Nanomedicine changes our lives by impacting diagnostics and therapeutics. In the biomedical domain, core–shell nanostructures have significant potential for photothermal therapy, diagnostics, sensing, drug delivery, and imaging. This work reviews the synergistic photothermal and photochemical effects of core–shell nanocomposites in the biomedical field. Several historical points in the development of nanostructures and fundamental core–shell plasmonic nanocomposites are provided in the introductory sections. Further, we analyzed the core–shell construction and its main biomedical applications: antimicrobial, cancer therapy, wound healing, and tissue regeneration. Moreover, we present relevant design considerations, performance optimization, and toxicity studies focused on synergistic photothermal–photochemical effects. Despite the promising biomedical research, several challenges remain before core–shell nanocomposites are widely translated into clinical settings and highlight the potential from technological and legal perspectives. The review concludes by outlining the pathways by which the synergistic photothermal–photochemical response of the core–shell nanocomposites plays a key role in nanomedicine and personalized medicine.
Developing new and effective therapeutics relies on using robust preclinical models that can closely mimic human physiological and immunological responses. Two-dimensional (2D) cell culture systems fail to replicate the complex tissular architecture and specialized microenvironments, which limits their ability to translate early findings into clinical success. Three-dimensional (3D) organoid models have also several drawbacks, such as handling complexity, variability in growth and differentiation, scalability issues, and reliability concerns, particularly in the context of high-throughput drug screening. This review provides a critical examination of skin related 2D and 3D models in the context of drug testing and disease modeling, evaluating their respective strengths and limitations. We also explore emerging technologies (e.g. immune-competent skin organoids) designed to overcome current barriers in organoid research, particularly those aimed at enhancing throughput, standardization, and data reproducibility in drug screening and toxicity testing.
There is a need for reconstructing the structural and functional complexity of human tissues such as skin to replace the animal models and provide accurate knowledge while solving ethical challenges in human medicine. Lately, microfluidics and tissue engineering have significantly advanced the development of 3D cell cultures and skin-on-chip (SoC), thus offering a cost-effective alternative to the generally used preclinical drug screening, toxicology applications, and cosmetic testing models. The current work presents a critical view on the SoC, from the fundamental concepts to the fabrication, applications, and commercialization. It comprehensively discusses the challenges faced by the 3D skin models and the perspectives of microphysiological skin platforms for preclinical pharmaceuticals and cosmeceuticals screening and disease research. It also highlights the technical and ethical requirements for successful SoC as physiological and pathological models applicable to personalized medicine. The SoC clinical and commercial translation depends on developing convergent biomanufacturing strategies and infrastructure focused on applications such as personalized skin disease models, skin grafts, and drug or cosmetics screening platforms.
As the burden of type 2 diabetes (T2D) continues to escalate globally, there is a growing need for novel, less-invasive biomarkers capable of early diabetes detection and monitoring of disease progression. Liquid biopsy, recognized for its minimally invasive nature, is increasingly being applied beyond oncology, and nevertheless shows its potential when the collection of the tissue biopsy is not possible. This diagnostic approach involves utilizing liquid biopsy markers such as cell-free nucleic acids, extracellular vesicles, and diverse metabolites for the molecular diagnosis of T2D and its related complications. In this context, we thoroughly examine recent developments in T2D liquid biopsy research. Additionally, we discuss the primary challenges and future prospects of employing liquid biopsy in the management of T2D. Prognosis, diagnosis and monitoring of T2D through liquid biopsy could be a game-changing technique for personalized diabetes management.
IntroductionGut microbes pose challenges like colon inflammation, deadly diarrhea, antimicrobial resistance dissemination, and chronic disease onset. Development of early, rapid and specific diagnosis tools is essential for improving infection control. Point-of-care testing (POCT) systems offer rapid, sensitive, low-cost and sample-to-answer methods for microbe detection from various clinical and environmental samples, bringing the advantages of portability, automation, and simple operation.Areas coveredRapid detection of gut microbes can be done using a wide array of techniques including biosensors, immunological assays, electrochemical impedance spectroscopy, mass spectrometry and molecular biology. Inclusion of Internet of Things, machine learning, and smartphone-based point-of-care applications is an important aspect of POCT. In this review, the authors discuss various fast diagnostic platforms for gut pathogens and their main challenges.Expert opinionDeveloping effective assays for microbe detection can be complex. Assay design must consider factors like target selection, real-time and multiplex detection, sample type, reagent stability and storage, primer/probe design, and optimizing reaction conditions for accuracy and sensitivity. Mitigating these challenges requires interdisciplinary collaboration among scientists, clinicians, engineers, and industry partners. Future efforts are essential to enhance sensitivity, specificity, and versatility of POCT systems for gut microbe detection and quantification, advancing infectious disease diagnostics and management.
Liquid biopsy has emerged as a transformative tool in oncology, offering a non-invasive alternative to traditional tissue biopsies. One approach utilizes circulating tumour cells (CTCs) from body fluids such as blood, urine, and saliva to provide insights into tumour genetics and dynamics. A method for isolating CTCs uses the dielectrophoresis phenomenon and microfluidic platforms. The present work reviews the advances in dielectrophoresis on a chip. First, we present the fundamental theory of dielectrophoresis, followed by the main operating principles. We further discuss some of the separation techniques using dielectrophoresis. We finally present the main challenges and concluding remarks. We finally present the main challenges and concluding remarks. Translating DEP technology from lab-scale to industrial applications remains challenging due to the complexities of creating large-scale, non-uniform electric fields.
Gene therapy is one of the most potential therapeutic approaches in direct and specific regulation of biological functions of macrophages at the gene level for efficient cell therapy. However, the delivery of genetic material to macrophages is extremely challenging, because of low stability, specificity and inability of therapeutic genes to efficiently enter the cells. Here, we present a method that uses the hybrid electrospun architectures based on gelatin-alginate decorated with carboxylated graphene oxide (HAG/G) as efficient substrate for loading and in vitro local and controlled delivery of plasmid DNA (pDNA) to macrophages as an alternative to systemic gene delivery carriers. Polyethyleneimine (PEI) is employed to assemble PEI/pDNA nanoparticles (Np) - used as model of carrier. The dispersion of GO-COOH sheets shifts the surface zeta potential of HAG/G to high negative value (SZP = -16.8 ± 2.21 mV) and further increases the encapsulation efficiency of PEI/pDNA Np onto hybrid HAG/G electrospun architectures to ∼ 69 % (HAG/G-Np). The in vitro biological investigations show a good metabolic activity of macrophages seeded onto HAG/G-Np (MTT assay), while gene expression experiments (fluorescent microscopy) show a 30 % increase in transient gene transfection of cells cultured in the presence of HAG/G-Np as compared to those incubated with free PEI/pDNA Np.
The rapid development of antimicrobial resistance due to broad antibiotic utilisation in the healthcare and food industries and the non-availability of novel antibiotics represents one of the most critical public health issues worldwide. Current advances in nanotechnology allow new materials to address drug-resistant bacterial infections in specific, focused, and biologically safe ways. The unique physicochemical properties, biocompatibility, and wide range of adaptability of nanomaterials that exhibit photothermal capability can be employed to develop the next generation of photothermally induced controllable hyperthermia as antibacterial nanoplatforms. Here, we review the current state of the art in different functional classes of photothermal antibacterial nanomaterials and strategies to optimise antimicrobial efficiency. The recent achievements and trends in developing photothermally active nanostructures, including plasmonic metals, semiconductors, and carbon-based and organic photothermal polymers, and antibacterial mechanisms of action, including anti-multidrug-resistant bacteria and biofilm removal, will be discussed. Insights into the mechanisms of the photothermal effect and various factors influencing photothermal antimicrobial performance, emphasising the structure–performance relationship, are discussed. We will examine the photothermal agents’ functionalisation for specific bacteria, the effects of the near-infrared light irradiation spectrum, and active photothermal materials for multimodal synergistic-based therapies to minimise side effects and maintain low costs. The most relevant applications are presented, such as antibiofilm formation, biofilm penetration or ablation, and nanomaterial-based infected wound therapy. Practical antibacterial applications employing photothermal antimicrobial agents, alone or in synergistic combination with other nanomaterials, are considered. Existing challenges and limitations in photothermal antimicrobial therapy and future perspectives are presented from the structural, functional, safety, and clinical potential points of view.
The low probability of a drug candidate's clinical success, the time consumed and the high cost of bringing a drug from concept to market emphasizes the need for new approaches to drug discovery. Recent innovations in microfluidic technologies, including organ-on-a-chip, droplet microfluidics and high-throughput screening are revealing the potential of these platforms to address some of these challenges, due to the small volume of samples consumed, short processing time, and improved process control. Here, we review selected recent progress in the development and application of microfluidic technologies in drug screening and drug delivery, highlighting the trends and associated challenges.
Microfluidic devices have a central role in many biomedical applications, and there are many fabrication methods to obtain microchannels and reservoirs. Polydimethylsiloxane (PDMS) based microfluidics register an intense development due to the well-known advantages of this material. New manufacturing methods are needed as an alternative to commonly used soft lithography in order to produce inexpensive microfluidic devices. In this paper, we present a simple and reliable technique to obtain PDMS based microfluidic devices. We used digital light processing (DLP) 3D printing for rapid fabrication of resin mold for PDMS structures. UV and thermal post-treatment of printed mold led to high quality molds. Thin aluminum film deposition on resin mold provided a buffer layer to prevent PDMS curing inhibition. Glass was used as substrate material and part of the microchannels wall. Resulted microfluidic parts have a reduced roughness and can ensure robust integrity for the microchannels and chambers.
Annually, antimicrobial-resistant infections-related mortality worldwide accelerates due to the increased use of antibiotics during the coronavirus pandemic and the antimicrobial resistance, which grows exponentially, and disproportionately to the current rate of development of new antibiotics. Nanoparticles can be an alternative to the current therapeutic approach against multi-drug resistance microorganisms caused infections. The motivation behind this work was to find a superior antibacterial nanomaterial, which can be efficient, biocompatible, and stable in time. This study evaluated the antibacterial activity of ZnO-based nanomaterials with different morphologies, synthesized through the solvothermal method and further modified with Au nanoparticles through wet chemical reduction. The structure, crystallinity, and morphology of ZnO and ZnO/Au nanomaterials have been investigated with XRD, SEM, TEM, DLS, and FTIR spectroscopy. The antibacterial effect of unmodified ZnO and ZnO/Au nanomaterials against Escherichia coli and Staphylococcus aureus was investigated through disc diffusion and tetrazolium/formazan (TTC) assays. The results showed that the proposed nanomaterials exhibited significant antibacterial effects on the Gram-positive and Gram-negative bacteria. Furthermore, ZnO nanorods with diameters smaller than 50 nm showed better antibacterial activity than ZnO nanorods with larger dimensions. The antibacterial efficiency against Escherichia coli and Staphylococcus aureus improved considerably by adding 0.2% (w/w) Au to ZnO nanorods. The results indicated the new materials’ potential for antibacterial applications.
Improper foot biomechanics associated with uneven bodyweight distribution contribute to impaired balance and fall risks. There is a need to complete the panel of commercially available devices for the self-measurement of BMI, fat, muscle, bone, weight, and hydration with one that measures weight-shifting at home as a pre-specialist assessment system. This paper reports the development of the Early Notice Pointer (ENP), a user-friendly screening device based on weighing scale technology. The ENP is designed to be used at home to provide a graphic indication and customised and evidence-based foot and posture triage. The device electronically detects and maps the bodyweight and distinct load distributions on the main areas of the feet: forefoot and rearfoot. The developed platform also presents features that assess the user's balance, and the results are displayed as a simple numerical report and map. The technology supports data display on mobile phones and accommodates multiple measurements for monitoring. Therefore, the evaluation could be done at non-specialist and professional levels. The system has been tested to validate its accuracy, precision, and consistency. A parallel study to describe the frequency of arch types and metatarsal pressure in young adults (1034 healthy subjects) was conducted to explain the importance of self-monitoring at home for better prevention of foot arch- and posture-related conditions. The results showed the potential of the newly created platform as a screening device ready to be wirelessly connected with mobile phones and the internet for remote and personalised identification and monitoring of foot- and body balance-related conditions. The real-time interpretation of the reported physiological parameters opens new avenues toward IoT-like on-body monitoring of human physiological signals through easy-to-use devices on flexible substrates for specific versatility.
Viral infections are a significant public health problem, primarily due to their high transmission rate, various pathological manifestations, ranging from mild to severe symptoms and subclinical onset. Laboratory diagnostic tests for infectious diseases, with a short enough turnaround time, are promising tools to improve patient care, antiviral therapeutic decisions, and infection prevention. Numerous microbiological molecular and serological diagnostic testing devices have been developed and authorised as benchtop systems, and only a few as rapid miniaturised, fully automated, portable digital platforms. Their successful implementation in virology relies on their performance and impact on patient management. This review describes the current progress and perspectives in developing micro- and nanotechnology-based solutions for rapidly detecting human viral respiratory infectious diseases. It provides a nonexhaustive overview of currently commercially available and under-study diagnostic testing methods and discusses the sampling and viral genetic trends as preanalytical components influencing the results. We describe the clinical performance of tests, focusing on alternatives such as microfluidics-, biosensors-, Internet-of-Things (IoT)-based devices for rapid and accurate viral loads and immunological responses detection. The conclusions highlight the potential impact of the newly developed devices on laboratory diagnostic and clinical outcomes.
The deleterious effects of the coronavirus disease 2019 (COVID-19) pandemic urged the development of diagnostic tools to manage the spread of disease. Currently, the "gold standard" involves the use of quantitative real-time polymerase chain reaction (qRT-PCR) for SARS-CoV-2 detection. Even though it is sensitive, specific and applicable for large batches of samples, qRT-PCR is labour-intensive, time-consuming, requires trained personnel and is not available in remote settings. This review summarizes and compares the available strategies for COVID-19: serological testing, Point-of-Care Testing, nanotechnology-based approaches and biosensors. Last but not least, we address the advantages and limitations of these methods as well as perspectives in COVID-19 diagnostics. The effort is constantly focused on understanding the quickly changing landscape of available diagnostic testing of COVID-19 at the clinical levels and introducing reliable and rapid screening point of care testing. The last approach is key to aid the clinical decision-making process for infection control, enhancing an appropriate treatment strategy and prompt isolation of asymptomatic/mild cases. As a viable alternative, Point-of-Care Testing (POCT) is typically low-cost and user-friendly, hence harbouring tremendous potential for rapid COVID-19 diagnosis.
Real-time "on-body" monitoring of human physiological signals through wearable systems developed on flexible substrates (e-skin) is the next target in human health control and prevention, while an alternative to bulky diagnostic devices routinely used in clinics. The present work summarizes the recent trends in the development of e-skin systems. Firstly, we revised the material development for e-skin systems. Secondly, aspects related to fabrication techniques were presented. Next, the main applications of e-skin systems in monitoring, such as temperature, pulse, and other bio-electric signals related to health status, were analyzed. Finally, aspects regarding the power supply and signal processing were discussed. The special features of e-skin as identified contribute clearly to the developing potential as in situ diagnostic tool for further implementation in clinical practice at patient personal levels.
The deposition of thin films by Plasma Enhanced Chemical Vapor Deposition (PECVD) method is a critical process in the fabrication of MEMS or semiconductor devices. The current paper presents an comprehensive overview of PECVD process. After a short description of the PECVD reactors main layers and their application such as silicon oxide, TEOS, silicon nitride, silicon oxynitride, silicon carbide, amorphous silicon, diamond like carbon are presented. The influence of the process parameters such as: chamber pressure, substrate temperature, mass flow rate, RF Power and RF Power mode on deposition rate, film thickness uniformity, refractive index uniformity and film stress were analysed. The main challenge of thin films PECVD deposition for Microelectromechanical Systems (MEMS)and semiconductor devices is to optimize the deposition parameters for high deposition rate with low film stress which and if is possible at low deposition temperature.
After two previous episodes, in 2002 and 2012, when two highly pathogenic coronaviruses (SARS, MERS) with a zoonotic origin emerged in humans and caused fatal respiratory illness, we are today experiencing the COVID-19 pandemic produced by SARS-CoV-2. The main question of the year 2021 is if naturally- or artificially-acquired active immunity will be effective against the evolving SARS-CoV-2 variants. This review starts with the presentation of the two compartments of antiviral immunity—humoral and cellular, innate and adaptive—underlining how the involved cellular and molecular actors are intrinsically connected in the development of the immune response in SARS-CoV-2 infection. Then, the SARS-CoV-2 immunopathology, as well as the derived diagnosis and therapeutic approaches, will be discussed.
Ultrashort peptides (USPs), composed of three to seven amino acids, can self-assemble into nanofibers in pure water. Here, using hydrodynamic focusing and a solvent exchange method on a microfluidic setup, we convert these nanofibers into globular nanoparticles with excellent dimensional control and polydispersity. Thanks to USP nanocarriers’ structure, different drugs can be loaded. We used Curcumin as a model drug to evaluate the performance of USP nanocarriers as a novel drug delivery vehicle. These nanoparticles can efficiently cross the cell membrane and possess nonlinear optical properties. Therefore, we envisage USP nanoparticles as promising future theranostic nanocarriers.
Human pluripotent stem cell (hPSC) is a great resource for generating cell derivatives for drug efficiency testing. Metabolites of nutraceuticals can exert anti-inflammatory effects on blood vessels. However, the concentration of nutraceutical metabolites produced in hPSC-derived hepatocytes (hPSC-HEPs) is usually low. To enable the detection of these metabolites under the in vitro environment, we have developed a co-culture model consisting of parallel co-culture chambers and a recirculating microfluidic system with minimum fluid volume, optimal cell culture environment. The model allows cells to be exposed continuously to nutraceutical metabolites. In this perfused culturing model, hPSC-derived endothelial cells and hPSC-HEPs are co-cultured without physical contact. When an anti-inflammatory nutraceutical, quercetin, was administrated to the co-culture, higher levels of quercetin metabolites were detected on-chip compared with static control. We further induced inflammation with Interleukin-1β in the co-culture model and measured interleukin 8 (IL-8) generation. The IL-8 level was suppressed more significantly by quercetin metabolites in the perfusion co-culture, as compared to static culture. This is due to enhanced metabolites production on-chip. This microfluidic co-culture model enables in vitro screening of nutraceuticals using hPSC-derived cells.
Deposition parameters of tetraethylorthosilicate (TEOS) layers on silicon substrate using Plasma Enhanced Chemical Vapor Deposition (PECVD) method were investigated We design the experiment taking into consideration chamber pressure, substrate temperature, RF Power and mass flow rate (oxygen and TEOS) to asses their influence on deposition rate, film uniformity, refractive index uniformity and film stress. All the results were evaluated for applications that require low temperature processing in order to avoid damage of Microelectromechanical Systems (MEMS) devices.