Doxorubicin-loaded liposome-like particles embedded in chitosan/hyaluronic acid-based hydrogels as a controlled drug release model for local treatment of glioblastoma.

Glioblastoma (GBM) resection and medication treatment are limited, and local drug therapies are required. This study aims to create a hybrid system comprising liposome-like particles (LLP-DOX) encapsulated in chitosan/hyaluronic acid/polyethyleneimine (CHI/HA/PEI) hydrogels, enabling controlled local delivery of doxorubicin (DOX) into the resection cavity for treating GBM. CHI/HA/PEI hydrogels were characterized morphologically, physically, chemically, mechanically, and thermally. Findings revealed a high network and compact micro-network structure, along with enhanced physical and thermal stability compared to CHI/HA hydrogels. Simultaneously, drug release from CHI/HA/PEI/LLP-DOX hydrogels was assessed, revealing continuous and controlled release up to the 148th hour, with no significant burst release. Cell studies showed that CHI/HA/PEI hydrogels are biocompatible with low genotoxicity. Additionally, LLP-DOX-loaded CHI/HA/PEI hydrogels significantly decreased cell viability and gene expression levels compared to LLP-DOX alone. It was also observed that the viability of GBM spheroids decreased over time when interacting with CHI/HA/PEI/LLP-DOX hydrogels, accompanied by a reduction in total surface area and an increase in apoptotic tendencies. In this study, we hypothesized that creating a hybrid drug delivery system by encapsulating DOX-loaded LLPs within a CHI/HA/PEI hydrogel matrix could achieve sustained drug release, improve anticancer efficacy via localized treatment, and effectively mitigate GBM progression for 3D microtissues.

Biosensors for prostate cancer detection.

Prostate cancer (PC) is one of the most common tumors and a leading cause of mortality among men, resulting in ~375 000 deaths annually worldwide. Various analytical methods have been designed for quantitative and rapid detection of PC biomarkers. Electrochemical (EC), optical, and magnetic biosensors have been developed to detect tumor biomarkers in clinical and point-of-care (POC) settings. Although POC biosensors have shown potential for detection of PC biomarkers, some limitations, such as the sample preparation, should be considered. To tackle such shortcomings, new technologies have been utilized for development of more practical biosensors. Here, biosensing platforms for the detection of PC biomarkers such as immunosensors, aptasensors, genosensors, paper-based devices, microfluidic systems, and multiplex high-throughput platforms, are discussed.

Electrochemiluminescent immunosensor for detection of carcinoembryonic antigen using luminol-coated silver nanoparticles.

Recently, electrochemiluminescent (ECL) immunosensors have received much attention in the field of biomarker detection. Here, a highly enhanced ECL immunosensing platform was designed for ultrasensitive detection of carcinoembryonic antigen (CEA). The surface of the glassy carbon electrode was enhanced by applying functional nanostructures such as thiolated graphene oxide (S-GO) and streptavidin-coated gold nanoparticles (SA-AuNPs). The selectivity and sensitivity of the designed immunosensor were improved by entrapping CEA biomolecules using a sandwich approach. Luminol/silver nanoparticles (Lu-SNPs) were applied as the main core of the signaling probe, which were then coated with streptavidin to provide overloading of the secondary antibody. The highly ECL signal enhancement was obtained due to the presence of horseradish peroxidase (HRP) in the signaling probe, in which the presence of H2O2 further amplified the intensity of the signals. The engineered immunosensor presented excellent sensitivity for CEA detection, with limit of detection (LOD) and linear detection range (LDR) values of 58 fg mL-1 and 0.1 pg mL-1 to 5 pg mL-1 (R2 = 0.9944), respectively. Besides its sensitivity, the fabricated ECL immunosensor presented outstanding selectivity for the detection of CEA in the presence of various similar agents. Additionally, the developed immunosensor showed an appropriate repeatability (RSD 3.8%) and proper stability (2 weeks). Having indicated a robust performance in the real human serum with stated LOD and LDR, the engineered immunosensor can be considered for the detection and monitoring of CEA in the clinic.

Additive manufacturing and three-dimensional printing in obstetrics and gynecology: a comprehensive review.

Three-dimensional (3D) printing, also known as additive manufacturing, is a technology used to create complex 3D structures out of a digital model that can be almost any shape. Additive manufacturing allows the creation of customized, finely detailed constructs. Improvements in 3D printing, increased 3D printer availability, decreasing costs, development of biomaterials, and improved cell culture techniques have enabled complex, novel, and customized medical applications to develop. There have been rapid development and utilization of 3D printing technologies in orthopedics, dentistry, urology, reconstructive surgery, and other health care areas. Obstetrics and Gynecology (OBGYN) is an emerging application field for 3D printing. This technology can be utilized in OBGYN for preventive medicine, early diagnosis, and timely treatment of women-and-fetus-specific health issues. Moreover, 3D printed simulations of surgical procedures enable the training of physicians according to the needs of any given procedure. Herein, we summarize the technology and materials behind additive manufacturing and review the most recent advancements in the application of 3D printing in OBGYN studies, such as diagnosis, surgical planning, training, simulation, and customized prosthesis. Furthermore, we aim to give a future perspective on the integration of 3D printing and OBGYN applications and to provide insight into the potential applications.

Nanotechnology-based electrochemical biosensors for monitoring breast cancer biomarkers.

Breast cancer is categorized as the most widespread cancer type among women globally. On-time diagnosis can decrease the mortality rate by making the right decision in the therapy procedure. These features lead to a reduction in medication time and socioeconomic burden. The current review article provides a comprehensive assessment for breast cancer diagnosis using nanomaterials and related technologies. Growing use of the nano/biotechnology domain in terms of electrochemical nanobiosensor designing was discussed in detail. In this regard, recent advances in nanomaterial applied for amplified biosensing methodologies were assessed for breast cancer diagnosis by focusing on the advantages and disadvantages of these approaches. We also monitored designing methods, advantages, and the necessity of suitable (nano) materials from a statistical standpoint. The main objective of this review is to classify the applicable biosensors based on breast cancer biomarkers. With numerous nano-sized platforms published for breast cancer diagnosis, this review tried to collect the most suitable methodologies for detecting biomarkers and certain breast cancer cell types.

3D-printed microrobots from design to translation.

Microrobots have attracted the attention of scientists owing to their unique features to accomplish tasks in hard-to-reach sites in the human body. Microrobots can be precisely actuated and maneuvered individually or in a swarm for cargo delivery, sampling, surgery, and imaging applications. In addition, microrobots have found applications in the environmental sector (e.g., water treatment). Besides, recent advancements of three-dimensional (3D) printers have enabled the high-resolution fabrication of microrobots with a faster design-production turnaround time for users with limited micromanufacturing skills. Here, the latest end applications of 3D printed microrobots are reviewed (ranging from environmental to biomedical applications) along with a brief discussion over the feasible actuation methods (e.g., on- and off-board), and practical 3D printing technologies for microrobot fabrication. In addition, as a future perspective, we discussed the potential advantages of integration of microrobots with smart materials, and conceivable benefits of implementation of artificial intelligence (AI), as well as physical intelligence (PI). Moreover, in order to facilitate bench-to-bedside translation of microrobots, current challenges impeding clinical translation of microrobots are elaborated, including entry obstacles (e.g., immune system attacks) and cumbersome standard test procedures to ensure biocompatibility.

Emerging Applications of Electrochemical Impedance Spectroscopy in Tear Film Analysis.

Human tear film, with a flow rate of 1-3 µL/min, is a rich bodily fluid that transmits a variety of metabolites and hormones containing proteins, lipids and electrolytes that provide clues about ocular and systemic diseases. Analysis of disease biomarkers such as proteins, mRNA, enzymes and cytokines in the tear film, collected by noninvasive methods, can provide significant results for sustaining a predictive, preventive and personalized medicine regarding various diseases such as glaucoma, diabetic retinopathy, keratoconus, dry eye, cancer, Alzheimer's disease, Parkinson's disease and COVID-19. Electrochemical impedance spectroscopy (EIS) offers a powerful technique for analyzing these biomarkers. EIS detects electrical equivalent circuit parameters related to biorecognition of receptor-analyte interactions on the electrode surface. This method is advantageous as it performs a label-free detection and allows the detection of non-electroactive compounds that cannot be detected by direct electron transfer, such as hormones and some proteins. Here, we review the opportunities regarding the integration of EIS into tear fluid sampling approaches.

Deep Learning-Enabled Technologies for Bioimage Analysis.

Deep learning (DL) is a subfield of machine learning (ML), which has recently demonstrated its potency to significantly improve the quantification and classification workflows in biomedical and clinical applications. Among the end applications profoundly benefitting from DL, cellular morphology quantification is one of the pioneers. Here, we first briefly explain fundamental concepts in DL and then we review some of the emerging DL-enabled applications in cell morphology quantification in the fields of embryology, point-of-care ovulation testing, as a predictive tool for fetal heart pregnancy, cancer diagnostics via classification of cancer histology images, autosomal polycystic kidney disease, and chronic kidney diseases.

Glioma-on-a-Chip Models.

Glioma, as an aggressive type of cancer, accounts for virtually 80% of malignant brain tumors. Despite advances in therapeutic approaches, the long-term survival of glioma patients is poor (it is usually fatal within 12-14 months). Glioma-on-chip platforms, with continuous perfusion, mimic in vivo metabolic functions of cancer cells for analytical purposes. This offers an unprecedented opportunity for understanding the underlying reasons that arise glioma, determining the most effective radiotherapy approach, testing different drug combinations, and screening conceivable side effects of drugs on other organs. Glioma-on-chip technologies can ultimately enhance the efficacy of treatments, promote the survival rate of patients, and pave a path for personalized medicine. In this perspective paper, we briefly review the latest developments of glioma-on-chip technologies, such as therapy applications, drug screening, and cell behavior studies, and discuss the current challenges as well as future research directions in this field.

Plant-Based Scaffolds in Tissue Engineering.

A wide range of platforms has been developed for 3D culture of cells in vitro to aggregate and align cells to resemble in vivo conditions in order to enhance communication between cells and promote differentiation. The cellulose skeleton of plant tissue can serve as an attainable scaffold for mammalian cells after decellularization, which is advantageous when compared to synthetic polymers or animal-derived scaffolds. Adjustable variables to modify the physical and biochemical properties of the resulting scaffolds include the protocol for the sodium dodecyl sulfate (SDS)-based decellularization procedure, surface coatings for cell attachment, plant type for decellularization, differentiation media, and integrity and shape of the substrate. These tunable cellulose platforms can host a wide range of mammalian cell types from muscle to bone cells, as well as malignancies. Here, fundamentals and applications of decellularized plant-based scaffolds are discussed. These biocompatible, naturally perfused, tunable, and easily prepared decellularized scaffolds may allow eco-friendly manufacturing frameworks for application in tissue engineering and organs-on-a-chip.

Sensing of electrolytes in urine using a miniaturized paper-based device.

Analyzing electrolytes in urine, such as sodium, potassium, calcium, chloride, and nitrite, has significant diagnostic value in detecting various conditions, such as kidney disorder, urinary stone disease, urinary tract infection, and cystic fibrosis. Ideally, by regularly monitoring these ions with the convenience of dipsticks and portable tools, such as cellphones, informed decision making is possible to control the consumption of these ions. Here, we report a paper-based sensor for measuring the concentration of sodium, potassium, calcium, chloride, and nitrite in urine, accurately quantified using a smartphone-enabled platform. By testing the device with both Tris buffer and artificial urine containing a wide range of electrolyte concentrations, we demonstrate that the proposed device can be used for detecting potassium, calcium, chloride, and nitrite within the whole physiological range of concentrations, and for binary quantification of sodium concentration.

Emerging Anti-Fouling Methods: Towards Reusability of 3D-Printed Devices for Biomedical Applications.

Microfluidic devices are used in a myriad of biomedical applications such as cancer screening, drug testing, and point-of-care diagnostics. Three-dimensional (3D) printing offers a low-cost, rapid prototyping, efficient fabrication method, as compared to the costly-in terms of time, labor, and resources-traditional fabrication method of soft lithography of poly(dimethylsiloxane) (PDMS). Various 3D printing methods are applicable, including fused deposition modeling, stereolithography, and photopolymer inkjet printing. Additionally, several materials are available that have low-viscosity in their raw form and, after printing and curing, exhibit high material strength, optical transparency, and biocompatibility. These features make 3D-printed microfluidic chips ideal for biomedical applications. However, for developing devices capable of long-term use, fouling-by nonspecific protein absorption and bacterial adhesion due to the intrinsic hydrophobicity of most 3D-printed materials-presents a barrier to reusability. For this reason, there is a growing interest in anti-fouling methods and materials. Traditional and emerging approaches to anti-fouling are presented in regard to their applicability to microfluidic chips, with a particular interest in approaches compatible with 3D-printed chips.

3D-printed smartphone-based point of care tool for fluorescence- and magnetophoresis-based cytometry.

In developing countries, there are often limited resources available to provide important medical diagnostics, which severely limits our ability to diagnose conditions and administer proper treatment, leading to high mortality rates for treatable conditions. Here, we propose a multiplex tool capable of density-based cell sorting via magnetic focusing in parallel with fluorescence imaging to provide highly specific clinical assays. While many cell sorting techniques and fluorescence microscopes generally are costly and require extensive user training, limiting accessibility and usability in developing countries, this device is compact, low-cost, and portable. The device can separate cells on the basis of density, which can be used to identify cell type and cell activity, and image the cells in either brightfield, darkfield, or fluorescent imaging modes using the built-in smartphone camera. The combination of these two powerful and versatile techniques - magnetic focusing and fluorescence imaging - will make this platform broadly applicable to a range of biomedical assays. Clinical applications include cell cytometry and immunocytochemistry-based assays in limited-resource settings, which can ultimately help to improve worldwide accessibility to medical diagnostics.

3D-printed microfluidic devices.

Microfluidics is a flourishing field, enabling a wide range of biochemical and clinical applications such as cancer screening, micro-physiological system engineering, high-throughput drug testing, and point-of-care diagnostics. However, fabrication of microfluidic devices is often complicated, time consuming, and requires expensive equipment and sophisticated cleanroom facilities. Three-dimensional (3D) printing presents a promising alternative to traditional techniques such as lithography and PDMS-glass bonding, not only by enabling rapid design iterations in the development stage, but also by reducing the costs associated with institutional infrastructure, equipment installation, maintenance, and physical space. With the recent advancements in 3D printing technologies, highly complex microfluidic devices can be fabricated via single-step, rapid, and cost-effective protocols, making microfluidics more accessible to users. In this review, we discuss a broad range of approaches for the application of 3D printing technology to fabrication of micro-scale lab-on-a-chip devices.

A Bioprinted Liver-on-a-Chip for Drug Screening Applications.

The need for a liver-on-a-chip tissue model for drug screening is particularly important in tissue engineering because of the high frequency of drug-induced liver injury. Recently, a liver tissue model conducive to hepatotoxicity testing was developed by bioprinting hepatic spheroids encapsulated in a hydrogel scaffold into a microfluidic device.

Bioprinting for cancer research.

Bioprinting offers the ability to create highly complex 3D architectures with living cells. This cutting-edge technique has significantly gained popularity and applicability in several fields. Bioprinting methods have been developed to effectively and rapidly pattern living cells, biological macromolecules, and biomaterials. These technologies hold great potential for applications in cancer research. Bioprinted cancer models represent a significant improvement over previous 2D models by mimicking 3D complexity and facilitating physiologically relevant cell-cell and cell-matrix interactions. Here we review bioprinting methods based on inkjet, microextrusion, and laser technologies and compare 3D cancer models with 2D cancer models. We discuss bioprinted models that mimic the tumor microenvironment, providing a platform for deeper understanding of cancer pathology, anticancer drug screening, and cancer treatment development.

Nanoplasmonic quantitative detection of intact viruses from unprocessed whole blood.

Infectious diseases such as HIV and hepatitis B pose an omnipresent threat to global health. Reliable, fast, accurate, and sensitive platforms that can be deployed at the point-of-care (POC) in multiple settings, such as airports and offices, for detection of infectious pathogens are essential for the management of epidemics and possible biological attacks. To the best of our knowledge, no viral load technology adaptable to the POC settings exists today due to critical technical and biological challenges. Here, we present for the first time a broadly applicable technology for quantitative, nanoplasmonic-based intact virus detection at clinically relevant concentrations. The sensing platform is based on unique nanoplasmonic properties of nanoparticles utilizing immobilized antibodies to selectively capture rapidly evolving viral subtypes. We demonstrate the capture, detection, and quantification of multiple HIV subtypes (A, B, C, D, E, G, and subtype panel) with high repeatability, sensitivity, and specificity down to 98 ± 39 copies/mL (i.e., HIV subtype D) using spiked whole blood samples and clinical discarded HIV-infected patient whole blood samples validated by the gold standard, i.e., RT-qPCR. This platform technology offers an assay time of 1 h and 10 min (1 h for capture, 10 min for detection and data analysis). The presented platform is also able to capture intact viruses at high efficiency using immuno-surface chemistry approaches directly from whole blood samples without any sample preprocessing steps such as spin-down or sorting. Evidence is presented showing the system to be accurate, repeatable, and reliable. Additionally, the presented platform technology can be broadly adapted to detect other pathogens having reasonably well-described biomarkers by adapting the surface chemistry. Thus, this broadly applicable detection platform holds great promise to be implemented at POC settings, hospitals, and primary care settings.

Flow induces epithelial-mesenchymal transition, cellular heterogeneity and biomarker modulation in 3D ovarian cancer nodules.

Seventy-five percent of patients with epithelial ovarian cancer present with advanced-stage disease that is extensively disseminated intraperitoneally and prognosticates the poorest outcomes. Primarily metastatic within the abdominal cavity, ovarian carcinomas initially spread to adjacent organs by direct extension and then disseminate via the transcoelomic route to distant sites. Natural fluidic streams of malignant ascites triggered by physiological factors, including gravity and negative subdiaphragmatic pressure, carry metastatic cells throughout the peritoneum. We investigated the role of fluidic forces as modulators of metastatic cancer biology in a customizable microfluidic platform using 3D ovarian cancer nodules. Changes in the morphological, genetic, and protein profiles of biomarkers associated with aggressive disease were evaluated in the 3D cultures grown under controlled and continuous laminar flow. A modulation of biomarker expression and tumor morphology consistent with increased epithelial-mesenchymal transition, a critical step in metastatic progression and an indicator of aggressive disease, is observed because of hydrodynamic forces. The increase in epithelial-mesenchymal transition is driven in part by a posttranslational up-regulation of epidermal growth factor receptor (EGFR) expression and activation, which is associated with the worst prognosis in ovarian cancer. A flow-induced, transcriptionally regulated decrease in E-cadherin protein expression and a simultaneous increase in vimentin is observed, indicating increased metastatic potential. These findings demonstrate that fluidic streams induce a motile and aggressive tumor phenotype. The microfluidic platform developed here potentially provides a flow-informed framework complementary to conventional mechanism-based therapeutic strategies, with broad applicability to other lethal malignancies.

Manipulating biological agents and cells in micro-scale volumes for applications in medicine.

Recent technological advances provide new tools to manipulate cells and biological agents in micro/nano-liter volumes. With precise control over small volumes, the cell microenvironment and other biological agents can be bioengineered; interactions between cells and external stimuli can be monitored; and the fundamental mechanisms such as cancer metastasis and stem cell differentiation can be elucidated. Technological advances based on the principles of electrical, magnetic, chemical, optical, acoustic, and mechanical forces lead to novel applications in point-of-care diagnostics, regenerative medicine, in vitro drug testing, cryopreservation, and cell isolation/purification. In this review, we first focus on the underlying mechanisms of emerging examples for cell manipulation in small volumes targeting applications such as tissue engineering. Then, we illustrate how these mechanisms impact the aforementioned biomedical applications, discuss the associated challenges, and provide perspectives for further development.