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The role of multidetector computed tomography (MDCT) in patients with acute infectious colitis is still unclear.To examine the usefulness of MDCT in distinguishing the etiology of acute infectious colitis.Overall, 244 patients who met the criteria for acute infectious colitis and visited the Hospital from February 2015 to 2018 were retrospectively enrolled and divided into two groups (bacterial: 204, viral: 40) according to causes of acute colitis, based on stool PCR. Eleven MDCT parameters, including wall thickening, submucosal edema, mucosal enhancement, serosa involvement, empty colon sign, small bowel involvement, comb sign, continuous distribution, accordion sign, mucosal thickening, and lymph node enlargement, were constructed in a blinded fashion.MDCT parameters of wall thickening (OR: 13.60; 95%CI: 5.80-31.88;MDCT provides many clues that can be useful in suggesting a specific etiology of acute infectious colitis.

In colonoscopy, good bowel preparation is an important factor in determining the quality of colonoscopy. However, an increase in residual gastric volume (RGV) can lead to a higher risk of aspiration pneumonia. Therefore, the purpose of this study was to investigate the factors related to an increase in RGV with the usage of 1L polyethylene glycol (PEG).We prospectively analyzed 268 patients who underwent both gastroscopy and colonoscopy at 2 hospitals from May to October 2021. Bowel preparation was performed using 1L in 127 patients (47.4%) and 2L PEG in 141 patients (52.6%). We investigated the time taken for bowel preparation solutions, the last water intake, total water intake, and RGV, and conducted a survey on taking compliance and satisfaction.The level of RGV was significantly increased in the 1L PEG group when compared to the 2L PEG group (1L, 52.26 ± 65.33 vs 2L, 23.55 ± 22.99; P .001). There was no difference between the 2 groups in the degree of bowel preparation, but there were more bubbles formed in the 1L group (1L, 1.91 ± 2.74 vs 2L, 1.10 ± 2.02; P = .007). In the case of RGV ≥ 50 mL, in multivariate analysis, the risk was higher in water intake within 5 hours and the patients who think the dose is too high (all P .05).Therefore, since RGV is higher in 1L PEG than in 2L PEG, it is necessary to be careful not to take water for at least 5 hours before the test.

3D spheroids are considered as the improved in vitro model to mimic the distinct arrangements of the cells in vivo. To date, low-attachment surfaces have been most widely used to induce the spontaneous aggregation of cells in suspension by simply tuning the relative strength of the cell-cell adhesion over cell-substrate adhesion. However, aggregating cancer cells into 3D clusters should mean more than just adjoining the cells in the physical proximity. The tumor cell functionality is strongly affected by the adhesion networks between cancer cells and extracellular matrix (ECM). Here, we performed an in-depth analysis of how the nonmetastatic breast cancer cells (MCF7) can be transformed to gain invasive phenotypes through compact aggregation into 3D spheroids on a functional polymer film surface, poly(2,4,6,8-tetravinyl-2,4,6,8-tetramethyl cyclotetrasiloxane) (pV4D4). By comparing the adhesion networks and invasion dynamics between 3D spheroids cultured on the pV4D4 surface with those cultured on conventional ultra-low-attachment (ULA) dishes, we report that only spheroids on the pV4D4 display active and sporadic cell-surface binding activities via dynamic protrusions, which correlates strongly with an increase in integrin β1. Moreover, localized laminin expression at the core of the pV4D4-cultured spheroids confirms the prominence of the intimate integrin-laminin interactions prompted by the exposure to pV4D4. This study suggests that structurally and functionally dissimilar 3D spheroids can be generated from the same type of cells on the surfaces of different physicochemical properties without any chemical treatment or genetic manipulation.

The aggregation of mesenchymal stem cells (MSCs) into three-dimensional (3D) spheroids has emerged as a promising therapeutic candidate for the treatment of a variety of diseases. In spite of the numerous 3D culture methods suggested recently for MSC spheroid generation, it is still elusive to fully reflect real stem cell niches; this effort majorly suffers from a lack of cell-extracellular matrix (ECM) interactions within the 3D spheroids. In this study, we develop a simple but versatile method for generating human MSC (hMSC) spheroids by culturing the cells on a functional polymer film surface, poly(2,4,6,8-tetravinyl-2,4,6,8-tetramethyl cyclotetrasiloxane) (pV4D4). Interestingly, the pV4D4-coated surface allows a dynamic cell adhesion to the polymer surface while developing the formation of 3D spheroids. The corresponding mechanotransduction promotes the expression of the endogenous ECM and, in turn, results in a remarkable improvement in self-renewal abilities, pro-angiogenic potency, and multilineage differentiation capabilities. This observation highlights the significance of our method compared to the conventional spheroid-generating methods in terms of recreating the ECM-rich microenvironment. We believe the developed surface can serve as a versatile but reliable method for stem cell-based tissue engineering and regenerative medicine.

For efficient therapeutic use of human mesenchymal stem cells (hMSCs), maximizing their self-renewal performance and multipotency must be fully retained. However, conventional trypsin-based cell passaging methods are known to damage the attached cells to be detached because of the inherent corrosive nature of trypsin, and continuous passaging substantially degrades the self-renewal and differentiation capacity of hMSCs. Therefore, it is imperative to secure a damage-free passaging method that supports cell growth as well as their stem cell function. Here, an enzyme-free cell detachment method using a poly(ethylene glycol dimethacrylate) (pEGDMA)-coated surface is developed, which allows for reduced integrin-dependent cell adhesion. Cell detachment can be facilitated simply by treating the plated cells on the pEGDMA surface with Ca

The ongoing concerns and regulations on long-chain fluorinated compounds (C8 or higher) for nonwetting coatings have driven the market to search for sustainable alternative chemistries. In this study, a copolymeric coating containing short-chain fluorinated groups was synthesized to achieve excellent nonwetting ability against hazardous chemical warfare agents (CWAs). A copolymer of 1

Background Dysbiosis of ulcerative colitis (UC) has been frequently investigated using readily accessible stool samples. However, stool samples might insufficiently represent the mucosa-associated microbiome status. We hypothesized that luminal contents including loosely adherent luminal bacteria after bowel preparation may be suitable for diagnosing the dysbiosis of UC. Methods This study included 16 patients with UC (9 men and 7 women, mean age: 52.13 ± 14.09 years) and 15 sex- and age-matched healthy individuals (8 men and 7 women, mean age: 50.93 ± 14.11 years). They donated stool samples before colonoscopy and underwent luminal content aspiration and endoscopic biopsy during the colonoscopy. Then, the composition of each microbiome sample was analyzed by 16S rRNA-based next-generation sequencing. Results The microbiome between stool, luminal contents, and biopsy was significantly different in alpha and beta diversities. However, a correlation existed between stool and luminal contents in the Procrustes test (p = 0.001) and Mantel test (p = 0.0001). The stool microbiome was different between patients with UC and the healthy controls. Conversely, no difference was found in the microbiome of luminal content and biopsy samples between the two subject groups. The microbiome of stool and lavage predicted UC, with AUC values of 0.85 and 0.81, respectively. Conclusion The microbiome of stool, luminal contents, and biopsy was significantly different. However, the microbiome of luminal contents during colonoscopy can predict UC, with AUC values of 0.81. Colonoscopic luminal content aspiration analysis could determine microbiome differences between patients with UC and the healthy control, thereby beneficial in screening dysbiosis via endoscopy. Trial registration: This trial was registered at http://cris.nih.go.kr. Registration No.: KCT0003352), Date: 2018–11-13.

Gene therapy holds the significance of correcting genetic defects. However, difficulties in the in vivo delivery to the targeted tissues and systemic delivery remain the biggest challenges to be overcome. Here, a robust system of biofunctionalized polymeric layer-mediated lentiviral delivery was designed for the site-specific spatial and temporal control of viral gene delivery. Poly glycidyl methacrylate (pGMA) modification of a substrate via initiated chemical vapor deposition (iCVD) followed by polyethyleneimine (PEI) immobilization provided the adhesion site for the lentivirus. Furthermore, the polymeric patch based gene delivery system showed a high rate of gene transduction compared to bolus treatment. Furthermore, by using mask patterning, we were able to spatially pattern the lentivirus which allowed spatially defined transfection.

Background: Dysbiosis of ulcerative colitis (UC) has been frequently investigated using readily accessible stool samples. However, stool samples might insufficiently represent the mucosa-associated microbiome status. We hypothesized that luminal contents including loosely adherent luminal bacteria after bowel preparation may be suitable for diagnosing the dysbiosis of UC.Methods: This study included 16 patients with UC (9 men and 7 women, mean age: 52.13 ± 14.09 years) and 15 sex- and age-matched healthy individuals (8 men and 7 women, mean age: 50.93 ± 14.11 years). They donated stool samples before colonoscopy and underwent luminal content aspiration and endoscopic biopsy during the colonoscopy. Then, the composition of each microbiome sample was analyzed by 16S rRNA-based next-generation sequencing.Results: The microbiome between stool, luminal contents, and biopsy was significantly different in alpha and beta diversities. However, a correlation existed between stool and luminal contents in the Procrustes test (p = 0.001) and Mantel test (p = 0.0001). The stool microbiome was different between patients with UC and the healthy controls. Conversely, no difference was found in the microbiome of luminal content and biopsy samples between the two subject groups. The microbiome of stool and lavage predicted UC, with AUC values of 0.85 and 0.81, respectively.Conclusion: The microbiome of stool, luminal contents, and biopsy was significantly different. However, the microbiome of luminal contents during colonoscopy can predict UC, with AUC values of 0.81. Colonoscopic luminal content aspiration analysis could determine microbiome differences between patients with UC and the healthy control, thereby beneficial in screening dysbiosis via endoscopy. Trial registration: This trial was registered at http://cris.nih.go.kr.Registration No.: KCT0003352), Date : 2018-11-13

Paclitaxel failure promotes collateral resistance to EGFR-targeted therapy by adaptive rewiring of the cellular stress response., Secondary drug resistance stems from dynamic clonal evolution during the development of a prior primary resistance. This collateral type of resistance is often a characteristic of cancer recurrence. Yet, mechanisms that drive this collateral resistance and their drug-specific trajectories are still poorly understood. Using resistance selection and small-scale pharmacological screens, we find that cancer cells with primary acquired resistance to the microtubule-stabilizing drug paclitaxel often develop tolerance to epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR-TKIs), leading to formation of more stable resistant cell populations. We show that paclitaxel-resistant cancer cells follow distinct selection paths under EGFR-TKIs by enriching the stemness program, developing a highly glycolytic adaptive stress response, and rewiring an apoptosis control pathway. Collectively, our work demonstrates the alterations in cellular state stemming from paclitaxel failure that result in collateral resistance to EGFR-TKIs and points to new exploitable vulnerabilities during resistance evolution in the second-line treatment setting.

Neurofibromatosis type 1 (NF1) is a rare genetic disease. Precapillary pulmonary hypertension (PH) with NF1 is an extremely severe complication. A 65-year-old woman was admitted in our hospital with 3-year history of gradually worsening dyspnea on exertion (New York Heart Association functional class III-IV). Considering her clinical feature and examination findings, she could be diagnosed as PH associated with NF1. She was treated with endothelin receptor antagonist. However her dyspnea was not significantly improved. This is the first Korean case of NF1 patient with PH which confirmed with right heart catheterization.

Summary Poly(lactate-co-glycolate), PLGA, is a representative synthetic biopolymer widely used in medical applications. Recently, we reported one-step direct fermentative production of PLGA and its copolymers by metabolically engineered Escherichia coli from xylose and glucose. In this study, we report development of metabolically engineered E. coli strains for the production of PLGA and poly(d-lactate-co-glycolate-co-d-2-hydroxybutyrate) having various monomer compositions from xylose as a sole carbon source. To achieve this, the metabolic flux towards Dahms pathway was modulated using five different synthetic promoters for the expression of Caulobacter crescentus XylBC. Further metabolic engineering to concentrate the metabolic flux towards d-lactate and glycolate resulted in production of PLGA and poly(d-lactate-co-glycolate-co-d-2-hydroxybutyrate) with various monomer fractions from xylose. The engineered E. coli strains produced polymers containing 8.8–60.9 mol% of glycolate up to 6.93 g l−1 by fed-batch cultivation in a chemically defined medium containing xylose. Finally, the biocompatibility of poly(d-lactate-co-glycolate-co-d-2-hydroxybutyrate) was confirmed by live/dead assay using human mesenchymal stem cells.

Background: Although there have been studies regarding the role of nebulized colistin as adjunctive therapy of ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii (CRAB), a paucity of information on the efficacy of nebulized colistin as monotherapy is available. Methods: We retrospectively reviewed 219 patients with VAP caused by CRAB treated with either intravenous (n=93) or nebulized colistin (n=126), from March 2010 to November 2015. Factors related to clinical failure was assessed using propensity-score-matched analysis. Results: Of 219 patients, 39 patients from each group (n=78) were matched after covariate adjustment using propensity score. There were no significant differences in baseline characteristics as well as the rates of clinical failure between the propensity-score-matched groups [Odds ratio (OR), 0.48; 95% confidence interval (CI), 0.19–1.19; P=0.11], while a significantly lower rate of acute kidney injury (AKI) during colistin therapy (18% vs . 49%, P=0.004) was observed in nebulized colistin group. In addition, multivariable analysis revealed that nebulized colistin did not significantly alter the rate of clinical failure [adjusted odds ratio (aOR), 0.36; 95% CI, 0.12–1.09; P=0.070]. Instead, medical intensive care unit (ICU) admission (aOR, 7.14; 95% CI, 1.60–32.00; P=0.010), and septic shock (aOR, 3.93; 95% CI, 1.27–12.17; P=0.018) were independent risk factors for clinical failure. Conclusions: Our findings suggest that nebulized colistin-based therapy, even without concurrent administration of intravenous colistin, may be an effective and safe treatment option for VAP caused by CRAB.

Biophysical cues, such as topography, and electrical cues can provide external stimulation for the promotion of stem cell neurogenesis. Here, we demonstrate an electroconductive surface nanotopography for enhancing neuronal differentiation and the functional maturation of human neural stem cells (hNSCs). The electroconductive nanopatterned substrates were prepared by depositing a thin layer of titanium (Ti) with nanograting topographies (150 to 300 nm groove/ridge, the thickness of the groove - 150 μm) onto polymer surfaces. The Ti-coated nanopatterned substrate (TNS) induced cellular alignment along the groove pattern via contact guidance and promoted focal adhesion and cytoskeletal reorganization, which ultimately led to enhanced neuronal differentiation and maturation of hNSCs as indicated by significantly elevated neurite extension and the upregulated expression of the neuronal markers Tuj1 and NeuN compared with the Ti-coated flat substrate (TFS) and the nanopatterned substrate (NS) without Ti coating. Mechanosensitive cellular events, such as β1-integrin binding/clustering and myosin-actin interaction, and the Rho-associated protein kinase (ROCK) and mitogen-activated protein kinase/extracellular signal regulated kinase (MEK-ERK) pathways, were found to be associated with enhanced focal adhesion and neuronal differentiation of hNSCs by the TNS. Among the neuronal subtypes, differentiation into dopaminergic and glutamatergic neurons was promoted on the TNS. Importantly, the TNS increased the induction rate of neuron-like cells exhibiting electrophysiological properties from hNSCs. Finally, the application of pulsed electrical stimulation to the TNS further enhanced neuronal differentiation of hNSCs due probably to calcium channel activation, indicating a combined effect of topographical and electrical cues on stem cell neurogenesis, which postulates the novelty of our current study. The present work suggests that an electroconductive nanopatterned substrate can serve as an effective culture platform for deriving highly mature, functional neuronal lineage cells from stem cells.

Cell sheet engineering, a technique utilizing a monolayer cell sheet, has recently emerged as a promising technology for scaffold-free tissue engineering. In contrast to conventional tissue-engineering approaches, the cell sheet technology allows cell harvest as a continuous cell sheet with intact extracellular matrix proteins and cell-cell junction, which facilitates cell transplantation without any other artificial biomaterials. A facile, non-thermoresponsive method is demonstrated for a rapid but highly reliable platform for cell-sheet engineering. The developed method exploits the precise modulation of cell-substrate interactions by controlling the surface energy of the substrate via a series of functional polymer coatings to enable prompt cell sheet harvesting within 100 s. The engineered surface can trigger an intrinsic cellular response upon the depletion of divalent cations, leading to spontaneous cell sheet detachment under physiological conditions (pH 7.4 and 37 °C) in a non-thermoresponsive manner. Additionally, the therapeutic potential of the cell sheet is successfully demonstrated by the transplantation of multilayered cell sheets into mouse models of diabetic wounds and ischemia. These findings highlight the ability of the developed surface for non-thermoresponsive cell sheet engineering to serve as a robust platform for regenerative medicine and provide significant breakthroughs in cell sheet technology.

In vitro culture systems for primary neurons have served as useful tools for neuroscience research. However, conventional in vitro culture methods are still plagued by challenging problems with respect to applications to neurodegenerative disease models or neuron-based biosensors and neural chips, which commonly require long-term culture of neural cells. These impediments highlight the necessity of developing a platform capable of sustaining neural activity over months. Here, we designed a series of polymeric bilayers composed of poly(glycidyl methacrylate) (pGMA) and poly(2-(dimethylamino)ethyl methacrylate) (pDMAEMA), designated pGMA:pDMAEMA, using initiated chemical vapor deposition (iCVD). Harnessing the surface-growing characteristics of iCVD polymer films, we were able to precisely engraft acetylcholine-like functionalities (tertiary amine and quaternary ammonium) onto cell culture plates. Notably, pGD3, a pGMA:pDMAEMA preparation with the highest surface composition of quaternary ammonium, fostered the most rapid outgrowth of neural cells. Clear contrasts in neural growth and survival between pGD3 and poly-l-lysine (PLL)-coated surfaces became apparent after 30 days in vitro (DIV). Moreover, brain-derived neurotrophic factor level continuously accumulated in pGD3-cultured neurons, reaching a 3-fold increase at 50 DIV. Electrophysiological measurements at 30 DIV revealed that the pGD3 surface not only promoted healthy maturation of hippocampal neurons but also enhanced the function of hippocampal ionotropic glutamate receptors in response to synaptic glutamate release. Neurons cultured long-term on pGD3 also maintained their characteristic depolarization-induced Ca

Although cancer stem cells (CSC) are thought to be responsible for tumor recurrence and resistance to chemotherapy, CSC-related research and drug development have been hampered by the limited supply of diverse, patient-derived CSC. Here, we present a functional polymer thin film (PTF) platform that promotes conversion of cancer cells to highly tumorigenic three-dimensional (3D) spheroids without the use of biochemical or genetic manipulations. Culturing various human cancer cells on the specific PTF, poly(2,4,6,8-tetravinyl-2,4,6,8-tetramethyl cyclotetrasiloxane) (pV4D4), gave rise to numerous multicellular tumor spheroids within 24 hours with high efficiency and reproducibility. Cancer cells in the resulting spheroids showed a significant increase in the expression of CSC-associated genes and acquired increased drug resistance compared with two-dimensional monolayer-cultured controls. These spheroids also exhibited enhanced xenograft tumor-forming ability and metastatic capacity in nude mice. By enabling the generation of tumorigenic spheroids from diverse cancer cells, the surface platform described here harbors the potential to contribute to CSC-related basic research and drug development. Significance: A new cell culture technology enables highly tumorigenic 3D spheroids to be easily generated from various cancer cell sources in the common laboratory.

Drug-eluting stents (DESs) have been used to treat coronary artery diseases by placing in the arteries. However, current DESs still suffer from polymer coating defects such as delamination and peeling-off that follows stent deployment. Such coating defects could increase the roughness of DES and might act as a source of late or very late thrombosis and might increase the incident of restenosis. In this regard, we modified the cobalt–chromium (Co–Cr) alloy surface with hydrophilic poly(2-hydroxyethyl methacrylate) (PHEMA) or hydrophobic poly(2-hydroxyethyl methacrylate)-grafted-poly(caprolactone) (PHEMA-g-PCL) brushes. The resulting surfaces were biocompatible and biodegradable, which could act as anchoring layer for the drug-in-polymer matrix coating. The two modifications were characterized by ATR-FTIR, XPS, water contact angle measurements, SEM and AFM. On the control and modified Co–Cr samples, a sirolimus (SRL)-containing poly(D,L-lactide) (PDLLA) were ultrasonically spray-coated, and the drug release was examined for 8 weeks under physiological conditions. The results demonstrated that PHEMA as a primer coating improved the coating stability and degradation morphology, and drug release profile for short-term as compared to control Co–Cr, but fails after 7 weeks in physiological buffer. On the other hand, the hydrophobic PHEMA-g-PCL brushes not only enhanced the stability and degradation morphology of the PDLLA coating layer, but also sustained SRL release for long-term. At 8-week of release test, the surface morphologies and release profiles of coated PDLLA layers verified the beneficial effect of hydrophobic PCL brushes as well as their thickness on coating stability. Our study concludes that 200 nm thickness of PHEMA-g-PCL as interfacial layer affects the stability and degradation morphology of the biodegradable coating intensively to be applied for various biodegradable-based DESs.

In this study, we present a method for assembling biofunctionalized paper into a multiform structured scaffold system for reliable tissue regeneration using an origami-based approach. The surface of a paper was conformally modified with a poly(styrene-co-maleic anhydride) layer via initiated chemical vapor deposition followed by the immobilization of poly-l-lysine (PLL) and deposition of Ca(2+). This procedure ensures the formation of alginate hydrogel on the paper due to Ca(2+) diffusion. Furthermore, strong adhesion of the alginate hydrogel on the paper onto the paper substrate was achieved due to an electrostatic interaction between the alginate and PLL. The developed scaffold system was versatile and allowed area-selective cell seeding. Also, the hydrogel-laden paper could be folded freely into 3D tissue-like structures using a simple origami-based method. The cylindrically constructed paper scaffold system with chondrocytes was applied into a three-ring defect trachea in rabbits. The transplanted engineered tissues replaced the native trachea without stenosis after 4 wks. As for the custom-built scaffold system, the hydrogel-laden paper system will provide a robust and facile method for the formation of tissues mimicking native tissue constructs.

Exquisite surface wettability control of separation system surface is required to achieve separation of liquids with low surface tension difference. Here, we demonstrate a series of surface-energy-controlled homogeneous copolymer films to control the surface wettability of polyester fabric, utilizing a vapor-phase process, termed as initiated chemical vapor deposition (iCVD). The homogeneous copolymer films consist of a hydrophobic polymer, poly(2,4,6,8-tetramethyl-2,4,6,8-tetravinylcyclotetrasiloxane), pV4D4, and a hydrophilic polymer, poly(4-vinylpyridine), p4VP. Because the mixing of two or more components is always favorable in vapor phase, the iCVD process allows the formation of homogeneous copolymers from two immiscible, hydrophilic/hydrophobic monomer pairs, which is highly challenging to achieve in liquid phase. Simply by tuning the flow rate ratio of monomer pairs, a series of homogeneous copolymers with systematically controlled surface energy were formed successfully. The fabricated separation...

In the last decade, titanium has been effectively used in the dental field for oral surgery as an implant material. However, disinfected Ti can be easily re-infected by the surrounding environment. Thus, a novel anti-fouling treatment for Ti implants is currently necessary. In this study, we designed an anti-fouling surface comprised of poly N-isopropylacylamide (PIPAAM) grafted Ti by introducing poly glycidyl methacrylate (pGMA) coating via an initiated chemical vapor deposition (iCVD) system to prevent bacterial infection. The results indicate that pristine Ti was well coated with pGMA with a film thickness of approximately 60 nm and uniformly grafted with PIPAAM. The bacteria were effectively detached after rinsing with a buffer solution at room temperature, while hADSCs were well attached on the surface treated Ti surface at oral temperature. All tests clearly confirm that our strategy may be a useful means of imparting anti-fouling characteristics to Ti in order to prevent bacterial adhesion and resultant peri-implantitis.

Chondroitin sulfate (CS) is the major component of glycosaminoglycan in connective tissue. In this study, we fabricated methacrylated PEGDA/CS-based hydrogels with varying CS concentration (0, 1, 5, and 10%) and investigated them as biomineralizing three-dimensional scaffolds for charged ion binding and depositions. Due to its negative charge from the sulfate group, CS exhibited an osteogenically favorable microenvironment by binding charged ions such as calcium and phosphate. Particularly, ion binding and distribution within negatively charged hydrogel was dependent on CS concentration. Furthermore, CS dependent biomineralizing microenvironment induced osteogenic differentiation of human tonsil-derived mesenchymal stem cells in vitro. Finally, when we transplanted PEGDA/CS-based hydrogel into a critical sized cranial defect model for 8 weeks, 10% CS hydrogel induced effective bone formation with highest bone mineral density. This PEGDA/CS-based biomineralizing hydrogel platform can be utilized for in situ bone formation in addition to being an investigational tool for in vivo bone mineralization and resorption mechanisms.

As reports of multidrug resistant pathogens have increased, patients with implanted medical catheters increasingly need alternative solutions to antibiotic treatments. As most catheter-related infections are directly associated with biofilm formation on the catheter surface, which, once formed, is difficult to eliminate, a promising approach to biofilm prevention involves inhibiting the initial adhesion of bacteria to the surface. In this study, we report an amphiphilic, antifouling polymer, poly(DMA-mPEGMA-AA) that can facilely coat the surfaces of commercially available catheter materials in water and prevent bacterial adhesion to and subsequent colonization of the surface, giving rise to an antibiofilm surface. The antifouling coating layer was formed simply by dipping a model substrate (polystyrene, PET, PDMS, or silicon-based urinary catheter) in water containing poly(DMA-mPEGMA-AA), followed by characterization by X-ray photoelectron spectroscopy (XPS). The antibacterial adhesion properties of the polymer-coated surface were assessed for Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) growth under static (incubation in the presence of a bacterial suspension) and dynamic (bacteria suspended in a solution under flow) conditions. Regardless of the conditions, the polymer-coated surface displayed significantly reduced attachment of the bacteria (antiadhesion effect∼8-fold) compared to the bare noncoated substrates. Treatment of the implanted catheters with S. aureus in vivo further confirmed that the polymer-coated silicon urinary catheters could significantly reduce bacterial adhesion and biofilm formation in a bacterial infection animal model. Furthermore, the polymer-coated catheters did not induce hemolysis and were resistant to the adhesion of blood-circulating cells, indicative of high biocompatibility. Collectively, the present amphiphilic antifouling polymer is potentially useful as a coating platform that renders existing medical devices resistant to biofilm formation.

Although there have been studies regarding the role of nebulized colistin as adjunctive therapy of ventilator-associated pneumonia (VAP) caused by carbapenem-resistantWe retrospectively reviewed 219 patients with VAP caused by CRAB treated with either intravenous (n=93) or nebulized colistin (n=126), from March 2010 to November 2015. Factors related to clinical failure was assessed using propensity-score-matched analysis.Of 219 patients, 39 patients from each group (n=78) were matched after covariate adjustment using propensity score. There were no significant differences in baseline characteristics as well as the rates of clinical failure between the propensity-score-matched groups [Odds ratio (OR), 0.48; 95% confidence interval (CI), 0.19-1.19; P=0.11], while a significantly lower rate of acute kidney injury (AKI) during colistin therapy (18%Our findings suggest that nebulized colistin-based therapy, even without concurrent administration of intravenous colistin, may be an effective and safe treatment option for VAP caused by CRAB.

Bioactive, functional scaffolds are required to improve the regenerative potential of stem cells for tissue reconstruction and functional recovery of damaged tissues. Here, we report a paper-based bioactive scaffold platform for stem cell culture and transplantation for bone reconstruction. The paper scaffolds are surface-engineered by an initiated chemical vapor deposition process for serial coating of a water-repellent and cell-adhesive polymer film, which ensures the long-term stability in cell culture medium and induces efficient cell attachment. The prepared paper scaffolds are compatible with general stem cell culture and manipulation techniques. An optimal paper type is found to provide structural, physical, and mechanical cues to enhance the osteogenic differentiation of human adipose-derived stem cells (hADSCs). A bioactive paper scaffold significantly enhances in vivo bone regeneration of hADSCs in a critical-sized calvarial bone defect. Stacking the paper scaffolds with osteogenically differentiated hADSCs and human endothelial cells resulted in vascularized bone formation in vivo. Our study suggests that paper possesses great potential as a bioactive, functional, and cost-effective scaffold platform for stem cell-mediated bone tissue engineering. To the best of our knowledge, this is the first study reporting the feasibility of a paper material for stem cell application to repair tissue defects.

Various antioxidants are being used to neutralize the harmful effects of reactive oxygen species (ROS) overproduced in the diseased tissue and contaminated environment. Polymer-directed crystallization of antioxidants has attracted attention as a way to control drug efficacy through molecular dissolution. However, most recrystallized antioxidants undertake the continuous dissolution independent of the ROS level, thus causing side-effects. This study demonstrates a unique method to assemble antioxidant crystals that modulate their dissolution rate in response to the ROS level. We hypothesized that antioxidants recrystallized using a ROS-labile polymer would be triggered to dissolve when ROS level increases. We examined this hypothesis by using catechin as a model antioxidant. Catechin was recrystallized using polyethylenimine cross-linked with ROS-labile diselanediylbis-(ethane-2,1-diyl)-diacrylate. Catechin crystallized with ROS-labile polymer displayed accelerated dissolution proportional to the H(2)O(2) concentration. The ROS-responsive catechin crystals protected vascular cells from oxidative insults by activating intracellular glutathione peroxidase expression and, in turn, inhibiting an increase in the intracellular oxidative stress. In addition, the ROS-responsive catechin crystals alleviated changes in the heart rate of Daphnia magna in the oxidative media. We propose that the results of this study would be broadly useful to improving the therapeutic efficacy of a broad array of drug compounds.

In article number 1801521, Hyunjoon Kong and co‐workers demonstrate that substrate topography regulates neural innervation by enhancing maturity of the myotubes. Neural stem cells are differentiated on the myotubes, formed on grooved substrates. The motor neurons innervate more actively to the mature myotubes formed on the 1600 nm groove width. Accordingly, those myotubes respond more rapidly to neurotransmitter and neuromuscular antagonists. The results of this study will be useful for improving the quality of engineered muscle used in applications such as drug screening, regeneration therapies, and biological machinery assembly.

Recreation of a muscle that can be controlled by the nervous system would provide a major breakthrough for treatments of injury and diseases. However, the underlying basis of how neuron–muscle interfaces are formed is still not understood sufficiently. Here, it is hypothesized that substrate topography regulates neural innervation and synaptic transmission by mediating the cross‐talk between neurons and muscles. This hypothesis is examined by differentiating neural stem cells on the myotubes, formed on the substrate with controlled groove width. The substrate with the groove width of 1600 nm, a similar size to the myofibril diameter, serves to produce larger and aligned myotubes than the flat substrate. The myotubes formed on the grooved substrate display increases in the acetylcholine receptor expression. Reciprocally, motor neuron progenitor cells differentiated from neural stem cells innervate the larger and aligned myotubes more actively than randomly oriented myotubes. As a consequence, mature and aligned myotubes respond to glutamate (i.e., an excitatory neurotransmitter) and curare (i.e., a neuromuscular antagonist) more rapidly and homogeneously than randomly oriented myotubes. The results of this study will be broadly useful for improving the quality of engineered muscle used in a series of applications including drug screening, regeneration therapies, and biological machinery assembly.

Poly(N-vinylcaprolactam) (PNVCL) is a thermoresponsive polymer known to be nontoxic, water soluble and biocompatible. Here, PNVCL homopolymer was successfully synthesized for the first time by use of a one-step vapor-phase process, termed initiated chemical vapor deposition (iCVD). Fourier transform infrared spectroscopy results showed that radical polymerization took place from N-vinylcaprolactam monomers without damaging the functional caprolactam ring. A sharp lower critical solution temperature transition was observed at 31 °C from the iCVD poly(N-vinylcaprolactam) (PNVCL) film. The thermoresponsive PNVCL surface exhibited a hydrophilic/hydrophobic alteration with external temperature change, which enabled the thermally modulated attachment and detachment of cells. The conformal coverage of PNVCL film on various substrates with complex topography, including fabrics and nano-patterns, was successfully demonstrated, which can further be utilized to fabricate cell sheets with aligned cell morphology. The advantage of this system is that cells cultured on such thermoresponsive surfaces could be recovered as an intact cell sheet by simply lowering the temperature, eliminating the need for conventional enzymatic treatments.

Coculturing stem cells with the desired cell type is an effective method to promote the differentiation of stem cells. The features of the membrane used for coculturing are crucial to achieving the best outcome. Not only should the membrane act as a physical barrier that prevents the mixing of the cocultured cell populations, but it should also allow effective interactions between the cells. Unfortunately, conventional membranes used for coculture do not sufficiently meet these requirements. In addition, cell harvesting using proteolytic enzymes following coculture impairs cell viability and the extracellular matrix (ECM) produced by the cultured cells. To overcome these limitations, we developed nanothin and highly porous (NTHP) membranes, which are ∼20-fold thinner and ∼25-fold more porous than the conventional coculture membranes. The tunable pore size of NTHP membranes at the nanoscale level was found crucial for the formation of direct gap junctions-mediated contacts between the cocultured cells. Differentiation of the cocultured stem cells was dramatically enhanced with the pore size-customized NTHP membrane system compared to conventional coculture methods. This was likely due to effective physical contacts between the cocultured cells and the fast diffusion of bioactive molecules across the membrane. Also, the thermoresponsive functionality of the NTHP membranes enabled the efficient generation of homogeneous, ECM-preserved, highly viable, and transfer-printable sheets of cardiomyogenically differentiated cells. The coculture platform developed in this study would be effective for producing various types of therapeutic multilayered cell sheets that can be differentiated from stem cells.