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ABSTRACT: Aim: While hydroxyapatite nanoparticles (HAPNs) have been reported to exhibit anticancer effects on several types of human cancer cells, no investigation has been performed to compare their cytotoxicity with different types of cancer cells. The objective of the present study is to investigate the cytotoxic action of HAPNs in different types of human cancer cell and to explore the possible mechanisms involved. Materials & methods: Rod-shaped HAPNs were prepared by the aqueous precipitation method and then labeled with fluorescein isothiocyanate to visualize the cellular uptake and distribution. Their cytotoxicity to three human carcinoma cell lines (gastric cancer cells [MGC80-3], cervical adenocarcinoma epithelial cells [HeLa] and hepatoma cells [HepG2], as well as to normal human hepatocyte cells [L-02]) was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell apoptosis was characterized by the changes in nuclear morphology with 4',6-diamidino-2-phenylindole staining and by flow cytometric analysis with Annexin V-fluorescein isothiocyanate/propidium iodide double staining. Furthermore, the activity of apoptotic proteins (caspase-3, -8 and -9), intracellular reactive oxygen species and glutathione levels were analyzed in HAPN-treated cells. The cellular uptake of HAPNs was studied using flow cytometry analysis, and changes in intracellular calcium levels were investigated using the Ca(2+)-sensitive fluorescent dye, fluo-3 AM. Results: HAPNs significantly inhibited cell proliferation and induced apoptosis of cancer cells with an order of MGC80-3 > HepG2 > HeLa, but had no impact on normal hepatic cells (L-02). The increase in apoptosis was accompanied by the activation of caspase-3 and -9, but not activation of caspase-8. Moreover, HAPN treatment led to reactive oxygen species generation and decreased intracellular glutathione in cancer cells, with the most remarkable reactive oxygen species burst in HeLa cells. The degree of cytotoxicity did not correlate with the cellular uptake efficiency of HAPNs. However, more HAPNs were found inside the nucleus of MGC80-3 cells, and an increase in the intracellular calcium level was observed in all cancer cells, with the highest level also detected in MGC80-3. Conclusion: Varying cytotoxicity of HAPNs was observed in different cancer cell types. Our results suggest that possible mechanisms of cytotoxicity in various types of cancer cells could be different. The elevated calcium concentration and nuclear localization of the particles might be the main mechanism of growth inhibition by HAPNs in cancer cells. Original submitted 18 April 2012; Revised submitted 14 September 2012.
Nanomedicine 04/2013; · 5.05 Impact Factor
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ABSTRACT: Premixed injectable calcium phosphate cement (p-ICPC) pastes have advantages over aqueous injectable calcium phosphate cement (a-ICPC) because p-ICPC remain stable during storage and harden only after placement into the defect. This paper focused on the suspension stability of p-ICPC paste by using fumed silica as a stabilizing agent and propylene glycol (PEG) as a continuous phase. Multiple light scanning techniques were first applied to evaluate the suspension stability. The results indicated that fumed silica effectively enhanced the suspension stability of p-ICPC pastes. The stabilizing effect of fumed silica results from the network structure formed in PEG because of its thixotropy. The p-ICPC could be eventually hydrated to form hydroxyapatite under aqueous circumstances by the unique replacement between water and PEG. p-ICPC (1) not only possesses proper thixotropy and compressive strength but has good injectability as well. p-ICPC (1) was cytocompatible and had no adverse effect on the attachment and proliferation of MG-63 cells in vitro. These observations may have applicability to the development of other nonaqueous injectable biomaterials for non-immediate filling and long-term storage.
Journal of Materials Science Materials in Medicine 04/2013; · 2.32 Impact Factor
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ABSTRACT: Vitamin E TPGS-functionalized polymeric nanoparticles have been developed as a promising drug delivery platform in recent years. Obtaining reproducible monodisperse TPGS/polymeric nanoparticles with high encapsulation efficiency (EE%) still remains a big challenge. In this study, an inverse-phase nanoprecipitation method was developed to synthesize TPGS-functionalized PLGA nanoparticles (TPNs) for controlled release of paclitaxel (PTX). To take advantages of lipids, a part of TPGS in the TPNs was replaced by lipids. The results showed that with weight ratio of TPGS-to-PLGA of 2-3 and a molar replacement of lecithin ratio of 30%, the PTX-loaded TPNs (PTPNs) and PTX-loaded lipid-containing TPNs (PLTPNs) exhibited controllable and nearly uniform size of 130-150nm and EE% of over 80%. Compared to Taxol®, both the PTPNs and PLTPNs significantly increased the intracellular uptake and exerted strong inhibitory effect on human lung cancer A549 model cells. Furthermore, a selective accumulation to tumor site and significant antitumor efficacy of TPNs in the A549 lung cancer xenografted nude mice were observed by intravenous administration, especially for the PTPNs group. Our data suggested that the inverse-phase nanoprecipitation method holds great potential for the fabrication of the paclitaxel-loaded TPNs and the TPNs prepared here is a promising controllable delivery system for paclitaxel.
International journal of pharmaceutics 02/2013; 446(1-2):24-33. · 2.96 Impact Factor
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Jun Zhao,
Shaoyi Wang,
Jianqiang Bao,
Xiaojuan Sun,
Xiaochen Zhang,
Xiuli Zhang,
Dongxia Ye,
Jie Wei, Changsheng Liu,
Xinquan Jiang,
Gang Shen,
Zhiyuan Zhang
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ABSTRACT: Calcium phosphate (Ca-P) scaffolds have been widely employed as a supportive matrix and delivery system for bone tissue engineering. Previous studies using osteoinductive growth factors loaded Ca-P scaffolds via passive adsorption often experience issues associated with easy inactivation and uncontrolled release. In present study, a new delivery system was fabricated using bone morphogenetic protein-2 (BMP-2) loaded calcium-deficient hydroxyapatite (CDHA) scaffold by lyophilization with addition of trehalose. The in vitro osteogenesis effects of this formulation were compared with lyophilized BMP-2/CDHA construct without trehalose and absorbed BMP-2/CDHA constructs with or without trehalose. The release characteristics and alkaline phosphatase (ALP) activity analyses showed that addition of trehalose could sufficiently protect BMP-2 bioactivity during lyophilization and achieve sustained BMP-2 release from lyophilized CDHA construct in vitro and in vivo. However, absorbed BMP-2/CDHA constructs with or without trehalose showed similar BMP-2 bioactivity and presented a burst release. Quantitative real-time PCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) demonstrated that lyophilized BMP-2/CDHA construct with trehalose (lyo-tre-BMP-2) promoted osteogenic differentiation of bone marrow stromal cells (bMSCs) significantly and this formulation could preserve over 70% protein bioactivity after 5 weeks storage at 25°C. Micro-computed tomography, histological and fluorescent labeling analyses further demonstrated that lyo-tre-BMP-2 formulation combined with bMSCs led to the most percentage of new bone volume (38.79% ±5.32%) and area (40.71% ±7.14%) as well as the most percentage of fluorochrome stained bone area (alizarin red S: 2.64% ±0.44%, calcein: 6.08% ±1.37%) and mineral apposition rate (4.13±0.62 µm/day) in critical-sized rat cranial defects healing. Biomechanical tests also indicated the maximum stiffness (118.17±15.02 Mpa) and load of fracture (144.67±16.13 N). These results lay a potential framework for future study by using trehalose to preserve growth factor bioactivity and optimize release profile of Ca-P based delivery system for enhanced bone regeneration.
PLoS ONE 01/2013; 8(1):e54645. · 4.09 Impact Factor
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ABSTRACT: The treatment of large osseous defects remains a challenging clinical problem in orthopedic surgery. Particularly, strategies to control the appropriate degradation rate adapting to the tissue reconstruction are of essential for tissue regeneration. Here we report on a strategy to achieve adaptive degradation rate using cell-secreted protease as a switch. Disulfide-containing PEG-based scaffolds have been synthesized, and demonstrated to be responsive to the cell-secreted redox microenvironment. Thus, the cell-triggered degradation and liberation of growth factor are achieved. The osteoinductive growth factor, recombinant human bone morphogenetic protein-2 (rhBMP-2), is incorporated into the scaffold for bioactivity promotion. Degradations under the stimuli of reduced glutathione (GSH) at intracellular and extracellular concentrations was studied with the results of duration time ranging from 0.5 h to 22 days regulated by both concentrations of redox medium and polymer precursors. The rhBMP-2 loaded scaffolds evidently induced the ectopic bone formation in the mouse thigh muscles. In addition, we further investigated the in vivo effects of rhBMP-2-loaded scaffolds in a rabbit radius critical defect by radiography, three dimensional micro-computed tomographic (μCT) and synchrotron radiation-based micro-computed tomography (SRμCT) imaging, histological analysis, and biomechanical measurement. Scaffolds underwent gradual resorption and replacement by new bone and induced reunion of bone marrow cavity at 12 weeks, much better than the effect of self-repairing group. The results indicated that both osteoinduction and appropriate degradation played a crucial role in accelerating and promoting bone augmentation, as well as effective proangiogenesis. Such a strategy appears promising as 3D temporal scaffolds for potential orthopedic applications.
Biomaterials 11/2012; · 7.40 Impact Factor
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ABSTRACT: Water-soluble chitin (WSC), partially acetylated, was prepared by using N-acetylation in mild conditions. The aggregation behavior of WSC in aqueous solution was investigated. the results showed
that the surface tension decreased with increasing WSC concentration in the high dilute solution, the critical aggregation
concentration was about 0.010 g/ml. The degree of deacetylation had an obvious effect on the surface tension. Introduction
of acetyl favored aggregation formation. The possible aggregation mechanism of WSC in water was attributed to the molecules’
conformation transition, resulting in change of intra- and inter-molecular interactions such as hydrogen bonding and hydrophobic
interaction.
Research on Chemical Intermediates 04/2012; 34(2):169-179. · 0.70 Impact Factor
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ABSTRACT: The aim of this study was to explore the effects of maxillary sinus floor elevation and simultaneous dental implantation with a tissue-engineered bone complex of calcium phosphate cement (CPC) scaffolds combined with bone marrow stromal cells (BMSCs). A large animal goat model is used with the tissue engineering method. Eighteen bilateral maxillary sinus of nine goats were randomly allocated into three groups; the CPC/BMSC complex (n=6) was used to elevate maxillary sinus floor with a simultaneous implant placement; the effects were compared with those treated with CPC alone (n=6) or autogenous bone (n=6). After a healing period of 3 months, sequential triad-color fluorescence labeling, micro-CT, as well as histological and histomorphometric analyses indicated that the tissue-engineered BMSC/CPC complex could promote earlier bone formation and mineralization, and maximally maintain the volume and height of the augmented maxillary sinus. By comparison, CPC-alone or autogenous bone achieved less bone formation and later mineralization. Besides, the average bone-implant contact value reflecting the osseointegration was 35.63%±9.42% in the BMSCs/CPC group, significantly higher than 22.47%±4.28% in the CPC-alone group or 28.26%±8.03% in the autogenous bone group. In conclusion, CPC serves as a potential substrate for BMSCs for the maxillary sinus floor augmentation and simultaneous implantation. The tissue-engineered bone might enhance the stability of implants and thus be of great significance to achieve improved quality to restore the oral function in clinic.
Tissue Engineering Part A 03/2012; 18(13-14):1464-78. · 4.64 Impact Factor
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ABSTRACT: The reconstruction of segmental bone defects remains an urgent problem in the orthopaedic field, and bone morphogenetic protein-2 (BMP-2) is known for its potent osteoinductive properties in bone regeneration. In this study, chitosan microspheres (CMs) were prepared and combined with absorbable collagen sponge to maintain controlled-release recombinant human bone morphogenetic protein-2 (rhBMP-2). The rhBMP-2-loaded composite scaffolds were implanted into 15 mm radius defects of rabbits and the bone-repair ability was evaluated systematically. CMs were spherical in shape and had a polyporous surface, according to SEM images. The complex scaffold exhibited an ideal releasing profile in vitro. The micro-computed tomographic analysis revealed that the rhBMP-2-loaded composite scaffold not only bridged the defects as early as 4 weeks, but also healed the defects and presented recanalization of the bone-marrow cavity at 12 weeks. These results were confirmed by x-ray. When compared with other control groups, the composite scaffold group remarkably enhanced new bone formation and mechanical properties, as evidenced by bone mineral content evaluation, histological observations and biomechanical testing. Moreover, the biocompatibility and appropriate degradation of the composite scaffold could be obtained. All of these results clearly demonstrated that the composite scaffold is a promising carrier of BMP-2 for the treatment of segmental bone defects.
Biomedical Materials 02/2012; 7(3):035002. · 2.16 Impact Factor
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ABSTRACT: A hydrogel which will undergo macroscopic transition responding to redox stimuli is prepared. Mercapto precursors are prepared from 4-armed polyethylene glycol and after deprotection of thiolate anions, they can transform into disulfide crosslinked hydrogels within 3 min by responding to oxidant H(2)O(2). Desirable elasticity is exhibited with a wide range of storage modulus from 50 Pa to 14 kPa through rheological investigation. In addition, the hydrogels are found to be hydrolytically stable but degrade within 75 days when exposed to reductant such as glutathione (GSH). So gelation time and degradation behavior can be regulated by concentrations of precursor, oxidant, reductant, temperature, and pH value. Notably, interest arises from the long-period degradation under low GSH concentration of 0.01 mM that is similar to extracellular level, but not the fast disintegration under high concentration intracellular, providing the possibility of "smart" degradation responding to those cell-secreted biomacromolecules during the process of tissue regeneration. Furthermore, both hydrogels and their degradation products show cell viability above 90% culturing with C2C12 cells, representing nontoxic properties. Such a stimuli-responsive degradation strategy will give promising application in tissue repair and regeneration; especially enable the achievement of matching the degradation kinetics with physiological environment.
Journal of Materials Science Materials in Medicine 02/2012; 23(3):697-710. · 2.32 Impact Factor
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ABSTRACT: The purpose of this study was to synthesize a self-setting bioactive cement by incorporation of wollastonite nanofibers (WNFs) into calcium phosphate cement (CPC). The composition, morphology, setting time, compressive strength, hydrophilicity, and degradation of WNF-doped CPC (wnf-CPC) were investigated. Scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, and inductively coupled plasma atomic emission spectroscopy were utilized. Additionally, methyl-thiazolyl-tetrazolium bromide assay, scanning electron microscopy, inductively coupled plasma atomic emission spectroscopy, and histological evaluation were used to study the cell and tissue responses to wnf-CPC, both in vitro and in vivo. The results confirmed that the addition of WNFs into CPC had no obvious effect on the setting time or the compressive strength of wnf-CPC, provided the WNF amount was not more than 10 wt%. However, the hydrophilicity and degradability of wnf-CPC were significantly improved by the addition of WNFs - this was because of the change of microstructure caused by the WNFs. The preferred dissolution of WNFs caused the formation of microporosity in wnf-CPC when soaked in tris hydrochloride solution. The microporosity enlarged the surface area of the wnf-CPC and so promoted degradation of the wnf-CPC when in contact with liquid. In addition, MG-63 cell attachment and proliferation on the wnf-CPC were superior to that on the CPC, indicating that incorporation of WNFs into CPC improved the biological properties for wnf-CPC. Following the implantation of wnf-CPC into bone defects of rabbits, histological evaluation showed that wnf-CPC enhanced the efficiency of new bone formation in comparison with CPC, indicating excellent biocompatibility and osteogenesis of wnf-CPC. In conclusion, wnf-CPC exhibited promising prospects in bone regeneration.
International Journal of Nanomedicine 01/2012; 7:3613-24. · 3.13 Impact Factor
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ABSTRACT: Hydroxyapatite nanoparticles (nano-HAP) have been reported to cause inflammatory reactions. Here, we aimed to compare the effects of four types of nano-HAP with different nanocrystal morphologies (short rod-like, long rod-like, spherical or needle-shaped crystals) and sizes (10-20, 10-30 or 20-40 nm) on growth inhibition and apoptosis in primary cultured rat osteoblasts. The osteoblasts was treated with the four types of nano-HAP at various concentrations (20, 40, 60, 80 or 100 mg l⁻¹). The nano-HAP specific surface area was detected using the Brunauer, Emmet and Teller method. The cell growth rate was detected using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay; apoptotic alterations and the level of reactive oxygen species in osteoblasts were measured using flow cytometry; and the amounts of apoptotic p53 and cytochrome c proteins were measured using western blotting. We observed that all four types of nano-HAP inhibited the growth of osteoblasts in a dose-dependent manner. These nano-HAP significantly induced apoptosis in osteoblasts. Nano-HAP with smaller specific surface areas induced lower apoptosis rates. The needle-shaped and the short rod-like particles induced greater cellular injury than the spherical and long rod-like particles, respectively. The increased apoptosis rates were accompanied by increased p53 and cytochrome c expression. These findings indicate that nano-HAP inhibit the activity of osteoblasts and also induce the apoptosis of osteoblasts in vitro. These findings also suggest that the nano-HAP-induced apoptotic pathway is mediated by a mitochondrial-dependent pathway. Moreover, the sizes, morphologies and concentrations of nano-HAP have significant effects on the apoptotic level.
Journal of Applied Toxicology 12/2011; 32(6):429-35. · 2.48 Impact Factor
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ABSTRACT: Well ordered mesoporous diopside (OMD) nanobiomaterial was synthesized by a sol-gel process. The in vitro bioactivity of the OMD was evaluated by investigating the apatite-forming ability in simulated body fluid (SBF), and the hemostatic activity of the OMD was determined by measuring the activated partial thromboplastin time (APTT) and prothrombin time (PT) in vitro. The results suggested that the OMD exhibited excellent in vitro bioactivity, with surface apatite formation for OMD exceeding that of non-mesoporous diopside (n-MD) at 7 days. Moreover, the OMD with high surface area possessed good hemostatic property because it could absorb a large number of water from the blood. In conclusion, the prepared OMD had excellent bioactivity and hemostatic activity, which can not only be applied as bone repair biomaterial for bone regeneration, but also as hemostatic agent for surgery hemostasis.
Journal of Nanoscience and Nanotechnology 12/2011; 11(12):10746-9. · 1.56 Impact Factor
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ABSTRACT: A simple seed-mediated growth route is developed to fabricate monodisperse, uniform superparamagnetic Fe(3)O(4) core/gold shell structured nanocomposites with tunable sizes and optical properties, in which gold seed formation and attachment onto the core surface via S-Au covalent bonding proceeds almost simultaneously in the one-pot synthesis. The as-prepared nanocomposite is demonstrated to have a great potential for magnetic resonance imaging (MRI)-guided, focused photothermal tumor therapy under near-IR laser radiation.
Advanced Materials 12/2011; 23(45):5392-7. · 13.88 Impact Factor
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ABSTRACT: Due to the unique physicochemical properties and membrane-permeable capacity, mesoporous silica nanoparticles (MSNs) are considered as an ideal carrier for intracellular delivery. Herein, we endeavored to address the size effect of MSNs on the cellular uptake, endosomal escape and controlled release, the key steps for the intracellular delivery. The well-ordered MSNs in the range from 55-nm to 440-nm with similar pore texture were prepared by modified base-catalyzed sol-gel method. With MC3T3-E1 model cell line, the in vitro results indicated that after 12 h cultivation, MSNs within 55 ~ 440 nm could all be internalized into the cells, and further escaped out of the endosomal compartment. The efficiency of the cellular uptake and endosomal escape strongly depended on the particle size, with the best efficiencies from 100-nm MSNs. Furthermore, the MTT results indicated that these MSNs materials were all biocompatible. The controlled release experiments with hydrophobic dexamethasone and hydrophilic vitamin C as models showed that for these small-molecular drugs, the loading amount all mainly determined by the surface area of the MSNs, and the subsequent release of the drug dramatically decreased with the increasing of the particle size. By contrast, the release rate of vitamin C was much quicker than that of the dexamethasone. These findings presented here could provide new means to tailor the size of MSNs and thus to guide the design of MSNs-based intracellular delivery system. Due to the good cell biocompatibility, high cellular uptake and endosomal escape, we conjectured that the 100-nm MSNs are more favorable for the intracellular delivery of drugs in live cells.
Biomedical Microdevices 11/2011; 14(2):259-70. · 3.03 Impact Factor
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ABSTRACT: By using a non-aqueous solution as the mixing liquid, the washout resistance of the calcium deficient apatite biocement (cd-AB) was significantly improved, over that of the conventional method of using cd-AB with water as the liquid phase. In this study, premixed and injectable cd-AB was prepared, which had the advantage of being stable in the syringe and hardens only after being delivered to the defect area. The cd-AB powder with a Ca/P ratio of 1.5 consists of a mixture of tetracalcium phosphate (TTCP) and dicalcium phosphate anhydrous (DCPA). A solution of polylactide (PLA) in N-methyl-2-pyrrolidone (NMP) was used as the liquid phase of the premixed cd-AB. The premixed cd-AB paste injected into an aqueous environment exhibited excellent washout resistance. The premixed cd-AB had longer setting time and lower compressive strength than conventional cd-AB. The hydration products of premixed cd-AB were a mixture of calcium deficient hydroxyapatite (cd-HA) and PLA. In vitro Tris-HCl immersion tests demonstrated that the premixed cd-AB could be degradable. The results revealed that the premixed cd-AB was cytocompatible and had no adverse effects on the attachment and proliferation of MG-63 osteoblast-like cells in vitro. The most distinct advantages of premixed and injectable PLA-modified cd-AB were its excellent washout resistance and in vitro degradability, suggesting that it may be a promising candidate for bone repair.
Colloids and surfaces. B, Biointerfaces 11/2011; 92:113-20. · 2.60 Impact Factor
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ABSTRACT: The objective of this study was to assess the effects of maxillary sinus floor elevation with a tissue-engineered bone constructed with bone marrow stromal cells (bMSCs) and calcium-magnesium phosphate cement (CMPC) material. The calcium (Ca), magnesium (Mg), and phosphorus (P) ions released from calcium phosphate cement (CPC), magnesium phosphate cement (MPC), and CMPC were detected by inductively coupled plasma atomic emission spectroscopy (ICP-AES), and the proliferation and osteogenic differentiation of bMSCs seeded on CPC, MPC, and CMPC or cultured in CPC, MPC, and CMPC extracts were measured by MTT analysis, alkaline phosphatase (ALP) activity assay, alizarin red mineralization assay, and real-time PCR analysis of the osteogenic genes ALP and osteocalcin (OCN). Finally, bMSCs were combined with CPC, MPC, and CMPC and used for maxillary sinus floor elevation in rabbits, while CPC, MPC, or CMPC without cells served as control groups. The new bone formation in each group was detected by histological finding and fluorochrome labeling at weeks 2 and 8 after surgical operation. It was observed that the Ca ion concentrations of the CMPC and CPC scaffolds was significantly higher than that of the MPC scaffold, while the Mg ions concentration of CMPC and MPC was significantly higher than that of CPC. The bMSCs seeded on CMPC and MPC or cultured in their extracts proliferated more quickly than the cells seeded on CPC or cultured in its extract, respectively. The osteogenic differentiation of bMSCs seeded on CMPC and CPC or cultured in the corresponding extracts was significantly enhanced compared to that of bMSCs seeded on MPC or cultured in its extract; however, there was no significant difference between CMPC and CPC. As for maxillary sinus floor elevation in vivo, CMPC could promote more new bone formation and mineralization compared to CPC and MPC, while the addition of bMSCs could further enhance its new bone formation ability significantly. Our data suggest that CMPC possesses moderate biodegradability and excellent osteoconductivity, which may be attributed to its Ca and Mg ion composition, and the tissue-engineered bone constructed of CMPC and bMSCs might be a potential alterative graft for maxillofacial bone regeneration.
Tissue Engineering Part A 11/2011; 18(7-8):870-81. · 4.64 Impact Factor
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ABSTRACT: The regenerative treatment of large osseous defects remains a formidable challenge in orthopedic surgery today. In the present study, we have synthesized biodegradable calcium/magnesium-doped silica-based scaffolds with hierarchically macro/mesoporous structure (CMMS), and incorporated recombinant human bone morphogenetic protein-2 (rhBMP-2) into the scaffolds to obtain a hybrid system for osteogenic factor delivery in the functional repair of bone defects. The developed CMMS/rhBMP-2 scaffolds presented interconnected porous network, macropores (200-500 μm) and mesopores (5.7 nm), as well as good bioactivity and biocompatibility and proper degradation rate. Combined with the capacity to deliver ions and growth factors, the CMMS/rhBMP-2 scaffolds significantly promoted the in vitro osteogenic differentiation of bone marrow stromal cells (bMSCs), as evidenced by the enhanced expression of Runx-2, osteopontin, osteocalcin and bone sialoprotein, and induced the ectopic bone formation in the thigh muscle pouches of mice. We further assessed the in vivo effects of CMMS/rhBMP-2 scaffolds in a rabbit femur cavity defect model by using synchrotron radiation-based μCT (SRμCT) imaging and histological analysis, indicating that the CMMS/rhBMP-2 scaffolds resulted in more bone regeneration compared to that observed with the CMMS scaffolds without rhBMP-2. Moreover, scaffolds with or without rhBMP-2 underwent gradual resorption and replacement with bone and almost disappeared at 12 weeks, while the dense CMMS/rhBMP-2 material showed slower degradation rate and promoted the least extensive neo-bone formation. This study suggested that the hybrid CMMS/rhBMP-2 scaffolds system demonstrates promise for bone regeneration in clinical case of large bone defects.
Biomaterials 08/2011; 32(33):8506-17. · 7.40 Impact Factor
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Jun Zhao,
Gang Shen, Changsheng Liu,
Shaoyi Wang,
Wenjie Zhang,
Xiaochen Zhang,
Xiuli Zhang,
Dongxia Ye,
Jie Wei,
Zhiyuan Zhang,
Xinquan Jiang
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ABSTRACT: Calcium phosphate cements (CPCs), which are widely used in bone regeneration, possess good biocompatibility and osteoconductivity and have been demonstrated to be candidate carriers for bone growth factors. However, limited release of growth factors from CPCs and slow degradation of the materials are not desirable for certain clinical applications. Previous studies have shown that calcium-deficient hydroxyapatite (CDHA) from CPCs presents more rapid degradation rate than CPCs. In this study, a hybrid growth factor delivery system was prepared by using bone morphogenetic protein 2 (BMP-2) loaded CDHA porous scaffold with sulfated chitosan (SCS) coating for improved release profile. We tested the BMP-2 release characteristic of CDHA/BMP-2/SCS composite in vitro and its ability to repair rat calvarial bone defects. A higher percentage of BMP-2 was released when sulfated chitosan coating was present compared with CDHA/BMP-2 group. Eight weeks postoperation, the repaired crania were evaluated by microcomputed tomography, sequential fluorescent labeling, histological analysis, and immunohistochemistry. CDHA/BMP-2/SCS group promoted the most extensive new bone formation than CDHA/BMP-2 and CDHA groups. Our observations suggest that sulfated chitosan coating could enhance the release profile of CDHA/BMP-2 composite in vitro and promote new bone formation in vivo. The hybrid CDHA/BMP-2/SCS system is a promising growth factor delivery strategy for bone regeneration.
Tissue Engineering Part A 08/2011; 18(1-2):185-97. · 4.64 Impact Factor
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ABSTRACT: Combination of chemotherapy and gene therapy of cancer has synergistic effects on overcoming drug resistance. Macromolecular materials such as dextran and PEI have been a potential module for chemotherapeutics and gene delivery. Herein, we hypothesize the combinational strategy of chemotherapy and gene therapy in a single dextran-PEI nanoplatform. The physicochemical properties, cytotoxicity, transfection efficiency were investigated in vitro. Ultra-violet spectrum and (1)H NMR revealed adriamycin and PEI were grafted to dextran chain. Agarose gel electrophoresis demonstrated that the migration of plasmid was completely retarded when the N/P ratio of complex was 4. The sizes of DEX-ADM-PEI/DNA nanoparticles decreased and the zeta potentials enhanced with the increasing N/P ratio. Transmission electron microscope indicated a round morphology of the nanoparticles. DEX-ADM-PEI conjugation has higher cytotoxicity, compared to free adriamycin, in MG-63 and Saos-2 osteosarcoma cells but DEX-PEI maintained over 65% cell viability at the concentration of 8 mg/mL. The transfection efficiency of DEX-ADM-PEI/pEGFP-N1 at N/P ratio of 4:1 both in MG-63 and Saos-2 cell were slightly low than that of PEI 25k. But our nanoplatform efficiently delivered both plasmid pEGFP-N1 and adriamycin into osteosarcoma cells. This study demonstrated that DEX-ADM-PEI efficiently and selectively delivered both plasmid pEGFP-N1 and adriamycin to osteosarcoma cells with low cytotoxicity.
International journal of biological macromolecules 08/2011; 49(2):173-80. · 2.37 Impact Factor
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ABSTRACT: In order to restore the badly carious lesion of human dental enamel, a crystalline paste of fluoride substituted apatite cement was synthesized by using the mixture of tetracalcium phosphate (TTCP), dicalcium phosphate anhydrous (DCPA) and ammonium fluoride. The apatite cement paste could be directly filled into the enamel defects (cavities) to repair damaged dental enamel. The results indicated that the hardened cement was fluorapatite [Ca(10)(PO(4))(6)F(2), FA] with calcium to phosphorus atom molar ratio (Ca/P) of 1.67 and Ca/F ratio of 5. The solubility of FA cement in Tris-HCl solution (pH = 5) was slightly lower than the natural enamel, indicating the FA cement was much insensitive to the weakly acidic solutions. The FA cement was tightly combined with the enamel surface, and there was no obvious difference of the hardness between the FA cement and natural enamel. The extracts of FA cement caused no cytotoxicity on L929 cells, which satisfied the relevant criterion on dental biomaterials, revealing good cytocompatibility. In addition, the results showed that the FA cement had good mechanical strength, hydrophilicity, and anti-bacterial adhesion properties. The study suggested that using FA cement was simple and promising approach to effectively and conveniently restore enamel defects.
Journal of Materials Science Materials in Medicine 06/2011; 22(6):1607-14. · 2.32 Impact Factor
