Sickle cell disease (SCD) is the most prevalent inherited blood disorder in the world. But the clinical manifestations of the disease are highly variable. In particular, it is currently difficult to predict the adverse outcomes within patients with SCD, such as, vasculopathy, thrombosis, and stroke. Therefore, for most effective and timely interventions, a predictive analytic strategy is desirable

1 NANOPARTICLE FOR TARGETING CARTILAGE IN OSTEOARTHRITIS Current treatments for osteoarthritis are limited in their ability to penetrate and persist within the cartilage matrix; furthermore, existing therapies primarily focus on managing pain and modulating joint function as opposed to therapeutic treatment. As such, there is a considerable need for the development of new therapeutics and delivery

Carbon tetrachloride (CCl4)‐induced liver injury is predominantly caused by free radicals, in which mitochondrial function of hepatocytes is impaired, accompanying with the production of ROS and decreased ATP energy supply in animals intoxicated with CCl4. Here we explored a novel therapeutic approach, mitochondrial transplantation therapy, for treating the liver injury. The results showed that mitochondria

Engineering complex tissues requires the use of advanced biofabrication techniques that allow the replication of the tissue's 3D microenvironment, architecture and cellular interactions. In the case of skin, the most successful strategies to introduce the complexity of hair follicle (HF) appendages have highlighted the importance of facilitating direct interaction between dermal papilla (DP) cells

In clinical terms, bone grafting currently involves the application of autogenous, allogeneic, or xenogeneic bone grafts, as well as natural or artificially synthesized materials, such as polymers, bioceramics, and other composites. Many of these are associated with limitations. The ideal scaffold for bone tissue engineering should provide mechanical support while promoting osteogenesis, osteoconduction

The S1 subunit of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) spike protein contains an immunogenic receptor‐binding domain (RBD), which is a promising candidate for the development of a potential vaccine. This study demonstrated that intradermal delivery of an S‐RBD vaccine using a dissolvable microneedle skin patch can induce both significant B‐cell and significant T‐cell responses

Glioblastoma is the most common and aggressive form of primary brain cancer, with median survival of 16–20 months and a 5‐year survival rates of <5%. Recent advances in immunotherapies have shown that addressing the tumor immune profile by targeting the colony‐stimulating factor 1 (CSF‐1) signaling pathway of tumor‐associated macrophages (TAMs) has the potential to improve glioblastoma therapy. However

Sutures are applied almost universally at the site of trauma or surgery, making them an ideal platform to modulate the local, postoperative biological response, and improve surgical outcomes. To date, the only globally marketed drug‐eluting sutures are coated with triclosan for antibacterial application in general surgery. Loading drug directly into the suture rather than coating the surface offers

As wearable healthcare monitoring systems advance, there is immense potential for biological sensing to enhance the management of type 1 diabetes (T1D). The aim of this work is to describe the ongoing development of biomarker analytes in the context of T1D. Technological advances in transdermal biosensing offer remarkable opportunities to move from research laboratories to clinical point‐of‐care applications

Biodistribution studies are essential in drug carrier design and translation, and radiotracing provides a sensitive quantitation for this purpose. Yet, for biodegradable formulations, small amounts of free‐label signal may arise prior to‐ or immediately after injection in animal models, causing potentially confounding biodistribution results. In this study, we refined a method to overcome this obstacle

Congenital disorders of the biliary tract are the primary reason for pediatric liver failure and ultimately for pediatric liver transplant needs. Not all causes of these disorders are well understood, but it is known that liver fibrosis occurs in many of those afflicted. The goal of this study is to develop a simple yet robust model that recapitulates physico‐mechanical and cellular aspects of fibrosis

Corneal endothelial decompensation is a serious condition that frequently requires treatment via corneal transplantation which contributes to a global shortage in donor corneas. Therefore, the purpose of this study was to analyze the influence of aqueous humor total antioxidant capacity (TAC) on corneal endothelial health. There is an urgent need for discovering protective factors to combat corneal

Treatments of glioblastoma (GBM) have not been very effective, largely due to the inefficiency of drugs in penetrating the blood brain barrier (BBB). In this study, we investigated the potential of exosome‐coated doxorubicin (DOX)‐loaded nanoparticles (ENPDOX) in BBB penetration, inducing immunogenic cell death (ICD) and promoting survival of GBM‐bearing mice. DOX‐loaded nanoparticles (NPDOX) were

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) led to multiple drug repurposing clinical trials that have yielded largely uncertain outcomes. To overcome this challenge, we used IDentif.AI, a platform that pairs experimental validation with artificial intelligence (AI) and digital drug development to rapidly pinpoint unpredictable drug interactions and optimize infectious

Focused ultrasound (FUS) mediated blood–brain barrier disruption (BBBD) targets the delivery of systemically‐administered therapeutics to the central nervous system. Preclinical investigations of BBBD have been performed on different anesthetic backgrounds; however, the influence of the choice of anesthetic on the molecular response to BBBD is unknown, despite its potential to critically affect interpretation

Myocardial infarction (MI) is the serious condition causing lots of death over the world. Myocytes apoptosis, inflammation, and fibrosis are three important factors implicated in pathogenesis of MI. Targeting these three factors has been shown to ameliorate MI and rescue cardiac function. Previous studies have demonstrated that microRNA (miR) 199a‐3p protect against MI. In this study, we prepare macrophage

Time‐of‐flight secondary ion mass spectrometry (TOF‐SIMS) is an imaging‐based analytical technique that can characterize the surfaces of biomaterials. We used TOF‐SIMS to identify important metabolites and oncogenic KRAS mutation expressed in human colorectal cancer (CRC). We obtained 540 TOF‐SIMS spectra from 180 tissue samples by scanning cryo‐sections and selected discriminatory molecules using

Tissue engineering (TE) seeks to fabricate implants that mimic the mechanical strength, structure, and composition of native tissues. Cartilage TE requires the development of functional personalized implants with cartilage‐like mechanical properties capable of sustaining high load‐bearing environments to integrate into the surrounding tissue of the cartilage defect. In this study, we evaluated the

Choline geranate deep eutectic solvent/ionic liquid (CAGE) has shown several desirable therapeutic properties including antimicrobial activity and ability to deliver drugs transdermally in research laboratories. Here, we describe the first report of clinical translation of CAGE from the lab into the clinic for the treatment of rosacea, a common chronic inflammatory skin disorder that affects the face

Intraplaque hemorrhage (IPH) plays a major role in the aggressive progression of vulnerable plaque, leading to acute cardiovascular events. We previously demonstrated that sonodynamic therapy (SDT) inhibits atherosclerotic plaque progression. In this study, we investigated whether SDT could also be applied to treat more advanced hemorrhagic plaque and addressed the underlying mechanism. SDT decreased

Soft micro‐ and nanostructures have been extensively developed for biomedical applications. The main focus has been on multifunctional composite materials that combine the advantages of hydrogels and colloidal particles. Magnetic microgels and nanogels can be realized by hybridizing stimuli‐sensitive gels and magnetic nanoparticles. They are of particular interest since they can be controlled in a

2020 marks an important year in the evolution of BioTM. We received our first impact factor of 6.091 this year. This is a massive accomplishment for all stakeholders of the journal. The journal was formally launched in 2015 and we published our first issue in 2016. Within a short period of 4 years, we were able to reach this significant milestone. Huge thanks to all BioTM authors who trusted the journal

In this issue of Bioengineering and Translational Medicine, we are pleased to introduce our Editorial Board Member, Professor W. Mark Saltzman. Professor Saltzman is the Goizueta Foundation Professor of Biomedical Engineering, Chemical and Environmental Engineering, and Physiology at Yale University. Professor Saltzman received his BS in chemical engineering from Iowa State University before earning

No one can predict the future, but that is not going to stop us from taking a shot at it. At BioTM, we do wonder what the future holds for our key scientific areas, including drug delivery, tissue engineering, cell therapy, and biosensors, among many others. Ultimately, the future will become what the future scientists aspire to do. With this realization, we figured that our best shot at predicting

The Coronavirus‐2019 (COVID‐19) pandemic has put tremendous strain on healthcare systems worldwide. It is challenging for clinicians to differentiate COVID‐19 from other acute respiratory tract infections via clinical symptoms because those who are infected display a wide range of symptoms. An effective, point‐of‐care (POC) diagnostic tool could mitigate healthcare system strain, protect healthcare

Hydrogel‐based three‐dimensional (3D) cellular models are attractive for bioengineering and pharmaceutical development as they can more closely resemble the cellular function of native tissue outside of the body. In general, these models are composed of tissue specific cells embedded within a support material, such as a hydrogel. As hydrogel properties directly affect cell function, hydrogel composition

Chronic kidney disease (CKD) affects 15% of the US adult population. However, most clinically available drugs for CKD show low bioavailability to the kidneys and non‐specific uptake by other organs which results in adverse side effects. Hence, a targeted, drug delivery strategy to enhance kidney drug delivery is highly desired. Recently, our group developed small, organic nanoparticles called peptide

Converting biopolymers to extracellular matrix (ECM)‐mimetic hydrogel‐based scaffolds has provided invaluable opportunities to design in vitro models of tissues/diseases and develop regenerative therapies for damaged tissues. Among biopolymers, gelatin and its crosslinkable derivatives, such as gelatin methacryloyl (GelMA), have gained significant importance for biomedical applications due to their

Mitochondrial NADPH protects cells against mitochondrial oxidative stress by serving as an electron donor to antioxidant defense systems. However, due to technical challenges, it still remains unknown as to the pool size of mitochondrial NADPH, its dynamics, and NADPH/NADP+ ratio. Here, we have systemically modulated production rates of H2O2 in mitochondria and assessed mitochondrial NADPH metabolism

Reconstructive surgery transfers viable tissue to cover defects and to restore aesthetic and functional properties. Failure rates after free flap surgery range from 3 to 7%. Co‐morbidities such as diabetes mellitus or peripheral vascular disease increase the risk of flap failure up to 4.5‐fold. Experimental therapeutic concepts commonly use a monocausal approach by applying single growth factors. The

Pancreatic ductal adenocarcinoma (PDAC) is often associated with a poor prognosis due to silent onset, resistance to therapies, and rapid spreading. Most patients are ineligible for curable surgery as they present with advanced disease at the time of diagnosis. Present diagnostic methods relying on anatomical changes have various limitations including difficulty to discriminate between benign and malignant

Supra‐maximum surgical tumor resection without neurological damage is highly valuable for treatment and prognosis of patients with glioblastoma multiforme (GBM). We developed a GBM‐specific fluorescence probe using IRDye800CW (peak absorption/emission, 778/795 nm) and bombesin (BBN), which (IRDye800‐BBN) targets the gastrin‐releasing peptide receptor, and evaluated the image‐guided resection efficiency

The purpose of these studies was to evaluate clinical, functional, and histopathological features of glaucoma drainage implants (GDIs) fabricated from novel, custom‐tailored expanded polytetrafluoroethylene (ePTFE). Implants of matching footprints were fabricated from silicone (Control) and novel, bilayered ePTFE. ePTFE implants included: (a) one that inflated with aqueous humor (AH) (High), (b) one

Male infertility affects millions of males worldwide and is rising in prevalence due to social and environmental conditions. However, men often feel too embarrassed to receive a semen analysis in the hospital due to social stigmas. To overcome this problem, we developed a 3‐(4,5‐Dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide test strip to distinguish semen samples with low total motile sperm

In this study, we take an important step toward clinical translation by generating the first canine‐induced neural stem cells (iNSCs). We explore key aspects of scale‐up, persistence, and safety of personalized iNSC therapy in autologous canine surgery models. iNSCs are a promising new approach to treat aggressive cancers of the brain, including the deadly glioblastoma. Created by direct transdifferentiation

Both extracellular vesicles (EVs) and long noncoding RNAs (lncRNAs) have been increasingly investigated as biomarkers, pathophysiological mediators, and potential therapeutics. While these two entities have often been studied separately, there are increasing reports of EV‐associated lncRNA activity in processes such as oncogenesis as well as tissue repair and regeneration. Given the powerful nature

Colorectal cancer, common in both men and women, occurs when tumors form in the linings of the colon. Common treatments of colorectal cancer include surgery, chemotherapy, and radiation therapy; however, many colorectal cancer treatments often damage healthy tissues and cells, inducing severe side effects. Conventional chemotherapeutic agents such as doxorubicin (Dox) can be potentially used for the

Precise monitoring of specific biomarkers in biological fluids with accurate biodiagnostic sensors is critical for early diagnosis of diseases and subsequent treatment planning. In this work, we demonstrated an innovative biodiagnostic sensor, portable reusable accurate diagnostics with nanostar antennas (PRADA), for multiplexed biomarker detection in small volumes (~50 μl) enabled in a microfluidic

The outbreak of the novel SARS‐CoV‐2 pathogen and corresponding coronavirus disease 2019 (COVID‐19) have had an enormous impact on both global health and the daily lives of billions of people worldwide. With a proven vaccine at least a year from being fully tested for safety and efficacy, there may be an opportunity to rapidly repurpose existing drugs in order to prevent SARS‐CoV‐2 infections and improve

1 DENDRIMER SIZE AND BRAIN TARGETING Nanotechnologies have demonstrated considerable success in targeting specific tissues and breaching biological barriers for the treatment of various cancers. As such, improving nanoparticle performance through optimization of their physicochemical properties represents one of the most widely investigated topics in preclinical nanotechnology research. In this issue

In this issue of Bioengineering and Translational Medicine , we are pleased to introduce our Editorial Board Member, Professor David J. Mooney (Figure 1). Professor Mooney is the Robert P. Pinkas Family Professor of Bioengineering at the John A. Paulson School of Engineering and Applied Sciences at Harvard University. He is a founding member of the Wyss Institute for Biologically Inspired Engineering

Once inside the cytoplasm of a cell, mRNA can be used to treat disease by upregulating the expression of any gene. Lipid nanoparticles (LNPs) can deliver mRNA to hepatocytes in humans, yet systemic non‐hepatocyte delivery at clinical doses remains difficult. We noted that LNPs have historically been formulated with phospholipids containing unconstrained alkyl tails. Based on evidence that constrained

Malignant gliomas are the most common and aggressive form of primary brain tumors, with a median survival of 15–20 months for patients receiving maximal interventions. Advances in nanomedicine have provided tumor‐specific delivery of chemotherapeutics to potentially overcome their off‐target toxicities. Recent advances in dendrimer‐based nanomedicines have established that hydroxyl‐terminated poly(amidoamine)

Recent heightened interest in inhaled bacteriophage (phage) therapy for combating antibacterial resistance in pulmonary infections has led to the development of phage powder formulations. Although phages have been successfully bioengineered into inhalable powders with preserved bioactivity, the stabilization mechanism is yet unknown. This paper reports the first study investigating the stabilization

Injectable hydrogels are one of the most widely investigated and versatile technologies for drug delivery and tissue engineering applications. Hydrogels’ versatility arises from their tunable structure, which has been enabled by considerable advances in fields such as materials engineering, polymer science, and chemistry. Advances in these fields continue to lead to invention of new polymers, new approaches

Microneedles (MNs) offer a rapid method of transdermal drug delivery through penetration of the stratum corneum. However, commercial translation has been limited by fabrication techniques unique to each drug. Herein, a broadly applicable platform is explored by drug‐loading via swelling effect of a hydrogel MN patch. A range of small molecule hydrophilic, hydrophobic, and biomacromolecule therapeutics

For patients carrying BRCA1 mutations, at least one-third develop triple negative breast cancer (TNBC). Not only is TNBC difficult to treat due to the lack of molecular target receptors, but BRCA1 mutations (BRCA1m) also result in chemotherapeutic resistance, making disease recurrence more likely. Although BRCA1m are highly heterogeneous and therefore difficult to target, BRCA1 gene's synthetic lethal

Endothelial cells play a central role in the process of inflammation. Their biologic relevance, as well as their accessibility to IV injected therapeutics, make them a strong candidate for treatment with molecularly‐targeted nanomedicines. Typically, the properties of targeted nanomedicines are first optimized in vitro in cell culture and then in vivo in rodent models. While cultured cells are readily

Nanoparticle‐based therapeutic formulations are being increasingly explored for the treatment of various ailments. Despite numerous advances, the success of nanoparticle‐based technologies in treating brain diseases has been limited. Translational hurdles of nanoparticle therapies are attributed primarily to their limited ability to cross the blood–brain barrier (BBB), which is one of the body's most

Conventional wound dressings are difficult to apply to large total body surface area (TBSA) wounds, as they typically are prefabricated, require a layer of adhesive coating for fixation, and need frequent replacement for entrapped exudate. Large TBSA wounds as well as orthopedic trauma and low-resource surgery also have a high risk of infection. In this report, a sprayable and intrinsically adhesive

Cell motility is a critical aspect of several processes, such as wound healing and immunity; however, it is dysregulated in cancer. Current limitations of imaging tools make it difficult to study cell migration in vivo. To overcome this, and to identify drivers from the microenvironment that regulate cell migration, bioengineers have developed 2D (two-dimensional) and 3D (three-dimensional) tissue

Local inflammation of the endothelium is associated with a plethora of cardiovascular diseases. Vascular‐targeted carriers (VTCs) have been advocated to provide focal effective therapeutics to these disease sites. Here, we examine the design of functionalized nanoparticles (NPs) as VTCs that can specifically localize at an inflamed vessel wall under pathological levels of high shear stress, associated

Obesity‐associated type 2 diabetes mellitus (T2DM) is characterized by low‐grade chronic systemic inflammation that arises primarily from the white adipose tissue. The interplay between various adipose tissue‐derived chemokines drives insulin resistance in T2DM and has therefore become a subje