electrostatic residues. Al2O3 NPs exhibited promising and selective anticancer features through reactive oxygen species (ROS) production, apoptosis induction, and elevation of Bax/Bcl-2 mRNA ratio. Furthermore, the Al2O3 NP showed a remarkable antibacterial activity against both Gram-negative and Gram-positive pathogens. In conclusion, it may be suggested that the synthesized Al2O3 NPs can be integrated in the development of anticancer and antipathogenic agents.

As the number of people infected with the newly identified 2019 novel coronavirus (SARS-CoV2) is continuously increasing every day, development of potential therapeutic platforms is vital. Based on the comparatively high similarity of receptor-binding domain (RBD) in SARS-CoV2 and SARS-CoV, it seems crucial to assay the cross-reactivity of anti-SARS-CoV monoclonal antibodies (mAbs) with SARS-CoV2 spike (S)-protein. Indeed, developing mAbs targeting SARS-CoV2 S-protein RBD could show novel applications for rapid and sensitive development of potential epitope-specific vaccines (ESV). Herein, we present an overview on the discovery of new CoV followed by some explanation on the SARS-CoV2 S-protein RBD site. Furthermore, we surveyed the novel therapeutic mAbs for targeting S-protein RBD such as S230, 80R, F26G18, F26G19, CR3014, CR3022, M396, and S230.15. Afterwards, the mechanism of interaction of RBD and different mAbs were explained and it was suggested that one of the SARS-CoV-specific human mAbs, namely CR3022, could show the highest binding affinity with SARS-CoV2 S-protein RBD. Finally, some ongoing challenges and future prospects for rapid and sensitive advancement of therapeutic mAbs targeting S-protein RBD were discussed. In conclusion, it may be proposed that this review may pave the way for recognition of RBD and different mAbs to develop potential therapeutic ESV.

Exosomes are biological nanoparticles (30−150 nm) secreted in the extracellular area from all of cells, that mediate intercellular message. Exosomes act as the carriers for numerous proteins, DNAs, RNAs and cell-signaling molecules. Therefore, exosomes secreted by the tumor cells are useful for diagnostic purposes because of their persistent presence in the blood and their provision of genetic cargo similar to those in tumor. Due to the risks of aggressive activity and ambiguity of biological activity in other tissues, the use of exosomes in drug delivery and imaging has been limited. However, their high loading, stability and longer circulation time, excellent targeting, high cell penetration performance, and optimal biodegradability have made them potential agents in targeted cancer treatment. Therefore, in addition to examining methods for isolating and loading exosomes, this paper discusses the applications of exosomes in biological measurement, imaging, and therapeutic activities. Also, this review describes the challenges of using exosomes compared to conventional methods and shows that it is very useful to use them due to less aggressive activities. Finally, this review attempts to provide an appropriate incentive by showing the performance of exosomes in cancer therapy through targeted drug delivery, gene therapy, imaging and diagnosis.

Syzygium cumini (S. cumini) is an evergreen tropical plant that is well recognized for its therapeutic potential of common diseases. In this study, the therapeutic potential and biomedical application of S. cumini are assessed in vitro and in vivo to find its effectiveness for different complications. The methanolic crude extract of S. cumini leaves were screened for total phenolic and flavonoid content. In vitro, the DPPH scavenging assay, XTT assay, prothrombin and activated partial thromboplastin time were used to assess antioxidant, cytoprotective and thrombolytic activity of the S. cumini extract, respectively. The anti-inflammatory potential and the analgesic activity of the S. cumini extract were analyzed in rabbits by the Carrageenan induced paw edema method and the writhing method, respectively. Phytochemical analysis showed the presence of considerable amounts of total phenolic (369.75 ± 17.9 mg GAE/g) and flavonoid (75.8 ± 5.3 mgRE/g) content in the S. cumini extract. The DPPH assay demonstrated a higher antioxidant potential (IC-50 value of 133 μg/ml), which was comparable to the IC-50 of ascorbic acid (122.4 μg/ml). Moreover, the S. cumini extract showed a dose dependent cytoprotective effect against H2O2 treated bone marrow mesenchymal stem cells (BM-MSCs). S. cumini also possesses significant anticoagulant activity with a prothrombin time of 28.3 ± 1.8 seconds vs 15.8 ± 0.2 seconds of control, p

Fruit and vegetable diets rich in phenolic compounds reduce the risk of various cancers and offer multiple other health benefits due to their bioactivity and powerful antioxidant properties. However, the human health benefits of most phenolic compounds are restricted due to their limited aqueous solubility, low absorption, restricted passive cellular efflux, and poor gastrointestinal stability. Nanotechnology has been used to deliver various therapeutic drugs to specific targets overcoming many of the limitations of direct treatments. This study was designed to develop poly(lactic-co-glycolic acid) (PLGA) nanoencapsulated phenolic-rich extracts from Callistemon citrinus and berberine and to evaluate their effectiveness against extremely invasive MDA-MB 231, moderately invasive MCF-10A, and minimally invasive MCF-7 breast cancers. We have achieved about 80% encapsulation of phenolics from C. citrinus. Most encapsulated nanoparticles were polygonal with particles sizes of 200 to 250 nm. Release of phenolics from encapsulation during storage was biphasic during the first week and then levelled off thereafter. Nanoencapsulated phenolics from C. citrinus extract, berberine, and combination of both enhanced their bioactivity against the three breast cancer cell lines by nearly 2-fold. Growth inhibition of cells was a linear curve relative to phenolic concentration, with a maximum inhibition of nearly 100% at 0.1 mg/ml compared to control.

Bone tissue engineering is an advanced field for treatment of fractured bones to restore/regulate biological functions. Biopolymeric/bioceramic-based hybrid nanocomposite scaffolds are potential biomaterials for bone tissue because of biodegradable and biocompatible characteristics. We report synthesis of nanocomposite based on acrylic acid (AAc)/guar gum (GG), nano-hydroxyapatite (HAp NPs), titanium nanoparticles (TiO2 NPs), and optimum graphene oxide (GO) amount via free radical polymerization method. Porous scaffolds were fabricated through freeze-drying technique and coated with silver sulphadiazine. Different techniques were used to investigate functional group, crystal structural properties, morphology/elemental properties, porosity, and mechanical properties of fabricated scaffolds. Results show that increasing amount of TiO2 in combination with optimized GO has improved physicochemical and microstructural properties, mechanical properties (compressive strength (2.96 to 13.31 MPa) and Young’s modulus (39.56 to 300.81 MPa)), and porous properties (pore size (256.11 to 107.42 μm) and porosity (79.97 to 44.32%)). After 150 min, silver sulfadiazine release was found to be ~94.1%. In vitro assay of scaffolds also exhibited promising results against mouse pre-osteoblast (MC3T3-E1) cell lines. Hence, these fabricated scaffolds would be potential biomaterials for bone tissue engineering in biomedical engineering.

The rampant spread of COVID-19 and the worldwide prevalence of infected cases demand a rapid, simple, and cost-effective Point of Care Test (PoCT) for the accurate diagnosis of this pandemic. The most common molecular tests approved by regulatory bodies across the world for COVID-19 diagnosis are based on Polymerase Chain Reaction (PCR). While PCR-based tests are highly sensitive, specific, and remarkably reliable, they have many limitations ranging from the requirement of sophisticated laboratories, need of skilled personnel, use of complex protocol, long wait times for results, and an overall high cost per test. These limitations have inspired researchers to search for alternative diagnostic methods that are fast, economical, and executable in low-resource laboratory settings. The discovery of Loop-mediated isothermal Amplification (LAMP) has provided a reliable substitute platform for the accurate detection of low copy number nucleic acids in the diagnosis of several viral diseases, including epidemics like Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). At present, a cocktail of LAMP assay reagents along with reverse transcriptase enzyme (Reverse Transcription LAMP, RT-LAMP) can be a robust solution for the rapid and cost-effective diagnosis for COVID-19, particularly in developing, and low-income countries. In summary, the development of RT-LAMP based diagnostic tools in a paper/strip format or the integration of this method into a microfluidic platform such as a Lab-on-a-chip may revolutionize the concept of PoCT for COVID-19 diagnosis. This review discusses the principle, technology and past research underpinning the success for using this method for diagnosing MERS and SARS, in addition to ongoing research, and the prominent prospect of RT-LAMP in the context of COVID-19 diagnosis.

Silver nanoparticles (AgNPs) synthesized from plant extracts are widely used for the cure of many diseases from fever to cancers. Keeping in view the medicinal value of AgNPs, here we report a cost-effective phytochemical method for the biosynthesis of silver nanoparticles from Ajuga bracteosa . A. bracteosa is an important medicinal plant used to cure fever, appetite-loss, and cancer. Silver-nanoparticles were prepared from the aqueous extract of the plant. The methanolic extract of A. bracteosa (ABMF) was separated and n-hexane (ABHF) and chloroform (ABCF) fractions were obtained from the methanolic crude extract. The AgNPs were characterized by UV-Visible spectrophotometer, FTIR, XRD, and TEM. The total phenolic contents (TPC) and total flavonoid contents (TFC) in different fractions were determined and compared with AgNPs. The medicinal value of ABMF, ABHF, ABCF, and AgNPs was evaluated by antibacterial, antioxidant, anti-inflammatory, and cytotoxicity bioassays. The UV-visible spectrum showed a peak at 484 nm while FTIR results suggested strong capping of phytochemicals on AgNPs which was confirmed by a high amount of TPC and TFC. XRD analysis depicted a high degree of crystallinity and smaller size of AgNPs. TEM results showed spherical shaped AgNPs of size range 50 ± 12 nm. The biosynthesized AgNPs showed better antibacterial activity than plant extract fractions. Similarly, AgNPs have shown better antioxidant, cytotoxicity against cancer cell lines in-vitro, and anti-inflammatory activity in-vivo than a plant extract. The great medicinal value of A. bracteosa might be due to the presence of pharmacologically active phytochemicals such as diterpenoids, neo-clerodane flavonol glycosides, ergosterol, iridoid glycosides, phytoecdysones, and other polyphenols. These phytochemicals surround the silver nanoparticles during green synthesis and therefore, this capping of phytochemicals over silver nanoparticles results in enhanced biomedical applications of plant extracts.

Hypospadias, characterized by misplacement of the urinary meatus in the lower side of the penis, is a frequent birth defect in male children. Because of the huge variation in the anatomic presentation of hypospadias, no single urethroplasty procedure is suitable for all situations. Hence, many surgical techniques have emerged to address the shortage of tissues required to bridge the gap in the urethra particularly in the severe forms of hypospadias. However, the rate of postoperative complications of currently available surgical procedures reaches up to one-fourth of the patients having severe hypospadias. Moreover, these urethroplasty techniques are technically demanding and require considerable surgical experience. These limitations have fueled the development of novel tissue engineering techniques that aim to simplify the surgical procedures and to reduce the rate of complications. Several types of biomaterials have been considered for urethral repair, including synthetic and natural polymers, which in some cases have been seeded with cells prior to implantation. These methods have been tested in preclinical and clinical studies, with variable degrees of success. This review describes the different urethral tissue engineering methodologies, with focus on the approaches used for the treatment of hypospadias. At present, despite many significant advances, the search for a suitable tissue engineering approach for use in routine clinical applications continues.

Heart attack is one of the leading causes of human death worldwide. Every year, about 610,000 people die of heart attack in the United States alone—that is one in every four deaths—but there are well understood early symptoms of heart attack that could be used to greatly help in saving many lives and minimizing damages by detecting and reporting at an early stage. On the other hand, every year, about 2.35 million people get injured or disabled from road accidents. Unexpectedly, many of these fatal accidents happen due to the heart attack of drivers that leads to the loss of control of the vehicle. The current work proposes the development of a wearable system for real-time detection and warning of heart attacks in drivers, which could be enormously helpful in reducing road accidents. The system consists of two subsystems that communicate wirelessly using Bluetooth technology, namely, a wearable sensor subsystem and an intelligent heart attack detection and warning subsystem. The sensor subsystem records the electrical activity of the heart from the chest area to produce electrocardiogram (ECG) trace and send that to the other portable decision-making subsystem where the symptoms of heart attack are detected. We evaluated the performance of dry electrodes and different electrode configurations and measured overall power consumption of the system. Linear classification and several machine algorithms were trained and tested for real-time application. It was observed that the linear classification algorithm was not able to detect heart attack in noisy data, whereas the support vector machine (SVM) algorithm with polynomial kernel with extended time–frequency features using extended modified B-distribution (EMBD) showed highest accuracy and was able to detect 97.4% and 96.3% of ST-elevation myocardial infarction (STEMI) and non-ST-elevation MI (NSTEMI), respectively. The proposed system can therefore help in reducing the loss of lives from the growing number of road accidents all over the world.

An acellular cholecyst derived extracellular matrix (b-CEM) of bubaline origin was prepared using anionic biological detergent. Healing potential of b-CEM was compared with commercially available collagen sheet (b-CS) and open wound (C) in full thickness skin wounds in rats. Thirty-six clinically healthy adult Sprague Dawley rats of either sex were randomly divided into three equal groups. Under general anesthesia, a full thickness skin wound (20 × 20 mm2) was created on the dorsum of each rat. The defect in group I was kept as open wound and was taken as control. In group II, the defect was repaired with commercially available collagen sheet (b-CS). In group III, the defect was repaired with cholecyst derived extracellular matrix of bovine origin (b-CEM). Planimetry, wound contracture, and immunological and histological observations were carried out to evaluate healing process. Significantly (P

Waterborne polyurethane (WPU) is a versatile and environment-friendly material with growing applications in both industry and academia. Silk fibroin (SF) is an attractive material known for its structural, biological and hemocompatible properties. The SF reinforced waterborne polyurethane (WPU) is a promising scaffold material for tissue engineering applications. In this work, we report synthesis and characterization of a novel nanocomposite using SF reinforced WPU. The rheological behaviors of WPU and WPU-SF dispersions with different solid contents were investigated with steady shear and dynamic oscillatory tests to evaluate the formation of the cross-linked gel structure. The average particle size and the zeta potential of WPU-SF dispersions with different SF content were examined at 25 °C to investigate the interaction between SF and WPU. FTIR, SEM, TEM and tensile testing were performed to study the effects of SF content on the structural morphology and mechanical properties of the resultant composite films. Experimental results revealed formation of gel network in the WPU dispersions at solid contents more than 17 wt %. The conjugate reaction between the WPU and SF as well as the hydrogen bond between them helped in dispersing the SF powder into the WPU matrix as small aggregates. Addition of SF to the WPU also improved the Young’s modulus from 0.30 to 3.91 MPa, tensile strength from 0.56 to 8.94 MPa, and elongation at break from 1067% to 2480%, as SF was increased up to 5 wt %. Thus, significant strengthening and toughening can be achieved by introducing SF powder into the WPU formulations.