A hydrogel microcapsule with an intermediate thin oil layer is presented to achieve smart release of a broad range of cargoes triggered via diverse stimuli. A microfluidic technique is used to ...produce triple emulsion droplets with a thin oil layer that separates the innermost aqueous phase from the hydrogel prepolymer phase, which transforms into a hydrogel shell via photopolymerization. The intermediate oil layer within the hydrogel microcapsule acts as an effective diffusion barrier, allowing encapsulation of various small cargoes within a porous hydrogel shell until a stimulus is applied to destabilize the oil layer. It is demonstrated that diverse stimuli including chemical dissolution, mechanical stress, and osmotic pressure can be utilized to release the encapsulated cargo on‐demand. In addition, osmotic pressure and the hydrogel shell thickness can be independently tuned to control the onset time of release as well as the release behavior of multi‐cargo encapsulated hydrogel microcapsule. The release can be either simultaneous or selective.
A hydrogel microcapsule with an intermediate thin oil layer enables smart release of a broad range of cargoes via diverse stimuli. The oil layer in the microcapsules acts as an effective diffusion barrier until only when the oil layer is destabilized. The osmotic pressure and the overall stiffness of the microcapsule can be fine‐tuned to control the release behavior of the multi‐cargo encapsulated microcapsule.
We evaluated the composition of individual clots retrieved during intra-arterial thrombectomy in relation to recanalization success, stroke subtype, and the presence of clot signs on initial brain ...images. We analyzed clot and interventional data from 145 retrieval trials performed for 37 patients (69.5±14.0 years, 20 men, large artery atherosclerosis, n = 7; cardioembolism, n = 22; undetermined etiology, n = 8) who had undergone intra-arterial thrombectomy. Rates of clot retrieval and successful recanalization (Arterial Occlusive Lesion score of 2-3) for separate retrieval trials were evaluated. The area occupied by red blood cell (RBC), fibrin/platelets, and white blood cell (WBC) was measured from digitized images of hematoxylin-eosin stained clots. Compositional differences were compared according to recanalization success, stroke subtype, and the presence of hyperdense clot sign on initial computed tomography and/or blooming artifact on magnetic resonance image. Of the 145 total retrieval trials (3.4±2.4 times per patient), clot was retrieved in 93 trials (64%), while recanalization was successful in 73 (50%). Fibrin/platelets (63%) occupied the greatest area in retrieved clots, followed by RBCs (33%) and WBCs (4%). Clots retrieved from successful recanalization exhibited higher RBC composition (37%) than those retrieved from non-recanalization trials (20%, p = 0.001). RBC composition was higher in cardioembolic stroke (38%) rather than large artery atherosclerosis (23%) and undetermined etiology (26%, p = 0.01). Clots exhibiting clot signs (40%) had higher RBC composition than those without clot signs (19%, p = 0.001). RBC-rich clots were associated with successful recanalization of intra-arterial thrombectomy, cardioembolic stroke, and the presence of clot-signs on initial brain images.
Angiogenesis induction into damaged sites has long been an unresolved issue. Local treatment with pro-angiogenic molecules has been the most common approach. However, this approach has critical side ...effects including inflammatory coupling, tumorous vascular activation, and off-target circulation. Here, the concept that a structure can guide desirable biological function is applied to physically engineer three-dimensional channel networks in implant sites, without any therapeutic treatment. Microchannel networks are generated in a gelatin hydrogel to overcome the diffusion limit of nutrients and oxygen three-dimensionally. Hydrogel implantation in mouse and porcine models of hindlimb ischemia rescues severely damaged tissues by the ingrowth of neighboring host vessels with microchannel perfusion. This effect is guided by microchannel size-specific regenerative macrophage polarization with the consequent functional recovery of endothelial cells. Multiple-site implantation reveals hypoxia and neighboring vessels as major causative factors of the beneficial function. This technique may contribute to the development of therapeutics for hypoxia/inflammatory-related diseases.
Mesenchymal stem cells (MSCs) are an attractive candidate for the treatment of inflammatory bowel disease (IBD), but their poor delivery rate to an inflamed colon is a major factor hampering the ...clinical potential of stem cell therapies. Moreover, there remains a formidable hurdle to overcome with regard to survival and homing in to injured sites. Here, we develop a strategy utilizing monodisperse hydrogel microcapsules with a thin intermediate oil layer prepared by a triple-emulsion drop-based microfluidic approach as an in-situ oral delivering carrier. The oral delivery of stem-cell-loaded hydrogel microcapsules (SC-HM) enhances MSC survival and retention in the hostile stomach environment due to the intermediate oil layer and low value of the overall stiffness, facilitating programmable cell release during gastrointestinal peristalsis. SC-HM is shown to induce tissue repair, reduce the colonic macrophage infiltration responsible for the secretion of the pro-inflammatory factors, and significantly mitigate the severity of IBD in a mouse model, where MSCs released by SC-HM successfully accumulate at the colonic crypt. Moreover, a metagenomics analysis reveals that SC-HM ameliorates the dysbiosis of specific bacterial genera, including Bacteroides acidifaciens, Lactobacillus (L.) gasseri, Lactobacillus reuteri, and L. intestinalis, implying optimization of the microorganism's composition and abundance. These findings demonstrate that SC-HM is a potential IBD treatment candidate.
Stem-cell-loaded hydrogel microcapsules (SC-HM) with a thin oil layer has the potential to rupture and release the encapsulated stem cells by the segmenting during the moment and peristalsis in the gut. Stem cells released from SC-HM induce the tissue repair, reduce the colonic macrophage infiltration responsible for the secretion of the pro-inflammatory factors, and significantly mitigate the severity of IBD in a mouse model. Moreover, SC-HM can restore gut microbiome dysbiosis and reestablish the composition of the gut microbiota in acute colitis. Display omitted
•We develop the SC-HM prepared by a triple-emulsion drop-based microfluidic approach.•The delivery of SC-HM augments the local retention of the cell at colonic sites.•Stem cells released from the SC-HM ameliorate gut inflammation in a mouse IBD model.•SC-HM restores gut microbiome dysbiosis in active colitis.
Most previous studies have been focused on the variation of tea chemical composition by fermentative processes as well as different cultivars and regions. The detailed changes of flavonoid profiles ...were described for the first time by each processing step of green and black tea leaves in this study. A total of 24 flavonoid derivatives including catechins, theaflavins, and flavonols were separated and identified from the tea samples based on UPLC-DAD-QToF/MS data and constructed library. Among these, the fragmentation pathway of theaflavins was proposed specifically in positive ionization mode for structural interpretation. During leaf processing, the individual flavonols were changed as diverse patterns according to their aglycone types and glycosylated forms, but their total content showed a slight difference. EGCG and ECG were increased after roasting approximately twofold higher than that of fresh leaves (EGCG, 2709.5 →6085.6; ECG, 1548.0 →2318.2 mg/100 g dry weight, respectively) in green tea while considerably decreased their contents due to oxidation and conversion to theaflavins after fermentation during black tea processing. Especially, the drying steps also found to be factor to influence positively to increase the flavonoid contents in both tea processing. Therefore, this result indicated that detailed conditions of each processing step played important roles in changing the flavonoid profiles from tea leaves.
Graphical abstract
The link between chronic lymphocytic thyroiditis (CLT) and papillary thyroid carcinoma (PTC) is widely recognized. Considering the strong association between raised antithyroidperoxidase antibody ...(TPOAb) and CLT, we postulated that the preoperative TPOAb can predict the prognosis of PTC, particularly for recurrence. A total of 2,070 patients who underwent total thyroidectomy for classical type PTC with tumor size ≥1 cm and with available data on preoperative TPOAb and TgAb were enrolled to compare disease‐free survival (DFS) according to the presence of preoperative TPOAb, TgAb, and coexistent CLT. Patients with positive preoperative TPOAb had a significantly better DFS compared to patients without positive preoperative TPOAb (hazard ratio (HR) 0.53; 95% confidence interval (CI) 0.30–0.94, p = 0.028) while no difference in DFS was found according to preoperative TgAb status. Positive preoperative TPOAb was an independent prognostic factor for structural persistent/recurrent disease after adjustment for major preoperative risk factors such as age, sex, and tumor size (HR 0.52, 95% CI 0.28–0.99, p = 0.048). Although the coexistence of CLT lowered the risk for structural persistence/recurrence in univariate analysis (HR 0.52, 95% CI 0.31–0.86, p = 0.012), it was not an independent favorable prognostic factor by multivariate analysis (HR 0.65, 95% CI 0.38–1.10, p = 0.106). However, when coexistent CLT was combined with positive preoperative TPOAb, it indicated an independent protective role in structural persistent/recurrent disease (HR 0.39, 95% CI 0.16–0.98, p = 0.045). Our study clearly showed that presence of preoperative TPOAb can be a novel prognostic factor in predicting structural persistence/recurrence of PTC.
What's new?
While chronic lymphocytic thyroiditis (CLT) is generally accepted as a risk factor for papillary thyroid carcinoma (PTC), it is also suspected to protect against PTC recurrence when it coexists with PTC. Our study indicates that coexistent CLT predicts PTC recurrence risk, wherein copositivity for both CLT and preoperative antithyroid peroxidase antibody (TPOAb) is associated with reduced risk of recurrent PTC. In addition, among PTC patients who underwent thyroidectomy, those with preoperative TPOAb positivity had significantly better disease‐free survival than those lacking TPOAb positivity. The findings suggest that preoperative TPOAb and CLT evaluation could help improve accuracy in PTC prognosis.
Atherosclerosis development leads to irreversible cascades, highlighting the unmet need for improved methods of early diagnosis and prevention. Disturbed flow formation is one of the earliest ...atherogenic events, resulting in increased endothelial permeability and subsequent monocyte recruitment. Here, a mesenchymal stem cell (MSC)‐derived nanovesicle (NV) that can target disturbed flow sites with the peptide GSPREYTSYMPH (PREY) (PMSC‐NVs) is presented which is selected through phage display screening of a hundred million peptides. The PMSC‐NVs are effectively produced from human MSCs (hMSCs) using plasmid DNA designed to functionalize the cell membrane with PREY. The potent anti‐inflammatory and pro‐endothelial recovery effects are confirmed, similar to those of hMSCs, employing mouse and porcine partial carotid artery ligation models as well as a microfluidic disturbed flow model with human carotid artery‐derived endothelial cells. This nanoscale platform is expected to contribute to the development of new theragnostic strategies for preventing the progression of atherosclerosis.
A new type of bioengineered nanovesicle is presented by generating outward display of PREY, a disturbed flow site‐targeting peptide, on the surface of stem cell nanovesicle for the diagnosis and prevention of atherosclerosis. Because potent anti‐inflammatory and pro‐endothelial recovery effect are confirmed, this system is expected to contribute to the development of new theragnostic strategies for preventing the progression of atherosclerosis.
•Fermentation changed soybean isoflavones, enhancing absorption and bioavailability.•Total isoflavone levels were similar in 24 h urine samples after FS or NFS diet.•Urinary genistein 7-O-sulfate ...level may discriminate between FS and NFS diets.•Isoflavone conjugate profiles might be a potential marker for FS diet.
Fermentation may enhance the nutritional properties of foods by increasing metabolite bioactivity or bioavailability. This study explored the effect of fermentation on isoflavone bioavailability and metabolism. Isoflavone metabolites were tracked in foods and biospecimens of healthy adults after fermented soybean (FS) or non-fermented soybean (NFS) consumption in a randomized, controlled, crossover intervention study. The change in soybean isoflavones caused by fermentation resulted in faster absorption and higher bioavailability after consumption of FS. Although the urinary level of total isoflavone metabolites was similar after the consumption of the two diets, urinary genistein 7-O-sulfate was derived as a discriminant metabolite for the FS diet by partial least squares discriminant analysis. This study suggests that an isoflavone conjugate profile might be a more appropriate marker than total isoflavone levels for discriminating between the consumption of FS and NFS diets.
Here, we report PNIPAm-co-PEGDA hydrogel shelled microcapsules with a thin oil layer to achieve tunable thermo-responsive release of the encapsulated small hydrophilic actives. We use a microfluidic ...device integrated with a temperature-controlled chamber for consistent and reliable production of the microcapsules by utilizing triple emulsion drops (W/O/W/O) with a thin oil layer as capsule templates. The interstitial oil layer between the aqueous core and the PNIPAm-co-PEGDA shell provides a diffusion barrier for the encapsulated active until the temperature reaches a critical point above which the destabilization of interstitial oil layer occurs. We find that the destabilization of the oil layer with temperature increase is caused by outward expansion of the aqueous core due to volume increase and the radial inward compression from the deswelling of the thermo-responsive hydrogel shell. The copolymerization of NIPAm with PEGDA increases the biocompatibility of the resulting microcapsule while offering the ability to alter the compressive modulus in broad ranges by simply varying crosslinker concentrations thereby to precisely tune the onset release temperature. Based on this concept, we further demonstrate that the release temperature can be enhanced up to 62 °C by adjusting the shell thickness even without varying the chemical composition of the hydrogel shell. Moreover, we incorporate gold nanorods within the hydrogel shell to spatiotemporally regulate the active release from the microcapsules by illuminating with non-invasive near infrared (NIR) light.
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Influenza viruses are known to cause pandemic flu outbreaks through both inter-human and animal-to-human transmissions. Therefore, the rapid and accurate detection of such pathogenic viruses is ...crucial for effective pandemic control. Here, we introduce a novel sensor based on affinity peptide-immobilized hydrogel microspheres for the selective detection of influenza A virus (IAV) H3N2. To enhance the binding affinity performance, we identified novel affinity peptides using phage display and further optimized their design. The functional hydrogel microspheres were constructed using the drop microfluidic technique, employing a structure composed of natural (chitosan) and synthetic (poly(ethylene glycol) diacrylate and PEG 6 kDa) polymers with the activation of azadibenzocyclooctyne for the subsequent click chemistry reaction. The binding peptide-immobilized hydrogel microsphere (BP-Hyd) was characterized by field emission scanning electron microscopy, X-ray photoelectron spectroscopy, and Fourier transform infrared spectroscopy and exhibited selective detection capability for the IAV H3N2. To capture the detected IAV H3N2, a Cy3-labeled IAV hemagglutinin antibody was utilized. By incorporating the affinity peptide with hydrogel microspheres, we achieved quantitative and selective detection of IAV H3N2 with a detection limit of 1.887 PFU mL–1. Furthermore, the developed suspension sensor exhibited excellent reproducibility and showed reusability potential. Our results revealed that the BP-Hyd-based fluorescence sensor platform could be feasibly employed to detect other pathogens because the virus-binding peptides can be easily replaced with other peptides through phage display, enabling selective and sensitive binding to different targets.
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