Nano-analytical characterization of endogenous minerals in healthy placental tissue: mineral distribution, composition and ultrastructure.

Despite its crucial role, the placenta is the least understood human organ. Recent clinical studies indicate a direct association between placental calcification and maternal and offspring health. This study reveals distinct characteristics of minerals formed during gestational ageing using cutting-edge nano-analytical characterization and paves the way for investigations focused on the identification of potential markers for disease risks in a clinical setting based on atypical placental mineral fingerprints.

All-solid-state potentiometric sensors with a multiwalled carbon nanotube inner transducing layer for anion detection in environmental samples.

While ion to electron transducing layers for the fabrication of potentiometric membrane electrodes for the detection of cations have been well established, similar progress for the sensing of anions has not yet been realized. We report for this reason on a novel approach for the development of all-solid-state anion selective electrodes using lipophilic multiwalled carbon nanotubes (f-MWCNTs) as the inner ion to electron transducing layer. This material can be solvent cast, as it conveniently dissolves in tetrahydrofuran (THF), an important advantage to develop uniform films without the need for using surfactants that might deteriorate the performance of the electrode. Solid contact sensors for carbonate, nitrate, nitrite, and dihydrogen phosphate are fabricated and characterized, and all exhibit comparable analytical characteristics to the inner liquid electrodes. For example, the carbonate sensor exhibits a Nernstian slope of 27.2 ± 0.8 mV·dec(-1), a LOD = 2.3 µM, a response time of 1 s, a linear range of four logarithmic units, and a medium-term stability of 0.04 mV·h(-1) is obtained in a pH 8.6 buffered solution. Water layer test, reversibility, and selectivity for chloride, nitrate, and hydroxide are also reported. The excellent properties of f-MWCNTs as a transducer are contrasted to the deficient performance of poly(3-octyl-thiophene) (POT) for carbonate detection. This is evidenced both with a significant drift in the potentiometric measures as well as a pronounced sensitivity to light (either sunlight or artificial light). This latter aspect may compromise its potential for environmental in situ measurements (night/day cycles). The concentration of carbonate is determined in a river sample (Arve river, Geneva) and compared to a reference method (automatic titrator with potentiometric pH detection). The results suggest that nanostructured materials such as f-MWCNTs are an attractive platform as a general ion-to-electron transducer for anion-selective electrodes.

Early Detection and Monitoring of Anastomotic Leaks via Naked Eye-Readable, Non-Electronic Macromolecular Network Sensors.

Anastomotic leakage (AL) is the leaking of non-sterile gastrointestinal contents into a patient's abdominal cavity. AL is one of the most dreaded complications following gastrointestinal surgery, with mortality rates reaching up to 27%. The current diagnostic methods for anastomotic leaks are limited in sensitivity and specificity. Since the timing of detection directly impacts patient outcomes, developing new, fast, and simple methods for early leak detection is crucial. Here, a naked eye-readable, electronic-free macromolecular network drain fluid sensor is introduced for continuous monitoring and early detection of AL at the patient's bedside. The sensor array comprises three different macromolecular network sensing elements, each tailored for selectivity toward the three major digestive enzymes found in the drainage fluid during a developing AL. Upon digestion of the macromolecular network structure by the respective digestive enzymes, the sensor produces an optical shift discernible to the naked eye. The diagnostic efficacy and clinical applicability of these sensors are demonstrated using clinical samples from 32 patients, yielding a Receiver Operating Characteristic Area Under the Curve (ROC AUC) of 1.0. This work has the potential to significantly contribute to improved patient outcomes through continuous monitoring and early, low-cost, and reliable AL detection.

Reversible Mechanical Contraception and Endometriosis Treatment Using Stimuli-Responsive Hydrogels.

Female sterilization via fallopian tube ligation is a common procedure; However, after the operation, over 10% of women seek re-fertilization, which is frequently unsuccessful. In addition, there is evidence that fallopian tubes contribute to the spread of endometriotic tissue as they serve as channels for proinflammatory media entering the abdominal cavity via retrograde menstruation. Here, stimuli-degradable hydrogel implants are presented for the functional, biocompatible, and reversible occlusion of fallopian tubes. The hydrogel implants, designed with customized swelling properties, mechanically occlude fallopian tubes in a high-performance manner with burst pressures reaching 255-558 mmHg, exceeding normal abdominal pressures (95 mmHg). Their damage-free removal can be achieved within 30 min using near-visible UV light or a glutathione solution, employing a method akin to standard fallopian tube perfusion diagnostics. Ultrasound-guided implant placement is demonstrated using a clinical hysteroscope in a human-scale uterus model and biocompatibility in a porcine in vivo model. Importantly, the prevention of live sperm as well as endometrial cell passage through blocked fallopian tubes is demonstrated. Overall, a multifunctional system is presented that constitutes a possible means of on-demand, reversible contraception along with the first-ever mechanical approach to abdominal endometriosis prevention and treatment.

Specific capture of Pseudomonas aeruginosa for rapid detection of antimicrobial resistance in urinary tract infections.

Urinary tract infections (UTIs) are among the most predominant microbial diseases, leading to substantial healthcare burdens and threatening human well-being. UTIs can become more critical when caused by Pseudomonas aeruginosa, particularly by antimicrobial-resistant types. Thereby a rapid diagnosis and identification of the antimicrobial-resistant P. aeruginosa can support and guide an efficient medication and an effective treatment toward UTIs. Herein, we designed a platform for prompt purification, and effective identification of P. aeruginosa to combat the notorious P. aeruginosa associated UTIs. A peptide (QRKLAAKLT), specifically binding to P. aeruginosa, was grafted onto PEGylated magnetic nanoclusters and enabled a successful capture and enrichment of P. aeruginosa from artificial human urine. Rapid identification of antimicrobial resistance of the enriched P. aeruginosa can be moreover accomplished within 30 min. These functionalized magnetic nanoclusters demonstrate a prominent diagnostic potential to combat P. aeruginosa associated UTIs, which can be extended to other P. aeruginosa involved infections.

Surgical Sealant with Integrated Shape-Morphing Dual Modality Ultrasound and Computed Tomography Sensors for Gastric Leak Detection.

Postoperative anastomotic leaks are the most feared complications after gastric surgery. For diagnostics clinicians mostly rely on clinical symptoms such as fever and tachycardia, often developing as a result of an already fully developed, i.e., symptomatic, surgical leak. A gastric fluid responsive, dual modality, electronic-free, leak sensor system integrable into surgical adhesive suture support materials is introduced. Leak sensors contain high atomic number carbonates embedded in a polyacrylamide matrix, that upon exposure to gastric fluid convert into gaseous carbon dioxide (CO2 ). CO2 bubbles remain entrapped in the hydrogel matrix, leading to a distinctly increased echogenic contrast detectable by a low-cost and portable ultrasound transducer, while the dissolution of the carbonate species and the resulting diffusion of the cation produces a markedly reduced contrast in computed tomography imaging. The sensing elements can be patterned into a variety of characteristic shapes and can be combined with nonreactive tantalum oxide reference elements, allowing the design of shape-morphing sensing elements visible to the naked eye as well as artificial intelligence-assisted automated detection. In summary, shape-morphing dual modality sensors for the early and robust detection of postoperative complications at deep tissue sites, opening new routes for postoperative patient surveillance using existing hospital infrastructure is reported.

Cellular fate and performance of group IV metal organic framework radioenhancers.

Nano-sized metal organic frameworks (nanoMOFs) have gained increasing importance in biomedicine due to their tunable properties. In addition to their use as carriers in drug delivery, nanoMOFs containing hafnium have been successfully employed as radio-enhancers augmenting damage caused by X-ray irradiation in tumor tissue. While results are encouraging, there is little mechanistic understanding available, and the biological fate of these radio-enhancer nanoparticles remains largely unexplored. Here, we synthesized a selection of group IV metal-based (Hf, Ti, Ti/Zr) nanoMOFs and investigated their cell compatibility and radio-enhancement performance in direct comparison to the corresponding metal oxides. We report surprising radio-enhancement performance of Ti-containing nanoMOFs reaching dose modifying ratios of 3.84 in human sarcoma cells and no relevant dose modification in healthy human fibroblasts. These Ti-based nanoMOFs even outperformed previously reported Hf-based nanoMOFs as well as equimolar group IV metal oxides in direct benchmarking experiments. While group IV nanoMOFs were well-tolerated by cells in the absence of irradiation, the nanoMOFs partially dissolved in lysosomal buffer conditions showing distinctly different chemical stability compared to widely researched group IV oxides (TiO2, ZrO2, and HfO2). Taken together, this study illustrates the promising potential of Ti-based nanoMOFs for radio-enhancement and provides insight into the intracellular fate and stability of group IV nanoMOFs.

The Role of Inorganics in Preeclampsia Assessed by Multiscale Multimodal Characterization of Placentae.

Preeclampsia is one of the most dangerous diseases in pregnancy. Because of the hypertensive nature of preeclampsia, placental calcifications are believed to be a predictor for its occurrence, analogous to their role in cardiovascular diseases. However, the prevalence and the relevance of calcifications for the clinical outcome with respect to preeclampsia remains controversial. In addition, the role of other inorganic components present in the placental tissue in the development of preeclampsia has rarely been investigated. In this work, we therefore characterized inorganic constituents in placental tissue in groups of both normotensive and preeclamptic patients (N = 20 each) using a multi-scale and multi-modal approach. Examinations included elemental analysis (metallomics), sonography, computed tomography (CT), histology, scanning electron microscopy, X-ray fluorescence and energy dispersive X-ray spectroscopy. Our data show that tissue contents of several heavy metals (Al, Cd, Ni, Co, Mn, Pb, and As) were elevated whereas the Rb content was decreased in preeclamptic compared to normotensive placentae. However, the median mineral content (Ca, P, Mg, Na, K) was remarkably comparable between the two groups and CT showed lower calcified volumes and fewer crystalline deposits in preeclamptic placentae. Electron microscopy investigations revealed four distinct types of calcifications, all predominantly composed of calcium, phosphorus and oxygen with variable contents of magnesium in tissues of both maternal and fetal origin in both preeclamptic and normotensive placentae. In conclusion our study suggests that heavy metals, combined with other factors, can be associated with the development of preeclampsia, however, with no obvious correlation between calcifications and preeclampsia.

Modular stimuli-responsive hydrogel sealants for early gastrointestinal leak detection and containment.

Millions of patients every year undergo gastrointestinal surgery. While often lifesaving, sutured and stapled reconnections leak in around 10% of cases. Currently, surgeons rely on the monitoring of surrogate markers and clinical symptoms, which often lack sensitivity and specificity, hence only offering late-stage detection of fully developed leaks. Here, we present a holistic solution in the form of a modular, intelligent suture support sealant patch capable of containing and detecting leaks early. The pH and/or enzyme-responsive triggerable sensing elements can be read out by point-of-need ultrasound imaging. We demonstrate reliable detection of the breaching of sutures, in as little as 3 hours in intestinal leak scenarios and 15 minutes in gastric leak conditions. This technology paves the way for next-generation suture support materials that seal and offer disambiguation in cases of anastomotic leaks based on point-of-need monitoring, without reliance on complex electronics or bulky (bio)electronic implantables.

Tailoring the Colloidal Stability, Magnetic Separability, and Cytocompatibility of High-Capacity Magnetic Anion Exchangers.

Extracorporeal blood purification has been applied to artificially support kidney or liver function. However, convection and diffusion based blood purification systems have limited removal rates for high molecular weight and hydrophobic molecules. This limitation is due to the finite volume of infusion and limited membrane permeability, respectively. Adsorption provides an attractive alternative for the removal of higher molecular weight compounds. The use of adsorption resins containing ion exchanging groups to capture specific molecules has become well-established. Instead of stationary adsorption resins, however, ion exchanging polymers may be immobilized on magnetic particles and serve as freely diffusing, mobile, high capacity solid phase of ion exchange chromatography. While small beads with high surface area are attractive in terms of mass transfer and binding, unifying high capturing capacity with rapid and quantitative bead recovery remains an issue. Therefore, most of the current magnetic ion exchangers are based on micron-sized beads or require long times to separate. In addition to unfavorable magnetic recovery rates, the usually poor cytocompatibility limits their applicability in biomedicine. Here, we report on the synthesis and performance of polycationic polymer coated magnetic nanoflowers (MNF) for highly efficacious anion capturing. We demonstrate accurate control over the polymer content and composition on the beads and show its direct influence on colloidal stability, capturing capacity and magnetic separability. We present the removal of clinically relevant targets by capturing bilirubin with capacities 2-fold higher than previous work as well as quantitative heparin removal. Additionally, we illustrate how copolymerization of poly(2-dimethylaminoethyl methacrylate) (PDMAEMA) with poly(ethylene glycol) methyl ether methacrylate (PEGMEMA) leads to improved cytocompatibility of the polymer-coated MNF capturing agents while retaining high capturing capacities. Taken together, we present a nanoparticle/polymer material, which upon future in vivo validation, unifies high binding capacities and magnetic separability for rapid toxin capturing and hence fulfills key requirements of clinical utility.