Introduction The 2019-novel coronavirus disease (COVID-19) is an intractable global health challenge resulting in an aberrant rate of morbidity and mortality worldwide. The mode of entry for SARS-CoV-2 into host cells occurs through clathrin-mediated endocytosis. As part of the efforts to mitigate COVID-19 infections, rapid and accurate detection methods, as well as smart vaccine and drug designs with

This Erratum is to add the 2nd affiliation for Ahmad Alassaf.

Introduction Transferring genes safely, targeting cells and achieving efficient transfection are urgent problems in gene therapy that need to be solved. Combining microbubbles (MBs) and viruses to construct double vectors has become a promising approach for gene delivery. Understanding the characteristic performance of MBs that carry genes is key to promoting effective gene transfer. Therefore, in

Introduction Interstitial hypertension, a rise in interstitial fluid pressure, is a common feature of many solid tumors as they progress to an invasive state. It is currently unclear whether this elevated pressure alters the probability that tumor cells eventually escape into a neighboring blood or lymphatic vessel. Methods In this study, we analyze the escape of MDA-MB-231 human breast tumor cells

A fast and low-cost fabrication process of flexible hanging drop chips for 3D spheroid cultures was proposed by cutting and bonding Parafilm®, a cohesive thermoplastic. The Parafilm® Hanging Drop Chip (PHDC) was assembled by two-layer of Parafilm® sheet with different sizes of holes. The hole on the upper layer of the Parafilm® is smaller than the hole on the bottom layer. The impact of hole size and

Introduction The biological and mechanical properties of circulating tumor cells (CTCs) in combination with the hemodynamics affect the preference of metastatic sites in the vasculature. Despite the extensive literature on the effects of biological properties on cell adhesion, the effects of hydrodynamic forces on primary attachment remains an active area of research. Using simulations in conjunction

Introduction Vascular devices such as stents, hemodialyzers, and membrane oxygenators can activate blood coagulation and often require the use of systemic anticoagulants to selectively prevent intravascular thrombotic/embolic events or extracorporeal device failure. Coagulation factor (F)XII of the contact activation system has been shown to play an important role in initiating vascular device surface-initiated

Introduction Neutrophils act as first responders during an infection, following signals from the pathogen as well as other host cells to migrate from blood vessels to the site of infection. This tightly regulated process is critical for pathogen clearance and, in many cases, eliminates the pathogen without the need for an additional immune response. It is, therefore, critical to understand what signals

Purpose SARS-CoV-2 is a SARS-like novel coronavirus strain first identified in December 2019 in Wuhan, China. The virus has since spread globally, resulting in the current ongoing coronavirus disease 19 (COVID-19) pandemic. SARS-CoV-2 spike protein is a critical factor in the COVID-19 pathogenesis via interactions with the host cell angiotensin-converting enzyme 2 (ACE2) PD domain. Worldwide, numerous

Introduction Human mesenchymal stem cells (hMSCs) have a great clinical potential for tissue regeneration purposes due to its multilineage capability. Previous studies have reported that a single addition of 5-azacytidine (5-AzaC) causes the differentiation of hMSCs towards a myocardial lineage. The aim of this work was to evaluate the effect of 5-AzaC addition frequency on hMSCs priming (i.e., indicating

Introduction The applied heat level and expose time are main issues in certain operations/applications, such as a laser assisted tissue welding, preparation of collagen-based biomaterials (films, implants). Therefore, the precise investigation of these parameters is crucial. The results can serve as a guideline to assess potential effects while maintaining the functionality of the collagen structures

Introduction Lactate secreted by tumors is not just a byproduct, but rather an active modulator of immune cells. There are few studies aimed at investigating the true effect of lactate, which is normally confounded by pH. Such a knowledge gap needs to be addressed. Herein, we studied the immunomodulatory effects of lactate on dendritic cells (DCs) and macrophages (MΦs). Methods Bone marrow-derived

Introduction Mathematical and computational modeling have a long history of uncovering mechanisms and making predictions for biological systems. However, to create a model that can provide relevant quantitative predictions, models must first be calibrated by recapitulating existing biological datasets from that system. Current calibration approaches may not be appropriate for complex biological models

Introduction The generation of affinity reagents that bind native membrane proteins with high specificity remains challenging. Most in vitro selection paradigms utilize different cell types for positive and negative rounds of selection (where the positive selection is against a cell that expresses the desired membrane protein and the negative selection is against a cell that lacks the protein). However

Introduction The expansion of insulin-producing beta cells during pregnancy is critical to maintain glucose homeostasis in the face of increasing insulin resistance. Prolactin receptor (PRLR) signaling is one of the primary mediators of beta cell expansion during pregnancy, and loss of PRLR signaling results in reduced beta cell mass and gestational diabetes. Harnessing the proliferative potential

The kidneys are susceptible to adverse effects from many diseases, including several that are not tissue-specific. Acute kidney injury is a common complication of systemic diseases such as diabetes, lupus, and certain infections including the novel coronavirus (SARS-CoV-2). Microfluidic devices are an attractive option for disease modeling, offering the opportunity to utilize human cells, control experimental

Introduction Cell structure and migration is impacted by the mechanical properties and geometry of the cell adhesive environment. Most studies to date investigating the effects of 3D environments on cells have not controlled geometry at the single-cell level, making it difficult to understand the influence of 3D environmental cues on single cells. Here, we developed microwell platforms to investigate

Background Volumetric tissue-engineered constructs are limited in development due to the dependence on well-formed vascular networks. Scaffold pore size and the mechanical properties of the matrix dictates cell attachment, proliferation and successive tissue morphogenesis. We hypothesize scaffold pore architecture also controls stromal-vessel interactions during morphogenesis. Methods The interaction

IntroductionThe emergence of a novel coronavirus, SARS-CoV-2, has highlighted the need for rapid, accurate, and point-of-care diagnostic testing. As of now, there is not enough testing capacity in the world to meet the stated testing targets, which are expected to skyrocket globally for broader testing during reopening AimThis review focuses on the development of lab-on-chip biosensing platforms for

Introduction Stromal cell derived factor-1a (SDF-1a) and its receptor CXCR4 modulate stem cell recruitment to neural injury sites. SDF-1a gradients originating from injury sites contribute to chemotactic cellular recruitment. To capitalize on this injury-induced cell recruitment, further investigation of SDF-1a/CXCR4 signaling dynamics are warranted. Here, we studied how exogenous SDF-1a delivery strategies

BackgroundNETosis is an innate immune response elicited by activated neutrophils to fight microbial infections. Activated neutrophils release DNA fibers decorated with anti-microbial proteins called neutrophil extracellular traps (NETs) into the extracellular space to trap and kill surrounding microbes. MethodsHere, we show that tumor-derived IL-8 released by cancer cells also activates the release

IntroductionInterventions that could prevent thrombosis, clinical decompensation, and respiratory compromise in patients with novel coronavirus disease (COVID-19) are key to decrease mortality rate. Studies show that profound cytokine release and excessive activation of blood coagulation appear to be key drivers of COVID-19 associated mortality. Since limited in vitro methods exist for assessing the

Background Ocular neovascularization is a hallmark of retinal diseases including neovascular age-related macular degeneration and diabetic retinopathy, two leading causes of blindness in adults. Neovascularization is driven by the interaction of soluble vascular endothelial growth factor (VEGF) ligands with transmembrane VEGF receptors (VEGFR), and inhibition of the VEGF pathway has shown tremendous

Introduction CXCR4 and epidermal growth factor receptor (EGFR) represent two major families of receptors, G-protein coupled receptors and receptor tyrosine kinases, with central functions in cancer. While utilizing different upstream signaling molecules, both CXCR4 and EGFR activate kinases ERK and Akt, although single-cell activation of these kinases is markedly heterogeneous. One hypothesis regarding

Introduction Recellularization of organ decellularized extracellular matrix (dECM) offers a potential solution for organ shortage in allograft transplantation. Cell retention rates have ranged from 10 to 54% in varying approaches for reseeding cells in whole organ dECM scaffolds. We aimed to improve recellularization by using soluble gelatin as a cell carrier to deliver endothelial cells to the coronary

New technologies are being developed toward the novel coronavirus SARS-CoV-2 to understand its pathogenesis and transmission, to develop therapeutics and vaccines, and to formulate preventive strategies. Animal models are indispensable to understand these processes and develop and test emerging technologies; however, the mechanism of infection for SARS-CoV-2 requires certain similarities to humans

COVID-19 is a disease that manifests itself in a multitude of ways across a wide range of tissues. Many factors are involved, and though impressive strides have been made in studying this novel disease in a very short time, there is still a great deal that is unknown about how the virus functions. Clinical data has been crucial for providing information on COVID-19 progression and determining risk

IntroductionPathological flows in patients with severe aortic stenosis are associated with acquired von Willebrand syndrome. This syndrome is characterized by excessive cleavage of von Willebrand factor by its main protease, A Disintegrin and Metalloproteinase with a Thrombospondin Type 1 Motif, Member 13 (ADAMTS13) leading to decreased VWF function and mucocutaneous bleeding. Aortic valve replacement

Introduction Maintaining a stable dry state is critical for long-term preservation of live biomaterials at suprazero temperatures. The objective of the study was to characterize the effect of moisture content on DNA integrity within the germinal vesicle (GV) of feline oocytes following dehydration and storage at 22–24 °C. Methods Using microwave-assisted drying, conditions that led to a predictable

Introduction Adipose tissue and adipocytes are primary regulators of insulin sensitivity and energy homeostasis. Defects in insulin sensitivity of the adipocytes predispose the body to insulin resistance (IR) that could lead to diabetes. However, the mechanisms mediating adipocyte IR remain elusive, which emphasizes the need to develop experimental models that can validate the insulin signaling pathways

Introduction Cells in the tumor microenvironment experience mechanical stresses, such as compression generated by uncontrolled cell growth within a tissue, increased substrate stiffness due to tumor cell extracellular matrix (ECM) remodeling, and leaky angiogenic vessels which involve low fluid shear stress. With our hypothesis that shear stress increases V–H\(^+\)-ATPase number density in prostate

Millions of people are being infected with COVID-19 around the globe. Though the majority of them will recover, cancer patients remain at a higher risk to SARS-CoV-2 infection and its related severe outcomes. Understanding how viruses contribute to human cancers provides us with new opportunities for preventing or treating virus-associated cancers. However, a limited amount of research has been done

Introduction Fibroblastic reticular cells (FRCs) support and remodel the lymph node (LN), express and present self-antigens to T cells to promote tolerance. In Type 1 diabetes (T1D), decrease in FRC frequency and in their expression of T1D-related self-antigens may hinder tolerogenic engagement of autoreactive T cells. FRC reticular organization in LNs is critical for adaptive immunity. Thus, we engineered

Introduction The intestinal epithelium contains specialized cells including enterocytes, goblet, Paneth, enteroendocrine, and stem cells. Impaired barrier integrity in Inflammatory Bowel Disease is characterized by elevated levels of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α). Prior studies in immortalized lines such as Caco-2, without native epithelial heterogeneity

Introduction Bacteria and cancer cells share a common trait—both possess an electronegative surface that distinguishes them from healthy mammalian counterparts. This opens opportunities to repurpose antimicrobial peptides (AMPs), which are cationic amphiphiles that kill bacteria by disrupting their anionic cell envelope, into anticancer peptides (ACPs). To test this assertion, we investigate the mechanisms

IntroductionThe COVID-19 pandemic has caused an unprecedented health and economic worldwide crisis. Innovative solutions are imperative given limited resources and immediate need for medical supplies, healthcare support and treatments. AimThe purpose of this review is to summarize emerging technologies being implemented in the study, diagnosis, and treatment of COVID-19. ResultsKey focus areas include

Introduction Antiplatelet therapy for neonates and infants is often extrapolated from the adult experience, based on limited observation of agonist-induced neonatal platelet hypoactivity and poor understanding of flow shear-mediated platelet activation. Therefore, thrombotic events due to device-associated disturbed flow are inadequately mitigated in critically ill neonates with indwelling umbilical

Introduction Sirtuin1 (SIRT1), one of NAD+-dependent protein deacetylases, is proved to be neuroprotective in aging diseases, but its effect on neuronal apoptosis has not been clarified. To investigate the role of SIRT1 in inhibiting neuronal apoptosis, SIRT1 was interfered or overexpressed in cortical neurons. Methods We exerted overloading laminar shear stress with 10 dyn/cm2 for 4, 8, and 12 h on

Patients with triple negative breast cancer (TNBC) typically receive chemotherapy, surgery, and radiation therapy. Although this treatment improves prognosis for most patients, some patients continue to experience recurrence within 5 years. Preclinical studies have shown that immune cell infiltration at the irradiated site may play a significant role in tumor cell recruitment; however, little is known

Introduction Multicellular platforms and linked multi organ on chip devices are powerful tools for drug discovery, and basic mechanistic studies. Often, a critical constraint is defining a culture medium optimal for all cells present in the system. In this study, we focused on the key cells of the neuromuscular junction i.e., skeletal muscle and motor neurons. Methods Formulation of a chemically defined

Introduction Chronic kidney disease (CKD) affects approximately 13% of the world’s population and will lead to dialysis or kidney transplantation. Unfortunately, clinically available drugs for CKD show limited efficacy and toxic extrarenal side effects. Hence, there is a need to develop targeted delivery systems with enhanced kidney specificity that can also be combined with a patient-compliant administration

Background Tissue ischemia contributes to necrosis and infection. While angiogenic cell therapies have emerged as a promising strategy against ischemia, current approaches to cell therapies face multiple hurdles. Recent advances in nuclear reprogramming could potentially overcome some of these limitations. However, under severely ischemic conditions necrosis could outpace reprogramming-based repair

Introduction Fibrin scaffolds are often utilized to treat chronic wounds. The monomer fibrinogen used to create such scaffolds is typically derived from adult human or porcine plasma. However, our previous studies have identified extensive differences in fibrin network properties between adults and neonates, including higher fiber alignment in neonatal networks. Wound healing outcomes have been linked

Introduction Lipid based nanoparticles (LNPs) are clinically successful vectors for hepatic delivery of nucleic acids. These systems are being developed for non-hepatic delivery of mRNA for the treatment of diseases like cystic fibrosis or retinal degeneration as well as infectious diseases. Localized delivery to the lungs requires aerosolization. We hypothesized that structural lipids within LNPs

Introduction Endothelial cells (ECs) morphology strongly depends on the imposed mechanical stimuli. These mechanical stimuli include wall shear stress (WSS) and biaxial cyclic stretches (CS). Under combined loading, the effect of CS is not as simple as pure CS. The present study investigates the morphological response of ECs to the realistic mechanical stimuli. Methods The cell population is theoretically

IntroductionInduced pluripotent stem cell (iPSC)-derived endothelial cells (ECs) have the potential for therapeutic application in several cardiovascular diseases. Mechanical strain is known to regulate EC behavior and stem cell differentiation and may play a role in directing EC differentiation of iPSCs. H19, a long non-coding RNA (lncRNA), is known to affect ECs in several mechanically relevant pathologies

IntroductionNeuronal cells are sensitive to mechanical properties of extracellular matrix (ECM) such as stiffness and topography. Cells contract and exert a force on ECM to detect the microenvironment, which activates the signaling pathway to influence the cell functions such as differentiation, migration, and proliferation. There are numerous transmembrane proteins that transmit signals; however,

IntroductionAtherosclerosis (ATH), the build up of fat in the arteries, is a principal cause of heart attack and stroke. Drug instability and lack of target specificity are major drawbacks of current clinical therapeutics. These undesirable effects can be eliminated by site-specific drug delivery. The endothelial surface over ATH lesions has been shown to overexpress vascular cell adhesion molecule1

IntroductionThe nature of the surface is critical in determining the biological activity of silica powders. A novel correlation between toxicity and surface properties of bioactive glass ceramics (BGCs) synthesized via the sol–gel method was attempted in this study. MethodsThe behavior of BGCs after their attachment to the surface of red blood cells (RBCs) was evaluated and their toxic effects were

IntroductionTissue factor (TF) and factor (F) VII, components of the extrinsic pathway of blood coagulation, are essential for hemostatic plug formation in response to injury; less clear are their roles in propagating thrombosis, as observational data in humans with congenital FVII deficiency suggests persistent thrombotic and bleeding risk even at significantly decreased FVII levels. We aimed to define

IntroductionAssessment of cartilage integrity during arthroscopy is limited by the subjective visual nature of the technique. To address this shortcoming in diagnostic evaluation of articular cartilage, near infrared spectroscopy (NIRS) has been proposed. In this study, we evaluated the capacity of NIRS, combined with machine learning techniques, to classify cartilage integrity. MethodsRabbit (n = 14)

[This corrects the article DOI: 10.1007/s12195-019-00574-3.].

IntroductionThe pathophysiological increase in microvascular permeability plays a well-known role in the onset and progression of diseases like sepsis and atherosclerosis. However, how interactions between neutrophils and the endothelium alter vessel permeability is often debated. MethodsIn this study, we introduce a microfluidic, silicon-membrane enabled vascular mimetic (μSiM-MVM) for investigating

IntroductionThe adhesion of tumor cells to vessel wall is a critical stage in cancer metastasis. Firm adhesion of cancer cells is usually followed by their extravasation through the endothelium. Despite previous studies identifying the influential parameters in the adhesive behavior of the cancer cell to a planer substrate, less is known about the interactions between the cancer cell and microvasculature

Cancers of the digestive tract cause nearly one quarter of the cancer deaths worldwide, and nearly half of these are due to cancers of the esophagus and colon. Early detection of cancer significantly increases the rate of survival, and thus it is critical that cancer within these organs is detected early. In this regard, endoscopy is routinely used to screen for transforming/cancerous (i.e. dysplastic

BackgroundDiabetes mellitus is characterized by hyperglycemia which displays insufficiency or resistance to insulin. One of the complications of diabetes is the increased risk of fracture and the impairment of bone repair and regulation. There have been evidences from previous studies that mesenchymal stem cells (MSCs) from bone marrow promote cartilage and callous formation. In addition, IL-10, an

As a nanoscale subset of extracellular vehicles, exosomes represent a new pathway of intercellular communication by delivering cargos such as proteins and nucleic acids to recipient cells. Importantly, it has been well documented that exosome-mediated delivery of such cargo is involved in many pathological processes such as tumor progression, cancer metastasis, and development of drug resistance. Innately

IntroductionProapoptotic peptide, (KLAKLAK)2, exhibits strong anti-tumor effect with the help of cell-penetrating peptides such as Pep2, targeting TLR2 with high expression in acute myeloid leukemia (AML). However, the applications are limited due to the peptide’s instability and high cost of synthesis. Recombinant PP7 bacteriophage-like particles (VLPs) can protect the peptides from degradation by