Intestinal anastomotic leaking, which involves the discharge of chemically aggressive, non‐sterile fluids into the abdomen, remains one of the most dreaded postoperative complications of abdominal surgery. Depending on the site and the patient condition, incidence ranging between 4% and 21% and mortality rates up to 27% are reported. Currently available surgical sealants only poorly address the issue, especially since most commonly used fibrin glues fail due to insufficient adhesion and chemical instability. Here, a chemically highly resistive, leak‐tight, and mucoadhesive hydrogel sealant, which is grafted on the surface of the intestinal wall using a mutually interpenetrating network that traverses hydrogel and tissue is presented. In contrast to clinically used fibrin‐based sealants (including Tachosil), the developed adhesive poly(acrylamide‐methyl acrylate‐acrylic acid) patch does not degrade and exhibits strong tissue adhesion even when exposed to intestinal fluid. The biocompatible hydrogel patch effectively seals anastomotic leaks in ex vivo intestinal models, greatly surpassing commercial sealants (time to patch‐failure >24 h compared to 5 min for commonly used Tachosil). Importantly, the developed adhesive patch paves the way for the application of both mechanically and chemically robust sealants suitable for the treatment and prevention of intestinal leaks.
This paper describes a comprehensive investigation of particle number concentrations including a multi-method comparison, theoretical modeling, and cellular dosimetry.
Extracellular vesicles (EVs) have gained increasing attention as novel disease biomarkers and as promising therapeutic agents. These cell-derived, phospholipid-based particles are present in many - if not all - physiological fluids. They have been shown to govern several physiological processes, such as cell-cell communication, but also to be involved in pathological conditions, for example tumour progression. In infectious diseases, EVs have been shown to induce host immune responses and to mediate transfer of virulence or resistance factors. Here, we discuss recent developments in using EVs as diagnostic tools for infectious diseases, the development of EV-based vaccines and the use of EVs as potential anti-infective entity. We illustrate how EV-based strategies could open a viable new avenue to tackle current challenges in the field of infections, including barrier penetration and growing resistance to antimicrobials.
Here, we report the use of rare earth element-doped nanocrystals as probes for correlative cathodoluminescence electron microscopy (CCLEM) bioimaging. This first experimental demonstration shows potential for the simultaneous acquisition of luminescence and electron microscopy images with nanometric resolution in focused ion beam cut biological samples.
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.
Nanoparticle-based
radio-enhancement has the potential to improve
cancer cell eradication by augmenting the photoelectric cross-section
of targeted cancer cells relative to the healthy surroundings. Encouraging
results have been reported for various nanomaterials, including gold
and hafnia. However, the lack of scalable synthesis methods and comparative
studies is prohibitive to rationalized material design and hampers
translation of this promising cancer management strategy. Here, we
present a scalable (>100 g day–1) and sterile
alternative
to conventional batch synthesis of group IV metal oxides (TiO2, ZrO2, and HfO2), which yields near-monodisperse
ultrasmall metal oxide nanoparticles with radio-enhancement properties.
Access to group IV oxide nanoparticles, which solely differ in atomic
number but otherwise exhibit comparable morphologies, sizes, and surface
chemistries, enables the direct comparison of their radio-enhancement
properties to rationally guide material selection for optimal radio-enhancement
performance. We show that the metal oxide nanoparticles exhibit atomic-number-dependent
radio-enhancement in cancer cells (HT1080 and HeLa), which is attenuated
to baseline levels in normal fibroblasts (normal human dermal fibroblasts).
The observed radio-enhancement effects show excellent agreement with
physical dose enhancement and nanoparticle dosimetry calculations.
Direct benchmarking against gold nanoparticles, the current gold standard
in the field, rationalizes the use of hafnia nanoparticles based on
their radio-enhancement performance, which is superior to equi-sized
gold nanoparticles. Taken together, the competitive radio-enhancement
properties for near-monodisperse nanoparticles produced by scalable
and sterile flame spray synthesis offer a route to overcoming key
roadblocks in the translation of nanoparticle-based radio-enhancers.
Differences in nanoparticle radio-enhancement efficiencies in 3D microtissues compared to conventional 2D cell cultures and contextualization with uptake and intratissural distribution data.
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