Preparation and property of a novel bone graft composite consisting of rhBMP-2 loaded PLGA microspheres and calcium phosphate cement

Calcium phosphate cement (CPC) is a highly promising bone substitute and an excellent carrier for delivering growth factors. Yet, the lack of macro-porosity and osteoinductive ability, limit its use. This study is aimed at developing a novel biodegradable biomaterial for bone repair with both highly osteoconductive and osteoinductive properties. RhBMP-2 loaded PLGA microspheres were incorporated into rhBMP-2/CPC for macropores for bone ingrowth. The compressive strength, crystallinity, microscopic structure, and bioactivity of the composites were investigated. The results showed that with the incorporation of rhBMP-2 loaded PLGA microspheres, the compressive strength was decreased from (29.48 ± 6.42) MPa to (8.26 ± 3.58) MPa. X-ray diffraction revealed that the crystallinity pattern of HA formed by CPC had no significant change. Inside the composite, the microspheres distributed homogeneously and contacted intimately with the HA matrix, as observed by scanning electron microscopy (SEM). When the PLGA microspheres dissolved after having been emerged in PBS for 56 days, macropores were created within the CPC. The rhBMP-2/PLGA/CPC composite, showing a 4.9% initial release of rhBMP-2 in 24 h, followed by a prolonged release for 28 days, should have a greater amount of rhBMP-2 released compared to the CPC delivery system. When rabbit marrow stromal cells were cocultured with the composite, the alkaline phosphatase (ALP) and osteocalcin (OC) showed a dose response to the rhBMP-2 released from the composite, indicating that the activity of rhBMP-2 was retained. This study shows that the new composite reveals more rhBMP-2 release and osteogenic activity. This novel BMP/PLGA/CPC composite could be a promising synthetic bone graft in craniofacial and orthopedic repairs.     

Fabrication of an rhBMP-2 loaded porous β-TCP microsphere-hyaluronic acid-based powder gel composite and evaluation of implant osseointegration

Methods to improve osseointegration that include implantation of rhBMP-2 with various kinds of carriers are currently of considerable interest. The present study was conducted to evaluate if the rhBMP-2 loaded β-TCP microsphere-hyaluronic acid-based powder-like hydrogel composite (powder gel) can act as an effective rhBMP-2 carrier for implantation in host bone with a bone defect or poor bone quality. The release pattern for rhBMP-2 was then evaluated against an rhBMP-2-loaded collagen sponge as a control group. Dental implants were also inserted into the tibias of three groups of rabbits: an rhBMP-2 (200 µg) loaded powder gel composite implanted group, an implant only group, and a powder gel implanted group. Micro-CT and histology of the implanted areas were carried out four weeks later. The rhBMP-2 powder gel released less rhBMP-2 than the collagen sponge, but it continued a slow release for more than 7 days. The rhBMP-2 powder gel composite improved osseointegration of the dental implant by increasing the amount of new bone formation in the implant pitch and it improved the bone quality and bone quantity of new bone. The histology results indicated that the rhBMP-2 powder gel composite improved the osseointegration in the cortical bone as well as the marrow space along the fixture. The bone-to-implant contact ratio of the rhBMP-2 (200 µg) loaded powder gel composite implanted group was significantly higher than those of the implant only group and the powder gel implanted group. The powder gel appeared to be a good carrier and could release rhBMP-2 slowly to promote the formation of new bone following implantation in a bone defect, thereby improving implant osseointegration.     

中空羟基磷灰石微球作为rhBMP-2缓释载体的研究

利用锂钙硼玻璃在磷酸盐溶液中的原位转化反应制备表面多孔且中空的羟基磷灰石(HA)微球, 将重组人骨形态发生蛋白2(rhBMP-2)装载到微球中, 研究了微球中rhBMP-2的体外缓释行为, 并采用体外细胞培养技术, 将载有rhBMP-2的微球和大鼠骨髓间充质干细胞(MSCs)一起培养, 测定细胞的碱性磷酸酶(ALP)活性, 并与单纯rhBMP-2的作用进行比较. 结果显示, 微球中所装载的rhBMP-2具有明显的缓释效应, 体外释放周期达到1000h以上, 该微球缓释系统具有一定的生物活性, 其作用效果优于单纯使用rhBMP-2.     

Effects of porous beta-tricalcium phosphate-based ceramics used as an E. coli-derived rhBMP-2 carrier for bone regeneration

Recombinant human bone morphogenetic protein-2 (rhBMP-2) requires carriers for clinical effectiveness. In this study, whether porous beta-tricalcium phosphate (β-TCP)-based ceramics are ideal carriers for rhBMP-2 was investigated. Hydroxyapatite (HA), β-TCP, TCP/HA (80 %/20 %), HA with rhBMP-2, TCP with rhBMP-2, and TCP/HA (80 %/20 %) with rhBMP-2 were manufactured by a sponge method with a pore size of 300 μm or more and macro-porosity of 83 %. The alkaline phosphatase (ALP) activity and ALP expression of the cells with 100 % β-TCP granules were more increased than the those of cells with 100 % HA and TCP/HA (80 %/20 %) at the baseline or when treated with 15 ng/ml of rhBMP-2. In an SD rat calvarial defect model, new bone formation was evidently shown in the TCP 100 %-rhBMP-2 and TCP/HA (80 %/20 %)-rhBMP-2 groups, showing that the most affected area was filled with newly-formed bone, that the percent bone volume and trabecular number were larger when compared to the groups without rhBMP-2 treatment at both 4 and 8 weeks after surgery using micro-CT and histology. Porous TCP-based ceramic granules enhanced the osteoblastic differentiation in the hMSC system when treated with 15 ng/ml of rhBMP-2 and accelerated bone-healing by trabecular number in a rat calvarial defect model. Thus, in this study it was proposed that TCP-based ceramics might be useful carriers of rhBMP-2.     

Injectable thermogelling chitosan for the local delivery of bone morphogenetic protein

The aim of the present study was to evaluate the in vivo biocompatibility of injectable thermo gelling chitosan-ammonium hydrogen phosphate solution (chitosan-AHP) and its efficacy to deliver recombinant human bone morphogenetic protein-2 (rhBMP-2) in a bioactive form. The thermogel showed a typical foreign body response upon subcutaneous implantation surrounded by a fibrous capsule. Even at 4 and 8?weeks post implantation, significant neutrophil infiltration was observed within the gel. Chitosan-AHP gel retained most of the loaded rhBMP-2 after a small initial release. The bioactivity of the released protein was demonstrated in vitro by the increase in alkaline phosphatase activity of mouse pre osteoblast cells (MC3T3-E1). Histological and micro-computed tomography (μCT) evaluation showed evidence of ectopic bone formation upon 4?μg/mL rhBMP-2 loaded chitosan-AHP injection. The study demonstrated a neutrophil mediated local tissue response to chitosan-AHP gel and its ability to encapsulate and maintain the bioactivity of rhBMP-2.     

Bioactivity of porous biphasic calcium phosphate enhanced by recombinant human bone morphogenetic protein 2/silk fibroin microsphere

To prepare a bioactive bone substitute, which integrates biphasic calcium phosphate (BCP) and rhBMP-2/silk fibroin (SF) microsphere, and to evaluate its characteristics. Hydroxyapatite and β-tricalcium phosphate were integrated with a ratio of 60–40 %. RhBMP-2/SF (0.5 μg/1 mg) microsphere was prepared, and its rhBMP-2-release kinetics was assed. After joining pore-forming agent (Sodium chloride, NaCl), porous BCP/rhBMP-2/SF were manufactured, and its characteristics and bioactivity in vitro were evaluated. Mean diameter of rhBMP-2/SF microsphere was 398.7 ± 99.86 nm, with a loading rate of 4.53 ± 0.08 %. RhBMP-2 was released in a dual-phase pattern, of which fast-release (nearly half of protein released) focused on the initial 3 days, and slow-release sustained more than 28 days. With the increase in concentration of NaCl, greater was porosity and pore size, but smaller mechanical strength of BCP/rhBMP-2/SF. Material with 150 % (w/v) NaCl had an optimal performance, with a porosity of 78.83 %, pore size of 293.25 ± 42.77μm and mechanical strength of 31.03 MPa. Proliferation of human placenta-derived mesenchymal stem cells (hPMSCs) on leaching extract medium was similar to the normal medium (P = 0.89), which was better than that on control group (P = 0.03). Activity of alkaline phosphatase on BCP/rhBMP-2/SF surface was higher than on pure BCP at each time point except at 1 day (P < 0.05). RhBMP-2 has a burst release on early times and a sustaining release on later times. BCP/rhBMP-2/SF with 150 % (w/v) pore-forming agent has excellent porosity, pore size and mechanical strength. The biomaterial induces proliferation and differentiation hPMSCs effectively.     

In vitro bioactivity, cytocompatibility, and antibiotic release profile of gentamicin sulfate-loaded borate bioactive glass/chitosan composites

Borate bioactive glass-based composites have been attracting interest recently as an osteoconductive carrier material for local antibiotic delivery. In the present study, composites composed of borate bioactive glass particles bonded with a chitosan matrix were prepared and evaluated in vitro as a carrier for gentamicin sulfate. The bioactivity, degradation, drug release profile, and compressive strength of the composite carrier system were studied as a function of immersion time in phosphate-buffered saline at 37 °C. The cytocompatibility of the gentamicin sulfate-loaded composite carrier was evaluated using assays of cell proliferation and alkaline phosphatase activity of osteogenic MC3T3-E1 cells. Sustained release of gentamicin sulfate occurred over ~28 days in PBS, while the bioactive glass converted continuously to hydroxyapatite. The compressive strength of the composite loaded with gentamicin sulfate decreased from the as-fabricated value of 24 ± 3 MPa to ~8 MPa after immersion for 14 days in PBS. Extracts of the soluble ionic products of the borate glass/chitosan composites enhanced the proliferation and alkaline phosphatase activity of MC3T3-E1 cells. These results indicate that the gentamicin sulfate-loaded composite composed of chitosan-bonded borate bioactive glass particles could be useful clinically as an osteoconductive carrier material for treating bone infection.     

Evaluation of microporous polycaprolactone matrices for controlled delivery of antiviral microbicides to the female genital tract

Acyclovir (ACV) as a model antiviral microbicide, was incorporated in controlled-release polycaprolactone (PCL) matrices designed for application as intra-vaginal ring inserts (IVRs). Microporous materials incorporating acyclovir up to a level of ~10 % w/w were produced by rapidly cooling suspensions of drug powder in PCL solution followed by solvent extraction from the hardened matrices. Around 21, 50 and 78 % of the drug content was gradually released from matrices over 30 days in simulated vaginal fluid at 37 °C, corresponding to drug loadings of 5.9, 7.0 and 9.6 % w/w. The release behaviour of matrices having the lowest drug loading followed a zero order model, whereas, the release kinetics of 7.0 and 9.6 % ACV-loaded PCL matrices could be described effectively by the Higuchi model, suggesting that Fickian diffusion is controlling drug release. Corresponding values of the diffusion co-efficient for ACV in the PCL matrices of 3.16 × 10^?9 and 1.07 × 10^?8 cm²/s were calculated. Plaque reduction assays provided an IC₅₀ value of 1.09 μg/mL for acyclovir against HSV-2 and confirmed the antiviral activity of released acyclovir against HSV-2 replication in primate kidney cells (Vero) at levels ~70 % that of non-formulated acyclovir at day 30. Estimated minimum in vivo acyclovir concentrations produced by a PCL IVR (19 μg/mL) exceeded by a factor of 20 the IC₅₀ value against HSV-2 and the reported ACV vaginal concentrations in women (0.5–1.0 μg/mL) following oral administration. These findings recommend further investigations of PCL matrices for vaginal delivery of antiviral agents in the treatment and prevention of sexually transmitted infections such as AIDS.     

负载淫羊藿苷的丝蛋白/β-磷酸三钙复合骨修复材料制备及性能

在多孔β-Ca_3(PO_4)_2(β-TCP)表面沉积含有淫羊藿苷(ICA)的丝蛋白(SF)层,制备可缓释ICA的SFICA/β-TCP骨修复复合材料,研究SF-ICA/β-TCP复合材料的相关性能。结果表明,SF-ICA/β-TCP复合材料中ICA的引入并未改变基体材料的微观形貌与孔隙率;体外释放实验表明,通过负载量的调控,可以实现SF-ICA/β-TCP复合材料中ICA的高浓度释放(2.80×10~(-4) mg/mL至7.00×10~(-4) mg/mL)和低浓度释放(5×10~(-6) mg/mL至1.0×10~(-5) mg/mL),累计释放量分别达到约5.2×10~(-3) mg和7.0×10~(-5) mg;细胞增殖实验与电镜观察表明,SF-ICA/β-TCP复合材料中ICA的负载对小鼠颅顶前骨细胞的增殖无显著性影响;但碱性磷酸酶活性检测实验表明,负载高含量ICA的SF-ICA/β-TCP复合材料中的细胞具有较高的碱性磷酸酶表达。所制备的负载ICA的SFICA/β-TCP复合材料在体内骨修复领域具有潜在的应用前景。     

In vitro antimicrobial activity of vancomycin-eluting bioresorbable β-TCP-polylactic acid nanocomposite material for load-bearing bone repair

Release of antimicrobial agents from bone healing devices can dramatically reduce the risk of implant-associated infection. Here we report the fabrication and antimicrobial activity of a multifunctional load-bearing bioresorbable material that can provide mechanical support to the healing bone all while slowly releasing an antibiotic drug. Dense beta-tricalcium phosphate (β-TCP)–40 vol% polylactic acid (PLA) nanocomposite containing 1 wt% vancomycin (VH) was high pressure consolidated at 2.5 GPa, at room temperature, or at 120 °C. Over the course of 5 weeks in TRIS solution, the β-TCP-PLA-VH nanocomposite released approximately 90 % of its drug load. Specimens consolidated at 120 °C had the highest initial mechanical properties and maintained 85 % of their compressive strength and 30 % of their bending strength after 5 weeks release. In vitro growth inhibition study showed significant antimicrobial efficacy of VH-impregnated β-TCP-PLA against methicillin-resistant Staphylococcus aureus when exposed to both high (2 × 10⁵ CFU/mL) and very high (1 × 10⁸ CFU/mL) bacterial concentrations. After 1 week, total eradication of the microorganisms was achieved. The results suggest that the developed high-strength antibiotic-eluting β-TCP-PLA nanocomposite can be a promising material for orthopedic surgical devices.     

Biocompatibility of artificial bone based on vancomycin loaded mesoporous silica nanoparticles and calcium sulfate composites

The aim of this study was to evaluate the in vitro and in vivo biocompatibility of artificial bone based on vancomycin loaded mesoporous silica nanoparticles and calcium sulfate composites. In vitro cytotoxicity tests by cholecystokinin octapeptide (CCK-8) assay showed that the 5 %Van-MSN-CaSO₄ and Van-CaSO₄ bone cements were cytocompatible for mouse osteoblastic cell line MC3T3-E1. The microscopic observation confirmed that MC3T3-E1cells incubated with Van-CaSO₄ group and 5 %Van-MSN-CaSO₄ group exhibited clear spindle-shaped changes, volume increase and maturation, showing that these cements supported adhesion of osteoblastic cells on their surfaces. In addition, the measurement of alkaline phosphatase activity revealed the osteoconductive property of these biomaterials. In order to assess in vivo biocompatibility, synthesized cements were implanted into the distal femur of twelve adult male and female New Zealand rabbits. After implantation in artificial defects of the distal femur, 5 %Van-MSN-CaSO₄ and Van-CaSO₄ bone cements did not damage the function of main organs of rabbits. In addition, the Van-MSN-CaSO₄ composite allowed complete repair of bone defects with new bone formation 3 months after implantation. These results show potential application of Van-MSN-CaSO₄ composites as bone graft materials for the treatment of open fracture in human due to its mechanical, osteoconductive and potential sustained drug release characteristics and the absence of adverse effects on the body.     

A novel injectable borate bioactive glass cement for local delivery of vancomycin to cure osteomyelitis and regenerate bone

Osteomyelitis (bone infection) is often difficult to cure. The commonly-used treatment of surgical debridement to remove the infected bone combined with prolonged systemic and local antibiotic treatment has limitations. In the present study, an injectable borate bioactive glass cement was developed as a carrier for the antibiotic vancomycin, characterized in vitro, and evaluated for its capacity to cure osteomyelitis in a rabbit tibial model. The cement (initial setting time = 5.8 ± 0.6 min; compressive strength = 25.6 ± 0.3 MPa) released vancomycin over ~25 days in phosphate-buffered saline, during which time the borate glass converted to hydroxyapatite (HA). When implanted in rabbit tibial defects infected with methicillin-resistant Staphylococcus aureus (MRSA)-induced osteomyelitis, the vancomycin-loaded cement converted to HA and supported new bone formation in the defects within 8 weeks. Osteomyelitis was cured in 87 % of the defects implanted with the vancomycin-loaded borate glass cement, compared to 71 % for the defects implanted with vancomycin-loaded calcium sulfate cement. The injectable borate bioactive glass cement developed in this study is a promising treatment for curing osteomyelitis and for regenerating bone in the defects following cure of the infection.     

Evaluation of collagen/heparin coated TCP/HA granules for long-term delivery of BMP-2

Bone morphogenetic proteins (BMPs) are the most potent osteoinductive growth factors. However, a delivery system is essential to take advantage of the osteoinductive effect of BMPs. The purpose of this study was to develop a sustained delivery system for recombinant human bone morphogenetic protein-2 (BMP-2). We covalently attached heparin to a cross-linked collagen type I coated tricalciumphosphate/hydroxyapatite (TCP/HA) bone substitute and subsequently loaded it with BMP-2. To systematically evaluate the contribution of each component with respect to the binding and release of BMP-2, six constructs were prepared and characterized: TCP/HA, TCP/HA with collagen (TCP/HACol), and TCP/HA with collagen and heparin (TCP/HAColHep) with and without BMP-2 (B). More BMP-2 bound to the TCP/HAColHep + B (92.9 ± 4.8 ng BMP-2/mg granule) granules as compared to the TCP/HACol + B (69.0 ± 9.6 ng BMP-2/mg granule) and TCP/HA + B granules (62.9 ± 5.4 ng BMP-2/mg granule). No difference in release pattern was found between the TCP/HA + B and TCP/HACol + B granules. Up to day 14, BMP-2 was still bound to the TCP/HAColHep + B granules, whereas most BMP had been released from TCP/HACol + B and TCP/HA + B granules at that time. After 21 days most BMP-2 also had been released from the TCP/HAColHep + B granules. The local and sustained delivery system for BMP-2 developed in this study may be useful as a carrier for BMP-2 and could possibly enhance bone regeneration efficacy for the treatment of large bone defects.     

Zonal release of proteins within tissue engineering scaffolds

The manufacture of a scaffold for tissue engineering applications that can control the location and timing of growth factor release is described. The scaffold is formed by the sintering of poly(DL-lactic acid) (P_DLLA) microparticles, plasticized with poly(ethylene glycol) (PEG), although the method can be used for many other polymer types. The microparticles were loaded with model proteins, trypsin and horseradish peroxidase (HRP), or recombinant human bone morphogenetic protein-2 (rhBMP-2). Entrapment efficiencies above 75% were achieved using a solid-in-oil-in-water system. Controlled release of active protein was achieved for at least 30 days. Microparticles were built into protein-loaded or protein-free layers and release of the protein was restricted to zones within the scaffold. Cell response to rhBMP-2 was tuneable by changing the dose of the rhBMP-2 released by varying the ratio of protein-loaded and protein-free microparticles within scaffolds. Zonal activity of rhBMP-2 on C2C12 cells was demonstrated. The scaffolds may find utility in applications where gradients of growth factors within 3D templates are required or where zonation of tissue growth is required.     

Synthesis of novel tricalcium phosphate-bioactive glass composite and functionalization with rhBMP-2

A functionalization is required for calcium phosphate-based bone substitute materials to achieve an entire bone remodeling. In this study it was hypothesized that a tailored composite of tricalcium phosphate and a bioactive glass can be loaded sufficiently with rhBMP-2 for functionalization. A composite of 40 wt% tricalcium phosphate and 60 wt% bioactive glass resulted in two crystalline phases, wollastonite and rhenanite after sintering. SEM analysis of the composite’s surface revealed a spongious bone-like morphology after treatment with different acids. RhBMP-2 was immobilized non-covalently by treating with chrome sulfuric acid (CSA) and 3-aminopropyltriethoxysilane (APS) and covalently by treating with CSA/APS, and additionally with 1,1′-carbonyldiimidazole. It was proved that samples containing non-covalently immobilized rhBMP-2 on the surface exhibit significant biological activity in contrast to the samples with covalently bound protein on the surface. We conclude that a tailored composite of tricalcium phosphate and bioactive glass can be loaded sufficiently with BMP-2.     

Three-dimensionally plotted MBG/PHBHHx composite scaffold for antitubercular drug delivery and tissue regeneration

A suitable drug-loaded scaffold that can postoperatively release an antituberculosis drug efficiently in a lesion area and help repair a bone defect is very important in the clinical treatment of bone tuberculosis (TB). In this study, a composite drug-loaded cylindrical scaffold was prepared by using three-dimensional printing technology in combination with the mesoporous confinement range, surface chemical groups, and gradual degradation of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate). This achieves the slow release of a drug for as long as possible. We implanted the drug-loaded compound scaffold into New Zealand rabbits’ femur defect model to study the in vivo drug release performance and osteogenic ability. The in vivo release of isoniazid and rifampicin from the prepared composites could be effectively sustained for 12 weeks in local tissues, whereas these drugs were sustained for just 2 weeks in a control group. The blood drug concentrations were very low and most concentrations were below 5 μg/ml. Therefore, the systemic toxic adverse effect is very low. In addition, the composite exhibits good osteogenic potential in a rabbit bone defect model. The results of this study indicate that this composite has great potential for treating osteoarticular TB.     

Nano-composite scaffolds for bone tissue engineering containing silver nanoparticles: preparation, characterization and biological properties

In this study nano-composite scaffolds to be used as bone grafts have been endowed with antibacterial properties owing to the presence of silver nanoparticles. The alginate/hydroxyapatite composite scaffolds were prepared by internal gelation followed by a freeze-drying procedure to obtain a porous structure. The nanoparticles were prepared in presence of a lactose modified-chitosan and this colloidal solution was adsorbed on the scaffolds by exploiting electrostatic interactions. The adsorption and release of the silver from the composite scaffold was measured by ICP-AES and spectrofluorimetry measurements. Micro-computed tomography analysis of the scaffolds showed a homogeneous porous structure with average pore sizes of 341.5 μm and porosity of 80 %. In vitro biological tests (MTS and killing kinetics assays) demonstrated that silver does not affect the ability of the scaffolds to promote osteoblasts proliferation and that at the same time it exerts a strong bactericidal effect against both Gram+ and Gram? bacterial strains. Overall, the combined results indicate that these biocompatible antimicrobial scaffolds possess ideal characteristics for tissue engineering applications.     

The effect of rhBMP-2 and PRP delivery by biodegradable β-tricalcium phosphate scaffolds on new bone formation in a non-through rabbit cranial defect model

This study evaluated whether the combination of biodegradable β-tricalcium phosphate (β-TCP) scaffolds with recombinant human bone morphogenetic protein-2 (rhBMP-2) or platelet-rich plasma (PRP) could accelerate bone formation and increase bone height using a rabbit non-through cranial bone defect model. Four non-through cylindrical bone defects with a diameter of 8-mm were surgically created on the cranium of rabbits. β-TCP scaffolds in the presence and absence of impregnated rhBMP-2 or PRP were placed into the defects. At 8 and 16 weeks after implantation, samples were dissected and fixed for analysis by microcomputed tomography and histology. Only defects with rhBMP-2 impregnated β-TCP scaffolds showed significantly enhanced bone formation compared to non-impregnated β-TCP scaffolds (P < 0.05). Although new bone was higher than adjacent bone at 8 weeks after implantation, vertical bone augmentation was not observed at 16 weeks after implantation, probably due to scaffold resorption occurring concurrently with new bone formation.     

Hydrophilic poly (ethylene glycol) coating on PDLLA/BCP bone scaffold for drug delivery and cell culture

A well developed porous poly-D-L-lactide (PDLLA)/biphasic calcium phosphate (BCP) scaffold was coated with a hydrophilic poly (ethylene glycol) (PEG)/vancomycin composite for drug delivery and surface modification. The PDLLA/BCP scaffold, obtained by a salt-leaching method, possessed highly inter-connected pores (250–350 μm) and a high porosity (83.8%). The hydrophilic PEG was used to effectively entrap the drug inside the scaffold and to enhance the wettability of the hydrophobic surface of the PDLLA/BCP matrix. The scaffold with PEG/vancomycin coatings was fabricated by injecting the PEG/vancomycin composite solution into the pre-vacuumized scaffold. A standardized bacterial assay showed that the drug was still active after association with the bone scaffold. The in-vitro drug release study of vancomycin showed an initial burst release followed by a slower sustained release. The drug release behavior in vitro was investigated in detail by controlling the composite solution parameters: PEG molecular weight and PEG concentration. The release profiles showed that an increase in the PEG molecular weight and concentration resulted in a slower drug release rate. The water contact angles of the scaffold surface decreased after being coated with PEG. The in-vitro osteoblast culture experiment confirmed the biocompatibility of the scaffold for the growth of osteoblasts.     

Synthesis,characterization and bactericidal activity of silica/silver core–shell nanoparticles

Silica/silver core–shell nanoparticles (NPs) were synthesized by coating silver NPs on silica core particles (size ~300 ± 10 nm) via electro less reduction method. The core–shell NPs were characterized for their structural, morphological, compositional and optical behavior using X-ray diffraction, scanning electron microscopy, energy dispersive X-ray analysis and UV–Visible spectroscopy, respectively. The size (16–35 nm) and loaded amount of silver NPs on the silica core were found to be dependent upon reaction time and activation method of silica. The bactericidal activity of the NPs was tested by broth micro dilution method against both Bacillus subtilis (gram positive) and Escherichia coli ATCC25922 (gram negative) bacterium. The bactericidal activity of silica/silver core–shell NPS is more against E. coli ATCC25922, when compared to B. subtilis. The minimal inhibitory concentration of the core–shell NPs ranged from 7.8 to 250 μg/mL and is found to be dependent upon the amount of silver on silica, the core. These results suggest that silica/silver core–shell NPs can be utilized as a strong substitutional candidate to control pathogenic bacterium, which are otherwise resistant to antibiotics, making them applicable in diverse medical devices.