Advancements in Porous Silicon Biosensors for Point of Care, Wearable, and Implantable Applications.

Biosensors play a critical role in modern diagnostics, offering high sensitivity and specificity for detecting various relevant clinical analytes as well as real-time monitoring and integrability in point-of-care (POC) platforms and wearable/implantable devices. Among the numerous materials used as biosensing substrates, porous silicon (pSi) has garnered significant attention due to its tunable properties, ease of fabrication, large surface area, and versatile surface chemistry. These attributes make pSi an ideal platform for transducer development, particularly in the fabrication of optical and electrochemical biosensors.

Clinical challenges and opportunities related to the biological responses experienced by indwelling and implantable bioelectronic medical devices.

Implantable electrodes have been utilized for decades to stimulate, sense, or monitor a broad range of biological processes, with examples ranging from glucose monitoring devices to cochlear implants. While the underlying science related to the application of electrodes is a mature field, preclinical and clinical studies have demonstrated that there are still significant challenges in vivo associated with a lack of control over tissue-material interfacial interactions, especially over longer time frames. Herein we discuss the current challenges and opportunities for implantable electrodes and the associated bioelectronic interfaces across the clinical landscape with a focus on emerging technologies and the obstacles of biofouling, microbial colonization, and the foreign body response.

An In Vitro-In Vivo Comparative Study Using Highly Sensitive Radioisotopic Assays to Assess the Predictive Power of Emerging Blood-Brain Barrier Models.

Microfluidic BBB-on-a-chip models (μBBB) aim to recapitulate the organotypic features of the human BBB with great potential to model CNS diseases and advance CNS therapeutics. Nevertheless, their predictive capacity for drug uptake into the brain remains uncertain due to limited evaluation with only a small number of model drugs. Here, the in vivo brain uptake of a panel of nine radiolabeled compounds is evaluated in Swiss-outbred mice following a single intravenously administered dose and compared against results from the microfluidic μBBB platform and the conventional Transwell BBB model.

High-density microneedle array-based wearable electrochemical biosensor for detection of insulin in interstitial fluid.

The development of point-of-care wearable devices capable of measuring insulin concentration has the potential to significantly improve diabetes management and life quality of diabetic patients. However, the lack of a suitable point-of-care device for personal use makes regular insulin level measurements challenging, in stark contrast to glucose monitoring. Herein, we report an electrochemical transdermal biosensor that utilizes a high-density polymeric microneedle array (MNA) to detect insulin in interstitial fluid (ISF).

A biosensory μvessel-gravity device for advancing vascular analysis in space medicine.

Studying vascular responses to microgravity (MG) poses significant challenges in space medicine due to the limitations of conventional cell culture and animal models. To address these challenges, we have developed an innovative biosensory μvessel-gravity device that integrates organ-on-a-chip technology, 3D printing, and a 3D clinostat. This device enables cell interaction monitoring and flow shear stress modeling, thereby allowing accurate blood vessel cell sensory to changed mechanical environment.

The Roles of Micro- and Nanoscale Materials in Cell-Engineering Systems.

Customizable manufacturing of ex vivo cell engineering is driven by the need for innovations in the biomedical field and holds substantial potential for addressing current therapeutic challenges; but it is still only in its infancy. Micro- and nanoscale-engineered materials are increasingly used to control core cell-level functions in cellular engineering. By reprogramming or redirecting targeted cells for extremely precise functions, these advanced materials offer new possibilities.

3D Polymeric Lattice Microstructure-Based Microneedle Array for Transdermal Electrochemical Biosensing.

Microneedles (MNs) or microneedle arrays (MNAs) are critical components of minimally invasive devices comprised of a single or a series of micro-scale projections. MNs can bypass the outermost layer of the skin and painlessly access microcirculation of the epidermis and dermis layers, attracting great interest in the development of personalized healthcare monitoring and diagnostic devices. However, MN technology has not yet reached its full potential since current micro- and nanofabrication methods do not address the need of fabricating MNs with complex surfaces to facilitate the development of clinically adequate devices.

Study of the Structure of Hyperbranched Polyglycerol Coatings and Their Antibiofouling and Antithrombotic Applications.

While blood-contacting materials are widely deployed in medicine in vascular stents, catheters, and cannulas, devices fail in situ because of thrombosis and restenosis. Furthermore, microbial attachment and biofilm formation is not an uncommon problem for medical devices. Even incremental improvements in hemocompatible materials can provide significant benefits for patients in terms of safety and patency as well as substantial cost savings.

Nanoinjection: A Platform for Innovation in Ex Vivo Cell Engineering.

ConspectusIn human cells, intracellular access and therapeutic cargo transport, including gene-editing tools (e.g., CRISPR-Cas9 and transposons), nucleic acids (e.

Delivery of miRNAs Using Porous Silicon Nanoparticles Incorporated into 3D Hydrogels Enhances MSC Osteogenesis by Modulation of Fatty Acid Signaling and Silicon Degradation.

Strategies incorporating mesenchymal stromal cells (MSC), hydrogels and osteoinductive signals offer promise for bone repair. Osteoinductive signals such as growth factors face challenges in clinical translation due to their high cost, low stability and immunogenicity leading to interest in microRNAs as a simple, inexpensive and powerful alternative. The selection of appropriate miRNA candidates and their efficient delivery must be optimised to make this a reality.

Folic Acid-Conjugated Brush Polymers Show Enhanced Blood-Brain Barrier Crossing in Static and Dynamic Models Toward Brain Cancer Targeting Therapy.

Over the past decades, evidence has consistently shown that treatment of central nervous system (CNS)-related disorders, including Alzheimer's disease, Parkinson's disease, stroke, multiple sclerosis, and brain cancer, is limited due to the presence of the blood-brain barrier (BBB). To assist with the development of new therapeutics, it is crucial to engineer a drug delivery system that can cross the BBB efficiently and reach target cells within the brain. In this study, we present a potentially efficient strategy for targeted brain delivery through utilization of folic acid (FA)-conjugated brush polymers, that specifically target the reduced folate carrier (RFC, SLC19A1) expressed on brain endothelial cells.

Angiopep-2-Functionalized Lipid Cubosomes for Blood-Brain Barrier Crossing and Glioblastoma Treatment.

Glioblastoma multiforme (GBM) is an aggressive brain cancer with high malignancy and resistance to conventional treatments, resulting in a bleak prognosis. Nanoparticles offer a way to cross the blood-brain barrier (BBB) and deliver precise therapies to tumor sites with reduced side effects. In this study, we developed angiopep-2 (Ang2)-functionalized lipid cubosomes loaded with cisplatin (CDDP) and temozolomide (TMZ) for crossing the BBB and providing targeted glioblastoma therapy.

Wearable Microneedle Patch for Transdermal Electrochemical Monitoring of Urea in Interstitial Fluid.

Microneedle-based wearable electrochemical biosensors are the new frontier in personalized health monitoring and disease diagnostic devices that provide an alternative tool to traditional blood-based invasive techniques. Advancements in micro- and nanofabrication technologies enabled the fabrication of microneedles using different biomaterials and morphological features with the aim of overcoming existing challenges and enhancing sensing performance. In this work, we report a microneedle array featuring conductive recessed microcavities for monitoring urea levels in the interstitial fluid of the skin.

Insights into Targeted and Stimulus-Responsive Nanocarriers for Brain Cancer Treatment.

Brain cancers, especially glioblastoma multiforme, are associated with poor prognosis due to the limited efficacy of current therapies. Nanomedicine has emerged as a versatile technology to treat various diseases, including cancers, and has played an indispensable role in combatting the COVID-19 pandemic as evidenced by the role that lipid nanocarrier-based vaccines have played. The tunability of nanocarrier physicochemical properties -including size, shape, surface chemistry, and drug release kinetics- has resulted in the development of a wide range of nanocarriers for brain cancer treatment.

Tackling catheter-associated urinary tract infections with next-generation antimicrobial technologies.

Urinary catheters and other medical devices associated with the urinary tract such as stents are major contributors to nosocomial urinary tract infections (UTIs) as they provide an access path for pathogens to enter the bladder. Considering that catheter-associated urinary tract infections (CAUTIs) account for approximately 75% of UTIs and that UTIs represent the most common type of healthcare-associated infections, novel anti-infective device technologies are urgently required. The rapid rise of antimicrobial resistance in the context of CAUTIs further highlights the importance of such preventative strategies.

Towards the rapid detection of haze-forming proteins.

Protein haze in white wine can be a serious quality defect because consumers perceive hazy wines as "spoiled". Unfortunately, a specific method for the detection, or selective treatment, of such proteins in affected wines does not exist. Herein we investigate on the development of an easy-to-use sensor device that allows detection of haze-forming proteins (HFPs).

Influence of Surface Ligand Density and Particle Size on the Penetration of the Blood-Brain Barrier by Porous Silicon Nanoparticles.

Overcoming the blood-brain barrier (BBB) remains a significant challenge with regard to drug delivery to the brain. By incorporating targeting ligands, and by carefully adjusting particle sizes, nanocarriers can be customized to improve drug delivery. Among these targeting ligands, transferrin stands out due to the high expression level of its receptor (i.

Staging of colorectal cancer using lipid biomarkers and machine learning.

Introduction: Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. Alteration in lipid metabolism and chemokine expression are considered hallmark characteristics of malignant progression and metastasis of CRC. Validated diagnostic and prognostic biomarkers are urgently needed to define molecular heterogeneous CRC clinical stages and subtypes, as liver dominant metastasis has poor survival outcomes.

Fluoropolymer Functionalization of Organ-on-Chip Platform Increases Detection Sensitivity for Cannabinoids.

Microfluidic technology is applied across various research areas including organ-on-chip (OOC) systems. The main material used for microfluidics is polydimethylsiloxane (PDMS), a silicone elastomer material that is biocompatible, transparent, and easy to use for OOC systems with well-defined microstructures. However, PDMS-based OOC systems can absorb hydrophobic and small molecules, making it difficult and erroneous to make quantitative analytical assessments for such compounds.

Electroactive nanoinjection platform for intracellular delivery and gene silencing.

Background: Nanoinjection-the process of intracellular delivery using vertically configured nanostructures-is a physical route that efficiently negotiates the plasma membrane, with minimal perturbation and toxicity to the cells. Nanoinjection, as a physical membrane-disruption-mediated approach, overcomes challenges associated with conventional carrier-mediated approaches such as safety issues (with viral carriers), genotoxicity, limited packaging capacity, low levels of endosomal escape, and poor versatility for cell and cargo types. Yet, despite the implementation of nanoinjection tools and their assisted analogues in diverse cellular manipulations, there are still substantial challenges in harnessing these platforms to gain access into cell interiors with much greater precision without damaging the cell's intricate structure.

Engineering Efficient CAR-T Cells via Electroactive Nanoinjection.

Chimeric antigen receptor (CAR)-T cell therapy has emerged as a promising cell-based immunotherapy approach for treating blood disorders and cancers, but genetically engineering CAR-T cells is challenging due to primary T cells' sensitivity to conventional gene delivery approaches. The current viral-based method can typically involve significant operating costs and biosafety hurdles, while bulk electroporation (BEP) can lead to poor cell viability and functionality. Here, a non-viral electroactive nanoinjection (ENI) platform is developed to efficiently negotiate the plasma membrane of primary human T cells via vertically configured electroactive nanotubes, enabling efficient delivery (68.

Recent Advances in Formulations for Long-Acting Delivery of Therapeutic Peptides.

Recent preclinical and clinical studies have focused on the active area of therapeutic peptides due to their high potency, selectivity, and specificity in treating a broad range of diseases. However, therapeutic peptides suffer from multiple disadvantages, such as limited oral bioavailability, short half-life, rapid clearance from the body, and susceptibility to physiological conditions (e.g.

X-Ray-Induced Drug Release for Cancer Therapy.

Drug delivery systems (DDSs) are designed to deliver therapeutic agents to specific target sites while minimizing systemic toxicity. Recent developments in drug-loaded DDSs have demonstrated promising characteristics and paved new pathways for cancer treatment. Light, a prevalent external stimulus, is widely utilized to trigger drug release.

Combination of Chemotherapy and Mild Hyperthermia Using Targeted Nanoparticles: A Potential Treatment Modality for Breast Cancer.

Despite the clinical benefits that chemotherapeutics has had on the treatment of breast cancer, drug resistance remains one of the main obstacles to curative cancer therapy. Nanomedicines allow therapeutics to be more targeted and effective, resulting in enhanced treatment success, reduced side effects, and the possibility of minimising drug resistance by the co-delivery of therapeutic agents. Porous silicon nanoparticles (pSiNPs) have been established as efficient vectors for drug delivery.