Population pharmacokinetics of cyclosporine A in pediatric patients with thalassemia undergoing allogeneic hematopoietic stem cell transplantation.

PURPOSE: To establish the population pharmacokinetics (PPK) model of cyclosporine A(CsA) in pediatric patients with thalassemia undergoing allogeneic hematopoietic stem cell transplantation (HSCT), aiming at providing a reference for clinical dose individualization of CsA. METHODS: Children with thalassemia who underwent allogeneic HSCT were enrolled retrospectively. The PPK structural model and the random variable model of CsA were established on NONMEN. And goodness of fit plots (GOFs), visual predictive check (VPC), and bootstrap and normalized prediction distribution errors (NPDE) were used to evaluate the final model. RESULTS: A one-compartment model with first-order absorption was employed to fit the base model. A total of 74 pediatric patients and 600 observations of whole blood concentration were included. The final model included weight (WT) in clearance (CL), alongside post-operative day (POD), fluconazole (FLUC), voriconazole (VORI), posaconazole (POSA), and red blood cell count (RBC) significantly. All the model evaluations were passed. CONCLUSION: In the PPK model based on the pediatric cohort on CsA with thalassemia undergoing allogeneic HSCT, WT, POD, FLUC, VORI, POSA, and RBC were found to be the significant factors influencing CL of CsA. The reliability and robustness of the final model were excellent. It is expected that the PPK model can assist in individualizing dosing strategy clinically.

1-Monopalmitin promotes lung cancer cells apoptosis through PI3K/Akt pathway in vitro.

Lung cancer is the leading cause of cancer-related death worldwide and non-small cell lung cancer (NSCLC) represents 85%. Mougeotia nummuloides and Spirulina major have been reported to possess anticancer properties. 1-Monopalmitin (1-Mono) is the principle active constituent in these natural plants. It is debating whether 1-Mono exerts antitumor effects. Therefore, we explored the role of 1-Mono in lung cancer in vitro. Results showed that 1-Mono significantly inhibited A549 and SPC-A1 cell proliferation, induced G2/M arrest and caspase-dependent apoptosis. Moreover, it suppressed the protein expression of inhibitors of apoptosis proteins (IAPs). It was further demonstrated that 1-Mono activated the PI3K/Akt pathway, suppression of PI3K/Akt activities with LY294002 and Wortmannin partially attenuated 1-Mono-mediated anticancer activities, indicating that 1-Mono-induced antitumor effects is dependent on PI3K/Akt pathway. 1-Mono induced cytoprotective autophagy since autophagy inhibitor Chloroquine dramatically enhanced 1-Mono-induced cytotoxicity. In summary, our results showed 1-Mono kills lung cancer through PI3K/Akt pathway, providing novel options for lung cancer administration.

The Structural Characterization of a Novel Water-Soluble Polysaccharide from Edible Mushroom Leucopaxillus giganteus and Its Antitumor Activity on H22 Tumor-Bearing Mice.

In the present study, a novel cold water-soluble polysaccharide fraction (LGP) with the average molecular weight of 1.78×106  Da was extracted and purified from Leucopaxillus giganteus and its primary structure as well as in vivo antitumor activity was evaluated. The monosaccharide composition of LGP was determined by ion chromatography to be galactose, xylose, glucose and fucose in a molar ratio of 2.568 : 1.209 : 1 : 0.853. Its backbone was composed of α-D-Glu, α-D-Xyl, α-D-Gal and α-L-Fuc. The results of in vivo antitumor experiment demonstrated that LGP could effectively protect immune organs, has excellent antitumor activity, and inhibit the proliferation of H22 solid tumors in a dose-dependent manner. By analyzing Annexin V-FITC/PI staining, cell cycle and mitochondrial membrane potential detection assay, we concluded that LGP induced apoptosis of H22 cells via S phase arrest and mitochondria-mediated apoptotic pathway. Our results could provide valuable information for the potential application of LGP as an anti-hepatoma agent.

Pathway optimization of China's carbon emission reduction and its provincial allocation under temperature control threshold.

As the largest carbon emitter in the world, China faces great pressure to fulfill the temperature control targets, i.e., 2 °C and 1.5 °C, proposed in the Paris Agreement. Thus, selecting a development path that could both meet the temperature targets and economic growth is essential and worth investigating. We propose an optimization model to analyze China's carbon dioxide emission paths from 2010 to 2050 in three scenarios, namely baseline, and 1.5 °C and 2 °C target scenarios. The marginal cost of carbon abatement in China's 30 provinces (excluding Hong Kong, Macao, Taiwan, and Tibet) were also calculated using the quadratic directional distance function model, and the quotas of carbon dioxide emission among provinces were allocated. Carbon dioxide emission peak will occur in 2040 under the 2 °C target scenario and in 2030 under the 1.5 °C target scenario. The marginal cost of carbon abatement to achieve the 1.5 °C goal is approximately 1.6 times more expensive than the 2 °C goal. We suggest to implement emission reduction policies in the Eastern coastal areas of China and to allocate greater carbon dioxide emission quotas in under-developed areas in the Central and Western regions. Provincial quota allocation may also help to balance regional development and achieve the mutually beneficial goal of economic growth and carbon emission reduction in China. Our findings provide practical guidance on achieving carbon dioxide emission reduction and critical enlightenments on policymaking.

Risk factors of bloodstream infection in erythroderma from atopic dermatitis, psoriasis, and drug reactions: a retrospective observational cohort study.

Background: Atopic dermatitis (AD), psoriasis, and drug reactions associated with erythroderma are frequently complicated by infections. However, bloodstream infection (BSI) have received less research attention. Objectives: This study aimed to investigate the clinical characteristics and risk factors associated with BSI in patients with erythroderma. Methods: A retrospective analysis was conducted on 141 erythroderma cases. Eleven cases were identified as having BSI. Clinical records of both BSI and non-BSI groups were reviewed and compared. Results: BSI was diagnosed in 7.80% (11/141) of erythroderma cases, with a breakdown of 7.14% in AD, 2.00% in psoriasis, and 17.14% in drug reactions. Notably, all positive skin cultures (7/7) showed bacterial isolates concordant with blood cultures. Univariate logistic regression analysis revealed several significant associations with BSI, including temperature (≤36.0 or ≥38.5 °C; odds ratio (OR) = 28.06; p < 0.001), chilling (OR = 22.10; p < 0.001), kidney disease (OR = 14.64; p < 0.001), etiology of drug reactions (OR = 4.18; p = 0.03), albumin (ALB) (OR = 0.86; p < 0.01), C-reaction protein (CRP) (OR = 1.01; p = 0.02), interleukin 6 (IL-6) (OR = 1.02; p = 0.02), and procalcitonin (PCT) (OR = 1.07; p = 0.03). Receiver operating characteristic (ROC) curves demonstrated significant associations with ALB (p < 0.001; the area under curve (AUC) = 0.80), PCT (p = 0.009; AUC = 0.74), and CRP (p = 0.02; AUC = 0.71). Conclusions: Increased awareness of BSI risk is essential in erythroderma management. Patients with specific risk factors, such as abnormal body temperature (≤36.0 or ≥38.5 °C), chilling sensations, kidney disease, a history of drug reactions, elevated CRP (≥32 mg/L), elevated PCT (≥1.00 ng/ml), and low albumin (≤31.0 g/L), require close monitoring for BSI development.

Biodistribution of 89Zr-DFO-labeled avian pathogenic Escherichia coli outer membrane vesicles by PET imaging in chickens.

Avian pathogenic Escherichia coli (APEC) is a serious systemic infectious disease in poultry infections, causing severe economic losses to the poultry industry. Previous studies have shown that secretion of virulence proteins was required for the pathogenicity of APEC through the secretion system. Outer membrane vesicles (OMVs) are a generalized secretion system of Gram-negative bacteria that play a key role in the long-distance delivery of virulence factors, but whether they are associated with the pathogenic mechanism of APEC has not been determined. In this study, OMVs were purified and characterized from AE17 (O2 serotype) by ultracentrifugation and density gradient centrifugation and their protein cargo was identified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). In addition, 89Zr was labeled after chelating AE17 OMVs by DFO and positron emission tomography PET imaging was used to track 89Zr-DFO-OMVs in chickens and to pathologically analyze the distribution sites. This study showed that AE17 OMVs were membrane vesicles ranging in size from 20 to 200 nm and proteomic analysis revealed the presence of virulence proteins, including adhesion proteins OmpA, OmpC, OmpF, OmpX, FimH, FimC and FigE, and serum resistance proteins OmpT and MliC and immune response regulator proteins (FliC). In addition, in vivo PET imaging to track the biodistribution of AE17 OMVs showed that AE17 OMVs were taken up by the lung region and the gastrointestinal and renal regions but were not detected in other areas. Pathological analysis of the tissue sites where AE17 OMVs were ingested showed inflammatory responses and damage. These findings suggested that AE17 OMVs not only contained a group of virulence proteins associated with AE17 infection but can also deliver these virulence proteins over long distances and caused tissue inflammatory damage. Our study revealed a previously unidentified causative microbial signal in the pathogenesis of APEC that could aid in the development of vaccines and antibiotics effective against APEC.

Fur Protein Regulates the Motility of Avian Pathogenic Escherichia coli AE17 Through Promoter Regions of the Flagella Key Genes flhD.

Avian pathogenic Escherichia coli (APEC) is an important pathogen causing several diseases in birds. It is responsible for local and systemic infections in poultry, seriously impeding the development of the poultry industry, and poses a potential risk to public health. The iron absorption regulatory protein Fur and the noncoding RNA, RyhB, that it negatively regulates are important factors in bacterial iron uptake, but the regulation of bacterial virulence genes varies greatly among different bacteria. We found that Fur is very important for the mobility of APEC. The expression of fur and RyhB is extensively regulated in APEC, and RyhB expression is also negatively regulated by Fur. A transcriptomic analysis showed that the genes significantly differentially regulated by Fur are related to cell movement, including pilus- or flagellum-dependent cell motility. To verify these results, we examined the effects of fur knockdown on cell movement by measuring the diameter of the bacteria colonies. Consistent with the RNA sequencing results, the mobility of AE17Δfur was significantly reduced compared with that of the wild type, and it had almost lost its ability to move. Using an electrophoretic mobility assay, we confirmed that the Fur protein directly binds to the promoter region of the key flagellum-related gene flhD, thereby affecting the assembly and synthesis of the APEC flagellum. This study extends our understanding of gene regulation in APEC.

Population pharmacokinetics of mycophenolate mofetil in pediatric patients early after liver transplantation.

Objective: To investigate the factors influencing the pharmacokinetics of mycophenolate mofetil (MMF) in pediatric patients after liver transplantation, and to establish a population pharmacokinetics model, which can provide a reference for clinical dosage adjustment. Methods: A prospective study in a single center was performed on pediatric patients who were administrated with mycophenolate mofetil dispersible tablets (MMFdt) for at least 4 days after liver transplantation continuously. Blood samples were collected in ethylene diamine tetraacetic acid anticoagulant tubes before dosing and 0.5, 1, 2, 4, 8, and 12 h after the morning intake of MMFdt. The concentrations of mycophenolic acid (MPA) in plasma were assayed with a validated reverse-phase high-performance liquid chromatography method. UGT1A8 518C > G, UGT1A9 -275T > A, UGT1A9 -2152C > T, UGT2B7 211G > T, SLC O 1B1 521T > C polymorphism were determined by Sanger sequencing. Nonlinear mixed effects modeling was used to establish the population pharmacokinetics (PPK) model. The predictability and stability of the model were internally evaluated by the goodness of fit plots, visual prediction check, normalized prediction errors, and bootstraps. Results: A two-compartment model with first-order absorption and first-order elimination was established with 115 MPA concentrations from 20 pediatric patients. The final model were: CL/F (L/h) = 14.8×(WT/7.5)0.75×(DOSE/11.16)0.452×е0.06, Ka (h-1) = 2.02×(WT/7.5)-0.25, Vc/F (L) = 6.01×(WT/7.5), Vp/F (L) = 269 (fixed), Q/F (L/h) = 15.4×(WT/7.5)0.75×е1.39. Where CL/F was the apparent clearance rate, Ka was the absorption rate constant, Vc/F was the apparent distribution volume of the central compartment, Vp/F was the apparent distribution volume of the peripheral compartment, Q/F was the atrioventricular clearance rate, WT was the body weight of the subject, and DOSE was the MMFdt administered dose. The model indicated there was large inter-individual variability in CL/F and Q/F after multiple dosing of MMFdt. Internal evaluation results showed that the final model had good stability and prediction performance. Conclusion: A stable and predictive population pharmacokinetic model of MMFdt in pediatric patients after the early stage of liver transplantation was established. The pediatric patient's weight and the dose of MMFdt can be a reference to adjust the MMFdt dose.

Berberine carried gelatin/sodium alginate hydrogels with antibacterial and EDTA-induced detachment performances.

Most existing hydrogel wound dressings lack gentle detachment property. In this work, novel hydrogels with anti-bacterial and induced detachment properties were prepared. Both gelatin (G) and sodium alginate (SA) are natural polymer materials. The G/SA hydrogels were prepared by dual cross-linking. The addition of SA significantly improves the mechanical properties of composite hydrogels. The tensile modulus and elongation at break of the G/SA hydrogels with 2.0% SA could reach 99.23 ± 2.18 kPa and 85.47 ± 5.01%, respectively. In addition, the interconnected porous network and high swelling ratio (over 9.99 ± 0.33) are beneficial to the transmission of oxygen and absorption of exudates to accelerate the healing of wound. Subsequently, berberine (BBR) was loaded into the G/SA hydrogels. The BBR/G/SA hydrogels show sustained drug release for 168 h and exhibit anti-bacterial effect against Staphylococcus aureus. The results of L929 cells cultured with the hydrogel extracts indicate good biocompatibility. Finally, results of EDTA-induced detachment performances demonstrate that the hydrogels could be removed from the wound as the internal structure destroyed. All illustrated results above demonstrated the BBR carried G/SA hydrogels have potential used as wound dressing materials in future.

Isolation of a novel calcium-binding peptide from phosvitin hydrolysates and the study of its calcium chelation mechanism.

A new peptide with strong calcium binding capacity was isolated from phosvitin hydrolysates. Taking calcium chelating rate as an indicator, phosvitin hydrolysates were separated gradually by anion-exchange chromatography, gel filtration chromatography and reversed-phase high performance liquid chromatography. A peptide with a molecular weight of 1106.44402 Da was identified by liquid chromatography-electrospray/mass spectrometry (LC-ESI/MS), and its amino acid sequence was DEEENDQVK, the calcium binding capacity reached 151.10 ± 3.57 mg/g. Its chelating mechanism was investigated. Results showed that, the ß-sheet structure of peptide increased after adding calcium ion, and the main binding sites were carboxyl oxygen atom and amino nitrogen atom. In vitro simulated digestion experiments showed that, the solubility and dialysis rate of calcium in peptide-calcium chelate were higher than those in CaCO3 and D-calcium gluconate. This finding would promote the development of calcium supplements from food resources.

Structural characterization of a novel polysaccharide from Pleurotus citrinopileatus and its antitumor activity on H22 tumor-bearing mice.

In this research, a novel polysaccharide (PCP) was extracted from Pleurotus citrinopileatus and purified by Sephadex G-150 gel column, and its antitumor activity was investigated using the model H22 tumor-bearing mice. PCP was found to be composed of arabinose, galactose, glucose, xylose, mannose and glucuronic acid in a proportion of 0.66: 14.59: 10.77: 1: 0.69: 0.23 with average molecular weight of 7.30 × 105 Da. Further analysis suggested that PCP was a pyranose with α-type and ß-type glycosidic residues. The antitumor assays in vivo indicated that PCP could effectively suppress H22 solid tumor growth, protect immune organs and improve inflammation and anemia. Besides, Annexin V-FITC/PI double staining and JC-1 staining demonstrated that PCP could induce apoptosis of H22 hepatoma cells. The PI staining assay revealed that PCP induced H22 hepatoma cells apoptosis by arresting cell cycle in S phase. These results suggest that the polysaccharide from Pleurotus citrinopileatus possesses potential value in the treatment of liver cancer.

Clinical application of an automatic facial recognition system based on deep learning for diagnosis of Turner syndrome.

PURPOSE: Automated facial recognition technology based on deep learning has achieved high accuracy in diagnosing various endocrine diseases and genetic syndromes. This study attempts to establish a facial diagnostic system for Turner syndrome (TS) based on deep convolutional neural networks. METHODS: Photographs of 207 TS patients and 1074 female controls were collected from July 2016 to April 2019. Finally, 170 patients diagnosed with TS and 1053 female controls were included. Deep convolutional neural networks were used to develop the facial diagnostic system. A prospective study, which included two TS patients and 35 controls, was conducted to test the efficacy in the real clinical setting. RESULTS: The average areas under the curve (AUCs) in three different scenarios were 0.9540 ± 0.0223, 0.9662 ± 0.0108 and 0.9557 ± 0.0119, separately. The average sensitivity and specificity of the prospective study were 96.7% and 97.0%, respectively. CONCLUSIONS: The facial diagnostic system achieved high accuracy. Prospective study results demonstrated the application value of this system, which is promising in the screening of Turner syndrome.

A simple and convenient electrochemiluminescence immunoassay by using gold nanoparticles as both label and co-reactant.

A simple and convenient electrochemiluminescence immunoassay (ECLIA) has been developed by using gold nanoparticles (AuNPs) as both label and co-reactant. In this novel ECLIA, the detection antibodies labeled with AuNPs as co-reactant reacts directly with ruthenium complex to produce electrochemiluminescence (ECL), which avoids the weakness of luminophore as a label. The feasibility of the new method was investigated through the sandwich ECL immunosensor for the determination of human immunoglobulin (HIgG), and excitation of luminescence was respectively driven by linear sweep voltammetry and step potential. Under the optimal conditions, ECL intensity of the immunosensor increased with HIgG concentration in a wide range from 0.01 to 10.0 ng/mL and displayed linear response to logarithm of HIgG concentration. The results showed that the detection limit was 5 pg/mL, and the relative error was no more than 4.6% for the repeated measurements. The relative standard deviation was less than 2.9% for the determination of the standard sample, which can meet the requirement of ECLIA.

Study on the mechanism of Gegen Qinlian Decoction for treating type II diabetes mellitus by integrating network pharmacology and pharmacological evaluation.

ETHNOPHARMACOLOGICAL RELEVANCE: Gegen Qinlian Decoction (GQD) is a classic traditional Chinese medicine prescription that is widely used to clinically treat diabetes mellitus. It is composed of Pueraria lobata (Willd.) Ohwi (ge gen), Scutellaria baicalensis Georgi (huang qin), Coptidis chinensis Franch. (huang lian), and Glycyrrhiza uralensis Fisch. (gan cao). However, the active ingredients in GQD and their mechanism of action are unclear. AIM OF THE STUDY: In this study, we aimed to verify the efficacy of GQD in improving insulin resistance (IR) in diabetic mice and used network pharmacology to identify potential targets and pathways underlying its mechanism of action. MATERIALS AND METHODS: A mouse model of diabetes was created by feeding mice a high-fat diet followed by an intraperitoneal injection of streptozotocin. These type II diabetic mice were administered either a clinical dose or a high dose of GQD, after which blood glucose and serum insulin levels were measured to assess its effects on IR. Network pharmacology was used to construct a 'component-pathway-target' network to elucidate the likely targets and pathways modulated in common by GQD components. Furthermore, mRNA transcript levels and protein expression levels of oestrogen receptor alpha (ESR1) were determined. RESULTS: The in vivo experiment showed that GQD markedly decreased blood glucose and increased serum insulin levels in type II diabetic mice. Network pharmacology and bioinformatics analysis indicated that GQD regulated 82 corresponding proteins and 59 relevant biological pathways associated with diabetes. One such target was ESR1, which was significantly decreased at both the mRNA and protein levels in diabetic mice, but whose levels were significantly increased by GQD treatment. CONCLUSIONS: This project provides a scientific basis for understanding the effectiveness of multi-component, multi-target compound formulas, as well as a new strategy for investigating therapeutic drugs for type II diabetes and other diseases.

Characterization of the Metabolic Fate of Datura metel Seed Extract and Its Main Constituents in Rats.

Datura metel L. has been frequently used in Chinese traditional medicine. However, little is known on the chemical composition and in vivo metabolism of its seeds. In this study, using the strategy "chemical analysis, metabolism of single representative compounds, and metabolism of extract at clinical dosage" that we propose here, 42 constituents were characterized from D. metel seeds water extract. Furthermore, the metabolic pathways of 13 representative bioactive compounds of D. metel seeds were studied in rats after the oral administration of D. metel seeds water extract at a clinical dosage (0.15 g/kg). These included three withanolides, two withanolide glucosides, four amides, one indole, one triterpenoid, one steroid, and one sesquiterpenoid, and with regard to phase II metabolism, hydroxylation, (de)methylation, and dehydrogenation reactions were dominant. Furthermore, the metabolism of D. metel seeds water extract provided to rats at a clinical dosage was investigated by liquid chromatography-tandem mass spectrometry based on the above metabolic pathways. Sixty-one compounds were detected in plasma, 83 in urine, and 76 in fecal samples. Among them, withanolides exhibited higher plasma exposure than the other types. To our knowledge, this is the first systematic study on the chemical profiling and metabolite identification of D. metel seeds, including all compounds instead of single constituents.

Electrochemiluminescence of gold nanoparticles and gold nanoparticle-labelled antibodies as co-reactants.

Gold nanoparticles (AuNPs) and AuNP-labelled antibodies can participate in the electrochemiluminescence (ECL) reaction of tris(2,2'-bipyridyl) ruthenium(ii) (Ru(bpy)3 2+) as a co-reactant. The electrochemical and spectral characteristics of this new ECL system were confirmed by experiments, and its reaction mechanism was speculated to be different from that of typical ECL. The experimental results showed that the new ECL system exhibited higher ECL efficiency, and AuNP-labelled substances can be sensitively measured with the help of AuNPs. Based on the dual role of AuNPs as a co-reactant and marker, the AuNP-Ru(bpy)3 2+ ECL system will be a useful tool in biochemical analysis.

Reinforced chitosan membranes by microspheres for guided bone regeneration.

In order to improve the osteogenic activity and mechanical strength of the guided bone regeneration (GBR) membrane for repairing bone defect, nano-hydroxyapatite/chitosan (nHA/CS) composite microspheres were prepared through in situ biomimetic method, then composite microspheres were incorporated into CS membrane. The morphologies and mechanical properties of the composite membranes were investigated through scanning electronic microscopy (SEM) and universal mechanical testing machine. The results show that the in situ biomimetic nHA/CS microspheres were embedded in CS membrane and were integrated tightly with CS matrix. The mechanical properties of GBR membranes containing in situ nHA/CS microspheres is significantly higher than that of membranes containing pure CS microspheres and blending nHA/CS microspheres. Its elongation rate at break reaches 5.61 ±â€¯0.95%. The elastic modulus and strength of the GBR membranes can reach 766.27 ±â€¯20.68 and 43.32 ±â€¯0.95 MPa, respectively. Further, The work-of-fracture of the membranes with in situ microspheres approaches 2.71 ±â€¯0.25 J/m2, which is about 3 times of the pure CS membrane. The cell culture results display that the GBR membranes containing in situ biomimetic nHA/CS microspheres exhibit good cytocompatibility.

Effect of hydroxyapatite fillers on the mechanical properties and osteogenesis capacity of bio-based polyurethane composite scaffolds.

A newly designed hydroxyapatite-polyurethane (HA-PU) composite scaffold was prepared by polymerizing glyceride of castor oil (GCO) with isophorone diisocyanate (IPDI) and HA as fillers. The aim of this study was to determine the effect of HA fillers on the mechanical properties and osteogenesis capacity of the composite scaffolds. The physical and biological properties of the scaffold were evaluated by SEM observation, mechanical testing, cell culture and animal experiments. The results showed that HA fillers enhanced the mechanical properties of PU composite scaffolds such as compressive strength and elastic modulus. The mechanical properties of the scaffolds were seen to increase with increase in HA loading. The compressive strength of composite scaffold with 0 wt%, 20 wt%, 40 wt% of HA was 0.6 ±â€¯0.1 MPa, 2.1 ±â€¯0.1 MPa, and 4.6 ±â€¯0.3 MPa, respectively. In vitro biodegradation studies of scaffolds were carried out. The results showed that all of the scaffolds were susceptible to cholesterol esterase (CE) -catalyzed degradation. HA-PU composite scaffolds exhibited a high affinity to osteoblastic cells and were good template for cell growth and proliferation. When implanted in bone defects of rats, PU scaffolds incorporated HA were biocompatible with the tissue host and had no immune rejection. Moreover, the higher the loading of HA in the composite scaffold, the better chances of osteogenesis. It confirmed that the prepared HA-PU composite scaffolds can be promising candidate for bone repair and bone tissue engineering.

Modified n-HA/PA66 scaffolds with chitosan coating for bone tissue engineering: cell stimulation and drug release.

The dipping-drying procedure and cross-linking method were used to make drug-loaded chitosan (CS) coating on nano-hydroxyapatite/polyamide66 (nHA/PA66) composite porous scaffold, endowing the scaffold controlled drug release functionality. The prefabricated scaffold was immersed into an aqueous drug/CS solution in a vacuum condition and then crosslinked by vanillin. The structure, porosity, composition, compressive strength, swelling ratio, drug release and cytocompatibility of the pristine and coating scaffolds were investigated. After coating, the scaffold porosity and pore interconnection were slightly decreased. Cytocompatibility performance was observed through an in vitro experiment based on cell attachment and the MTT assay by MG63 cells which revealed positive cell viability and increasing proliferation over the 11-day period in vitro. The drug could effectively release from the coated scaffold in a controlled fashion and the release rate was sustained for a long period and highly dependent on coating swelling, suggesting the possibility of a controlled drug release. Our results demonstrate that the scaffold with drug-loaded crosslinked CS coating can be used as a simple technique to render the surfaces of synthetic scaffolds active, thus enabling them to be a promising high performance biomaterial in bone tissue engineering.

Interfacial and biological properties of the gradient coating on polyamide substrate for bone substitute.

Fabrication of bioactive and mechanical matched bone substitutes is crucial for clinical application in bone defects repair. In this study, nano-hydroxyapatite/polyamide (nHA/PA) composite was coated on injection-moulded PA by a chemical corrosion and phase-inversion technique. The shear strength, gradient composition and pore structure of the bioactive coating were characterized. Osteoblast-like MG63 cells were cultured on pure PA and composite-coated PA samples. The cells' adhesion, spread and proliferation were determined using MTT assay and microscopy. The results confirm that the samples with the nHA/PA composite coating have better cytocompatibility and have no negative effects on cells. To investigate the in vivo biocompatibility, both pure PA and composite-coated PA cylinders were implanted in the trochlea of rabbit femurs and studied histologically, and the bonding ability with bone were determined using push-out tests. The results show that composite-coated implants exhibit better biocompatibility and the shear strength of the composite-coated implants with host bone at 12 weeks can reach 3.49±0.42 MPa, which is significantly higher than that of pure PA implants. These results indicate that composite-coated PA implants have excellent biocompatibility and bonding abilities with host bone and they have the potential to be applied in repair of bone defects.