Zeolite-Loaded Hydrogels as Wound pH-Modulating Dressings for Diabetic Wound Healing.

Wound pH has emerged as a promising therapeutic target in diabetic foot ulcers (DFU). Here, we aimed to develop a microparticle-loaded hydrogel for pH modulation in wound fluid. In a screen of polymeric and inorganic microparticles, zeolites were identified as pH-modulating microparticles. Zeolites were encapsulated in a calcium cross-linked alginate hydrogel, a biocompatible matrix clinically used as a wound dressing. This hydrogel potently neutralized hydroxide ions in serum-containing simulated wound fluid. These findings encourage a further development of this pH-modulating device as a molecular therapeutic system for DFUs.

Real-Time Tracking of In Situ-Forming Alginate Hydrogel by Contrast-Enhanced Computed Tomography.

Hydrogel-based biomaterials have gained broad acceptance for tissue engineering and drug delivery applications. As their function generally depends on their localization, identifying the hydrogel position in the body is relevant and will alert physicians about potentially dangerous hydrogel migration. Monitoring the localization of hydrogels by imaging is challenging due to their high water content. Here, we developed a method to render alginate hydrogels visible on computed tomography (CT) and X-ray for real-time tracking of hydrogels inside the body. This method is based on physically immobilizing emulsion droplets of ethiodized oil, an FDA-approved positive CT contrast agent, in calcium-crosslinked alginate hydrogels. We prepared an oil-in-water emulsion of ethiodized oil with micron-sized emulsion droplets and encapsulated it in a calcium-crosslinked alginate hydrogel. This injectable in situ-forming hydrogel was stable for at least 2 weeks in vitro, visible on CT and X-ray in mice, and showed contrast agent concentration-dependent signal intensities. Hydrogels retrieved from mice after imaging had suitable rheological properties with a storage modulus of about 2 kPa and a loss modulus of about 0.35 kPa. This proof-of-concept study highlights the potential of ethiodized oil to localize hydrogels in real time inside the body and identifies a new use of this FDA-approved contrast agent.

Portable Near-Infrared Fluorometer for a Liposomal Blood Lactate Assay.

In sepsis, plasma lactate is a key biomarker of disease severity, prognosis, and treatment success. However, the median time to result for clinical lactate tests is 3 h. We recently reported a near-infrared fluorescent (NIRF) blood lactate assay that relies on a two-step enzymatic reaction in a liposomal reaction compartment. This assay was optimized in human blood and was capable of quantifying lactate in fresh capillary blood from human volunteers at clinically relevant concentrations in 2 min. However, these studies were performed with a tabletop fluorescence plate reader. For translation to the point of care, the liposomal lactate assay needs to be combined with a small portable NIR fluorometer. Portable NIR fluorometers were successfully used for the analysis of skin and soil samples, but reports for blood metabolite assays are scarce. We aimed at testing the performance of the liposomal lactate assay in combination with a commercial small portable NIR fluorometer. First, we tested the fluorophore of the liposomal lactate assay using the NIR dye sulfo-cyanine 7; we observed strong fluorescence signals and high linearity. Second, we performed the liposomal lactate assay in lactate-spiked human arterial blood using the portable fluorometer as the detector and observed strong and highly linear lactate sensing at clinically relevant lactate concentrations after 2 min. Finally, spiking fresh mouse blood with three clinically relevant lactate concentrations led to a significantly different response to all three concentrations after 5 min. These results highlight the usefulness of the tested portable NIR fluorometer for the liposomal lactate assay and motivate a clinical evaluation of this rapid and easy-to-use lactate assay.

Comparison of gadolinium-based contrast agents for MR cholangiography in saline, blood and bile: a phantom study.

BACKGROUND: We compared T1- and T2-weighted signal intensities of liver-specific (gadoxetate, gadobenate) and non-specific (gadoterate) gadolinium contrast agents (CAs) in a bile phantom. METHODS: In a phantom study, gadoxetate, gadobenate, and gadoterate were diluted in saline, blood, and bile at different concentrations (0, 0.25, 0.5. 1, 2.5, 5, 10, and 25 mM) and imaged in a 3-T magnetic resonance imaging (MRI) system using T1- and T2-weighted sequences. The maximum signal intensities of CAs were compared for each sequence separately and across all T1-weighted sequences using one-way ANOVA. RESULTS: Using T1-weighted sequences, CA concentration-dependent signal intensity increase was followed by decrease due to T2* effects. Comparing CAs for each sequence in bile yielded higher maximum signal intensities with gadobenate than gadoxetate and gadoterate using T1-weighted spin-echo (p < 0.010), multiecho gradient- and spin-echo (p < 0.001), and T1-weighted high-resolution isotropic volume excitation (eTHRIVE) sequences (p < 0.010). Comparing across all T1-weighted sequences in the bile phantom, gadobenate imaged using T1-weighted turbo field-echo (TFE) sequence showed the highest signal intensity, significantly higher than that using other CAs agents or sequences (p < 0.004) except for gadobenate and gadoxetate evaluated with three-dimensional multiecho fast field-echo (3D-mFFE) and gadoxetate with T1-weighted TFE sequence (p > 0.141). Signal reduction with CA concentration-dependent decrease was observed on T2-weighted images. CONCLUSION: In this bile phantom study of gadolinium-based CA, gadobenate and gadoxetate showed high signal intensity with T1-weighted TFE and 3D-mFFE sequences, which supports their potential utility for contrast-enhanced hepatobiliary MRI. KEY POINTS: • Contrast-enhanced magnetic resonance (MR) cholangiography depends on contrast agent type, kinetics, and concentration in bile, • We compared signal intensities of three contrast agents in a bile phantom study. • Gadobenate, gadoxetate, and gadoterate demonstrated different signal intensities at identical concentrations. • Gadoxetate and gadobenate showed high signal intensities on T1-weighted MR sequences.

175 Years of Bilirubin Testing: Ready for Point-of-Care?

Bilirubin was first detected in blood in 1847 and since then has become one of the most widely used biomarkers for liver disease. Clinical routine bilirubin testing is performed at the hospital laboratory, and the gold standard colorimetric test is prone to interferences. The absence of a bedside test for bilirubin delays critical clinical decisions for patients with liver disease. This clinical care gap has motivated the development of a new generation of bioengineered point-of-care bilirubin assays. In this Perspective, recently developed bilirubin assays are critically discussed, and their translational potential evaluated.