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1.
This study examines the link(s) between the suspension behavior of calcium deficient apatites (CDAs) and biphasic calcium phosphate (BCP), as measured by the zeta-potential, with respect to both whole bone and osteoblasts. CDA is fabricated by hydrolyzing an acidic CaP such as dicalcium diphosphate dihydrate (DCPD; CaHPO4.2H2O) and has a structure and composition close to bone apatite. Sintering CDA results in the formation of BCP ceramics consisting of mixtures of hydroxyapatite (HA) and beta-tricalcium phosphate (beta-TCP), with the HA/beta-TCP weight ratio proportional to the Ca/P ratio of CDA. The choice of the base for the DCPD hydrolysis allows various ionic partial substitution of the formed CDA. Na for Ca partial substitution is of interest because of the resulting improvement in mechanical properties of the resulting BCP ceramics and NH4OH was used as a negative control. The zeta-potential was measured for these materials and the stability of the ceramic to bone interaction calculated. zeta-potential values decrease for CDA(NH4OH) versus CDA(NaOH) and increase for BCP(NH4OH) versus BCP(NaOH). While results of these analyses indicate that NH4OH and NaOH processed CDA and BCP will likely yield osteoblast attachment in vivo, differences in the zeta-potentials may explain varying degrees of cell attachment.  相似文献   

2.
CaSiO3 (CS) ceramic has been extensively studied for biomedical applications. The main advantages are its ability to induce bone-like apatite formation and the beneficial effects of the dissolution products on the bone cells, resulting from high reactivity of CS in liquid solutions. However, the high reactivity also results in a rapid degradation rate and accordingly leads to a high pH value in the body fluid, adversely affecting bone cell responses, especially when CS is used as a highly porous scaffold. In this study, we provide an approach to minimize this pH-dependent cell damage and maximize the beneficial effects of the dissolution products of the CS scaffold by adding chemically stable and biocompatible Zn-containing hardystonite (Ca2ZnSi2O7, HT) into the CS scaffold, the resultant composite scaffold is referred to as HT–CS. We investigated the responses of primary human osteoblasts (HOBs) to the CS, HT and the HT–CS scaffolds. HOBs on HT and HT–CS scaffolds attached better than on the CS scaffold. HOBs cultured on the HT–CS scaffolds expressed higher gene expression levels for Runx-2, osteopontin (OPN), osteocalcin (OCN), bone sialoprotein (BSP), and collagen type I (Col-I) and enhanced alkaline phosphatase (ALP) activity compared to those on the CS and HT scaffolds. The higher activity of the HOBs cultured on the HT–CS scaffold was ascribed to the moderate pH variation and the dissolution products containing Ca, Si and Zn.  相似文献   

3.
Simvastatin (Sim) is a widely known drug in the treatment of hyperlipidemia, which has attracted so much attention in bone regeneration due to its potential osteoanabolic effect. However, repurposing of Sim in bone regeneration will require suitable delivery systems that can negate undesirable off-target/side effects. In this study, we have investigated a new lipid nanoparticle (NP) platform that was fabricated using a binary blend of emulsifying wax (Ewax) and glyceryl monooleate (GMO). Using the binary matrix materials, NPs loaded with Sim (0–500?µg/mL) were prepared and showed an average particle size of about 150?nm. NP size stability was dependent on Sim concentration loaded in NPs. The suitability of NPs prepared with the binary matrix materials in Sim delivery for potential application in bone regeneration was supported by biocompatibility in pre-osteoclastic and pre-osteoblastic cells. Additional data demonstrated that biofunctional Sim was released from NPs that facilitated differentiation of osteoblasts (cells that form bones) while inhibiting differentiation of osteoclasts (cells that resorb bones). The overall work demonstrated the preparation of NPs from Ewax/GMO blends and characterization to ascertain potential suitability in Sim delivery for bone regeneration. Additional studies on osteoblast and osteoclast functions are warranted to fully evaluate the efficacy of Sim-loaded Ewax/GMO NPs using in-vitro and in-vivo approaches.  相似文献   

4.
Compounds belonging to the calcium phosphate (CaP) system are known to be major constituents of bone and are bioactive to different extents in vitro and in vivo. Their chemical similarity makes them prime candidates for implants and bone tissue engineering scaffolds. CaP nanoparticles of amorphous hydroxyapatite (aHA) and dicalcium phosphate dihydrate (DCPD) were synthesized using chemical precipitation. Uniaxially pressed aHA and DCPD powders were subjected to microwave radiation to promote solid state phase transformations resulting in crystalline hydroxyapatite (HA), tricalcium phosphate (TCP) and biphasic compositions: HA/TCP and TCP/calcium pyrophosphate (CPP) and their subsequent densification. Phase composition of microwave sintered compacts was confirmed via X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). Solution pH during crystal growth was found to have a profound effect on particle morphology and post-sintered phases, despite constant sintering temperature.Cytocompatibility assessment using 7F2 cells, corresponding to adult mouse osteoblasts, on microwave and conventional, furnace sintered samples demonstrated that manufacturing method does not impact cellular viability after 24 h or proliferation over 7 days. New CaP deposition and extracellular matrix components were observed in vitro via scanning electron microscopy (SEM).  相似文献   

5.
Aluminium oxide (Al2O3) and titanium dioxide (TiO2) nanoparticles (NPs) have been widely used in nanotechnology-based products. Recently, researchers and the public have raised concerns about the adverse effects of these NPs in biological systems, particularly in humans. The aim of this study was to investigate the possible adverse effects of these two common metal oxide NPs on human lung epithelium cells (A549) and to investigate NP size-dependent effects on these cells, considering both the primary and hydrodynamic particle size. NPs were found to inhibit cell viability and proliferation at the highest concentration level (10?mg/mL) included in this study, as measured by a clonogenic assay. Moreover, cell viability, proliferation and metabolism were impaired to a greater extent by the smaller NPs (5?nm TiO2 and 10?nm Al2O3) relative to the larger particles (200?nm TiO2 and 50?nm Al2O3) included in this study, as measured by cell proliferation and metabolism. Notably, the observed cytotoxic effects correlated to the primary size, rather than the hydrodynamic size. Similarly, NP cytotoxicity was found to be correlated with the NP surface area. These findings highlight the importance of including primary size and surface area information in NP characterisation in cytotoxicity studies.  相似文献   

6.
This work deals with the biocompatibility of dense nano- and micro-structured Hydroxyapatite/Titania composites prepared by two step and conventional sintering, respectively. By application of two step sintering, it was shown that the final grain size of HA–15 wt.%TiO2 is maintained lower than 100 nm while by the application of conventional sintering it reaches higher than 100 nm. Biocompatibility of the dense bulks was evaluated by cell attachment and proliferation experiments. Cell morphology, and viability on each nano- and micro-structured Hydroxyapatite/Titania composites were examined at different time points. The nanostructured HA/Titania dense bulk exhibited higher cell viability than a microstructured one. In addition, the effects of ionic products from nano- and micro-structured bulk dissolution on osteoblasts were studied. The MTT test confirmed that the products from nanostructured HA/Titania dense bulk significantly promoted osteoblast proliferation within a certain concentration range.  相似文献   

7.
Composites were developed using calcium phosphate (CaP)/collagen (COL) doped with Zn+2 to attempt the materials association with adequate properties for biological applications in the recovery of the bone tissue by trauma or pathogenies. Hydroxyapatite (HAP) and hydroxyapatite-βtricalcium phosphate (HAPβTCP) were synthesized and doped with zinc nitrate. High purity grade type I collagen was extracted and purified from bovine pericardium. CaP doped and undoped with Zn+2 were produced with COL and the composites were developed using a simple mixture process. All samples were characterized by Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR) and X-ray diffraction analysis (XRD. In addition, biocompatibility and cell viability were assessed by MTT assay (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) using osteoblast cell culture. The results have indicated that both morphological and structural features and chemical composition of the composites were very similar to their precursors, collagen and calcium phosphate components. Also, the biocomposites presented a homogeneous aspect with the calcium phosphate particles aggregated to the collagen fibers. The biological evaluation of the composites in vitro showed cellular viability, presenting proliferation of the osteoblasts compared to the control cells (P < 0.05). The composites showed appropriate physical and biological properties creating more biologically active scaffolds that may support bone growth. Therefore, the novel developed biocomposites have high potential to be used for rebuilding small lesions in bone tissue engineering.  相似文献   

8.
Magnetic poly(l-lactide) (PLLA)/Fe3O4 composite nanofibers were prepared with the purpose to develop a substrate for bone regeneration. To increase the dispersibility of Fe3O4 nanoparticles (NPs) in the PLLA matrix, a modified chemical co-precipitation method was applied to synthesize Fe3O4 NPs in the presence of PLLA. Trifluoroethanol (TFE) was used as the co-solvent for all the reagents, including Fe(II) and Fe(III) salts, sodium hydroxide, and PLLA. The co-precipitated Fe3O4 NPs were surface-coated with PLLA and demonstrated good dispersibility in a PLLA/TFE solution. The composite nanofiber electrospun from the solution displayed a homogeneous distribution of Fe3O4 NPs along the fibers using various contents of Fe3O4 NPs. X-ray diffractometer (XRD) and vibration sample magnetization (VSM) analysis confirmed that the co-precipitation process had minor adverse effects on the crystal structure and saturation magnetization (Ms) of Fe3O4 NPs. The resulting PLLA/Fe3O4 composite nanofibers showed paramagnetic properties with Ms directly related to the Fe3O4 NP concentration. The cytotoxicity of the magnetic composite nanofibers was determined using in vitro culture of osteoblasts (MC3T3-E1) in extracts and co-culture on nanofibrous matrixes. The PLLA/Fe3O4 composite nanofibers did not show significant cytotoxicity in comparison with pure PLLA nanofibers. On the contrary, they demonstrated enhanced effects on cell attachment and proliferation with Fe3O4 NP incorporation. The results suggested that this modified chemical co-precipitation method might be a universal way to produce magnetic biodegradable polyester substrates containing well-dispersed Fe3O4 NPs. This new strategy opens an opportunity to fabricate various kinds of magnetic polymeric substrates for bone tissue regeneration.  相似文献   

9.
Abstract

Because calcium phosphate (Ca–P) ceramics have been used as bone substitutes, it is necessary to investigate what effects the ceramics have on osteoblast maturation. We prepared three types of Ca–P ceramics with different Ca–P ratios, i.e. hydroxyapatite (HA), beta-tricalcium phosphate (β-TCP), and biphasic calcium phosphate (BCP) ceramics with dense-smooth and porous structures. Comprehensive gene expression microarray analysis of mouse osteoblast-like cells cultured on these ceramics revealed that porous Ca–P ceramics considerably affected the gene expression profiles, having a higher potential for osteoblast maturation. In the in vivo study that followed, porous Ca–P ceramics were implanted into rat skeletal muscle. Sixteen weeks after the implantation, more alkaline-phosphatase-positive cells were observed in the pores of hydroxyapatite and BCP, and the expression of the osteocalcin gene (an osteoblast-specific marker) in tissue grown in pores was also higher in hydroxyapatite and BCP than in β-TCP. In the pores of any Ca–P ceramics, 16 weeks after the implantation, we detected the expressions of marker genes of the early differentiation stage of chondrocytes and the complete differentiation stage of adipocytes, which originate from mesenchymal stem cells, as well as osteoblasts. These marker gene expressions were not observed in the muscle tissue surrounding the implanted Ca–P ceramics. These observations indicate that porous hydroxyapatite and BCP had a greater potential for promoting the differentiation of mesenchymal stem cells into osteoblasts than β-TCP.  相似文献   

10.
Sunscreens containing ZnO and TiO2 nanoparticles (NPs) are increasingly applied to skin over long time periods to reduce the risk of skin cancer. However, long‐term toxicological studies of NPs are very sparse. The in vitro toxicity of ZnO and TiO2 NPs on keratinocytes over short‐ and long‐term applications is reported. The effects studied are intracellular formation of radicals, alterations in cell morphology, mitochondrial activity, and cell‐cycle distribution. Cellular response depends on the type of NP, concentration, and exposure time. ZnO NPs have more pronounced adverse effects on keratinocytes than TiO2. TiO2 has no effect on cell viability up to 100 μg mL?1, whereas ZnO reduces viability above 15 μg mL?1 after short‐term exposure. Prolonged exposure to ZnO NPs at 10 μg mL?1 results in decreased mitochondrial activity, loss of normal cell morphology, and disturbances in cell‐cycle distribution. From this point of view TiO2 has no harmful effect. More nanotubular intercellular structures are observed in keratinocytes exposed to either type of NP than in untreated cells. This observation may indicate cellular transformation from normal to tumor cells due to NP treatment. Transmission electron microscopy images show NPs in vesicles within the cell cytoplasm, particularly in early and late endosomes and amphisomes. Contrary to insoluble TiO2, partially soluble ZnO stimulates generation of reactive oxygen species to swamp the cell redox defense system thus initiating the death processes, seen also in cell‐cycle distribution and fluorescence imaging. Long‐term exposure to NPs has adverse effects on human keratinocytes in vitro, which indicates a potential health risk.  相似文献   

11.
Steric barriers such as collagen I sharply limit interstitial delivery of macromolecular and nanoparticle (NP) based therapeutic agents. Collagenase-linked superparamagnetic NPs overcame these barriers and moved through in vitro extracellular matrix (ECM) at 90 microm h(-1), a rate similar to invasive cells, under the influence of a magnetic field. NP migration in ECM diminished linearly over 5 days. The collagenase-NP construct overcame two of the most significant barriers to nano- and microscale therapeutics deployment: proteolytic enzyme stability was maintained during a clinically useful time frame by immobilization on the NP surface and degradation of interstitial barriers to tissue biodistribution was enabled by the conjugated microbial protease.  相似文献   

12.
P.K. Kuiri  J. Ghatak 《Vacuum》2010,85(2):135-138
SnO2 nanoparticles (NPs) of average diameter of ∼10.5 nm, synthesized in SiO2 using Sn ions implantation combined with thermal annealing, were irradiated with 1.5 MeV Au2+ ions at room temperature. The NP structure was studied as a function of ion fluence by transmission electron microscopy and micro-Raman spectroscopy. Prior to ion irradiation, SnO2 NPs have been found to exhibit the rutile crystal structure. Upon irradiation, amorphization in the nanocrystals has been seen to increase with increase in ion fluence. In particular, at a fluence of 1 × 1014 ions cm−2 we argue for the presence of an amorphous SnO2 phase. Beyond this fluence, the NPs have been found to dissolve in the matrix. The observed results are explained in the frame work of ion irradiation induced defects production in the NPs as well as in the NP/matrix interface.  相似文献   

13.
Nanodrug‐based cancer therapy is impeded by poor penetration into deep tumor tissues mainly due to the overexpression of hyaluronic acid (HA) in the tumor extracellular matrix (ECM). Although modification of nanoparticles (NPs) with hyaluronidase (HAase) is a potent strategy, it remains challenging to get a uniform distribution of drug at the tumor site because of the internalization of NPs by the cells in the tumor and HA regeneration. Herein, an intelligent nanocarrier, which can release HAase in response to the acidic tumor microenvironment (pH 6.5) and perform a strong neighboring effect with size reduction to overcome the above two problems and accomplish drug deep tumor penetration in vivo, is reported. In this design, HAase is encapsulated on the surfaces of doxorubicin (DOX) preloaded ZnO‐DOX NPs using a charge convertible polymer PEG‐PAH‐DMMA (ZDHD). The polymer can release HAase to degrade HA in the tumor ECM (pH 6.5). ZnO‐DOX NPs can release DOX in lysosomes (pH 4.5) to induce cell apoptosis, and exert a neighboring effect with size reduction to infect neighboring cells. The hierarchical targeted release of HAase and drugs is demonstrated to enhance tumor penetration and decrease side effects in vivo. This work shows promise for further application of ZDHD NPs in cancer therapy.  相似文献   

14.
A series of Sr-substituted hydroxyapatites (HA), of general formula Ca(10 ? x)Srx(PO4)6(OH)2, where x = 2 and 4, were synthesized by solid state methods and characterized extensively. The reactivity of these materials in cell culture medium was evaluated, and the behavior towards MG-63 osteoblast cells (in terms of cytotoxicity and proliferation assays) was studied. Future in vivo studies will give further insights into the behavior of the materials.A paper by Lagergren et al. (1975), concerning Sr-substituted HA prepared by a solid state method, reports that the presence of Sr in the apatite composition strongly influences the apatite diffraction patterns. Zeglinsky et al. (2012) investigated Sr-substituted HA by ab initio methods and Rietveld analyses and reported changes in the HA unit cell volume and shape due to the Sr addition.To further clarify the role played by the addition of Sr on the physico-chemical properties of these materials we prepared Sr-substituted HA compositions by a solid state method, using different reagents, thermal treatments and a multi-technique approach. Our results indicated that the introduction of Sr at the levels considered here does influence the structure of HA. There is also evidence of a decrease in the crystallinity degree of the materials upon Sr addition. The introduction of increasing amounts of Sr into the HA composition causes a decrease in the specific surface area and an enrichment of Sr-apatite phase at the surface of the samples. Bioactivity tests show that the presence of Sr causes changes in particle size and/or morphology during soaking in MEM solution; on the contrary the morphology of pure HA does not change after 14 days of reaction. The presence of Sr, as Sr-substituted HA and SrCl2, in cultures of human MG-63 osteoblasts did not produce any cytotoxic effect. In fact, Sr-substituted HA increased the proliferation of osteoblast cells and enhanced cell differentiation: Sr in HA has a positive effect on MG-63 cells. In contrast, Sr ions alone, at the concentrations released by Sr-HA (1.21–3.24 ppm), influenced neither cell proliferation nor differentiation. Thus the positive effects of Sr in Sr-HA materials are probably due to the co-action of other ions such as Ca and P.  相似文献   

15.
《Advanced Powder Technology》2020,31(3):1023-1031
We investigated the effects of different metal oxide (MO) nanoparticles (e.g., CuO, KIO4, Fe2O3) on the combustion and gas-generating characteristics of sodium azide microparticle (NaN3 MP; gas-generating agent) and aluminum nanoparticle (Al NP; heat source) composite powders. The NaN3 MP/Al NP/MO NP composite powders were stably ignited using a microhotplate (MHP) heater. The addition of CuO and KIO4 to the NaN3 MP/Al NP composite powders resulted in relatively high burn rates and high pressurization rates upon MHP-assisted ignition. This suggests that the highly reactive CuO and KIO4 NPs significantly increased the combustion of the Al NPs; as a result, sufficient heat energy was generated via the active aluminothermic reaction to thermally decompose the NaN3 MPs. Finally, the gas generating properties of NaN3 MP/Al NP composite powders mixed with various MO NPs were tested using homemade inflatable small airbags. The airbags were fully inflated within ~20 ms when CuO and KIO4 NPs were added to the NaN3 MP/Al NP composite powders. However, the addition of Fe2O3 NPs to the NaN3 MP/Al NP composite powder resulted in a slow and only partial inflation of the airbag due to an incomplete aluminothermic reaction, which was due to a slow combustion reaction between the Al NPs and relatively weak oxidizer of the Fe2O3 NPs. This suggests that the rapid, stable, and complete thermal decomposition of NaN3 MP/Al NP composites can be effectively achieved by employing highly reactive nanoscale oxidizers.  相似文献   

16.
Deliberately inorganic nanoparticles (NP)s in polymer matrices significantly affect their characteristics and therefore their applications, but key factor to achieve the expected efficiency is well dispersion of the NPs in polymer matrix. The work presented here deals with the polymerization of amino acid-based monomer to synthesize optically active poly(ester-imide) (PEI) with hydroxyl terminated groups, using tosyl chloride/pyridine/N,N-dimethylformamide system as a condensing agent. The synthesized polymer was used for the preparation of bionanocomposite (BNC) containing modified titanium dioxide (TiO2) NPs using ultrasonic irradiation. With the aim of γ-amidopropyl-triethoxylsilicane as a coupling agent, the surface of nanoscale TiO2 was modified to decrease aggregation of the NPs in polymer matrix. The obtained PEI/TiO2 BNCs were characterized with fourier transfer infrared (FT–IR), thermogravimetric analysis, field emission scanning electron microscopy (FE–SEM), X-ray diffraction and transmission electron microscopy (TEM) techniques. Morphology study of resulting PEI/TiO2 BNCs by FE–SEM and TEM analyses demonstrated that the hydroxyl-terminated polymer chains reduced aggregation of the NPs and thus lead to better dispersion of the NPs in the polymer matrix.  相似文献   

17.
Calcium phosphate (CaP) spheres with nanopores were synthesized using poly(acrylic acid) (PAA) as the structuring unit. In this method, colloidal droplets of the PAA/Ca2+ complex were prepared by adding a Ca(NO3)2 solution to a PAA aqueous solution and then mixed with an (NH4)2HPO4 solution, which allowed the nucleation and growth of CaP nanocrystals in the PAA matrix. Thereafter, the as-synthesized PAA/CaP spheres were heat-treated at 550 °C for 3 h to remove the PAA phase, followed by treatment in ammonium nitrate solution to remove the CaO phase formed as an impurity. The prepared CaP spheres showed a narrow size distribution with an average diameter of 146 ± 43 nm and nanopores formed via the removal of the CaO phase.  相似文献   

18.
The use of tissue engineered biodegradable porous scaffolds has become an important focus of the biomedical research field. The precursor materials used to form these structures play a vital role in their overall performance thus making the study and synthesis of these selected materials imperative. The authors present a comparison and characterisation of hydroxyapatite (HA), a popular calcium phosphate (CaP) biomaterial, synthesised by an aqueous precipitation (AP) method. The influence of various reaction conditions on the phase, crystallinity, particle size as well as morphology, molecular structure, potential in-vivo bioactivity and cell viability were assessed by XRD, SEM and TEM, FTIR, a simulated body fluid (SBF) test and a live/dead assay using MC3T3 osteoblast precursor cells, respectively. Naturally carbonated nanoparticles of HA with typically needle-like morphology were synthesised by the reported AP method. Initial pH was found to influence the crystallisation process and determine the CaP phase formed as well as the resultant particle and crystallite sizes. A marked change in particle morphology was also observed above pH 9. The use of toluene as a replacement solvent for water up to 60 % was found to reduce the crystallinity of as-synthesised HA. This has marked influence on the effect of ethanolamine (5 wt%), which was found to improve HA crystallinity. SEM and EDS were used to confirm the growth of carbonated apatite on the surface of HA pellets immersed in SBF for up to 28 days. Cell culture results revealed viable cells on all samples where pH was controlled and maintained at 10–11 during precipitation, including those that used ethanolamine and toluene in preparation. When the initial alkali pH was not maintained non-viable cells were observed on HA substrates.  相似文献   

19.
A multifunctional one‐dimensional nanostructure incorporating both CdSe quantum dots (QDs) and Fe3O4 nanoparticles (NPs) within a SiO2‐nanotube matrix is successfully synthesized based on the self‐assembly of preformed functional NPs, allowing for control over the size and amount of NPs contained within the composite nanostructures. This specific nanostructure is distinctive because both the favorable photoluminescent and magnetic properties of QD and NP building blocks are incorporated and retained within the final silica‐based composite, thus rendering it susceptible to both magnetic guidance and optical tracking. Moreover, the resulting hydrophilic nanocomposites are found to easily enter into the interiors of HeLa cells without damage, thereby highlighting their capability not only as fluorescent probes but also as possible drug‐delivery vehicles of interest in nanobiotechnology.  相似文献   

20.
Bioresorbable and bioactive tissue engineering scaffolds based on bioactive glass (45S5 Bioglass®) particles and macroporous poly(DL-lactide) (PDLLA) foams were fabricated. A slurry dipping technique in conjunction with pretreatment in ethanol was used to achieve reproducible and well adhering bioactive glass coatings of uniform thickness on the internal and external surfaces of the foams. In vitro studies in simulated body fluid (SBF) demonstrated rapid hydroxyapatite (HA) formation on the surface of the composites, indicating their bioactivity. For comparison, composite foams containing Bioglass® particles as filler for the polymer matrix (in concentration of up to 40 wt %) were prepared by freeze-drying, enabling homogenous glass particle distribution in the polymer matrix. The formation of HA on the composite surfaces after immersion in phosphate buffer saline (PBS) was investigated to confirm the bioactivity of the composites. Human osteoblasts (HOBs) were seeded onto as-fabricated PDLLA foams and onto PDLLA foams coated with Bioglass® particles to determine early cell attachment and spreading. Cells were observed to attach and spread on all surfaces after the first 90 min in culture. The results of this study indicate that the fabricated composite materials have potential as scaffolds for guided bone regeneration.  相似文献   

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