Vancomycin Hydrochloride Loaded Hydroxyapatite Mesoporous Microspheres with Micro/Nano Surface Structure to Increase Osteogenic Differentiation and Antibacterial Ability

2021 ◽  
Vol 17 (8) ◽  
pp. 1668-1678
Author(s):  
Beizhi Zhang ◽  
Yunhui Chai ◽  
Kai Huang ◽  
Xuejie Wei ◽  
Zhiqing Mei ◽  
...  

As infection induced by the implant will lead to operation failure, the implant material must be endowed with certain antibacterial properties. Hydroxyapatite (HA) mesoporous microspheres have been widely used in bone repair due to their advantages, including simple synthesis, good osteogenic properties and drug loading capacity. In this study, vancomycin hydrochloride-loaded mesoporous hydroxyapatite microspheres with micro/nanosurface structures were synthesized to increase osteogenic differentiation and antibacterial ability. Phytic acid (IP6) was used as a template to prepare mesoporous hydroxyapatite microspheres composed of fibres, flakes and smooth surfaces by the hydrothermal homogeneous precipitation method, and the corresponding specific surface areas were 65.20 m2/g, 75.13 m2/g and 71.27 m2/g, respectively. Vancomycin hydrochloride (Van) was used as the drug model to study the drug loading and release characteristics of the microspheres, as well as the in vitro antibacterial properties after treatment. In addition, during cocultivation with MC3T3-E1 preosteoblasts, HA microspheres assembled via flakes exhibited better cell compatibility, which promoted cell proliferation, alkaline phosphatase (ALP) activity, and the formation of calcium nodules and increased the expression of osteogenic differentiation-related proteins such as Runx-2, osteopontin (OPN) and collagen I (COL I). These results indicated that the HA microspheres prepared in this experiment have broad application prospects in drug delivery systems and bone repair.

2021 ◽  
Vol 11 (12) ◽  
pp. 2313-2320
Author(s):  
Jian Zhao ◽  
Wei Li ◽  
Xin Dong ◽  
Jiying Chen

Based on bioactive glasses (BG) of 58S, sol–gel method is used to prepare strontium oxide substituted bioactive glasses (SrO-BG) with different strontium content. SrO-BG and nano hydroxyapatite (HAp) composite materials were synthesized using precipitation method. The phase composition and morphologies of the prepared materials were examined by x-ray diffraction (XRD) and scanning electron microscopy (SEM) techniques. The dissolution and bio-mineralization of SrO-BG and SrO-BG/HAp composites in SBF are investigated by immersion method. The effects of secretion components of macrophages regulated by strontium doped SrO-BG/HAp composites on the osteogenic differentiation (OD) of bone marrow mesenchymal stem cells (BMSCs) are analyzed. The results demonstrate that the SrO-BG can inhibit the dissolution of BG. Different proportions of SrO-BG/HAp composites show good ability to induce HAp in SBF. The bio-mineralization ability of SrO-BG/HAp composites increases with the increase of SrO-BG content. The results of dissolution behavior and bio-mineralization of SrO-BG/HAp composite show that the dissolution rate of each ion can be controlled by adjusting the content of SrO-BG in the composite, and then the degradation rate can effectively be controlled. The results of in vitro experiments show that SrO-BG/HAp composites with 2%, 5% and 8% strontium content are more effective in promoting M2 polarization of macrophages than SrO-BG/HAp composites with 0% strontium content. Among them, 5% strontium doped SrO-BG/HAp has the strongest effect on M2 polarization of macrophages, and the secretion of macrophages regulated by 5% strontium doped SrO-BG/HAp composite is more conducive to bone repair.


2017 ◽  
Vol 6 (6) ◽  
pp. 517-526 ◽  
Author(s):  
Permender Rathee ◽  
Anjoo Kamboj ◽  
Shabir Sidhu

AbstractBackground:Piperine helps in the improvement of bioavailability through pharmacokinetic interaction by modulating metabolism when administered with other drugs. Nisoldipine is a substrate for cytochrome P4503A4 enzymes. The study was undertaken to assess the influence of piperine on the pharmacokinetics and pharmacodynamics of nisoldipine nanoparticles in rats.Methods:Optimization studies of nanoparticles were performed using Taguchi L9 orthogonal array, and the nanoparticles were formulated by the precipitation method. The influence of piperine and nanoparticles was evaluated by means of in vivo kinetic and dynamic studies by oral administration in rats.Results:The entrapment efficiency, drug loading, ζ potential, and average particle size of optimized nisoldipine-piperine nanoparticles was 89.77±1.06%, 13.6±0.56%, −26.5 mV, and 132±7.21 nm, respectively. The in vitro release in 0.1 n HCl and 6.8 pH phosphate buffer was 96.9±0.48% and 98.3±0.26%, respectively. Pharmacokinetic studies showed a 4.9-fold increase in oral bioavailability and a >28.376±1.32% reduction in systemic blood pressure by using nanoparticles as compared to control (nisoldipine suspension) in Wistar rats.Conclusion:The results revealed that piperine being an inhibitor of cytochrome P4503A4 enzymes enhanced the bioavailability of nisoldipine by 4.9-fold in nanoparticles.


Author(s):  
Masaaki TAKECHI ◽  
Megumi TAKAMOTO ◽  
Yoshiaki NINOMIYA ◽  
Shigehiro ONO ◽  
Kuniko MIZUTA ◽  
...  

Polymers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 853 ◽  
Author(s):  
Dewi Sartika ◽  
Chih-Hsin Wang ◽  
Ding-Han Wang ◽  
Juin-Hong Cherng ◽  
Shu-Jen Chang ◽  
...  

Recently, stem cell-based bone tissue engineering (BTE) has been recognized as a preferable and clinically significant strategy for bone repair. In this study, a pure 3D silk fibroin (SF) scaffold was fabricated as a BTE material using a lyophilization method. We aimed to investigate the efficacy of the SF scaffold with and without seeded human adipose-derived mesenchymal stem cells (hASCs) in facilitating bone regeneration. The effectiveness of the SF-hASCs scaffold was evaluated based on physical characterization, biocompatibility, osteogenic differentiation in vitro, and bone regeneration in critical rat calvarial defects in vivo. The SF scaffold demonstrated superior biocompatibility and significantly promoted osteogenic differentiation of hASCs in vitro. At six and twelve weeks postimplantation, micro-CT showed no statistical difference in new bone formation amongst all groups. However, histological staining results revealed that the SF-hASCs scaffold exhibited a better bone extracellular matrix deposition in the defect regions compared to other groups. Immunohistochemical staining confirmed this result; expression of osteoblast-related genes (BMP-2, COL1a1, and OCN) with the SF-hASCs scaffold treatment was remarkably positive, indicating their ability to achieve effective bone remodeling. Thus, these findings demonstrate that SF can serve as a potential carrier for stem cells, to be used as an osteoconductive bioscaffold for BTE applications.


2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Adnan Haider ◽  
Kailash Chandra Gupta ◽  
Inn-Kyu Kang

Tissue engineering is faced with an uphill challenge to design a platform with appropriate topography and suitable surface chemistry, which could encourage desired cellular activities and guide bone tissue regeneration. To develop such scaffolds, composite nanofiber scaffolds of nHA and sHA with PLGA were fabricated using electrospinning technique. nHA was synthesized using precipitation method, whereas sHA was purchased. The nHA and sHA were suspended in PLGA solution separately and electrospun at optimized electrospinning parameters. The composite nanofiber scaffolds were characterized by FE-SEM, EDX analysis, TEM, XRD analysis, FTIR, and X-ray photoelectron. The potential of the HA/PLGA composite nanofiber as bone scaffolds in terms of their bioactivity and biocompatibility was assessed by culturing the osteoblastic cells onto the composite nanofiber scaffolds. The results fromin vitrostudies revealed that the nHA/PLGA composite nanofiber scaffolds showed higher cellular adhesion, proliferation, and enhanced osteogenesis performance, along with increased Ca+2ions release compared to the sHA/PLGA composite nanofiber scaffolds and pristine PLGA nanofiber scaffold. The results show that the structural dependent property of HA might affect its potential as bone scaffold and implantable materials in regenerative medicine and clinical tissue engineering.


2018 ◽  
Vol 47 (2) ◽  
pp. 694-706 ◽  
Author(s):  
Zengfa Huang ◽  
Cheng Cheng ◽  
Beibei Cao ◽  
Jing Wang ◽  
Hui Wei ◽  
...  

Background/Aims: Glucocorticoid (GC)-related osteonecrosis of the femoral head (ONFH) is a common complication following administration of steroids to treat many diseases. Our previous study demonstrated that icariin (ICA) might have a beneficial effect on the bone marrow mesenchymal stem cells (BMSCs) of patients with steroid-associated osteonecrosis. In this study, we investigated the underlying mechanisms of ICA associated with the potential enhancement of osteogenesis and anti-adipogenesis in GC-related ONFH. Methods: In vitro cell proliferation was evaluated by CCK-8 assay. Alizarin red S and alkaline phosphatase (ALP) activity were used to measure osteogenic differentiation, while adipogenic differentiation was revealed by oil red O staining and TG content assay. The expression level of osteogenesis-associated genes and PPARγ was evaluated by RT-qPCR, western blotting and immunofluorescence. A total of 30 female SD rats were randomly separated into three groups: a control group, a methylprednisolone (MPS) group and a MPS + ICA group. Serum ALP and TG (triglyceride), micro-CT scanning, histological and immunohistochemical analyses were performed in the animal model. Results: In the in vitro study, ICA promoted proliferation, improved osteogenic differentiation and suppressed adipogenic differentiation of BMSCs treated with MPS. The group treated with MPS and 10-6 M ICA expressed higher levels of Runx2, ALP, bone morphogenetic protein (BMP) 2, and OC and lower expression of PPARγ than the MPS group. In the in vivo study, ICA prevented bone loss in a rat model of GC-related ONFH as shown by micro-CT scanning, histological and immunohistochemical analyses. Conclusions: ICA is an effective compound for promoting bone repair and preventing or delaying the progression of GC-associated ONFH in rats. This effect can be explained by its ability to improve the balance between adipogenesis and osteogenesis, indicating that ICA is an effective candidate for management of GC-associated ONFH.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lan Ma ◽  
Yijun Yu ◽  
Hanxiao Liu ◽  
Weibin Sun ◽  
Zitong Lin ◽  
...  

AbstractThe repair of skeletal defects in maxillofacial region remains an intractable problem, the rising technology of bone tissue engineering provides a new strategy to solve it. Scaffolds, a crucial element of tissue engineering, must have favorable biocompatibility as well as osteoinductivity. In this study, we prepared berberine/polycaprolactone/collagen (BBR/PCL/COL) scaffolds with different concentrations of berberine (BBR) (25, 50, 75 and 100 μg/mL) through electrospinning. The influence of dosage on scaffold morphology, cell behavior and in vivo bone defect repair were systematically studied. The results indicated that scaffolds could release BBR stably for up to 27 days. Experiments in vitro showed that BBR/PCL/COL scaffolds had appropriate biocompatibility in the concentration of 25–75 μg/mL, and 50 and 75 μg/mL scaffolds could significantly promote osteogenic differentiation of dental pulp stem cells. Scaffold with 50 μg/mL BBR was implanted into the critical bone defect of rats to evaluate the ability of bone repair in vivo. It was found that BBR/PCL/COL scaffold performed more favorable than polycaprolactone/collagen (PCL/COL) scaffold. Overall, our study is the first to evaluate the capability of in vivo bone repair of BBR/PCL/COL electrospun scaffold. The results indicate that BBR/PCL/COL scaffold has prospective potential for tissue engineering applications in bone regeneration therapy.


2021 ◽  
Vol 12 ◽  
Author(s):  
Lei He ◽  
Jun Xiao ◽  
Lei Song ◽  
Rui Zhou ◽  
Zhigang Rong ◽  
...  

Bone defects are a common orthopaedic concern, and an increasing number of tissue-engineered bones (TEBs) are used to repair bone defects. Allogeneic mesenchymal stem cells (allo-MSCs) are used as seed cells in many approaches to develop TEB constructs, but the immune response caused by allogeneic transplantation may lead to transplant failure. V gamma 4 T (Vγ4T) cells play an important role in mediating the immune response in the early stage after transplantation; therefore, we wanted to verify whether suppressing Vγ4T cells by herpesvirus entry mediator (HVEM)/B and T lymphocyte attenuator (BTLA) signalling can promote MSCs osteogenesis in the transplanted area. In vitro experiments showed that the osteogenic differentiation of MSCs and Vγ4T cells was weakened after co-culture, and an increase in interleukin-17 (IL-17) and interferon-γ (IFN-γ) levels was detected in the culture supernatant. HVEM-transfected MSCs (MSCs-HVEM) still exhibited osteogenic differentiation activity after co-culture with Vγ4T cells, and the levels of IL-17 and IFN-γ in the co-culture supernatant were significantly reduced. In vivo experiments revealed that inflammation in the transplanted area was reduced and osteogenic repair was enhanced after Vγ4T cells were removed. MSCs-HVEM can also consistently contribute to reduced inflammation in the transplanted area and enhanced bone repair in wild-type (WT) mice. Therefore, our experiments verified that HVEM can promote the osteogenesis of allo-MSCs by inhibiting IL-17 and IFN-γ secretion from Vγ4T cells.


Author(s):  
Mustafa R. Abdulbaqi

Objective: This study aimed to evaluate the application of nanotechnology in improving the solubility and biologic activity as the antibacterial and antifungal drug of metronidazole (MTZ).Methods: Nanoparticles of bismuth sulfide (Bi2S3) were used as the nanocarriers for metronidazole (MTZ) and they were synthesized by chemical co-precipitation method. Drug loading on Bi2S3 nanoparticles, lattice property alteration and average particles sizes were evaluated using fourier transform infrared (FTIR) spectroscopy, atomic force microscopy (AFM), and powder X-ray diffraction (PXRD). The evaluation of the release of MTZ from Bi2S3 nanoparticles was carried out using USP type II rotating paddle apparatus. The antimicrobial activity of MTZ before and after loading was carried out by disc diffusion method against two aerobic gram+ve and one aerobic gram–ve bacteria, in addition to two fungi.Results: This study showed successful loading process as well as particles size reduction of MTZ after loading on Bi2S3 nanoparticles. In vitro release study showed a significant* increase in solubility and dissolution of MTZ after loading on Bi2S3 nanoparticles. MTZ showed a significant* increase in antibacterial (against gram+ve aerobic staphylococcus aureus and bacillus subtilis) and antifungal (Candida glabrata and Candida tropicalis) activities after loading process.Conclusion: Nanotechnology was applied successfully to improve both, solubility and biologic activity of the model drug used, metronidazole (MTZ). 


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Chengyong Li ◽  
Tingting Yan ◽  
Zhenkai Lou ◽  
Zhimin Jiang ◽  
Zhi Shi ◽  
...  

Abstract Background Large bone defects have always been a great challenge for orthopedic surgeons. The use of a good bone substitute obtained by bone tissue engineering (BTE) may be an effective treatment method. Artificial hydroxyapatite, a commonly used bone defect filler, is the main inorganic component of bones. Because of its high brittleness, fragility, and lack of osteogenic active elements, its application is limited. Therefore, its fragility should be reduced, its osteogenic activity should be improved, and a more suitable scaffold should be constructed. Methods In this study, a microhydroxyapatite whisker (mHAw) was developed, which was doped with the essential trace active elements Mg2+ and Sr2+ through a low-temperature sintering technique. After being formulated into a slurry, a bionic porous scaffold was manufactured by extrusion molding and freeze drying, and then SiO2 was used to improve the mechanical properties of the scaffold. The hydrophilicity, pore size, surface morphology, surface roughness, mechanical properties, and release rate of the osteogenic elements of the prepared scaffold were detected and analyzed. In in vitro experiments, Sprague–Dawley (SD) rat bone marrow mesenchymal stem cells (rBMSCs) were cultured on the scaffold to evaluate cytotoxicity, cell proliferation, spreading, and osteogenic differentiation. Results Four types of scaffolds were obtained: mHAw-SiO2 (SHA), Mg-doped mHAw-SiO2 (SMHA), Sr-doped mHAw-SiO2 (SSHA), and Mg-Sr codoped mHAw-SiO2 (SMSHA). SHA was the most hydrophilic (WCA 5°), while SMHA was the least (WCA 8°); SMHA had the smallest pore size (247.40 ± 23.66 μm), while SSHA had the largest (286.20 ± 19.04 μm); SHA had the smallest Young's modulus (122.43 ± 28.79 MPa), while SSHA had the largest (188.44 ± 47.89 MPa); and SHA had the smallest compressive strength (1.72 ± 0.29 MPa), while SMHA had the largest (2.47 ± 0.25 MPa). The osteogenic active elements Si, Mg, and Sr were evenly distributed and could be sustainably released from the scaffolds. None of the scaffolds had cytotoxicity. SMSHA had the highest supporting cell proliferation and spreading rate, and its ability to promote osteogenic differentiation of rBMSCs was also the strongest. Conclusions These composite porous scaffolds not only have acceptable physical and chemical properties suitable for BTE but also have higher osteogenic bioactivity and can possibly serve as potential bone repair materials.


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