A novel sheep vertebral bone defect model for injectable bioactive vertebral augmentation materials

New injectable bone substitutes have been developed that are, unlike polymethylmethacrylate, biologically active and have an osteogenic effect leading to osteogenesis and bone remodeling for vertebroplasty or kyphoplasty. In this study, we developed a sheep vertebral bone defect model to evaluate the new bioactive materials and assessed the feasibility of the model in vivo. Bone voids were experimentally created on lumbar vertebrae L2–L5 with L1 and L6 left intact as a normal control in mature sheep. The defect vertebrae L2–L5 in each sheep were randomized to receive augmentation with calcium phosphate cement (CPC) or sham. Vertebrae (L1–L6) were collected after 2 and 24 weeks of the cement augmentation and their strength and stiffness, as well as osseointegration activity and biodegradability, were evaluated. Finally, CPC significantly improved the strength and stiffness of vertebrae but did not yet restore it to the normal level at 24 weeks. Osteogenesis occurred at a substantially high level after 24 weeks of CPC augmentation or sham. Therefore, the sheep vertebral model with one void, 6.0 mm in diameter and 15.0 mm in depth, is replicable and can be used for evaluating the new injectable bioactive materials in vertebral augmentation or reconstruction.     

Biodegradable and bioactive properties of a novel bone scaffold coated with nanocrystalline bioactive glass for bone tissue engineering

The development of the new technologies of bone tissue engineering requires the production of bioactive and biodegradable macroporous scaffolds. Hydroxyapatite (HA) ceramics are useful bone substitutes, but they degrade minimally. Tricalcium phosphates also show poor ability of Ca-P formation both in-vitro and in-vivo, although they are degradable. The present study introduces a biodegradable, bioactive, and macroporous scaffold with suitable mechanical properties. The prepared hydroxyapatite scaffold was coated with a nanocrystalline bioactive glass layer to be subsequently sintered at different temperatures. The bioactivity and degradability of the coated scaffolds were investigated by standard procedures. The ability to induce Ca-P formation in SBF (simulated body fluid) was also investigated semi-quantitatively. BS1 scaffolds (scaffolds sintered at 800 °C with a holding time of 2 h) showed remarkable bioactivity and degradability simultaneously. Formation of a nanocrystalline phase (Si₂PO₇) during the sintering considerably decreased the capability of BS1 scaffolds for Ca-P formation and the rate of degradation but enhanced their mechanical properties. The BS1 scaffolds showed not only significant bioactivity but also good degradability and suitable mechanical property.     

Preparation and characterization of a novel bioactive bone cement: Glass based nanoscale hydroxyapatite bone cement

A novel type of glass-based nanoscale hydorxypatite (HAP) bioactive bone cement (designed as GBNHAPC) was synthesized by adding nanoscale hydroxyapatite (HAP) crystalline (20–40 nm), into the self-setting glass-based bone cement (GBC). The inhibition rate of nanoscale HAP and micron HAP on osteosarcoma U2-OS cells was examined. The effects of nanoscale HAP on the crystal phase, microstructure and compressive strength of GBNHAPC were studied respectively. It was concluded that nanoscale HAP could inhibit the cell proliferation, while micron HAP could not, and that nanoscale HAP could be dispersed in the cement evenly and the morphology did not change significantly after a longer immersion time. XRD and FTIR results show nanoscale HAP did not affect the setting reaction of the cement. Furthermore, GBNHAPC had a higher compressive strength (92 MPa) than GBC. It was believed that GBNHAPC might be a desirable biomaterial that could not only fill bone defects but also inhibit cancer cell growth.     

A novel vehicle for local protein delivery to the inner ear: injectable and biodegradable thermosensitive hydrogel loaded with PLGA nanoparticles

Delivery of biomacromolecular drugs into the inner ear is challenging, mainly because of their inherent instability as well as physiological and anatomical barriers. Therefore, protein-friendly, hydrogel-based delivery systems following local administration are being developed for inner ear therapy. Herein, biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) containing interferon α-2?b (IFN α-2?b) were loaded in chitosan/glycerophosphate (CS/GP)-based thermosensitive hydrogel for IFN delivery by intratympanic injection. The injectable hydrogel possessed a physiological pH and formed semi-solid gel at 37?°C, with good swelling and deswelling properties. The CS/GP hydrogel could slowly degrade as visualized by scanning electron microscopy (SEM). The presence of NPs in CS/GP gel largely influenced in vitro drug release. In the guinea pig cochlea, a 1.5- to 3-fold increase in the drug exposure time of NPs-CS/GP was found than those of the solution, NPs and IFN-loaded hydrogel. Most importantly, a prolonged residence time was attained without obvious histological changes in the inner ear. This biodegradable, injectable, and thermosensitive NPs-CS/GP system may allow longer delivery of protein drugs to the inner ear, thus may be a potential novel vehicle for inner ear therapy.     

A glass polyalkenoate cement carrier for bone morphogenetic proteins

Journal of Materials Science: Materials in Medicine - A series of high molecular weight polymers were prepared by ring opening polymerization of l-lactide (l-LA), 1,3-trimethylene carbonate (TMC)...     

Investigation of emulsified,acid and acid-alkali catalyzed mesoporous bioactive glass microspheres for bone regeneration and drug delivery

Acid-catalyzed mesoporous bioactive glass microspheres (MBGMs-A) and acid-alkali co-catalyzed mesoporous bioactive glass microspheres (MBGMs-B) were successfully synthesized via combination of sol-gel and water-in-oil (W/O) micro-emulsion methods. The structural, morphological and textural properties of mesoporous bioactive glass microspheres (MBGMs) were characterized by various techniques. Results show that both MBGMs-A and MBGMs-B exhibit regularly spherical shape but with different internal porous structures, i.e., a dense microstructure for MBGMs-A and internally porous structure for MBGMs-B. ²⁹Si NMR data reveal that MGBMs have low polymerization degree of silica network. The in vitro bioactivity tests indicate that the apatite formation rate of MBGMs-B was faster than that of MBGMs-A after soaking in simulated body fluid (SBF) solution. Furthermore, the two kinds of MBGMs have similar storage capacity of alendronate (AL), and the release behaviors of AL could be controlled due to their unique porous structure. In conclusion, the microspheres are shown to be promising candidates as bone-related drug carriers and filling materials of composite scaffold for bone repair.     

Novel bioresorbable and bioactive composites based on bioactive glass and polylactide foams for bone tissue engineering

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.     

Study on injectable and degradable cement of calcium sulphate and calcium phosphate for bone repair

Injectable calcium sulphate/phosphate cement (CSPC) with degradable characteristic was developed by introduction of calcium sulphate (CS) into calcium phosphate cement (CPC). The setting time, compressive strength, composition, degradation, cells and tissue responses to the CSPC were investigated. The results show that the injectable CSPC with optimum L/P ratio exhibited good injectability, and had suitable setting time and mechanical properties. Furthermore, the CSPC had good degradability and its degradation significantly faster than that of CPC in Tris–HCl solution. Cell culture results indicate that CSPC was biocompatible and could support MG63 cell attachment and proliferation. To investigate the in vivo biocompatibility and osteogenesis, the CSPC were implanted in the bone defects of rabbits. Histological evaluation shows that the introduction of CS into CPC enhanced the efficiency of new bone formation, and CSPC exhibited good biocompatibility, degradability and osteoconductivity with host bone in vivo. It can be concluded that the injectable CSPC had a significant clinical advantage over CPC, and might have potential to be applied in orthopedic, reconstructive and maxillofacial surgery, especially for minimally invasive techniques.     

Bioactive glass granules and polytetrafluoroethylene membrane in the repair of bone defects adjacent to titanium and bioactive glass implants

An experimental animal model was used to investigate the effect of bioactive glass (BG) granules and nonresorbable polytetrafluoroethylene (PTFE) membrane on the repair of cortical bone defects adjacent to titanium and BG implants. Thirty-two Astra® (diameter 3.5 mm) dental implants were inserted bicortically and 42 conical BG implants (diameter 2.5–3.0 mm) monocortically, into fitted holes of rabbit tibia. Before implantation, a standardized bone defect was created by drilling an extra hole (diameter 3.0 mm) adjacent to each implant site. Twenty-eight defects were filled with BG granules (diameter 630–800 m) (BG group) and 28 defects were left empty but covered with PTFE membrane (PTFE group). No material was used in 18 control defects (control group). Morphometrical evaluation with a digital image analysis system was used to measure bone repair as percentages of the defect area on scanning electron microscopy (SEM) and light microscopy pictures. Bone–implant contact was measured as percentages of the thickness of the cortical bone. At 6 and 12 wk, bone repair in defects in connection with titanium implants was 23.2% and 36.6% in the BG group, 23.2% and 32.4% in the PTFE group, and 47.2% and 46.2% in control defects. Corresponding figures for BG implants were 33.2% and 40.1% in the BG group, 16.6% and 33.5% in the PTFE group, and 25.7% and 54.9% in control defects, BG granules and new bone together filled 82.7% and 68.5% of the defect area adjacent to titanium implants, and 75.9% and 74.4% of the defect adjacent to BG implants at 6 and 12 wk, respectively. Better bone–implant contact was achieved at the defect side with BG than titanium implants (77.0% versus 45.0% at 12 wk). The results indicate that BG granules are useful in treatment of bone defects adjacent to dental implants. BG coating of the implant seems to improve osseointegration in the defect area.     

Hydrogel/bioactive glass composites for bone regeneration applications: Synthesis and characterisation

Due to the deficiencies of current commercially available biological bone grafts, alternative bone graft substitutes have come to the forefront of tissue engineering in recent times. The main challenge for scientists in manufacturing bone graft substitutes is to obtain a scaffold that has sufficient mechanical strength and bioactive properties to promote formation of new tissue. The ability to synthesise hydrogel based composite scaffolds using photopolymerisation has been demonstrated in this study. The prepared hydrogel based composites were characterised using techniques including Fourier Transform Infrared Spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), Energy-dispersive X-ray spectrometry (EDX), rheological studies and compression testing. In addition, gel fraction, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), porosity and swelling studies of the composites were carried out. It was found that these novel hydrogel bioglass composite formulations did not display the inherent brittleness that is typically associated with bioactive glass based bone graft materials and exhibited enhanced biomechanical properties compared to the polyethylene glycol hydrogel scaffolds along. Together, the combination of enhanced mechanical properties and the deposition of apatite on the surface of these hydrogel based composites make them an ideal candidate as bone graft substitutes in cancellous bone defects or low load bearing applications.     

Macro-to-micro porous special bioactive glass and ceftriaxone-sulbactam composite drug delivery system for treatment of chronic osteomyelitis: an investigation through in vitro and in vivo animal trial

A systematic and extensive approach incorporating in vitro and in vivo experimentation to treat chronic osteomyelitis in animal model were made using antibiotic loaded special bioactive glass porous scaffolds. After thorough characterization for porosity, distribution, surface charge, a novel drug composite were infiltrated by using vacuum infiltration and freeze-drying method which was subsequently analyzed by SEM-EDAX and studied for in vitro drug elution in PBS and SBF. Osteomyelitis in rabbit was induced by inoculation of Staphylococcus aureus and optimum drug-scaffold were checked for its efficacy over control and parenteral treated animals in terms of histopathology, radiology, in vivo drug concentration in bone and serum and implant-bone interface by SEM. It was optimized that 60P samples with 60-65% porosity (bimodal distribution of macro- to micropore) with average pore size ~60 μm and higher interconnectivity, moderately high antibiotic adsorption efficiency (~49%) was ideal. Results after 42 days showed antibiotic released higher than MIC against S. aureus compared to parenteral treatment (2 injections a day for 6 weeks). In vivo drug pharmacokinetics and SEM on bone-defect interface proved superiority of CFS loaded porous bioactive glass implants over parenteral group based on infection eradication and new bone formation.     

Bioactive borate glass scaffolds: in vitro and in vivo evaluation for use as a drug delivery system in the treatment of bone infection

The objective of this work was to evaluate borate bioactive glass scaffolds (with a composition in the system Na₂O–K₂O–MgO–CaO–B₂O₃–P₂O₅) as devices for the release of the drug Vancomycin in the treatment of bone infection. A solution of ammonium phosphate, with or without dissolved Vancomycin, was used to bond borate glass particles into the shape of pellets. The in vitro degradation of the pellets and their conversion to a hydroxyapatite-type material in a simulated body fluid (SBF) were investigated using weight loss measurements, chemical analysis, X-ray diffraction, and scanning electron microscopy. The results showed that greater than 90% of the glass in the scaffolds degraded within 1 week, to form poorly crystallized hydroxyapatite (HA). Pellets loaded with Vancomycin provided controlled release of the drug over 4 days. Vancomycin-loaded scaffolds were implanted into the right tibiae of rabbits infected with osteomyelitis. The efficacy of the treatment was assessed using microbiological examination and histology. The HA formed in the scaffolds in vivo, resulting from the conversion of the glass, served as structure to support the growth of new bone and blood vessels. The results in this work indicate that bioactive borate glass could provide a promising biodegradable and bioactive material for use as both a drug delivery system and a scaffold for bone repair.     

Evaluation of two novel aluminum-free,zinc-based glass polyalkenoate cements as alternatives to PMMA bone cement for use in vertebroplasty and balloon kyphoplasty

Vertebroplasty (VP) and balloon kyphoplasty (BKP) are now widely used for treating patients in whom the pain due to vertebral compression fractures is severe and has proved to be refractory to conservative treatment. These procedures involve percutaneous delivery of a bolus of an injectable bone cement either directly to the fractured vertebral body, VB (VP) or to a void created in it by an inflatable bone tamp (BKP). Thus, the cement is a vital component of both procedures. In the vast majority of VPs and BKPs, a poly(methyl methacrylate) (PMMA) bone cement is used. This material has many shortcomings, notably lack of bioactivity and very limited resorbability. Thus, there is room for alternative cements. We report here on two variants of a novel, bioactive, Al-free, Zn-based glass polyalkenoate cement (Zn-GPC), and how their properties compare to those of an injectable PMMA bone cement (SIMPL) that is widely used in VP and BKP. The properties determined were injectability, radiopacity, uniaxial compressive strength, and biaxial flexural modulus. In addition, we compared the compression fatigue lives of a validated synthetic osteoporotic VB model (a polyurethane foam cube with an 8 mm-diameter through-thickness cylindrical hole), at 0–2300 N and 3 Hz, when the hole was filled with each of the three cements. A critical review of the results suggests that the performance of each of the Zn-GPCs is comparable to that of SIMPL; thus, the former cements merit further study with a view to being alternatives to an injectable PMMA cement for use in VP and BKP.     

Surface modification of a novel glass to optimise strength and deliverability of an injectable alginate composite

It is estimated that 1–6% of the adult population have an intracranial aneurysm. Aneurysm coiling is the current preferred treatment method; however, over 20% of coiled aneurysms recur. A novel glass–alginate composite hydrogel has been developed to treat aneurysms, which is designed to completely fill the aneurysm space and prevent aneurysm recurrence. This hydrogel is composed of a polymeric alginate, a novel bioactive glass and glucono-delta-lactone. This novel injectable hydrogel exhibits characteristics suitable for the treatment of cerebral aneurysms. However, poor hydrophilicity of the glass phase results in inhomogeneity and agglomerate formation within the composite, resulting in suboptimal deliverability and strength. This study examines the effect of surface modification of the glass particles using an acid washing technique, designed to increase glass surface hydrophilicity resulting in a homogeneous sample. This study found that acid washing of the glass not only decreased agglomeration and inhomogeneity but also lengthened working times and increased strength of the resultant hydrogel. This lengthened working time, allowed for an increased glass content and, as a result, further increased compressive strength and radiopacity of the resultant hydrogel. Glass particle size analysis revealed that the relative quantity of fine particles was reduced. Surface analysis of the glass particles revealed an increase in hydrophilic silanol groups and increased surface network connectivity. These factors, combined with a decreased surface calcium and an increased surface gallium content, are postulated as the likely reasons for the observed increased strength, working time and hardening time.     

Differentiation of preosteoblasts using a delivery system with BMPs and bioactive glass microspheres

Bone morphogenetic proteins (BMPs) and 45S5 Bioglass microspheres (bioactive GM) can increase the differentiation of osteoblasts. Recombinant human BMP-2 (rhBMP-2) is presently the BMP most frequently used in delivery systems and it has already been used in clinical bone healing studies. We have developed a delivery system that combines a collagen Type I gel, BMP and bioactive GM. Since BMP-9 seems to be more osteogenic than BMP-2, we compared the differentiation of MC3T3-E1 preosteoblasts induced by our delivery system containing either a peptide derived from BMP-9 (pBMP-9), or rhBMP-2, both at 100 ng/mL. After 5 days, alkaline phosphatase staining showed that pBMP-9 induced more differentiation than rhBMP-2 in all experimental conditions. Also, bioactive GM increased this BMP effect. Since preosteoblasts secreted matrix metalloproteinases (MMPs) that can degrade collagen, we then studied the influence of the delivery system on MMPs production. We observed that MMP-2 was the major MMP involved in all experimental conditions. In addition, pBMP-9 with bioactive GM generated less MMP-2 than did rhBMP-2 on days 3 and 5. Thus, a delivery system using collagen Type I gel with pBMP-9 and bioactive GM seems to be a promising system for bone regeneration.     

Synthesis and in vitro bioactivity of novel mesoporous hollow bioactive glass microspheres

The remarkable tissue-repairing bioactivity and biocompatibility of bioactive glass make it suitable for a wide range of applications. Here, novel mesoporous hollow bioactive glass microspheres (MHBGMs) with a uniform diameter range of 2-5 µm were prepared by a sol-gel method. Structural characterization indicated that the shell of hollow sphere had a mesopore size range between 2 and 10 nm and a thickness about 500 nm. The in vitro bioactivity test indicated that the novel structure exhibited high in vitro bioactivity. The uniform microspherical morphology and mesoporous hollow structure of MHBGMs, together with their high bioactivity, turn them into a good candidate as an injectable and drug-loading biomaterial for in vivo tissue regeneration and drug control release.     

Preparation and characterization of mesoporous bioactive glass/polycaprolactone nanofibrous matrix for bone tissues engineering

A polycaprolactone (PCL) nanofibrous composite matrix having mesoporous bioactive glass nanoparticles (MBG) was fabricated using the electrospinning method, and the microstructural, physical and biological properties of the composite matrix were characterized. The fiber diameters of PCL, 5?% MBG/PCL (5?M-PCL) and 10?% MBG/PCL (10?M-PCL) were 575?±?162?nm, 312?±?134?nm and 321?±?144?nm, respectively. The bioactivity of the composite matrix was evaluated by soaking the matrix in 1.5× simulated body fluid; the MBG/PCL matrix showed a better biomineralization capability than did the PCL matrix. The biological performance of the PCL and the MBG/PCL were evaluated using an in vitro culture of MG63 osteoblast-like cells. We found that the cell attachment and proliferation rates were significantly higher on the 10?M-PCL than on the PCL. Moreover, the expression of several genes, including ANX-V, type I collagen and OCN, ALP activity, the deposition of calcium, and the BSP protein, were also significantly higher on 10?M-PCL than PCL. These results indicated that MBG/PCL has the ability to support cell attachment, growth, and differentiation and can also yield high bioactivity. Therefore, MBG/PCL could be potentially applied in bone implants.     

Characterizing the hierarchical structures of bioactive sol-gel silicate glass and hybrid scaffolds for bone regeneration

Bone is the second most widely transplanted tissue after blood. Synthetic alternatives are needed that can reduce the need for transplants and regenerate bone by acting as active temporary templates for bone growth. Bioactive glasses are one of the most promising bone replacement/regeneration materials because they bond to existing bone, are degradable and stimulate new bone growth by the action of their dissolution products on cells. Sol-gel-derived bioactive glasses can be foamed to produce interconnected macropores suitable for tissue ingrowth, particularly cell migration and vascularization and cell penetration. The scaffolds fulfil many of the criteria of an ideal synthetic bone graft, but are not suitable for all bone defect sites because they are brittle. One strategy for improving toughness of the scaffolds without losing their other beneficial properties is to synthesize inorganic/organic hybrids. These hybrids have polymers introduced into the sol-gel process so that the organic and inorganic components interact at the molecular level, providing control over mechanical properties and degradation rates. However, a full understanding of how each feature or property of the glass and hybrid scaffolds affects cellular response is needed to optimize the materials and ensure long-term success and clinical products. This review focuses on the techniques that have been developed for characterizing the hierarchical structures of sol-gel glasses and hybrids, from atomic-scale amorphous networks, through the covalent bonding between components in hybrids and nanoporosity, to quantifying open macroporous networks of the scaffolds. Methods for non-destructive in situ monitoring of degradation and bioactivity mechanisms of the materials are also included.     

Tungsten disulfide nanoparticle-containing PCL and PLGA-coated bioactive glass composite scaffolds for bone tissue engineering applications

Journal of Materials Science - In the study, tungsten disulfide (WS2) nanoparticle-containing polymer-coated bioactive glass composite scaffolds were prepared for bone tissue engineering...     

Spectroscopic analysis of a novel Nd3+-activated barium borate glass for broadband laser amplification

Spectroscopic parameters of a novel Nd³⁺-activated barium borate (BBONd) glass have been analyzed for broadband laser amplification. The Judd–Ofelt (JO) intensity parameters were determined through a systematic analysis of the absorption spectrum of Nd³⁺ ions in the BBONd glass. High values of the JO intensity parameters reveal a great centro-symmetrical loss of the Nd³⁺ sites and high covalency degree of the ligand field. The very high Ω₆ intensity parameter value makes evident both a great structural distortion of the Nd³⁺ sites and a strong electron–phonon coupling between Nd³⁺ and free OH⁻ ions, which is consistent with the phonon energy maximum (3442.1 cm⁻¹) recorded by Raman spectroscopy. This strong electron–phonon coupling favors high effective bandwidth and gain bandwidth values of the laser emission (⁴F_3/2 → ⁴I_11/2) of Nd³⁺ ions. The electric-dipole oscillator strengths of all the Nd³⁺ absorption transitions, and in particular that of the hypersensitive transition (⁴I_9/2 → ⁴G_5/2), are enhanced by this great structural distortion of the host. Broadband laser amplification of the ⁴F_3/2 → ⁴I_11/2 emission (1062 nm) of Nd³⁺ ions in the BBONd glass pumped at 805 nm (⁴I_9/2 → ⁴F_5/2 + ²H_9/2) is evaluated through the main fluorescent parameters in competition with non-radiative processes. In general, the BBONd glass exhibits spectroscopic parameters comparable with those reported in the literature for broadband laser amplification into the IR region.