Circ_0000285 regulates proliferation, migration, invasion and apoptosis of osteosarcoma by miR-409-3p/IGFBP3 axis.

BACKGROUND: Circular RNAs (circRNAs) are important regulators in the pathogenesis of diseases and affects the occurrence and development of diseases. However, the role of circRNAs in osteosarcoma (OS) has not been fully elucidated. METHODS: The expression of circ_0000285, miR-409-3p and insulin-like growth factor binding protein 3 (IGFBP3) was detected using quantitative real-time PCR (qRT-PCR). The protein level of IGFBP3 was measured using western blot. CCK-8 and colony formation assays were used to determine cell proliferation. Flow cytometry was applied to measure cell cycle and cell apoptosis. Transwell assay was used to assess cell invasion and migration. Dual-luciferase reporter assay and RNA Binding Protein Immunoprecipitation (RIP) assay were performed to determine the relationship among circ_0000285, miR-409-3p and IGFBP3. The animal experiments were performed to determine the function of circ_0000285 in vivo. RESULTS: In this study, we found that the expression of circ_0000285 was significantly increased in OS tissues and cells and was enriched in the cytoplasm. Knockdown of circ_0000285 inhibited OS growth in vitro and in vivo. Moreover, miR-409-3p was a target miRNA of circ_0000285 and miR-409-3p targets to IGFBP3 in OS. Besides, circ_0000285 could promote proliferation, migration, invasion and inhibit apoptosis of osteosarcoma by miR-409-3p/IGFBP3 axis. CONCLUSION: In this study, circ_0000285 regulated proliferation, migration, invasion and apoptosis of OS cells by miR-409-3p/IGFBP3 axis, implying that circ_0000285 was a potential target for OS therapy.

The mechanism research of non-Smad dependent TAK1 signaling pathway in the treatment of bone defects by recombination BMP-2-loaded hollow hydroxyapatite microspheres/chitosan composite.

AIMS: The present study aimed to evaluate whether the non-Smad dependent TAK1 signaling pathway (BMP-2-TAK1-p38-Osx signaling pathway) played an important role in bone repair mediated by hollow hydroxyapatite (HA) microspheres/chitosan (CS) composite. METHODS: Firstly, the biological activity of rhBMP-2 released from the complex was investigated. Then, differentiation test of osteoblasts including ALP activity and calcium deposition, X-ray scoring and three-point bending test were performed. Finally, the mRNAs expression of TAK1, p38, Osx and osteogenic markers was tested by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: RhBMP-2 could be loaded and released from the complex in bioactive form. Additionally, the complex provided a prolonged period of time compared with HA/CS scaffolds. Serum ALP activity was significantly decreased in the TAK1 inhibitor group and p38 inhibitor group. In the X-ray radiography, bone callus was observed in rhBMP-2-loaded hollow HA microspheres/CS composite group. In the three-point bending test, load values in p38 inhibitor group decreased. In the animal model, the mRNA expression of BSP on day 90 was significantly decreased in the p38 inhibitor group and TAK1 inhibitor group. In MC3T3-E1 cells, the mRNA expression of OSX was remarkably up-regulated in both rhBMP-2 group or rhBMP-2-loaded hollow HA microspheres/CS composite group; while the mRNA expression of OSX was significantly down-regulated in TAK1 inhibitor group and p38 inhibitor group. CONCLUSION: The BMP-2-TAK1-p38-OSX signaling pathway may play an important role in bone formation and repair mediated by rhBMP-2-loaded hollow HA microspheres/CS composite.

A novel surgical method for treating fractures of the middle third of the clavicle.

BACKGROUND: The clavicle is recognized as the bone most vulnerable to fractures. Moreover, approximately 80% of fractures occur in the middle third of the clavicle. Conservative treatment is associated with a higher rate of nonunion, while surgical treatment of fracture via internal fixation may have a variety of postoperative complications. Therefore, to improve patient satisfaction and reduce the complications related to internal fixation techniques, we modified the surgical approach to external fixation. OBJECTIVE: The purpose of this study was to assess the modified intervention's prospects for clinical application. METHODS: A total of 36 patients with middle clavicle fractures were treated with screw-rod external fixation between April 2015 and October 2019. We observed the operative time, intraoperative blood loss, length of hospital stay, and fracture healing time. The patients were followed up regularly, and the clinical efficacy of the modified intervention was evaluated. Finally, the patients' shoulder function was assessed based on the disabilities of the arm, shoulder, and hand (DASH) score. RESULTS: For the screw-rod external fixation, the mean operative time was found to be 48.6 ± 6.8 min, the intraoperative blood loss was 30.6 ± 17.2 mL, the length of hospital stay was 4.5 ± 1.5 days, and the fracture healing time was 2.8 ± 0.4 months. Eventually, all the patients healed well, with the combined "excellent" and "good" rate of shoulder function being assessed to be as high as 94.44%. Furthermore, the DASH scores were all less than 10, with the average score being 4.65 ± 3.34. CONCLUSIONS: The screw-rod external fixation technique offers the advantages of convenience, reliability, and good aesthetics, suggesting that it could be used as an alternative treatment method for fractures of the middle third of the clavicle.

Osteoblast-derived exosomes promote osteogenic differentiation of osteosarcoma cells via URG4/Wnt signaling pathway.

Osteosarcoma is a primary malignant bone tumor. Although surgery and chemotherapy are the main treatment methods, the overall curative effect remains unsatisfactory. Therefore, there is an urgent need to develop new therapeutic options for osteosarcoma. In this study, the effect and molecular mechanism of osteoblast-derived exosomes on the treatment of osteosarcoma were evaluated. Human primary osteoblasts were cultured to observe the effects of osteoblast-derived exosomes on the osteogenic differentiation of osteosarcoma cells both in vitro and in vivo. Alizarin red staining and alkaline phosphatase detection were used to evaluate the degree of osteogenic differentiation, and immunofluorescence and Western blotting were used to detect protein expression. The results showed that osteoblast-derived exosomes effectively inhibited the proliferation of osteosarcoma cells and promoted their mineralization in vitro. The exosomes also significantly inhibited tumor growth and promoted tumor tissue mineralization in vivo. Osteoblast-derived exosomes upregulated the expression of bone sialoprotein, osteonectin, osteopontin, runt-related transcription factor 2, and Wnt inhibitory factor 1, downregulated the expression of cyclin D1, and suppressed the nuclear accumulation of ß-catenin and promoted its phosphorylation in vitro and in vivo. However, these effects were significantly reversed by upregulated gene (URG) 4 overexpression. These findings suggest that osteoblast-derived exosomes could activate the osteogenic differentiation process in osteosarcoma cells and promote their differentiation by targeting the URG4/Wnt signaling pathway.

DLP fabrication of HA scaffold with customized porous structures to regulate immune microenvironment and macrophage polarization for enhancing bone regeneration.

The immune microenvironment plays a pivotal role in osteoanagenesis. Biomaterials can modulate osteogenic efficacy by inducing specific local immune reactions. As 3D-printing technology advances, digital light projection printing has emerged as a promising method for creating large scale, high-precision biomaterial scaffolds. By adjusting the solid content and the sintering conditions during printing, the pore size of biomaterials can be meticulously controlled. Yet, the systematic influence of pore size on the immune microenvironment remains uncharted. We fabricated 3D-printed hydroxyapatite bioceramic scaffolds with three distinct pore sizes: 400 µm, 600 µm, and 800 µm. Our study revealed that scaffolds with a pore size of 600 µm promote macrophage M2 polarization, which is achieved by upregulating interferon-beta and HIF-1α production. When these materials were implanted subcutaneously in rats and within rabbit skulls, we observed that the 600 µm scaffolds notably improved the long-term inflammatory response, fostered vascular proliferation, and augmented new bone growth. This research paves the way for innovative therapeutic strategies for treating large segmental bone defects in clinical settings.

Chestnut-Inspired Hollow Hydroxyapatite 3D Printing Scaffolds Accelerate Bone Regeneration by Recruiting Calcium Ions and Regulating Inflammation.

This study aims to overcome the drawbacks associated with hydroxyapatite (HAP) dense structures after sintering, which often result in undesirable features such as large grain size, reduced porosity, high crystallinity, and low specific surface area. These characteristics hinder osseointegration and limit the clinical applicability of the material. To address these issues, a new method involving the preparation of hollow hydroxyapatite (hHAP) microspheres has been proposed. These microspheres exhibit distinctive traits including weak crystallization, high specific surface area, and increased porosity. The weak crystallization aligns more closely with early mineralization products found in the human body and animals. Moreover, the microspheres' high specific surface area and porosity offer advantages for protein loading and facilitating osteoblast attachment. This innovative approach not only mitigates the limitations of conventional HAP structures but also holds the potential for improving the effectiveness of hydroxyapatite in biomedical applications, particularly in enhancing osseointegration. Three-dimensional printed hHAP/chitosan (CS) scaffolds with different hHAP concentration gradients were manufactured, and the physical and biological properties of each group were systematically evaluated. In vitro and in vivo experiments show that the hHAP/CS scaffold has excellent performance in bone remodeling. Furthermore, in-scaffold components, hHAP and CS were cocultured with bone marrow mesenchymal stem cells to explore the regulatory role of hHAP and CS in the process of bone healing and to reveal the cell-level specific regulatory network activated by hHAP. Enrichment analysis showed that hHAP can promote bone regeneration and reconstruction by recruiting calcium ions and regulating inflammatory reactions.

FAM60A promotes osteosarcoma development and progression.

BACKGROUND: Osteosarcoma (OS) is a highly malignant primary bone tumor. Family of homology 60A (FAM60A) reportedly contributes to the malignant growth of some tumors. METHODS: Herein we investigated the mRNA expression level of FAM60A by combining OS and non-cancer samples from public databases. Immunohistochemistry was performed to determine protein expression levels of FAM60A in patients with OS. Further, RT-qPCR and western blotting were conducted to evaluate FAM60A expression in various OS cell lines. CCK-8 assay, colony formation assay, and flow cytometry were applied to determine the function of FAM60A. Finally, functional enrichment analysis was performed based on FAM60A co-expressed genes. RESULTS: FAM60A mRNA expression level was found to be significantly upregulated (standardized mean difference = 1.27, 95% CI [0.67-1.88]). Survival analyses suggested that higher expression of FAM60A was indicative of poor prognoses. Similarly, FAM60A protein expression level was also observed to be upregulated. Knocking down FAM60A expression inhibited OS cell proliferation, increased apoptosis, and blocked cells from entering the S phase. Besides, cell cycle was the most prominently enriched pathway, and BUB1, DTL, and EXO1 were identified as hub genes. CONCLUSIONS: FAM60A expression was found to be markedly upregulated in OS; furthermore, FAM60A was observed to promote OS cell proliferation, inhibit apoptosis, and participate in cell cycle regulation. Besides, FAM60A may interact with hub genes to participate in the progress of OS.

Hollow Hydroxyapatite Microspheres Loaded with rhCXCL13 to Recruit BMSC for Osteogenesis and Synergetic Angiogenesis to Promote Bone Regeneration in Bone Defects.

Introduction: Bone tissue engineering is a promising method to treat bone defects. However, the current methods of preparing composite materials that mimic the complex structure and biological activity of natural bone are challenging for recruitment of bone marrow mesenchymal stem cells (BMSCs), which affects the application of these materials in situ bone regeneration. Hollow hydroxyapatite microspheres (HHMs) possess a natural porous bone structure, good adsorption, and slow release of chemokines, but have low ability to recruit BMSCs and induce osteogenesis. In this study, The HHM/chitosan (CS) and recombinant human C-X-C motif chemokine ligand 13 (rhCXCL13)-HHM/CS biomimetic scaffolds that optimize bone regeneration and investigated their mechanism of BMSC recruitment and osteogenesis through cell and animal experiments and transcriptomic sequencing. Methods: Evaluate the physical characteristics of the HHM/CS and rhCXCL13-HHM/CS biomimetic scaffolds through Scanning Electron Microscopy (SEM), X-Ray Diffraction (XRD), and the cumulative release curve of rhCXCL13. Transwell migration experiments and co-culture with BMSCs were conducted to study the recruitment ability and osteogenic differentiation of the scaffolds. Transcriptomic sequencing was performed to analyze the osteogenic differentiation mechanism. The osteogenesis and bone healing performance were evaluated using a rabbit radial defect model. Results: SEM demonstrated that the rhCXCL13-HHM/CS scaffold comprised hydroxyapatite microspheres in a porous three-dimensional network. The rhCXCL13 showed excellent sustained release capability. The rhCXCL13-HHM/CS scaffold could recruit BMSCs and induce bone regeneration. Transcriptome sequencing and experimental results showed that the osteogenesis mechanism of rhCXCL13-HHM/CS was through the PI3K-AKT pathway. In vivo, the rhCXCL13-HHM/CS scaffold significantly promoted osteogenesis and angiogenesis at 12 weeks after surgery. Conclusion: The rhCXCL13-HHM/CS scaffold demonstrates excellent potential for BMSC recruitment, osteogenesis, vascularized tissue-engineered bone reconstruction, and drug delivery, providing a theoretical basis for material osteogenesis mechanism study and promising clinical applications for treating large bone defects.

The association between basal metabolic rate and osteoarthritis: a Mendelian randomization study.

BACKGROUND: The role of the basal metabolic rate (BMR) in osteoarthritis (OA) remains unclear, as previous retrospective studies have produced inconsistent results. Therefore, we performed a Mendelian randomization (MR) study to systematically investigate the causal relationship between the BMR and OA. METHODS: Single-nucleotide polymorphism (SNP) data related to BMR and OA were collected in a genome-wide association study. Using OA as the outcome variable and BMR as the exposure factor, SNPs with strong correlation with the BMR as the tool variable were screened. The correlation between the BMR and OA risk was evaluated using the inverse-variance weighted method, and heterogeneity and pleiotropy were evaluated using a sensitivity analysis. RESULTS: There was a potential causal relationship between the BMR and OA risk (odds ratio [OR], 1.014; 95% confidence interval [CI], 1.008-1.020; P = 2.29e - 6). A causal relationship was also revealed between the BMR and knee OA (OR, 1.876; 95% CI, 1.677-2.098; P = 2.98e - 28) and hip OA (OR, 1.475; 95% CI, 1.290-1.686; P = 1.26e - 8). Sensitivity analysis confirmed the robustness of these results. CONCLUSION: Here, we identified a latent causal relationship between the BMR and the risk of OA. These results suggest that the risk of OA in the hip or knee joint may be reduced by controlling the BMR.

Study on the influence of scaffold morphology and structure on osteogenic performance.

The number of patients with bone defects caused by various bone diseases is increasing yearly in the aging population, and people are paying increasing attention to bone tissue engineering research. Currently, the application of bone tissue engineering mainly focuses on promoting fracture healing by carrying cytokines. However, cytokines implanted into the body easily cause an immune response, and the cost is high; therefore, the clinical treatment effect is not outstanding. In recent years, some scholars have proposed the concept of tissue-induced biomaterials that can induce bone regeneration through a scaffold structure without adding cytokines. By optimizing the scaffold structure, the performance of tissue-engineered bone scaffolds is improved and the osteogenesis effect is promoted, which provides ideas for the design and improvement of tissue-engineered bones in the future. In this study, the current understanding of the bone tissue structure is summarized through the discussion of current bone tissue engineering, and the current research on micro-nano bionic structure scaffolds and their osteogenesis mechanism is analyzed and discussed.

L-Histidinium Chiral Ionic Liquid Functionalized ß-Cyclodextrin as Chiral Selector in Capillary Electrophoresis.

Nowadays, ionic liquids (ILs) functionalized cyclodextrins (CDs) have drawn increasing attention in chiral separation. Herein, a novel ß-CD derivative functionalized by L-histidinium IL, mono-6-deoxy-6-L-histidinium-ß-cyclodextrin chloride (L-HMCDCl), was synthesized for the first time and utilized for enantioseparation of nefopam and chlorphenamine in capillary electrophoresis. The L-HMCDCl exhibited superior enantioselectivity compared with native ß-CD. The effect of some key parameters such as chiral selector concentration, buffer pH and applied voltage on the enantioseparation was investigated in detail. In the interest of the chiral discrimination mechanism and the enhanced enantioselectivity of L-HMCDCl, molecular modeling with AutoDock was employed to study the interaction, which was in good agreement with experimental results.

Clinical application of multiple 3D-printed guide plates for precise reduction and fixation of comminuted patellar fractures.

Because of the lack of anatomical landmarks during reduction of multiple articular surfaces and fragments in comminuted patellar fractures, loss of bone fragments or aggravation of soft tissue and ligament injuries readily occurs. In the present case, we used multiple three-dimensional (3D)-printed guide plates to reduce and fix a comminuted patellar fracture. A 22-year-old man was hospitalized for 2 days because of left knee joint pain and limited movement caused by a traffic accident. Preoperative imaging revealed a comminuted fracture of the left patella (type 34-C3 according to the AO/OTA classification). Throughout a 2-year follow-up, the patient remained in generally good condition with no significant limitation of his left knee joint activity. Application of multiple 3D-printed guide plates is a safe and effective auxiliary technique for the treatment of comminuted patellar fractures. This novel technique can shorten the operation time, reduce the number of fluoroscopic procedures, and ensure fracture healing and recovery of knee joint function through reliable reduction of the articular surface.

Study of PLGA microspheres loaded with pOsx/PEI nanoparticles for repairing bone defects in vivo and in vitro.

BACKGROUND: Autogenous or allogenic bone transplantation is the main treatment for bone defects and nonunions. However, the shortcomings of autogenous or allogenic bone transplantation limit its wide application in clinical use. OBJECTIVES: This study investigated the effect of poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with pOsterix (pOsx)/polyethylenimine (PEI) nanoparticles in repairing bone defects and explored its mechanism. MATERIAL AND METHODS: Poly(lactic-co-glycolic acid) microspheres loaded with pOsx/PEI nanoparticles were constructed. The Osx transfection effect was detected by fluorescence quantitative PCR and western blotting methods. 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-diphenytetrazoliumromide (MTT) and flow cytometry methods were used to detect cell proliferation. The collagen I (Col-1), osteopontin (OPN) and osteocalcin (OC) expression levels were detected using real-time polymerase chain reaction (RT-PCR) and western blotting methods. Bone defect model was constructed. Bone repair was detected using X-ray, hematoxylin and eosin (H&E) staining, and Mason staining methods. RESULTS: PLGA@pOsx/PEI has transfection effect both in vitro and in vivo, does not affect cell proliferation and is safe for cells. PLGA@pOsx/PEI could promote the expression of Col-1, OPN and OC in vitro and in vivo. PLGA@pOsx/PEI could promote osteogenesis in vivo. CONCLUSIONS: PLGA@pOsx/PEI with high Osx expression could promote the expression of OC, OPN, and COL-I. PLGA@pOsx/PEI can be used as a material for repairing bone defects and can promote bone formation. These results provide a theoretical and practical basis for its further clinical application.

Synthesis and application of amino triazolium-modified lactobionic acid as chiral selector in capillary electrophoresis.

In this paper, a chiral selector, N-(4-H-1, 2, 4-triazolium)-lactobionamides (LA-ATM), was synthesized and applied for enantioseparation in capillary electrophoresis (CE) for the first time. Compared with lactobionic acid (LA) separation system, enhanced enantioseparation of five tested drugs was achieved in this modification system. In order to achieve good chiral separation, several parameters such as chiral selector concentration, buffer pH, applied voltage as well as the type and proportion of organic modifier were systematically investigated. Molecular modeling was applied to demonstrate the chiral recognition mechanism of the LA-ATM, which well supported the experimental results. Furthermore, a mathematical equation built up based on the molecular mechanics calculations was used in predicting resolution of tested drugs using LA or LA-ATM mediated CE, the predicted result was well correlated with the experimental result.

Study of bone repair mediated by recombination BMP-2/ recombination CXC chemokine Ligand-13-loaded hollow hydroxyapatite microspheres/chitosan composite.

AIMS: The present study aimed to investigate the mechanism of bone repair mediated by recombination BMP-2 (rhBMP-2)/recombination CXC chemokine ligand-13 (rhCXCL13)-loaded hollow hydroxyapatite (HA) microspheres/chitosan (CS) composite. MATERIALS AND METHODS: Firstly, the biological activity of rhBMP-2 and rhCXCL13 released from the complex was investigated. Secondly, the effect of rhBMP-2 sustained release solution on ALP activity and rhCXCL13 sustained release solution on cell migration of rat bone marrow mesenchyme stem cells was tested. Thirdly, osteoblasts differentiation test, X-ray scoring and three-point bending test were performed. Finally, the mRNAs expression of osteogenic marker genes and the protein expression of Runx2 was tested by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting (WB), respectively. KEY FINDINGS: RhBMP-2 could significantly promote the proliferation and differentiation, and RhCXCL13 could promote the migration of rat bone marrow MSCs. Detection of ALP activity and calcium salt deposition showed that rhBMP-2 and rhCXCL13 could significantly improve the biological activity and promote cell differentiation ability. X-ray scoring of radius and flexural strength test showed that rhBMP-2 and rhCXCL13 could promote bone healing and improve the bending resistance of bone tissue. The in vitro molecular experiments including RT-PCR and WB further demonstrated the roles of rhBMP-2 and rhCXCL13 in bone formation and bone repair. SIGNIFICANCE: Our results indicated that the hollow HA microspheres/CS composite could be effective as a delivery vehicle for rhBMP-2 and rhCXCL13 in bone regeneration and bone repair. In this process, rhBMP-2 may promote bone regeneration by regulating bone marrow MSCs cells recruited by rhCXCL13.

Bone repair scaffold coated with bone morphogenetic protein-2 for bone regeneration in murine calvarial defect model: Systematic review and quality evaluation.

To systematically assess the effects of hydroxyapatite bone repair scaffold coated with bone morphogenetic protein-2 on murine calvarial defect models and to determine the quality of studies according to the Animal Research Reporting in In Vivo Experiments guidelines. Internet search was performed in duplicate using PubMed, MEDLINE, Ovid and Embase databases (without restrictions on publication date). The Animal Research Reporting in In Vivo Experiments guidelines were used to evaluate the quality of selected studies. Following screening, 12 studies were eligible for the review. Studies with average quality coefficients predominated (66.67%), followed by poor (25%) and excellent (8.33%) quality coefficients. Minimum quality scores were assigned to the Animal Research Reporting in In Vivo Experiments guideline items: housing and husbandry (9), allocation (11), outcomes (12), interpretation (18) and generalizability (19). Sprague-Dawley rats were the most frequently used (50%) species, and most studies had a sample size of more than 30 (58.33%). A defect dimension of 5 mm was the most common (33.33%). The biological hydroxyapatite composite scaffold was common (50%), and the bioactive factors were bone morphogenetic protein-2 (50%) and recombinant human bone morphogenetic protein-2 (50%). Histomorphometric results showed that bone morphogenetic protein-2 enhanced the capacity to regenerate bone considerably. In addition, scaffolds with bone morphogenetic protein-2 resulted in a significant increase in the blood vessel in the new bone. The findings suggested that data on animal experiments of hydroxyapatite scaffold coated with bone morphogenetic protein-2 in murine calvarial defect models lack homogeneity. Animal experiment should follow the Animal Research Reporting in In Vivo Experiments guidelines to promote the high quality, integrity and reproducibility. This systematic review suggested that bone morphogenetic protein-2 enhanced the capacity to regenerate bone and the angiogenesis in the new bone.

Establishment and molecular modeling study of maltodextrin-based synergistic enantioseparation systems with two new hydroxy acid chiral ionic liquids as additives in capillary electrophoresis.

Discovering more superior performance of ionic liquids for the separation science has triggered increasing interest. In this work, two new Hydroxy acid-based chiral ionic liquids (CILs) (tertramethylammonium-d-pantothenate (TMA-d-PAN), tertramethylammonium-d-quinate (TMA-d-QUI)) were designed and first used as additives to establish the maltodextrin-based synergistic systems for enantioseparation in capillary electrophoresis (CE). Compared to traditional single maltodextrin chiral separation system, significantly improved separations of all tested drugs in the CIL/Maltodextrin synergistic systems were obtained. Some parameters (CIL concentration, maltodextrin concentration, buffer pH, and applied voltage) in the TMA-d-PAN/Maltodextrin synergistic system have been examined and optimized for analytes. The molecular docking software AutoDock was applied to simulate the recognition process and surmise feasible resolution mechanism in the Maltodextrin/CILs synergistic systems, which has certain guiding value.

Synthesis and application of ionic liquid functionalized ß-cyclodextrin, mono-6-deoxy-6-(4-amino-1,2,4-triazolium)-ß-cyclodextrin chloride, as chiral selector in capillary electrophoresis.

Recently,ionic liquids (ILs) functionalized cyclodextrins (CDs) have attracted more and more attention in the fields of enantioseparation. In this study, a novel IL amino triazolium functionalized ß-CD derivative, mono-6-deoxy-6-(4-amino-1,2,4-triazolium)-ß-cyclodextrin chloride (4-ATMCDCl), was synthesized for the first time and managed to separate dansyl amino acids and naproxen by capillary electrophoresis (CE). Compared with native ß-CD, the new selector exhibited good water solubility and enhanced enantioselectivity. Several crucial parameters such as selector concentration, buffer pH, and applied voltage were systematically investigated. The molecular docking program Autodock was applied to further demonstrate the mechanism of chiral recognition and the enhanced enantioselectivity of 4-ATMCDCl, which showed good agreement with our experimental results.

Scaffolds for the repair of bone defects in clinical studies: a systematic review.

BACKGROUND: This systematic review aims to summarize the clinical studies on the use of scaffolds in the repair of bony defects. METHODS: The relevant articles were searched through PubMed database. The following keywords and search terms were used: "scaffolds," "patient," "clinic," "bone repair," "bone regeneration," "repairing bone defect," "repair of bone," "osteanagenesis," "osteanaphysis," and "osteoanagenesis." The articles were screened according to inclusion and exclusion criteria, performed by two reviewers. RESULTS: A total of 373 articles were obtained using PubMed database. After screening, 20 articles were identified as relevant for the purpose of this systematic review. We collected the data of biological scaffolds and synthetic scaffolds. There are eight clinical studies of biological scaffolds included collagen, gelatin, and cellular scaffolds for bone healing. In addition, 12 clinical studies of synthetic scaffolds on HAp, TCP, bonelike, and their complex scaffolds for repairing bone defects were involved in this systematic review. CONCLUSIONS: There are a lot of clinical evidences showed that application of scaffolds had a good ability to facilitate bone repair and osteogenesis. However, the ideal and reliable guidelines are insufficiently applied and the number and quality of studies in this field remain to be improved.

BMP2-loaded hollow hydroxyapatite microspheres exhibit enhanced osteoinduction and osteogenicity in large bone defects.

The regeneration of large bone defects is an osteoinductive, osteoconductive, and osteogenic process that often requires a bone graft for support. Limitations associated with naturally autogenic or allogenic bone grafts have demonstrated the need for synthetic substitutes. The present study investigates the feasibility of using novel hollow hydroxyapatite microspheres as an osteoconductive matrix and a carrier for controlled local delivery of bone morphogenetic protein 2 (BMP2), a potent osteogenic inducer of bone regeneration. Hollow hydroxyapatite microspheres (100±25 µm) with a core (60±18 µm) and a mesoporous shell (180±42 m(2)/g surface area) were prepared by a glass conversion technique and loaded with recombinant human BMP2 (1 µg/mg). There was a gentle burst release of BMP2 from microspheres into the surrounding phosphate-buffered saline in vitro within the initial 48 hours, and continued at a low rate for over 40 days. In comparison with hollow hydroxyapatite microspheres without BMP2 or soluble BMP2 without a carrier, BMP2-loaded hollow hydroxyapatite microspheres had a significantly enhanced capacity to reconstitute radial bone defects in rabbit, as shown by increased serum alkaline phosphatase; quick and complete new bone formation within 12 weeks; and great biomechanical flexural strength. These results indicate that BMP2-loaded hollow hydroxyapatite microspheres could be a potential new option for bone graft substitutes in bone regeneration.