Owing to the importance of stem cell culture systems in clinical applications, researchers have extensively studied them to optimize the culture conditions and increase efficiency of cell culture. A ...spheroid culture system provides a similar physicochemical environment in vivo by facilitating cell-cell and cell-matrix interaction to overcome the limitations of traditional monolayer cell culture. In suspension culture, aggregates of adjacent cells form a spheroid shape having wide utility in tumor and cancer research, therapeutic transplantation, drug screening, and clinical study, as well as organic culture. There are various spheroid culture methods such as hanging drop, gel embedding, magnetic levitation, and spinner culture. Lately, efforts are being made to apply the spheroid culture system to the study of drug delivery platforms and co-cultures, and to regulate differentiation and pluripotency. To study spheroid cell culture, various kinds of biomaterials are used as building forms of hydrogel, film, particle, and bead, depending upon the requirement. However, spheroid cell culture system has limitations such as hypoxia and necrosis in the spheroid core. In addition, studies should focus on methods to dissociate cells from spheroid into single cells.
•Cancer cell membrane coated the nanocarriers (CCMCNCs) can mimic the source cell adhesion properties.•CCMCNCs can be used for targeted drug delivery in cancer therapy.•We reviewed the method of ...preparation and applications of CCMCNCs.•CCMCNCs can be custom modified for selctive adhesion to target cells through homo- and hetero-typic adhesion properties.
Cancer is a leading cause of death worldwide. The use of nanocarriers (NCs) has generated significant interest to improve cancer therapy by targeted delivery. However, conventional NCs in general lack specificity and have poor biodistribution, resulting in low efficacy in cancer therapy. To circumvent this problem, there has been an increasing focus on cancer cell membrane-coated NCs (CCMCNCs), which can deliver therapeutics directly to tumor cells. CCMCNCs comprise active cancer cell surface adhesive molecules combined with other functional proteins, and offer extended blood circulation with robust cell-specific targeting, ensuring enhanced intratumoral penetration and higher tumor-specific accumulation of NCs. In this review, we discuss the preparation, homologous targeting mechanisms, and application of CCMCNCs in targeted cancer therapy.
A stretchable polyaniline nanofiber temperature sensor array with an active matrix consisting of single‐walled carbon nanotube thin‐film transistors is demonstrated. The integrated temperature sensor ...array gives mechanical stability under biaxial stretching of 30%, and the resultant spatial temperature mapping does not show any mechanical or electrical degradation.
Schematic of fabrication process for FGF-2/BMP-2-immobilized hydroxyapatite/gelatin nanofibrous scaffold for bone tissue regeneration.
Display omitted
•Avidin surface-functionalized nanofiber can ...bind with biotinylated FGF-2 and BMP-2.•Avidin-Biotin conjugation provided the sustained releases function.•Nanofibers were coated with hydroxyapatite in different pattern using modified SBF.•The synergism between growth factors and hydroxyapatite enhanced osteogenesis.
To improve bone growth and to imitate the function of natural extracellular matrix for sustained release of multiple growth factors, a scaffold of porous gelatin nanofibers were electrospun, coated with hydroxyapatite using a simulated body fluid solution, and surface-functionalized with avidin to facilitate binding with biotinylated growth factors, namely bone morphogenetic protein-2 (BMP-2) and fibroblast growth factor-2 (FGF-2) at different ratios. Scanning electron microscopy was used for structure characterization and Fourier-transform infrared spectroscopy and calcium assay were performed to evaluate the calcium composition. Immunostaining techniques confirmed the conjugation of multiple growth factors. The effects of the two growth factors and hydroxyapatite on osteogenic cell differentiation were studied using quantitative polymerase chain reaction analysis. Multiple growth factors were successfully conjugated onto the functionalized surface by controlling the FGF-2/BMP-2 ratio. Comparisons of the factor release profiles with those of the physical adsorption showed that avidin-biotin conjugation was more effective for sustained release. Bone regeneration was enhanced via synergism between multiple growth factor delivery and the hydroxyapatite nanofiber coating, as confirmed by the increased expression of osteogenic gene markers. The nanofibers thus provide a promising osteoconductive scaffold with controlled multiple growth factor delivery for bone tissue engineering.
Background
Microbes in the airway have been shown to be associated with the pathogenesis of asthma. The upper airway microbiome influences the dysbiosis of the lower airway microbiome. However, to ...date, the influence of upper airway microbiome for adult and elderly asthma has not been fully elucidated. Here, the metagenome of upper airway microbiome of young adults and elderly was analyzed to identify their association with adult asthma.
Methods
Nasopharyngeal swabs were collected from young adult and elderly asthma patients and non‐asthmatic subjects. The compositions and functional genes of airway microbiome were analyzed by high‐throughput sequencing.
Results
The composition of microbiota differed between young adult and elderly, and it was different between asthmatics and non‐asthmatics in each age group. Different bacteria were related to FEV1% predicted in each age group. Genes related to lysine degradation, N‐glycan biosynthesis, caprolactam degradation, and PPAR signaling pathway, which could be related to the reduction in inflammation and degradation of air pollutants, were higher in non‐asthmatics. Genes related to pentose phosphate pathway, lipopolysaccharide biosynthesis, flagella assembly, and bacterial chemotaxis—which may all be related to increased inflammation and colonization of pathogenic bacteria—were higher in young adult asthmatic patients. However, the functional genes of airway microbiome in elderly patients were not significantly different according to asthma morbidity.
Conclusions
These results suggest that the composition and function of upper airway microbiome could influence asthma pathogenesis, and the microbiome could play various roles depending on the age group.
The upper airway microbiome was different between young adults and elderly, and their association with asthma was also different.
The microbiome genes reducing airway inflammation and degrading air pollutants were lower in asthmatics, whereas genes enhancing inflammation and mucosal bacterial colonization were higher in asthmatics of young adults.
The composition and function of upper airway microbiome could influence asthma pathogenesis, and the microbiome could play various roles depending on the age group.
Nanoparticles have been extensively used to deliver therapeutic drugs to tumor tissues through the extravasation of a leaky vessel via enhanced permeation and retention effect (EPR, passive ...targeting) or targeted interaction of tumor-specific ligands (active targeting). However, the therapeutic efficacy of drug-loaded nanoparticles is hampered by its heterogeneous distribution owing to limited penetration in tumor tissue. Inspired by the fact that cancer cells can recruit inflammatory immune cells to support their survival, we developed a click reaction-assisted immune cell targeting (CRAIT) strategy to deliver drug-loaded nanoparticles deep into the avascular regions of the tumor. Immune cell-targeting CD11b antibodies are modified with trans-cyclooctene to enable bioorthogonal click chemistry with mesoporous silica nanoparticles functionalized with tetrazines (MSNs-Tz). Sequential injection of modified antibodies and MSNs-Tz at intervals of 24 h results in targeted conjugation of the nanoparticles onto CD11b+ myeloid cells, which serve as active vectors into tumor interiors. We show that the CRAIT strategy allows the deep tumor penetration of drug-loaded nanoparticles, resulting in enhanced therapeutic efficacy in an orthotopic 4T1 breast tumor model. The CRAIT strategy does not require ex vivo manipulation of cells and can be applied to various types of cells and nanovehicles.
Since around the year 2000, hundreds of people in Korea have developed humidifier disinfectant‐associated lung injury (HDLI). We collected all HD exposure‐related information from the field ...investigations into the locations in which the 1199 registered patients had used HD. Among the people who registered, 38% (1st round = 214, 2nd = 73, 3rd = 166) were confirmed as HDLI patients. Children aged under eight years old made up the highest proportion of HDLI cases (N = 279, 62%), followed by pregnant women (N = 31, 7%). One hundred thirty‐three (29%) of the confirmed HDLI patients died. Fifty‐seven percent of HDLI patients (N = 259) developed HDLI after <1 year of HD use. The number of HDLI patients who used only the Oxy Saksak HD brand was found to be 176 (39%), followed by the brands Cefu (N = 27, 6%) and Aekyung (N = 22, 5%). HD products containing only polyhexamethylene guanidine phosphate (PHMG‐P) were the most frequently used among HDLI patients (N = 234, 52%), followed by oligo (2‐(2‐ethoxy)ethoxyethyl) guanidinium (PGH) (N = 27, 6%) and a mixture of chloromethylisothiazolinone (CMIT) and methylisothiazolinone (MIT) (N = 26, 6%). The average PHMG‐P inhalation level estimated from the patient group classified as suffering lung injury definitely associated with HD use was 145.1 μg/m3 (N = 91, SD = 395.1 μg/m3), higher than levels estimated from both the probable and possible HDLI patient groups. In conclusion, HD exposure‐related variables, including type of HD brand and estimated inhalation HD level, were associated with the risk of HDLI.
This study reports on the fabrication of pressure/temperature/strain sensors and all‐solid‐state flexible supercapacitors using only polydimethylsiloxane coated microporous polypyrrole/graphene foam ...composite (PDMS/PPy/GF) as a common material. A dual‐mode sensor is designed with PDMS/PPy/GF, which measures pressure and temperature with the changes of current and voltage, respectively, without interference to each other. The fabricated dual‐mode sensor shows high sensitivity, fast response/recovery, and high durability during 10 000 cycles of pressure loading. The pressure is estimated using the thermoelectric voltage induced by simultaneous increase in temperature caused by a finger touch on the sensor. Additionally, a resistor‐type strain sensor fabricated using the same PDMS/PPy/GF could detect the strain up to 50%. Flexible, high performance supercapacitor used as a power supply is fabricated with electrodes of PPy/GF for its high surface area and pseudocapacitance. Furthermore, an integrated system of such fabricated multifunctional sensors and a supercapacitor on a skin‐attachable flexible substrate using liquid–metal interconnections operates well, whereas sensors are driven by the power of the supercapacitor. This study clearly demonstrates that the appropriate choice of a single functional material enables fabrication of active multifunctional sensors for pressure, temperature, and strain, as well as the supercapacitor, that could be used in wirelessly powered wearable devices.
High‐performance solid‐state supercapacitors and multifunctional sensors sensitive to pressure, temperature, and strain are fabricated using a single common active material of microporous polydimethylsiloxane coated microporous polypyrrole/graphene foam composite. Furthermore, these sensors could be wirelessly driven with the integrated supercapacitors on a single flexible and skin‐attachable substrate.
Adipose tissue-derived mesenchymal stem cells (AT-MSCs) offer potential as a therapeutic option for chronic discogenic low back pain (LBP) because of their immunomodulatory functions and capacity for ...cartilage differentiation. The goal of this study was to assess the safety and tolerability of a single intradiscal implantation of combined AT-MSCs and hyaluronic acid (HA) derivative in patients with chronic discogenic LBP.
We performed a single-arm phase I clinical trial with a 12-month follow-up and enrolled 10 eligible chronic LBP patients. Chronic LBP had lasted for more than 3 months with a minimum intensity of 4/10 on a visual analogue scale (VAS) and disability level ≥ 30% on the Oswestry Disability Index (ODI). The 10 patients underwent a single intradiscal injection of combined HA derivative and AT-MSCs at a dose of 2 × 10
cells/disc (n = 5) or 4 × 10
cells/disc (n = 5). Safety and treatment outcomes were evaluated by assessing VAS, ODI, Short Form-36 (SF-36), and imaging (lumbar spine X-ray imaging and MRI) at regular intervals over 1 year.
No patients were lost at any point during the 1-year clinical study. We observed no procedure or stem cell-related adverse events or serious adverse events during the 1-year follow-up period. VAS, ODI, and SF-36 scores significantly improved in both groups receiving both low (cases 2, 4, and 5) and high (cases 7, 8, and 9) cell doses, and did not differ significantly between the two groups. Among six patients who achieved significant improvement in VAS, ODI, and SF-36, three patients (cases 4, 8, and 9) were determined to have increased water content based on an increased apparent diffusion coefficient on diffusion MRI.
Combined implantation of AT-MSCs and HA derivative in chronic discogenic LBP is safe and tolerable. However, the efficacy of combined AT-MSCs and HA should be investigated in a randomized controlled trial in a larger population.
ClinicalTrials.gov NCT02338271 . Registered 7 January 2015.
PDF
