Identifying novel clinical phenotypes of acute respiratory distress syndrome using trajectories of daily fluid balance: a secondary analysis of randomized controlled trials.

BACKGROUND: Previously identified phenotypes of acute respiratory distress syndrome (ARDS) could not reveal the dynamic change of phenotypes over time. We aimed to identify novel clinical phenotypes in ARDS using trajectories of fluid balance, to test whether phenotypes respond differently to different treatment, and to develop a simplified model for phenotype identification. METHODS: FACTT (conservative vs liberal fluid management) trial was classified as a development cohort, joint latent class mixed models (JLCMMs) were employed to identify trajectories of fluid balance. Heterogeneity of treatment effect (HTE) for fluid management strategy across phenotypes was investigated. We also constructed a parsimonious probabilistic model using baseline data to predict the fluid trajectories in the development cohort. The trajectory groups and the probabilistic model were externally validated in EDEN (initial trophic vs full enteral feeding) trial. RESULTS: Using JLCMM, we identified two trajectory groups in the development cohort: Class 1 (n = 758, 76.4% of the cohort) had an early positive fluid balance, but achieved negative fluid balance rapidly, and Class 2 (n = 234, 24.6% of the cohort) was characterized by persistent positive fluid balance. Compared to Class 1 patients, patients in Class 2 had significantly higher 60-day mortality (53.5% vs. 17.8%, p < 0.001), and fewer ventilator-free days (0 vs. 20, p < 0.001). A significant HTE between phenotypes and fluid management strategies was observed in the FACTT. An 8-variables model was derived for phenotype assignment. CONCLUSIONS: We identified and validated two novel clinical trajectories for ARDS patients, with both prognostic and predictive enrichment. The trajectories of ARDS can be identified with simple classifier models.

Pharmacological Activity of Matrine in Inhibiting Colon Cancer Cells VM Formation, Proliferation, and Invasion by Downregulating Claudin-9 Mediated EMT Process and MAPK Signaling Pathway.

Purpose: Matrine (Mat), the main active ingredient of traditional Chinese herbal plant Sophora flavescens Ait, has significant antitumor effects, but its pharmacological mechanism on colon cancer (CC) remains unclear. This study aimed to investigate the therapeutic effect of Mat on CC as well as the potential mechanism. Methods: The vasculogenic mimicry (VM) of CC cells was observed by three-dimensional (3D) Matrigel cell culture. Cell proliferation, apoptosis, migration, invasion, and actin filament integrity were detected by CCK8, flow cytometry, wound healing, Transwell and Phalloidin staining assays. qRT-PCR and Western blotting were applied to detect the expression of EMT factors. RNA-sequencing was conducted to screen differentially expressed genes (DEGs), and the GO and KEGG pathway enrichment analyses were performed. Then, the expression of the key MAPK pathway genes and the target gene Claudin-9 (Cldn9) were analyzed. RNA interference was used to silence Cldn9 expression, and the effects of Cldn9 silencing and simultaneous treatment with Mat on VM formation, proliferation, apoptosis, invasion, and migration were investigated. Finally, the expression of EMT factors and MAPK pathway key genes was detected. Results: CT26 cells formed the most typical VM structure. Mat disrupted the VM of CT26 cells, significantly suppressed their proliferation, migration, invasion, actin filament integrity, induced apoptosis, and inhibited EMT process. RNA-sequencing revealed 163 upregulated genes and 333 downregulated genes in Mat-treated CT26 cells, and the DEGs were significantly enriched in cell adhesion molecules and MAPK signaling pathways. Further confirmed that Mat significantly inhibited the phosphorylation levels of JNK and ERK, and the target gene Cldn9 was significantly upregulated in human CC tissues. Silencing Cldn9 markedly inhibited the VM, proliferative activity, invasiveness, and actin filament integrity of CT26 cells, blocked the EMT process, and downregulated the phosphorylation of JNK and ERK, whereas Mat intervention further strengthened the above trends. Conclusion: This study indicated that Mat may synergistically inhibit the EMT process and MAPK signaling pathway through downregulation Cldn9, thereby exerting pharmacological effects on inhibiting VM formation, proliferation, and invasion of CC cells.

Bifunctional scaffolds for tumor therapy and bone regeneration: Synergistic effect and interplay between therapeutic agents and scaffold materials.

Bone tumor patients often face the problems with cancer cell residues and bone defects after the operation. Therefore, researchers have developed many bifunctional scaffolds with both tumor treatment and bone repair functions. Therapeutic agents are usually combined with bioactive scaffolds to achieve the "bifunctional". However, the synergistic effect of bifunctional scaffolds on tumor therapy and bone repair, as well as the interplay between therapeutic agents and scaffold materials in bifunctional scaffolds, have not been emphasized and discussed. This review proposes a promising design scheme for bifunctional scaffolds: the synergistic effect and interplay between the therapeutic agents and scaffold materials. This review summarizes the latest research progress in bifunctional scaffolds for therapeutic applications and regeneration. In particular, it summarizes the role of tumor therapeutic agents in bone regeneration and the role of scaffold materials in tumor treatment. Finally, a perspective on the future development of bifunctional scaffolds for tumor therapy and bone regeneration is discussed.

Characteristics of frailty phenotype in Chinese nursing home population and significance of motor function indicators in frailty assessment.

The objectives of this study were to analyze the distribution characteristics of frailty phenotypes in older adults of Chinese nursing homes, and to compare some motor function characteristics of older adults in nursing homes between frailty and non-frailty, to determine which motor function and frailty are related. This cross-sectional study included 177 older adults living in nursing homes. Frailty was diagnosed by Fried's phenotype, and motor function assessment characteristics (including muscle tone, ROM, and balance) were also evaluated. Chi-square and logistic regression analyses were performed. Frailty prevalence was 53% in nursing homes in big Chinese cities (average age 82.0 ±â€…6.1). Low levels of physical activity (90.4% in frail elder), decreased handgrip strength (98.9% in frail elder) and slowed walking speed (100% in frail elder) were the 3 main components of the frailty phenotype of frail adults in nursing homes in China. It is worth noting that 74.7% of the non-frail elders also had reduced handgrip strength. Further analysis showed that balance (P < .001), muscle tone (upper, P = .028, lower, P = .001) and the range of motion (P < .001) were associated with frailty in older adults. The frailty of the elders in Chinese nursing homes was characterized by the decline of motor function. And surprisingly, both frail and non-frail elders were found to have poor strength. Frail nursing home seniors also have body muscle tone, range of motion and balance problems. The elderly of China should focus on strength, stretch and balance training to improve motor function, especially strength training, which is important for prevention frailty.

Synergistic Effect of Surface Chemistry and Surface Topography Gradient on Osteogenic/Adipogenic Differentiation of hMSCs.

Much attention has been paid to understanding the individual effects of surface chemistry or topography on cell behavior. However, the synergistic influence of both surface chemistry and surface topography on differentiation of human mesenchymal stem cells (hMSCs) should also be addressed. Here, gold nanoparticles were immobilized in an increasing number density manner to achieve a surface topography gradient; a thin film rich in amine (-NH2) or methyl (-CH3) chemical groups was plasma-polymerized to adjust the surface chemistry of the outermost layer (ppAA and ppOD, respectively). hMSCs were cultured on these model substrates with defined surface chemistry and surface topography gradient. The morphology and focal adhesion (FA) formation of hMSCs were first examined. hMSC differentiation was then co-induced in osteogenic and adipogenic medium, as well as in the presence of extracellular-signal-regulated kinase1/2 (ERK1/2) and RhoA/Rho-associated protein kinase (ROCK) inhibitors. The results show that the introduction of nanotopography could enhance FA formation and osteogenesis but inhibited adipogenesis on both ppAA and ppOD surfaces, indicating that the surface chemistry could regulate hMSC differentiation, in a surface topography-dependent manner. RhoA/ROCK and ERK1/2 signaling pathways may participate in this process. This study demonstrated that surface chemistry and surface topography can jointly affect cell morphology, FA formation, and thus osteogenic/adipogenic differentiation of hMSCs. These findings highlight the importance of the synergistic effect of different material properties on regulation of cell response, which has important implications in designing functional biomaterials.

Somatic Mutation Profiling of Papillary Thyroid Carcinomas by Whole-exome Sequencing and Its Relationship with Clinical Characteristics.

The incidence of papillary thyroid carcinomas (PTCs) has increased rapidly during the past several decades. Until now, the mechanisms underlying the tumorigenesis of PTCs have remained largely unknown. Next-generation-sequencing (NGS) provides new ways to investigate the molecular pathogenesis of PTCs. To characterize the somatic alterations associated with PTCs, we performed whole-exome sequencing (WES) of PTCs from 23 Chinese patients. This study revealed somatic mutations in genes with relevant functions for tumorigenesis, such as BRAF, BCR, CREB3L2, DNMT1, IRS2, MSH6, and TP53. We also identified novel somatic gene alterations which may be potentially involved in PTC progression. Gene set enrichment analysis revealed that the cellular response to hormone stimulus, epigenetic modifications, such as protein/histone methylation and protein alkylation, as well as MAPK, PI3K-AKT, and FoxO/mTOR signaling pathways, were significantly altered in the PTCs studied here. Moreover, Protein-Protein Interaction (PPI) network analysis of our mutated gene selection highlighted EP300, KRAS, PTEN, and TP53 as major core genes. The correlation between gene mutations and clinicopathologic features of the PTCs defined by conventional ultrasonography (US) and contrast-enhanced ultrasonography (CEUS) were assessed. These analyses established significant associations between subgroups of mutations and respectively taller-than-wide, calcified, and peak time iso- or hypo-enhanced and metastatic PTCs. In conclusion, our study supplements the genomic landscape of PTCs and identifies new actionable target candidates and clinicopathology-associated mutations. Extension of this study to larger cohorts will help define comprehensive genomic aberrations in PTCs and validate target candidates. These new targets may open methods of individualized treatments adapted to the clinicopathologic specifics of the patients.

Comparing the regeneration potential between PLLA/Aragonite and PLLA/Vaterite pearl composite scaffolds in rabbit radius segmental bone defects.

Mussel-derived nacre and pearl, which are natural composites composed CaCO3 platelets and interplatelet organic matrix, have recently gained interest due to their osteogenic potential. The crystal form of CaCO3 could be either aragonite or vaterite depending on the characteristics of mineralization template within pearls. So far, little attention has been paid on the different osteogenic capacities between aragonite and vaterite pearl. In the current work, aragonite or vaterite pearl powders were incorporated into poly-l-lactic acid (PLLA) scaffold as bio-functional fillers for enhanced osteogenesis. In intro results revealed that PLLA/aragonite scaffold possessed stronger stimulatory effect on SaOS-2 cell proliferation and differentiation, evidenced by the enhanced cell viability, alkaline phosphatase activity, collagen synthesis and gene expressions of osteogenic markers including osteocalcin, osteopotin and bone sialoprotein. The bone regeneration potential of various scaffolds was evaluated in vivo employing a rabbit critical-sized radial bone defect model. The X-ray and micro-CT results showed that significant bone regeneration and bridging were achieved in defects implanted with composite scaffolds, while less bone formation and non-bridging were found for pure PLLA group. Histological evaluation using Masson's trichrome and hematoxylin/eosin (H&E) staining indicated a typical endochondral bone formation process conducted at defect sites treated with composite scaffolds. Through three-point bending test, the limbs implanted with PLLA/aragonite scaffold were found to bear significantly higher bending load compared to other two groups. Together, it is suggested that aragonite pearl has superior osteogenic capacity over vaterite pearl and PLLA/aragonite scaffold can be employed as a potential bone graft for bone regeneration.

Elevated PCT at ICU discharge predicts poor prognosis in patients with severe traumatic brain injury: a retrospective cohort study.

PURPOSE: Disease severity and inflammatory response status are closely related to a poor prognosis and must be assessed in patients with severe traumatic brain injury (STBI) before intensive care unit (ICU) discharge. Whether elevated serum procalcitonin (PCT) levels can predict a poor prognosis in STBI patients before ICU discharge is unclear. METHODS: This retrospective observational cohort study enrolled 199 STBI patients who were in the ICU for at least 48 hours and survived after discharge. Based on serum PCT levels at discharge, patients were divided into the high-PCT group (PCT ≥ 0.25 ng/mL) and the low-PCT group (PCT < 0.25 ng/mL). We assessed the relationship between serum PCT levels and a poor prognosis. RESULTS: The high-PCT group had a higher rate of adverse outcomes compared with the low-PCT group. Multivariate logistic regression analysis showed that the Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Sequential Organ Failure Assessment (SOFA) score, white blood cell (WBC) count, C-reactive protein (CRP) level, and PCT level at discharge were significantly associated with adverse outcomes. CONCLUSIONS: Elevated PCT levels at ICU discharge were associated with a poor prognosis in STBI patients. The serum PCT level as a single indicator has limited value for clinical decision-making.

Comprehensive circular RNA profiling reveals that hsa_circ_0001368 is involved in growth hormone-secreting pituitary adenoma development.

Growth hormone-secreting pituitary adenoma (GHPA) represents about 20% of all histological subtypes of pituitary adenoma (PA), which may result in serious complications and shortened lifespan via growth-hormone (GH) hypersecretion. To date, no biomarkers of early diagnosis or therapeutic targets for GHPA treatment have yet been found. Recently, growing evidence has indicated that circular RNAs (circRNAs) are critical for the development and progression of numerous diseases, including cancers; however, their role in the pathogenesis of GHPA has not been reported. Here, we revealed the expression profile of circRNAs in GHPA using a circRNA microarray, and found 1938 circRNAs were upregulated and 1601 circRNAs were downregulated in GHPA versus normal control. Then the ten most up-regulated circRNAs were selected for the mapping of a circRNA-miRNA-target gene interaction network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses further indicate that target genes were mostly enriched in the mTOR and the Wnt signaling pathway. Among these differentially expressed circRNAs, hsa_circ_0001368 was verified significant up-regulated by qRT-PCR, which was specific up-regulated in GHPA and correlated with the invasiveness and serum GH level of GHPA; functional studies indicated that knockdown of hsa_circ_0001368 significantly inhibited the proliferation, invasion and GH secreting level of GHPA primary culture cells. Moreover, hsa_circ_0001368 had a significant positive correlation with the pituitary-specific transcription factor Pit-1. In conclusion, our study identified a wealth of candidate circRNAs involved in GHPA and proposed that hsa_circ_0001368 may represent a novel potential biomarker and therapeutic target of GHPA.

Silver nanoparticles stimulate osteogenesis of human mesenchymal stem cells through activation of autophagy.

Aim: Previously, different results have been achieved regarding effects of silver nanoparticles (Ag NPs) on osteogenesis of stem cells and the mechanisms have not been disclosed yet, which are quite important for potential application of Ag NPs in bone reconstruction. Materials & methods: Effects of Ag NPs on osteogenesis of human mesenchymal stem cells (hMSCs) with underlying mechanisms were investigated. Results: Ag NPs at 2.5 and 5 µg/ml increased osteogenic proteins expression and mineralization of hMSCs. Meanwhile, autophagy was activated by Ag NPs and it could be inhibited by 3-methyladenine. Furthermore, osteogenesis induced by Ag NPs could also be reversed by 3-methyladenine. Conclusion: These findings suggest that autophagy is involved in stimulating osteogenesis of hMSCs induced by Ag NPs.

Nanoparticles and their effects on differentiation of mesenchymal stem cells.

Over the past decades, advancements in nanoscience and nanotechnology have resulted in numerous nanomedicine platforms. Various nanoparticles, which exhibit many unique properties, play increasingly important roles in the field of biomedicine to realize the potential of nanomedicine. Due to the capacity of self-renewal and multilineage mesenchymal differentiation, mesenchymal stem cells (MSCs) have been widely used in the area of regenerative medicine and in clinical applications due to their potential to differentiate into various lineages. There are several factors that impact the differentiation of MSCs into different lineages. Many types of biomaterials such as polymers, ceramics, and metals are commonly applied in tissue engineering and regenerative therapies, and they are continuously refined over time. In recent years, along with the rapid development of nanotechnology and nanomedicine, nanoparticles have been playing more and more important roles in the fields of biomedicine and bioengineering. The combined use of nanoparticles and MSCs in biomedicine requires greater knowledge of the effects of nanoparticles on MSCs. This review focuses on the effects of four inorganic or metallic nanoparticles (hydroxyapatite, silica, silver, and calcium carbonate), which are widely used as biomaterials, on the osteogenic and adipogenic differentiation of MSCs. In this review, the cytotoxicity of these four nanoparticles, their effects on osteogenic/adipogenic differentiation of MSCs and the signalling pathways or transcription factors involved are summarized. In addition, the chemical composition, size, shape, surface area, surface charge and surface chemistry of nanoparticles, have been reported to impact cellular behaviours. In this review, we particularly emphasize the influence of their size on cellular responses. We envision our review will provide a theoretical basis for the combined application of MSCs and nanoparticles in biomedicine.

Acetylcholinesterase modified AuNPs-MoS2-rGO/PI flexible film biosensor: Towards efficient fabrication and application in paraoxon detection.

A flexible acetylcholinesterase (AChE) film biosensor, based on a AuNPs-MoS2-reduced graphene oxide/polyimide flexible film (rGO/PI) electrode, has been synthesized for paraoxon detection. In this study, the rGO/PI film acts as the flexible substrate and AuNPs are reduced by monolayer MoS2 under illumination. Transmission electron microscopy revealed that AuNPs are uniformly dispersed on the MoS2-rGO/PI electrode surface with a diameter ~10nm. X-ray photoelectron spectroscopy indicated that a strong binding force exists between reduced AuNPs and monolayer MoS2. The AChE modified AuNPs-MoS2-rGO/PI flexible film biosensor is used to hydrolyze acetylcholine chloride and obtain a large current response at 0.49V by differential pulse voltammetry, demonstrating successful immobilization of AChE. In view of the inhibition of paraoxon on the AChE, under optimal conditions, the AChE/AuNPs-MoS2-rGO/PI film biosensor shows a linear response over a concentration range 0.005-0.150µg/mL, a sensitivity of 4.44 uA/µg/mL, a detection limit of 0.0014µg/mL, acceptable reproducibility and stability to paraoxon. The flexible film biosensor has also proved used for detection of paraoxon in real samples.

3D Printing of Conductive Tissue Engineering Scaffolds Containing Polypyrrole Nanoparticles with Different Morphologies and Concentrations.

Inspired by electrically active tissues, conductive materials have been extensively developed for electrically active tissue engineering scaffolds. In addition to excellent conductivity, nanocomposite conductive materials can also provide nanoscale structure similar to the natural extracellular microenvironment. Recently, the combination of three-dimensional (3D) printing and nanotechnology has opened up a new era of conductive tissue engineering scaffolds exhibiting optimized properties and multifunctionality. Furthermore, in the case of two-dimensional (2D) conductive film scaffolds such as periosteum, nerve membrane, skin repair, etc., the traditional preparation process, such as solvent casting, produces 2D films with defects of unequal bubbles and thickness frequently. In this study, poly-l-lactide (PLLA) conductive scaffolds incorporated with polypyrrole (PPy) nanoparticles, which have multiscale structure similar to natural tissue, were prepared by combining extrusion-based low-temperature deposition 3D printing with freeze-drying. Furthermore, we creatively integrated the advantages of 3D printing and solvent casting and successfully developed a 2D conductive film scaffold with no bubbles, uniform thickness, and good structural stability. Subsequently, the effects of concentration and morphology of PPy nanoparticles on electrical properties and mechanical properties of 3D conductive scaffolds and 2D conductive films scaffolds have been studied, which provided a new idea for the design of both 2D and 3D electroactive tissue engineering scaffolds.

Micro/nanostructured TiO2/ZnO coating enhances osteogenic activity of SaOS-2 cells.

Although titanium implants account for a large proportion of the commercial dental market, their bioactivity are inadequate in many applications. A micro- and nano- scale hierarchical surface topography of the implant is suggested for rapid osseointegration from the biomimetic perspective. Moreover, Zinc (Zn) is an essential element in the skeletal system. Thus, a micro/nanostructured TiO2/ZnO coating, produced by micro-arc oxidation, and hydrothermal treatment, and heat treatment, was designed to endow the implant surface with enhanced osteogenic capacity. Physiochemical properties and biological effects of this coating were investigated in our study. The annealed micro/nanostructured TiO2/ZnO coating exhibited higher hydrophilicity and fibronectin adsorption ability compared to the micro-arc oxidation modified TiO2 coating. SaOS-2 cells grown on the annealed micro/nanostructured TiO2/ZnO coating showed increased alkaline phosphatase activity and collagen secretion, and immunofluorescence labeling revealed an upregulation of osteopontin, collagen type ι and osteocalcin. The micro/nanostructure and incorporation of Zn were considered to perform positive effect on the enhanced osteogenic activity of SaOS-2 cells. In conclusion, the micro/nanostructured TiO2/ZnO structure is simple, stable, and easy to produce and scale up, has promising applications in the surface modification of titanium implants.

Effect of in vitro collagen fibrillogenesis on Langmuir-Blodgett (LB) deposition for cellular behavior regulation.

Collagen fibrillogenesis is of special significance for the maintenance of collagen scaffold's mechanical stability and biological performance. Comprehensive information about the mechanism of collagen fibrillogenesis in vitro, as well as the effect of fibrillogenesis on deposited layers of ordered collagen molecules for cellular behavior regulation is thus crucial. In the current study, the pH, phosphate ion as well as reconstitution time impacting on the in vitro fibrillogenesis was systematically investigated, including the zeta potential and turbidity measurement. Furthermore, the fibrillogenesis impacting on the π-a isotherms of collagen assembly at the air/water interface was then fully evaluated. By applying LB technique, collagen fibril-assembling arrays structure can be successfully transferred to form surface deposition onto the mica and glass substrate. The morphology and collagen content were subsequently assessed by atomic force microscopy (AFM) and hydrolyzing examination respectively. Effect of collagen LB deposition on the adhesion and proliferation of SD rat bone marrow mesenchymal stem cells were estimated by Rhodamine Phalloidin/DIPI staining and CCK8 proliferation assays. The results show that highly oriented and collagen-abundant thin film can further facilitate cell adhesion and proliferation, indicating an innovative direction for tissue engineering.

Noninvasive Continuous Monitoring of Adipocyte Differentiation: From Macro to Micro Scales.

3T3-L1 cells serve as model systems for studying adipogenesis and research of adipose tissue-related diseases, e.g. obesity and diabetes. Here, we present two novel and complementary nondestructive methods for adipogenesis analysis of living cells which facilitate continuous monitoring of the same culture over extended periods of time, and are applied in parallel at the macro- and micro-scales. At the macro-scale, we developed visual differences mapping (VDM), a novel method which allows to determine level of adipogenesis (LOA)-a numerical index which quantitatively describes the extent of differentiation in the whole culture, and percentage area populated by adipocytes (PAPBA) across a whole culture, based on the apparent morphological differences between preadipocytes and adipocytes. At the micro-scale, we developed an improved version of our previously published image-processing algorithm, which now provides data regarding single-cell morphology and lipid contents. Both methods were applied here synergistically for measuring differentiation levels in cultures over multiple weeks. VDM revealed that the mean LOA value reached 1.11 ± 0.06 and the mean PAPBA value reached >60%. Micro-scale analysis revealed that during differentiation, the cells transformed from a fibroblast-like shape to a circular shape with a build-up of lipid droplets. We predict a vast potential for implementation of these methods in adipose-related pharmacological research, such as in metabolic-syndrome studies.

Silica-gentamicin nanohybrids: combating antibiotic resistance, bacterial biofilms, and in vivo toxicity.

INTRODUCTION: Antibiotic resistance is a growing concern in health care. Methicillin-resistant Staphylococcus aureus (MRSA), forming biofilms, is a common cause of resistant orthopedic implant infections. Gentamicin is a crucial antibiotic preventing orthopedic infections. Silica-gentamicin (SiO2-G) delivery systems have attracted significant interest in preventing the formation of biofilms. However, compelling scientific evidence addressing their efficacy against planktonic MRSA and MRSA biofilms is still lacking, and their safety has not extensively been studied. MATERIALS AND METHODS: In this work, we have investigated the effects of SiO2-G nanohybrids against planktonic MRSA as well as MRSA and Escherichia coli biofilms and then evaluated their toxicity in zebrafish embryos, which are an excellent model for assessing the toxicity of nanotherapeutics. RESULTS: SiO2-G nanohybrids inhibited the growth and killed planktonic MRSA at a minimum concentration of 500 µg/mL. SiO2-G nanohybrids entirely eradicated E. coli cells in biofilms at a minimum concentration of 250 µg/mL and utterly deformed their ultrastructure through the deterioration of bacterial shapes and wrinkling of their cell walls. Zebrafish embryos exposed to SiO2-G nanohybrids (500 and 1,000 µg/mL) showed a nonsignificant increase in mortality rates, 13.4±9.4 and 15%±7.1%, respectively, mainly detected 24 hours post fertilization (hpf). Frequencies of malformations were significantly different from the control group only 24 hpf at the higher exposure concentration. CONCLUSION: Collectively, this work provides the first comprehensive in vivo assessment of SiO2-G nanohybrids as a biocompatible drug delivery system and describes the efficacy of SiO2-G nanohybrids in combating planktonic MRSA cells and eradicating E. coli biofilms.

Hydroxyapatite/collagen coating on PLGA electrospun fibers for osteogenic differentiation of bone marrow mesenchymal stem cells.

The architecture and composition of bone tissue engineering scaffolds play important roles in modulating the growth of bone tissue. Composite fibers composed of poly(lactic-co-glycolic acid) (PLGA) skeleton coated with hydroxyapatite (HA) or hydroxyapatite/collagen (HA/Col) were successfully produced via electrospinning, biomimetic process, and adsorption. The PLGA skeleton fabricated by electrospinning process with a nanofibrous structure (diameter ranging from 200 to 400 nm) showed a morphologic similarity to the extracellular matrix (ECM). SEM, EDX, and XRD analysis confirmed the presence of HA and Col on the composite fibers. Mesenchymal stem cells were used to evaluate the cellular behaviors including cell attachment and spreading, proliferation, and osteogenic differentiation on these fibers (PLGA, PLGA/HA, and PLGA/HA/Col). The results demonstrated that the HA and HA/Col coating improved the interaction between mesenchymal stem cells and the composite fibers reflected by accelerated cell spreading, increased alkaline phosphatase (ALP) activity and enhanced expression of osteogenic-related genes. The HA/Col coating was more effective in improving this interaction compared with HA coating. The PLGA/HA/Col composite fibers may be promising as a candidate scaffold for bone tissue engineering. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2863-2870, 2018.

Incorporation of silica nanoparticles to PLGA electrospun fibers for osteogenic differentiation of human osteoblast-like cells.

The development of bone tissue engineering scaffolds still remains a challenging field, although various biomaterials have been developed for this purpose. Electrospinning is a promising approach to fabricate nanofibers with an interconnected porous structure, which can support cell adhesion, guide cell proliferation and regulate cell differentiation. The aim of this study is to fabricate composite fibers composed of poly(lactic-co-glycolic acid) (PLGA) and silica nanoparticles (NPs) via electrospinning and investigate the effect of PLGA/SiO2 composite fibers on the cellular response of osteoblast-like cells (SaOS-2 cells). SEM and EDX analysis showed that silica NPs were homogenously dispersed in the composite fibers. The mechanical behavior of the fibers showed that silica NPs acted as reinforcements at concentrations of 2.5 and 5 mg/ml. The incorporation of silica NPs led to enhancement of cell attachment and spreading on PLGA/SiO2 composite fibers. SaOS-2 cells cultured on PLGA/SiO2 composite fibers exhibited increased alkaline phosphatase activity, collagen secretion and bone nodules formation. The bone nodules formation of SaOS-2 cells increased along with the amount of incorporated silica NPs. The present findings indicate that PLGA/SiO2 composite fibers can stimulate osteogenic differentiation of SaOS-2 cells and may be a promising candidate scaffold for bone tissue engineering.

In Vitro Uptake of Hydroxyapatite Nanoparticles and Their Effect on Osteogenic Differentiation of Human Mesenchymal Stem Cells.

There have been many applications in biomedical fields based on hydroxyapatite nanoparticles (HA NPs) over the past decades. However, the biocompatibility of HANPs is affected by exposure dose, particle size, and the way of contact with cells. The objective of this study is to investigate the effect of HA NPs with different sizes on osteogenesis using human mesenchymal stem cells (hMSCs). Three different-sized HA NPs (~50, ~100, and ~150 nm, resp.) were synthesized to study the cytotoxicity, cellular uptake, and effect on osteogenic differentiation of hMSCs. The results clearly showed that each size of HA NPs had dose-dependent cytotoxicity on hMSCs. It was found that HA NPs could be uptaken into hMSCs. The osteogenic differentiation of hMSCs was evaluated through alkaline phosphatase (ALP) activity measurement, ALP staining, immunofluorescent staining for osteopontin (OPN), and real-time polymerase chain reaction (RT-PCR) examination. As expected, HA NPs of all sizes could promote the differentiation of hMSCs towards osteoblast lineage. Among the three sizes, smaller-sized HA NPs (~50 and ~100 nm) appeared to be more effective in stimulating osteogenic differentiation of hMSCs.