Acta Biomaterialia

Published by Elsevier
Print ISSN: 1742-7061
The aim of this investigation was to test the in vitro performance of a self-adhesive resin composite core build-up in comparison with two typical conventional etch-and-rinse composite core build-up materials, before and after 1year of storage in 0.5% chloramine solution (LTS). Sixty human maxillary central incisors were divided into three groups. Teeth were root filled and decoronated. Specimens were restored using glass fiber posts cemented with a self-adhesive resin cement. Core build-ups were made with a self-adhesive (U) and two core build-up materials (C and L) applied with their corresponding bonding systems. All specimens received adhesively luted lithium disilicate crowns. Ten specimens of each group were exposed to LTS and examined monthly for cracks or other alterations. All specimens were thermocycled, mechanically loaded (TCML) and finally loaded until failure occurred. There was no statistical significant difference in regard to the number of failures during TCML without and with LTS (log rank: p = 0.225 and 0.609, respectively). The median fracture load values after static loading without LTS and with LTS did not differ significantly (Kruskal-Wallis test: p = 0.057 and 0.106, respectively), though the fracture patterns between the groups without (p = 0.024) and with LTS (p = 0.027) did. Self-adhesive cements used for core build-up have no significantly higher risk of failure compared to conventional core build-up materials in both LTS and TCML test scenarios.
Mg-4 wt.% Zn-0.5 wt.% Zr (ZK40) alloy was studied as a candidate material for biodegradable metallic implants in terms of its biocorrosion resistance, mechanical properties and cytocompatibility. The corrosion characteristics of ZK40 alloy were assessed by potentiodynamic polarization and immersion testing in DMEM + 10% FBS solution. Analysis of the degradation characteristics by potentiodynamic polarization measurements shows the corrosion rates of ZK40 alloy in as-cast and solution treatment (T4) condition were slightly higher than those of pure Mg or as-drawn AZ31. Determination of the corrosion rate by the weight loss technique reveals that the as-cast ZK40 resulted in slower degradation than other alloy specimens after 7 days of immersion but exhibited accelerated degradation after 14 and 21 days, respectively. T4-treated ZK40 exhibited stable degradation rates compared to as-cast ZK40 and close to those of pure Mg and AZ31 during immersion testing for 14 and 21 days. In order to examine the in vitro cytocompatibility of ZK40 alloy, live/dead cell viability assay and indirect MTT assay were performed using a murine osteoblast-like cell line (MC3T3). After 3 days of direct culture of MC3T3 on ZK40 alloys the live/dead assay indicated favorable cell viability and attachment. The degradation product of ZK40 also showed minimal cytotoxicity when assessed in indirect MTT assay. The mechanical properties of the as-cast and T4-treated ZK40 alloy were superior to those of pure Mg and comparable to as-drawn AZ31. Solution treatment did not significantly enhance the cytocompatibility and mechanical properties of ZK40 alloy. Overall, the ZK40 alloy exhibited favorable cytocompatibility, biocorrosion, and mechanical properties rendering it a potential candidate for degradable implant applications.
Cationic polymers are desirable gene carriers because of their better safety profiles than viral delivery systems. Low molecular weight (MW) polymers are particularly attractive, since they display little cytotoxicity, but they are also ineffective for gene delivery. To create effective carriers from low MW polymers palmitic acid (PA) was substituted on 0.6-2.0 kDa polyethylenimines (PEIs) and their efficiency for plasmid DNA (pDNA) delivery was evaluated. The extent of lipid substitution was dependent on the lipid/PEI feed ratio and the polymer MW. While the hydrodynamic size of the polymer/pDNA complexes (polyplexes) increased or decreased depending on the extent of lipid substitution, the ζ potential of the assembled complexes was consistently higher as a result of lipid substitution. Lipid substitution generally increased the in vitro toxicity of the PEIs, but it was significantly lower than that of the 25 kDa branched PEI. The in vitro transfection efficiency of the lipid-substituted polymers was higher than that of native PEIs, which were not at all effective. The delivery efficiency was proportional to the extent of lipid substitution as well as the polymer MW. This correlated with the increased uptake of lipid-substituted polyplexes, based on confocal microscopic investigations with FITC-labeled pDNA. The addition of chloroquine further increased the transfection efficiency of lipid-substituted PEIs, indicating that endosomal release was a limiting factor affecting the efficiency of these carriers. This study indicates that lipid substitution on low MW PEIs makes their assembly more effective, resulting in better delivery of pDNA into mammalian cells.
Hydrogels are unique supramolecular solid-like assemblies mainly composed of water molecules that are held by molecular networks. Physical hydrogels that are formed by a set of non-covalent interactions to establish a well-ordered scaffold devoid of any chemical cross-linking are especially intriguing for various biotechnological and medical applications. Peptides are particularly interesting building blocks of physical gels due to the role of polypeptides as structural elements in biological systems, the extensive ability for their chemical and biological decoration and functionalization, and the facile synthesis of natural and modified peptides. In this review, we describe the assembly and properties of physical hydrogels that have been formed by the self-association of very simple peptide building blocks. Natural short peptides, as short as dipeptides, can form ordered gel assemblies. Moreover, in the case of N-terminal protection, even a protected amino-acid can serve as an efficient hydrogelator. Further elucidation of hydrogelators assembly, as well as the characterization of their physical properties, can guide the rational design of building blocks for a desired application. The possible mechanism of self-assembly is discussed in line with the chemical nature of the short peptides. Different methods have been used to induce hydrogel assembly that may significantly affect the mechanical characteristics of the resulting gels. Here, special emphasis is given to methods that allow either spatial control of hydrogel formation or modulation of physical properties of the gel. Finally, we describe the parameters that influence hydrogelation and provide insights for their design.
Hydrogels have been proposed as candidates for tissue replacement; however, current systems are often highly susceptible to hydrolytic degradation and have not been shown to mimic the viscoelastic behavior of the native tissue when subjected to dynamic loading conditions. In the present work, 1,2-epoxy-5-hexene modified poly(vinyl alcohol) was crosslinked via photopolymerization to generate non-degradable hydrogels with mechanical properties and network characteristics that could be modulated through variation in the type and percentage of a monomeric additive. Complex shear moduli obtained from dynamic frequency sweeps in torsional shear were used to exemplify the differences in the viscoelastic behavior of the materials, and the corresponding changes in crosslink density were determined by rubber elasticity theory. Hydrolysis resistance was assessed by monitoring variations in the moduli of hydrogels submerged in Hank's balanced salt solution for progressively longer periods of time. Over the time-frame of the experiment, no change in the viscoelastic behavior was observed. Direct contact assays and elution tests were used to demonstrate that the system was non-cytotoxic. This study represents a successful attempt to generate a non-degradable hydrogel system with viscoelastic behavior that can be readily modulated to match that of soft biological tissues for use in tissue replacement.
Biodegradable magnesium-based materials have a high potential for cardiovascular stent applications; however, there exist concerns on corrosion-control and biocompatiblity. A surface-eroding coating of poly(1,3-trimethylene carbonate) (PTMC) on magnesium (Mg) alloy was studied, and its dynamic degradation behavior, electrochemical corrosion, hemocompatiblity and histocompatibility were investigated. The PTMC coating effectively protected the corrosion of the Mg alloy in the dynamic degradation test. The corrosion current density of the PTMC-coated alloy reduced by three orders and one order of magnitude compared to controls, bare and poly(ε-caprolactone) (PCL)-coated Mg alloy, respectively. Static and dynamic blood tests in vitro indicated that significantly fewer platelets were adherent and activated, and fewer erythrocytes attached on the PTMC-coated surface and showed less hemolysis than on the controls. The PTMC coating after 16 weeks subcutaneous implantation in rats maintained ∼ 55% of its original thickness and presented a homogeneously flat surface demonstrating surface erosion; in contrast to the PCL coated control which exhibited non-uniform bulk erosion. The Mg alloy coated with PTMC showed less volume reduction and fewer corrosion products as compared to the controls after 52 weeks in vivo. Excessive inflammation, necrosis and hydrogen gas accumulation were not observed. The homogeneous surface erosion of the PTMC coating from exterior to interior (surface-eroding behavior) and its charge neutral degradation products contribute to its excellent protective performance. It is concluded that PTMC is a promising candidate for a surface-eroding coating applied to Mg-based implants.
A continuous flow measurement system with sensitive on-line ion analysis has been applied to study the initial dissolution behaviour of biocompatible glasses in Tris. Altogether 16 glasses with widely varying compositions were studied. The measurement system allowed for quantitative determination of the time-dependent rates of dissolution of sodium, potassium, calcium, magnesium, silicon and phosphorus during the first 10-15min in contact with Tris solution. The dissolution rates of the different ions showed significant glass to glass variations, but all glasses studied showed one of four distinct dissolution patterns. The ion dissolution rates after an exposure of 1000s, expressed as the normalized surface-specific mass loss rates, were compared with the in vitro and in vivo reactivity of the glasses as predicted by models in the literature. The results showed a clear correlation between the dissolution rates of the glasses in Tris and their reactivity as measured by other different methods. Consequently, the measured short-term dissolution patterns could be used to determine which glasses are suitable as bioactive, biodegradable, or inert biomaterials for medical devices.
Using phase separation micromolding (PSmicroM) we developed porous micro-patterned sheets from amorphous poly(1,3-trimethylene carbonate) (PTMC). The use of these PTMC sheets can be advantageous in tissue engineering applications requiring highly flexible constructs. Addition of poly(ethylene oxide) (PEO) in various amounts to PTMC casting solutions provides PTMC sheets with tailored porosity and pore sizes in the range 2-20 microm. The pore-forming effect of PEO during the phase separation process is evaluated and glucose transport measurements show that the pores are highly interconnected. Additionally, tailoring the micro-pattern design yields PTMC sheets with various surface topographies. Cell culturing experiments with C2C12 pre-myoblasts revealed that cell attachment and proliferation on these sheets is relatively high and that the micro-pattern topography induces a clearly defined cell organization.
The objective of this study was to evaluate the coupled effects of three-dimensional poly(1,8-octanediol-co-citrate) (POC) scaffold pore shape and permeability on chondrogenesis using primary chondrocytes in vivo. Chondrogenesis was characterized as cartilage matrix formation by sulfated glycosaminoglycan (sGAG) quantification, relative mRNA expression of the cartilage-related proteins collagen types I, II and X, aggrecan and matrix metalloproteinases 13 and 3 and the compressive mechanical properties of the tissue/scaffold construct. A low permeability design with a spherical pore shape showed a significantly greater increase in cartilage matrix formation over 6 weeks in vivo than a high permeability design with a cubical pore shape. This increase in cartilage matrix synthesis corresponded with increases in mechanical compressive nonlinear elastic properties and histological data demonstrating darker red Safranin-O staining. There was higher mRNA expression for both cartilage-specific proteins and matrix degradation proteins in the high permeability design, resulting in overall less sGAG retained in the high permeability scaffold compared with the low permeability scaffold. Controlled POC scaffolds with a spherical pore shape and low permeability correlated with significantly increased cartilage matrix production using primary seeded chondrocytes. These results indicate that the low permeability design with a spherical pore shape provided a better microenvironment for chondrogenesis than the high permeability design with a cubical pore shape. Thus, scaffold architecture and material design may have a significant impact on the success of matrix-based clinical cartilage repair strategies.
Biopolymer-coated nanocrystalline hydroxyapatite (HA) made as macroporous foams which are degradable and flexible are promising candidates as orthopaedic implants. The C-terminal (107-111) epitope of parathyroid hormone-related protein (PTHrP) exhibits osteogenic properties. The main aim of this study was to evaluate whether PTHrP (107-111) loading into gelatin-glutaraldehyde biopolymer-coated HA (HAGlu) scaffolds would produce an optimal biomaterial for tissue engineering applications. HAGlu scaffolds with and without PTHrP (107-111) were implanted into a cavitary defect performed in both distal tibial metaphysis of adult rats. Animals were sacrificed after 4 weeks for histological, μ-computerized tomography and gene expression analysis of the callus. At this time, bone healing occurred only in the presence of PTHrP (107-111)-containing HAGlu implant, related to an increase of bone volume/tissue volume and trabecular thickness, cortical thickness, and gene expression of osteocalcin and vascular cell adhesion molecule 1, but a decreased gene expression of Wnt inhibitors, SOST and dickkopf homolog 1. The autonomous osteogenic effect of the PTHrP (107-111)-loaded HAGlu scaffolds was confirmed in mouse and human osteoblastic cell cultures. Our findings demonstrate the advantage of loading PTHrP (107-111) into degradable HAGlu scaffolds for achieving an optimal biomaterial that is promising for low load bearing clinical applications.
The present work investigates the corrosion behaviour, the element distribution in the corrosion layer and the cytocompatibility of alloy Mg-10Dy. The corrosion experiments were performed in a cell culture medium (CCM) under cell culture conditions close to the in vivo environment. The element distribution on the surface as well as in cross-sections of the corrosion layer was investigated using scanning electron microscopy, energy-dispersive X-ray analysis, X-ray photoelectron spectroscopy and X-ray diffraction. The cytocompatibility of alloy Mg-10Dy with primary human osteoblasts was evaluated by MTT, cell adhesion and live/dead staining tests. The results show that the corrosion layer was enriched in Dy, while the P and Ca content gradually decreased from the surface to the bottom of the corrosion layer. In addition, large amounts of MgCO(3)·3H(2)O formed in the corrosion layer after 28days immersion. Both extracts and the Dy-enriched corrosion layer of alloy Mg-10Dy showed no cytotoxicity to primary human osteoblasts.
The objective of the present cross-sectional study was to determine in vivo titanium ion levels following cementless total hip arthroplasty (THA) using a modular stem system with different shapes for femoral canal fit and multiple neck options. A consecutive series of 173 patients (190 hips) who underwent cementless modular neck THA and a ceramic on polyethylene bearing with a median follow-up of 9 (7-13) years was evaluated retrospectively. According to a standardised protocol, titanium ion measurements were performed for 67 patients using high-resolution inductively coupled plasma-mass spectrometry (HR-ICP-MS). Ion levels were compared to a control group comprising patients with non-modular titanium implants (n=11) and to individuals without implants (n=23). Modular neck THA did not result in elevated titanium ion levels compared to non-modular THA. Compared to individuals without implants, both modular THA and non-modular THA showed elevated titanium ion levels. Absolute titanium ion levels, however, were comparatively low for both implants. The data suggest that the present modular stem system does not result in elevated systemic titanium ion levels in the medium-term when compared to non-modular stems. Further longitudinal studies are needed to evaluate the use of systemic titanium ion levels as an objective diagnostic tool to identify THA failure and to monitor patients following revision surgery.
Bacterial infection represents a major cause of implant failure in dentistry. A common approach to overcome this issue and treat peri-implant infection consists in the use of antibiotics. However, the rise of multidrug resistant bacteria poses serious concerns to this strategy. A promising alternative is the use of antimicrobial peptides due to their broad-spectrum activity against bacteria and reduced bacterial resistance responses. The aim of the present study was to determine the in vitro antibacterial activity of the human lactoferrin-derived peptide hLf1-11 anchored to titanium surfaces. To this end, titanium samples were functionalized with the hLf1-11 peptide either by silanization methods or physical adsorption. X-ray photoelectron spectroscopy analyses confirmed the successful covalent attachment of the hLf1-11 peptide onto titanium surfaces. Lactate dehydrogenase assay determined that hLf1-11 peptide did not affect fibroblast viability. An outstanding reduction in the adhesion and early stages of biofilm formation of Streptococcus sanguinis and Lactobacillus salivarius was observed on the biofunctionalized surfaces compared to control non-treated samples. Furthermore, samples coated with the hLf1-11 peptide inhibited the early stages of bacterial growth. Thus, this strategy holds great potential to develop antimicrobial biomaterials for dental applications.
(A) Chitosan modification with NAC or Sp; (B) hLF1-11 immobilization by establishment of a covalent disulfide bridge. 
Surface characterization of chitosan-modified films as determined by (A) ellipsometry (surface thickness); (B) water optical contact angle measurements; (C) AFM (surface roughness). 
Reaction of carbodiimide (EDC) and NHS with chitosan free amines. 
IRRAS spectra of chitosan modified films and hLF1-11 immobilized chitosan films. 
hLF1-11 (GRRRRSVQWCA) is an antimicrobial peptide (AMP) with high activity against methicillin-resistant Staphylococcus aureus (MRSA), the most prevalent species in implant-associated infection. During this work, the effect of the surface immobilization on hLF1-11 antimicrobial activity was studied. Immobilization was performed onto chitosan thin films as a model for an implant coating due to its reported osteogenic and antibacterial properties. Chitosan thin films were produced by spin-coating on gold surfaces. hLF1-11 was immobilized onto these films by its C-terminal cysteine, orientation that expose the antimicrobial activity-related arginine-rich portion of the peptide. Two levels of exposure (with and without a PEG spacer) were analised. Covalent immobilization was further compared with the AMP physical adsorption onto chitosan films. Surfaces were characterized using ellipsometry, contact angle measurements, atomic force microscopy, infrared and X-ray photoelectron spectroscopies and using a fluorimetric assay for hLF1-11 quantification. Surfaces antimicrobial activity was assessed through surface adhesion and viability assays using a MRSA (S. aureus ATCC 33591). The incorporation of hLF1-11 increased significantly bacterial adhesion to chitosan films. However, the presence of hLF1-11, namely when immobilized through a PEG spacer, decreased the viability of adherent bacteria regarding control surface. These results demonstrated that hLF1- 11 after covalent immobilization by its cysteine can maintain activity, particularly if a spacer is applied. However, further studies, exploring the opposite orientation or the same C-terminal orientation, but non- cysteine related, can help to clarify the potential of the hLF1-11 immobilization strategy.
Scaffolds of 13-93 bioactive glass (composition 6.0 Na₂O, 7.9 K₂O, 7.7 MgO, 22.1 CaO, 1.7 P₂O₅, 54.6 SiO₂ (mol.%)) containing oriented pores of controllable diameter were prepared by unidirectional freezing of camphene-based suspensions (10 vol.% particles) on a cold substrate (-196 °C or 3 °C). By varying the annealing time (0-72 h) to coarsen the camphene phase, constructs with the same porosity (86 ± 1%) but with controllable pore diameters (15-160 μm) were obtained after sublimation of the camphene. The pore diameters had a self-similar distribution that could be fitted by a diffusion-controlled coalescence model. Sintering (1 h at 690 °C) was accompanied by a decrease in porosity and pore diameter, the magnitude of which depended on the pore size of the green constructs, giving scaffolds with a porosity of 20-60% and average pore diameter of 6-120 μm. The compressive stress vs. deformation response of the sintered scaffolds in the orientation direction was linear, followed by failure. The compressive strength and elastic modulus in the orientation direction varied from 180 MPa and 25 GPa (porosity=20%) to 16 MPa and 4 GPa (porosity=60%), respectively, which were 2-3 times larger than the values in the direction perpendicular to the orientation. The potential use of these 13-93 bioactive glass scaffolds for the repair of large defects in load-bearing bones, such as segmental defects in long bones, is discussed.
A polymer foam replication technique was used to prepare porous scaffolds of 13-93 bioactive glass with a microstructure similar to that of human trabecular bone. The scaffolds, with a porosity of 85+/-2% and pore size of 100-500 microm, had a compressive strength of 11+/-1 MPa, and an elastic modulus of 3.0+/-0.5 GPa, approximately equal to the highest values reported for human trabecular bone. The strength was also considerably higher than the values reported for polymeric, bioactive glass-ceramic and hydroxyapatite constructs prepared by the same technique and with the equivalent level of porosity. The in vitro bioactivity of the scaffolds was observed by the conversion of the glass surface to a nanostructured hydroxyapatite layer within 7 days in simulated body fluid at 37 degrees C. Protein and MTT assays of in vitro cell cultures showed an excellent ability of the scaffolds to support the proliferation of MC3T3-E1 preosteoblastic cells, both on the surface and in the interior of the porous constructs. Scanning electron microscopy showed cells with a closely adhering, well-spread morphology and a continuous increase in cell density on the scaffolds during 6 days of culture. The results indicate that the 13-93 bioactive glass scaffolds could be applied to bone repair and regeneration.
This in vitro study was conducted to evaluate the ability of two types of constructs of bioactive, silica-based 13-93 glass fibers to support the growth and differentiation of MC3T3-E1 osteoblastic cells. The two types of constructs tested included single-layer 13-93 glass fiber rafts and three-dimensional porous scaffolds formed from sintered 13-93 fibers. Scanning electron micrographs showed a closely adhering, well-spread morphology of MC3T3-E1 cells seeded on both types of constructs. The scanning electron microscopy images also showed a continuous increase in cell densities during a 6 day incubation on 13-93 glass fiber rafts and scaffolds. Quantitative fluorescence measurements of DNA also revealed a linear increase in cell density during a 6 day incubation on both types of 13-93 constructs. Examination of scaffolds incubated in MTT containing medium showed the presence of metabolically active viable cells within the interior of the scaffold. The addition of ascorbic acid to MC3T3-E1 cells cultured on the 13-93 glass fibers triggered a threefold increase in alkaline phosphatase, a key indicator of osteoblast differentiation. The sintered scaffolds were found to have open, interconnected pores favorable for tissue ingrowth with a compressive strength similar to cancellous bone. Collectively, the results indicate that 13-93 glass fiber scaffolds are a favorable substrate for the growth and differentiation of osteoblasts and a promising material for bone tissue engineering and repair of bone defects.
There is a need for synthetic bone graft substitutes to repair large bone defects resulting from trauma, malignancy and congenital diseases. Bioactive glass has attractive properties as a scaffold material but factors that influence its ability to regenerate bone in vivo are not well understood. In the present work, the ability of strong porous scaffolds of 13-93 bioactive glass with an oriented microstructure to regenerate bone was evaluated in vivo using a rat calvarial defect model. Scaffolds with an oriented microstructure of columnar pores (porosity=50%; pore diameter=50-150μm) showed mostly osteoconductive bone regeneration, and new bone formation, normalized to the available pore area (volume) of the scaffolds, increased from 37% at 12weeks to 55% at 24weeks. Scaffolds of the same glass with a trabecular microstructure (porosity=80%; pore width=100-500μm), used as the positive control, showed bone regeneration in the pores of 25% and 46% at 12 and 24weeks, respectively. The brittle mechanical response of the as-fabricated scaffolds changed markedly to an elastoplastic response in vivo at both implantation times. These results indicate that both groups of 13-93 bioactive glass scaffolds could potentially be used to repair large bone defects, but scaffolds with the oriented microstructure could also be considered for the repair of loaded bone.
There is a need to develop synthetic scaffolds to repair large defects in load-bearing bones. Bioactive glasses have attractive properties as a scaffold material for bone repair, but data on their mechanical properties are limited. The objective of the present study was to comprehensively evaluate the mechanical properties of strong porous scaffolds of silicate 13-93 bioactive glass fabricated by robocasting. As-fabricated scaffolds with a grid-like microstructure (porosity 47%, filament diameter 330μm, pore width 300) were tested in compressive and flexural loading to determine their strength, elastic modulus, Weibull modulus, fatigue resistance, and fracture toughness. Scaffolds were also tested in compression after they were immersed in simulated body fluid (SBF) in vitro or implanted in a rat subcutaneous model in vivo. As fabricated the scaffolds had a strength of 86±9MPa, elastic modulus of 13±2GPa, and a Weibull modulus of 12 when tested in compression. In flexural loading the strength, elastic modulus, and Weibull modulus were 11±3MPa, 13±2GPa, and 6, respectively. In compression the as-fabricated scaffolds had a mean fatigue life of ∼106 cycles when tested in air at room temperature or in phosphate-buffered saline at 37°C under cyclic stresses of 1-10 or 2-20MPa. The compressive strength of the scaffolds decreased markedly during the first 2weeks of immersion in SBF or implantation in vivo, but more slowly thereafter. The brittle mechanical response of the scaffolds in vitro changed to an elasto-plastic response after implantation for longer than 2-4weeks in vivo. In addition to providing critically needed data for designing bioactive glass scaffolds the results are promising for the application of these strong porous scaffolds in loaded bone repair.
Scaffolds of 13-93 bioactive glass (6Na(2)O, 12K(2)O, 5MgO, 20CaO, 4P(2)O(5), 53SiO(2); wt.%) with an oriented pore architecture were formed by unidirectional freezing of camphene-based suspensions, followed by thermal annealing of the frozen constructs to grow the camphene crystals. After sublimation of the camphene, the constructs were sintered (1 h at 700°C) to produce a dense glass phase with oriented macropores. The objective of this work was to study how constant freezing rates (1-7°C min(-1)) during the freezing step influenced the pore orientation and mechanical response of the scaffolds. When compared to scaffolds prepared by freezing the suspensions on a substrate kept at a constant temperature of 3°C (time-dependent freezing rate), higher freezing rates resulted in better pore orientation, a more homogeneous microstructure and a marked improvement in the mechanical response of the scaffolds in compression. Scaffolds fabricated using a constant freezing rate of 7°C min(-1) (porosity=50±4%; average pore diameter=100 μm), had a compressive strength of 47±5 MPa and an elastic modulus of 11±3 GPa (in the orientation direction). In comparison, scaffolds prepared by freezing on the constant-temperature substrate had strength and modulus values of 35±11 MPa and 8±3 GPa, respectively. These oriented bioactive glass scaffolds prepared by the constant freezing rate route could potentially be used for the repair of defects in load-bearing bones, such as segmental defects in the long bones.
The repair of large bone defects, such as segmental defects in the long bones of the limbs, is a challenging clinical problem. Our recent work has shown the ability to create porous scaffolds of silicate 13-93 bioactive glass by robocasting which have compressive strengths comparable to human cortical bone. The objective of this study was to evaluate the capacity of those strong porous scaffolds with a grid-like microstructure (porosity = 50%; filament width = 330 μm; pore width = 300 μm) to regenerate bone in a rat calvarial defect model. Six weeks postimplantation, the amount of new bone formed within the implants was evaluated using histomorphometric analysis. The amount of new bone formed in implants composed of the as-fabricated scaffolds was 32% of the available pore space (area). Pretreating the as-fabricated scaffolds in an aqueous phosphate solution for 1, 3, and 6 days, to convert a surface layer to hydroxyapatite prior to implantation, enhanced new bone formation to 46%, 57%, and 45%, respectively. New bone formation in scaffolds pretreated for 1, 3, and 6 days and loaded with bone morphogenetic protein-2 (BMP-2) (1 μg/defect) was 65%, 61%, and 64%, respectively. The results show that converting a surface layer of the glass to hydroxyapatite or loading the surface-treated scaffolds with BMP-2 can significantly improve the capacity of 13-93 bioactive glass scaffolds to regenerate bone in an osseous defect. Based on their mechanical properties evaluated previously and their capacity to regenerate bone found in this study, these 13-93 bioactive glass scaffolds, pretreated or loaded with BMP-2, are promising in structural bone repair.
Titanium alloys are known to nucleate an apatite layer when in contact with simulated body fluid. This improves the bioactivity of titanium implants and accelerates osseointegration. Promoting the formation of hydroxyapatite on biocompatible metals is, therefore, a very important topic of biomaterials research. In this paper, the formation of hydroxyapatite (HA) on the near-beta Ti-13Nb-13Zr alloy by immersion in minimal essential medium (MEM), with and without H(2)O(2) addition, has been studied using electrochemicals methods, scanning electron microscopy and X-ray photoelectron spectroscopy. The in vitro biocompatibility of this alloy was evaluated by cytotoxicity tests. The Ti-13Nb-13Zr alloy exhibits passive behaviour over a wide potential range in MEM and the passive film is composed of an inner barrier layer and an outer porous layer. The addition of H(2)O(2) leads to a thickening of the outer porous layer and strongly reduced current density. With regard to the surface composition, immersion in MEM solution results in the formation of an island-like distribution of HA+amino acids. Addition of H(2)O(2) to the MEM solution strongly promotes the formation of a thicker, continuous but porous nanocomposite layer of HA+amino acids. The Ti-13Nb-13Zr alloy is non-toxic and the nanocomposite HA+amino acid layer formed in the MEM solution favours the growth of osteoblast cells. For Ti alloys, the release of H(2)O(2) in the anti-inflammatory response appears to be an important beneficial process as it accelerates osseointegration.
For spinal-fixation applications, implants should have high Young's modulus to reduce springback during operations, but low Young's modulus is required to prevent stress shielding for patients after surgeries. In the present study, Ti-29Nb-13Ta-4.6Zr alloy (TNTZ) with a low Young's modulus was modified by adding Cr to obtain higher deformation-induced Young's modulus in order to satisfy the contradictory requirements of the Young's modulus for spinal-fixation applications. Two newly designed alloys, TNTZ-8Ti-2Cr and TNTZ-16Ti-4Cr, possess more stable β phases than TNTZ. These alloys consist of single β phases and exhibit relatively low Young's moduli of <65 GPa after solution treatment. However, after cold rolling, they exhibit higher Young's moduli owing to a deformation-induced ω-phase transformation. These modified TNTZ alloys show significantly less springback than the original TNTZ alloy based on tensile and bending loading-unloading tests. Thus, the Cr-added TNTZ alloys are beneficial for spinal-fixation applications.
The magnetic susceptibility of cold-rolled Zr-14Nb was evaluated to apply a new metallic medical device used for magnetic resonance imaging (MRI). The magnetic susceptibility of cold-rolled Zr-14Nb decreased up to the reduction ratio of 30%, followed by a gradual decrease up to the ratio of 90%. The TEM observation revealed the strain-induced ω phase formation after cold rolling at the reduction ratio of 5%, indicating that the initial decrease of magnetic susceptibility was caused by the formation of the ω phase. The formation of the ω phase was saturated at the reduction ratio of 30%. The formation of the ω phase was explicable on the basis of the increase of the Young's modulus and Vickers hardness of cold-rolled Zr-14Nb. The effect of texture formation was not obvious for these properties in cold-rolled Zr-14Nb. The magnetic susceptibility of Zr-14Nb can be reduced by applying cold rolling, because of the formation of the strain-induced ω phase, to as low as that of as-cast Zr-9Nb, which is one-third that of Ti and Ti alloys. Therefore, the cold-workable Zr-14Nb with low magnetic susceptibility could be a promising alloy for medical devices under MRI.
The role of nanofeatured titanium surfaces in a number of aspects of in vivo bone-implant integration, and, in particular, their potential advantages over microfeatured titanium surfaces, as well as their specific contribution to osteoconductivity, is largely unknown. This study reports the creation of a unique nanobimorphic titanium surface comprised of nanotrabecular and nanotuft-like structures and determines how the addition of this nanofeature to a microroughened surface affects bone-implant integration. Machined surfaces without microroughness, sandblasted microroughened surfaces, and micro-nano hybrid surfaces created by sandblasting and alkali and heat treatment of Ti-15Mo-5Zr-3Al alloy were subjected to biomechanical, interfacial and histological analyses in a rat model. The presence of microroughness enabled accelerated establishment of biomechanical implant fixation in the early stages of healing compared to the non-microroughened surfaces; however, it did not increase the implant fixation at the late stages of healing. The addition of nanobimorphic features to the microroughened surfaces further increased the implant fixation by as much as 60-100% over the healing time. Bone area within 50 μm of the implant surface, but not beyond this distance, was significantly increased by the presence of nanobimorphic features. Although the percentage of bone-implant contact was also significantly increased by the addition of nanobimorphic features, the greatest improvement was found in the soft tissue intervention between the bone and the implant, which was reduced from >30% to <5%. Mineralized tissue densely deposited with calcium-binding globular proteins was observed in an extensive area of nanobimorphic surfaces after biomechanical testing. This study clearly demonstrates the nanofeature-enhanced osteoconductivity of titanium by an alkali- and heat-treated nanobimorphic surface compared to that by microfeatured surfaces, which results not only in an acceleration but also an improvement of bone-implant integration. The identified biological parameters that successfully detect the advantages of nanofeatures over microfeatures will be useful in evaluating new implant surfaces in future studies.
The formation of grain boundary (GB) brittle carbides with a complex three-dimensional (3D) morphology can be detrimental to both the fatigue properties and corrosion resistance of a biomedical titanium alloy. A detailed microscopic study has been performed on an as-sintered biomedical Ti-15Mo alloy containing 0.032 wt.% C. A noticeable presence of a carbon-enriched phase has been observed along the GB, although the carbon content is well below the maximum carbon limit of 0.1 wt.% specified by ASTM Standard F2066. Transmission electron microscopy (TEM) identified that the carbon-enriched phase is fcc-Ti2C. 3D tomography reconstruction revealed that the Ti2C structure has morphology similar to primary α-Ti. Nanoindentation confirmed the high hardness and high Young's modulus of the GB Ti2C phase. To avoid GB carbide formation in Ti-15Mo, the carbon content should be limited to 0.006 wt.% by Thermo-Calc predictions. Similar analyses and characterisation of the carbide formation in biomedical unalloyed Ti, Ti-6Al-4V and Ti-16Nb have also been performed.
Apatite formation on the surface of titanium and its alloys is effective for inducing osteoconductivity when implanted in bony defects. The aim of this study was to investigate the effects of thermal oxidation on apatite formation in macro-grooves on Ti-15Zr-4Ta-4Nb. Thermal oxidation at 500 and 600 degrees C in air led to modification of the Ti-15Zr-4Ta-4Nb surface to rutile phase titanium oxide. Ti-15Zr-4Ta-4Nb thermally oxidized at 500 degrees C in air showed no changes in metallographic structure, but not at 600 degrees C. After soaking in a simulated body fluid for 7days, the formation of apatite could be observed on the internal surfaces of macro-grooves 500mum deep and wide on Ti-15Zr-4Ta-4Nb thermally oxidized at 500 and 600 degrees C in air. These results indicate the potential for osteoconductivity of Ti-15Zr-4Ta-4Nb without changing its metallographic structure, by fabricating only the macro-grooves, i.e., spatial design, and by performing thermal oxidation at 500 degrees C.
Multidrug resistance (MDR) of tumor cells is a major obstacle to the success of cancer chemotherapy. Poloxamers have been used in cancer therapy to overcome MDR. The objective of this research is to test the feasibility of paclitaxel-loaded poly(epsilon-caprolactone)/Poloxamer 188 (PCL/Poloxamer 188) nanoparticles to overcome MDR in a paclitaxel-resistant human breast cancer cell line. Paclitaxel-loaded nanoparticles were prepared by a water-acetone solvent displacement method using commercial PCL and self-synthesized PCL/Poloxamer 188 compound, respectively. PCL/Poloxamer 188 nanoparticles were found to be of spherical shape and tended to have a rough and porous surface. The nanoparticles had an average size of around 220nm, with a narrow size distribution. The in vitro drug release profile of both nanoparticle formulations showed a clear biphasic release pattern. There was an increased level of uptake of PCL/Poloxamer 188 nanoparticles (PPNP) in the paclitaxel-resistant human breast cancer cell line MCF-7/TAX, in comparison with PCL nanoparticles. The cytotoxicity of PCL nanoparticles was higher than commercial Taxol in the MCF-7/TAX cell culture, but the differences were not significant. However, the PCL/Poloxamer 188 nanoparticles achieved a significantly higher level of cytotoxicity than both of PCL nanoparticle formulation and Taxol(R), indicating that paclitaxel-loaded PCL/Poloxamer 188 nanoparticles could overcome MDR in human breast cancer cells and therefore could have considerable therapeutic potential for breast cancer.
In this study, the microstructures, mechanical properties, corrosion behaviors, in vitro cytocompatibility and magnetic susceptibility of Zr-1X alloys with various alloying elements, including Ti, Nb, Mo, Cu, Au, Pd, Ag, Ru, Hf and Bi were systematically investigated to explore their potential use in biomedical application. The experimental results indicated that annealed Zr-1X alloys consisted entirely or primarily of α phase. The alloying elements significantly increased the strength and hardness of pure Zr and had relatively slight influence on elastic modulus. Ru was the most effective enhancing element and Zr-1Ru alloy had the largest elongation. The results of electrochemical corrosion indicated that adding various elements into Zr improved its corrosion resistance as indicated by the reduced corrosion current density. The extracts of the studied Zr-1X alloys produced no significant deleterious effect to osteoblast-like cells (MG 63), indicating good in vitro cytocompatibility. All except for Zr-1Ag alloy showed decreased magnetic susceptibility compared to pure Zr and Zr-1Ru alloy had the lowest magnetic susceptibility value, being comparable to that of α'-phase Zr-Mo alloy and Zr-Nb alloy and far lower than that of Co-Cr alloy and Ti-6Al-4V alloy. Among the experimental Zr-1X alloys, Zr-1Ru alloy possessing high strength coupled with good ductility, good in vitro cytocompatibility and low magnetic susceptibility, may be a good candidate alloy for medical devices within a magnetic resonance imaging (MRI) environment.
Many cell therapies rely on the ability of mesenchymal stromal cells (MSCs) to diffuse and localize throughout the target tissue - such as tumoral and ischemic tissues-, in response to specific cytokine signals, rather than being concentrated at the site of implantation. Therefore, it is fundamental to engineer biomaterial carriers as reservoirs, from which cells can migrate, possibly in a controlled manner. In this work, microcarriers (μCs) made of polylactic acid are characterized as MSC delivery vehicles capable of modulating key chemotactic pathways. The effect of different functionalization strategies on MSC migratory behavior from the μCs is studied in vitro in relation to SDF-1α/CXCR4 axis, - a major actor in MSC recruitment, chemotaxis and homing. Collagen and arginine-glycine-aspartic acid (RGD) peptides were either covalently grafted or physisorbed on μC surface. While stable covalent modifications promoted better cell adhesion and higher proliferation compared to physisorption, the functionalization method of the μCs also affected the cells migratory behavior in response to SDF-1α (CXCL12) stimulation. Less stable coatings (physisorbed) showed sensibly higher number of migrating cells than covalent collagen/RGD coatings. The combination of physic-chemical cues provided by protein/peptide functionalization and stimuli induced by 3D culture on μCs improved MSC expression of CXCR4, and exerted a control over cell migration, a condition suitable to promote cell homing after transplantation in vivo. These are key findings to highlight the impact of surface modification approaches on chemokine-triggered cell release, and allow designing biomaterials for efficient and controlled cell delivery to damaged tissues. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Failure of synthetic small-diameter vascular grafts is determined mainly by the lack of endothelial cells, as these cells inhibit thrombosis and intimal hyperplasia. Coating of graft material with homing factors for circulating stem cells has the potential to improve endogenous endothelialization of these grafts and to reduce graft failure. Synthetic knitted polyester grafts (6mm diameter) were coated with FN and SDF-1α before surgical interposition in the carotid artery of sheep. Similar uncoated vascular grafts were implanted in the contralateral side as internal controls. To study the early attraction of stem cells, grafts were implanted in a first series of nine sheep and explanted after 1 or 3 days. In coated grafts, four times higher fractions of CD34(+) and three to four times higher fractions of CD117(+) cells adhering to the vessel walls were found than in control grafts (P<0.05). When such coated and non-coated grafts were implanted in 12 other sheep and explanted after 3 months, all coated grafts were patent, while one control graft was occluded. EcNOS staining revealed that FN-SDF-1α coating significantly increased coverage with endothelial cells from 27 ± 4% of the graft to 48 ± 4% compared with the controls (P=0.001). This was associated with a significant reduction of intimal hyperplasia (average thickness 1.03 ± 0.09 mm in controls vs. 0.69 ± 0.04 mm in coated grafts; P=0.009) and significantly less adhesion of thrombotic material in the middle part of the graft (P=0.029). FN-SDF-1α coating of synthetic small-caliber vascular grafts stimulated the attraction of stem cells and was associated with improved endothelialization and reduced intimal hyperplasia and thrombosis.
Today, more than 200years after the first production of metallic magnesium by Sir Humphry Davy in 1808, biodegradable magnesium-based metal implants are currently breaking the paradigm in biomaterial science to develop only highly corrosion resistant metals. This groundbreaking approach to temporary metallic implants is one of the latest developments in biomaterials science that is being rediscovered. It is a challenging topic, and several secrets still remain that might revolutionize various biomedical implants currently in clinical use. Magnesium alloys were investigated as implant materials long ago. A very early clinical report was given in 1878 by the physician Edward C. Huse. He used magnesium wires as ligature for bleeding vessels. Magnesium alloys for clinical use were explored during the last two centuries mainly by surgeons with various clinical backgrounds, such as cardiovascular, musculoskeletal and general surgery. Nearly all patients benefited from the treatment with magnesium implants. Although most patients experienced subcutaneous gas cavities caused by rapid implant corrosion, most patients had no pain and almost no infections were observed during the postoperative follow-up. This review critically summarizes the in vitro and in vivo knowledge and experience that has been reported on the use of magnesium and its alloys to advance the field of biodegradable metals. Copyright © 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
This article has been retracted: please see Elsevier Policy on Article Withdrawal ( This article has been retracted at the request of the Editor-in-Chief. Due to highly unethical practices, which include serial self plagiarism, data manipulation and falsification of results found across multiple papers in Acta Biomaterialia. One of the conditions of submission of a paper for publication is that authors declare explicitly that their work is original and has not appeared in a publication elsewhere. Re-use of any data should be appropriately cited. As such this article represents a severe abuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process.
We here describe the structure-process-property relationship of graphene oxide-mediated proliferation and growth of osteoblasts in conjunction with the physico-chemical, mechanical, and structural properties. Chitosan-graphene network structure scaffolds were synthesized by covalent linkage of the carboxyl groups of graphene oxide with the amine groups of chitosan. The negatively charged graphene oxide in chitosan scaffolds was an important physico-chemical factor influencing cell-scaffold interactions. Furthermore, it was advantageous in enhancing the biocompatibility of the scaffolds and the degradation products of the scaffolds. The high water retention ability, hydrophilic nature, and high degree of interconnectivity of the porous structure of chitosan-graphene oxide scaffolds facilitated cell attachment and proliferation and improved the stability against enzymatic degradation. The cells infiltrated and colonized the pores of the scaffolds and established cell-cell interactions. The interconnectivity of the porous structure of the scaffolds helps the flow of medium throughout the scaffold for even cell adhesion. Moreover, the seeded cells were able to infiltrate inside the pores of chitosan-graphene oxide scaffolds, suggesting that the incorporation of polar graphene oxide in scaffolds is promising for bone tissue engineering.
This article has been retracted: please see Elsevier Policy on Article Withdrawal ( This article has been retracted at the request of the Editor-in-Chief. Due to highly unethical practices, which include serial self plagiarism, data manipulation and falsification of results found across multiple papers in Acta Biomaterialia. One of the conditions of submission of a paper for publication is that authors declare explicitly that their work is original and has not appeared in a publication elsewhere. Re-use of any data should be appropriately cited. As such this article represents a severe abuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process.
This article has been retracted: please see Elsevier Policy on Article Withdrawal ( This article has been retracted at the request of the Editor-in-Chief. Due to highly unethical practices, which include serial self plagiarism, data manipulation and falsification of results found across multiple papers in Acta Biomaterialia. One of the conditions of submission of a paper for publication is that authors declare explicitly that their work is original and has not appeared in a publication elsewhere. Re-use of any data should be appropriately cited. As such this article represents a severe abuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process.
This article has been retracted: please see Elsevier Policy on Article Withdrawal ( This article has been retracted at the request of the Editor-in-Chief. Due to highly unethical practices, which include serial self plagiarism, data manipulation and falsification of results found across multiple papers in Acta Biomaterialia. One of the conditions of submission of a paper for publication is that authors declare explicitly that their work is original and has not appeared in a publication elsewhere. Re-use of any data should be appropriately cited. As such this article represents a severe abuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process.
Macrophages have been classified as having plastic phenotypes which exist along a spectrum between M1 (classically activated; pro-inflammatory) and M2 (alternatively activated; regulatory, homeostatic). To date, the effects of polarization towards an M1 or M2 phenotype have been studied largely in the context of response to pathogen or cancer. Recently, M1 and M2 macrophages have been shown to play distinct roles in tissue remodeling following injury. In the present study, the M1/M2 paradigm was utilized to examine the role of macrophages in the remodeling process following implantation of 14 biologically derived surgical mesh materials in the rat abdominal wall. In situ polarization of macrophages responding to the materials was examined and correlated to a quantitative measure of the observed tissue remodeling response to determine whether macrophage polarization is an accurate predictor of the ability of a biologic scaffold to promote constructive tissue remodeling. Additionally the ability of M1 and M2 macrophages to differentially recruit progenitor-like cells in vitro, which are commonly observed to participate in the remodeling of those ECM scaffolds which have a positive clinical outcome, was examined as a possible mechanism underlying the differences in the observed remodeling responses. The results of the present study show that there is a strong correlation between the early macrophage response to implanted materials and the outcome of tissue remodeling. Increased numbers of M2 macrophages and higher ratios of M2:M1 macrophages within the site of remodeling at 14 days were associated with more positive remodeling outcomes (r(2)=0.525-0.686, p<0.05). Further, the results of the present study suggest that the constructive remodeling outcome may be due to the recruitment and survival of different cell populations to the sites of remodeling associated with materials that elicit an M1 vs. M2 response. Both M2 and M0 macrophage conditioned media were shown to have higher chemotactic activities than media conditioned by M1 macrophages (p<0.05). A more thorough understanding of these issues will logically influence the design of next generation biomaterials and the development of regenerative medicine strategies for the formation of functional host tissues.
A human co-culture model of osteoblasts and osteoclasts, derived from bone marrow stromal cells and monocytes respectively, was used to characterize the influence of biomaterial modification on the bioactivity and ultimately the ratio of bone-forming to bone-resorbing cells cultivated directly on the surface. Nanocomposites of silica and collagen have been shown to function as skeletal structures in nature and were reproduced in vitro by using a sol-gel approach. The resulting xerogels exhibit a number of features that make it a valuable system for the development of innovative materials for bone substitution applications. In the present study, the incorporation of different calcium phosphate phases in silica/collagen-based gels was demonstrated to enhance the bioactivity of these samples. This ability of the biomaterial to precipitate calcium phosphate on the surface when incubated in simulated body fluids or cell culture medium is generally considered to an advantageous property for bone substitution materials. By co-cultivating human osteoblasts and osteoclasts up to 42days on the xerogels, we demonstrate that the long-term ratio of these cell types depends on the level of bioactivity of the substrate samples. Biphasic silica/collagen xerogels exhibited comparably low bioactivity but encouraged proliferation of osteoblasts in comparison to osteoclast formation. A balanced ratio of both cell types was detected for moderately bioactive triphasic xerogels with 5% calcium phosphate. However, enhancing the bioactivity of the xerogel samples by increasing the calcium phosphate phase percentage to 20% resulted in a diminished number of osteoblasts in favor of osteoclast formation. Quantitative evaluation was carried out by biochemical methods (calcium, DNA, ALP, TRAP 5b) as well as RT-PCR (ALP, BSP II, OC, RANKL, TRAP, CALCR, VTNR, CTSK), and was supported by confocal laser scanning microscopy (cell nuclei, actin, CD68, TRAP) as well as scanning electron microscopy.
Colloidal semiconductor nanoparticles (quantum dots) have attracted a lot of interest in technological and biomedical research, given their potent fluorescent properties. However, the use of heavy metal-containing nanoparticles remains an issue of debate. The possible toxic effects of quantum dots remain a hot research topic and several questions such as possible intracellular degradation of quantum dots and the effect thereof on both cell viability and particle functionality remain unresolved. In the present work, poly(methacrylic acid)-coated CdSe/ZnS quantum dots were synthesized and characterized, after which their effects on cultured cells were evaluated using a multiparametric setup. The data reveal that the quantum dots are taken up through endocytosis and when exposed to the low pH of the endosomal structures, they partially degrade and release cadmium ions, which lowers their fluorescence intensity and augments particle toxicity. Using the multiparametric method, the quantum dots were evaluated at non-toxic doses in terms of their ability to visualize labeled cells for longer time periods. The data revealed that comparing different particles in terms of their applied dose is challenging, likely due to difficulties in obtaining accurate nanoparticles concentrations, but evaluating particle toxicity in terms of their biological functionality enables an easy and straightforward comparison.
The use of nanostructuring to improve the stability of passive thin films on biomaterials can enhance their effectiveness in corrosion resistance and reduce the release of ions. The thickness of the ultrathin films that cover Ti and Ti alloys (only several nanometers) has prevented researchers from establishing systematic methods for their characterization. This study employed a multifunctional biomedical titanium alloy Ti-24Nb-4Zr-8Sn (wt%) as a model material. Coarse-grained (CG) and nanostructured (NS) alloys were analyzed in 0.9% NaCl solution at 37°C. To reveal the details of the passive film, a method of sample preparation producing a passive layer suitable for transmission electron microscope analysis was developed. Electrochemical corrosion behavior was evaluated by potentiodynamic polarization tests and Mott-Schottky measurements. Surface depth chemical profile and morphology evolution were performed by X-ray photoelectron spectroscopy and in-situ atomic force microscopy, respectively. A mechanism was proposed on the basis of point defect model to compare the corrosion resistance of the passive film on NS and CG alloys. Results showed that the protective amorphous film on NS alloy is thicker, denser and more homogeneous with fewer defects than on CG alloy. The film on NS alloy contains more oxygen and corrosion resistant elements (Ti and Nb), as well as their suboxides when compared with the film on CG alloy. These characteristics can be attributed to the rapid, uniform growth of the passive film facilitated by nanostructuring.
In this paper, the elastic deformation behaviour of a recently developed beta-type titanium alloy Ti-24Nb-4Zr-7.9Sn (wt.%) that consists of non-toxic elements and is intended for biomedical applications is described. Tensile tests show that this alloy in the as hot-rolled state exhibits peculiar non-linear elastic behaviour with maximum recoverable strain up to 3.3% and incipient Young's modulus of 42GPa. Solution treatment at high temperature has trivial effect on super-elasticity but decreases strength and slightly increases the incipient Young's modulus. Ageing treatment in the (alpha+beta) two-phase field increases both strength and Young's modulus and results in a combination of high strength and relatively low elastic modulus. In spite of the formation of the alpha phase, short time ageing has no effect on super-elasticity, whereas the non-linear elastic behaviour transforms gradually to normal linear elasticity with the increase of ageing time. We suggest sluggish, partially reversible processes of stress-induced phase transformation and/or incipient kink bands as the origin of the above peculiar elastic behaviour.
In recent years, Ti-Zr-Nb alloys have become increasingly attractive as biomedical implant materials. In the present communication, we report the formation of self-organized nanotube oxide layers on a Ti-28Zr-8Nb biomedical alloy surface in 1M (NH4)2SO4 containing 0.25M NH4F. The morphology of the nanotube layers (the diameter and the length) is affected by the electrochemical conditions used (applied potential and time). Under specific conditions oxide layers consisting of highly ordered nanotubes with a wide range of diameters and lengths can be formed, varying, respectively, from approx. 50 to 300nm and from approx. 500nm to 22microm. The present results are highly promising for this biomedical alloy, as the large surface area and the tunable nanoscale geometry of the surface oxide provide novel pathways for the interaction of the materials with biorelevant species, such as cells and proteins.
MicroRNAs are important post-transcriptional regulators of skeletal biology, and miRNA-based therapeutics have the potential to aid bone repair. However, efficient tools to deliver miRNA mimics or inhibitors to specific target tissues are limited. Polymeric nanofibers closely mimic natural extracellular matrix morphology, and are attractive candidates to support delivery of cells and bone-anabolic reagents. We hypothesized that gelatin nanofibers could be used for the localized transient delivery of miRNA-based therapeutics, using miR-29a inhibitor as a prototype to increase extracellular matrix (ECM) deposition. miR-29 family members are negative regulators of ECM synthesis, targeting the mRNAs of selected collagens and osteonectin/SPARC. Inhibiting miR-29 activity may therefore, increase extracellular matrix production by cells. miR-29a inhibitor loaded gelatin nanofibers, prepared by electrospinning, demonstrated continuous release of miRNA inhibitor over 72 hours. Pre-osteoblastic murine MC3T3-E1 cell line seeded on miR-29a inhibitor loaded nanofibers synthesized more osteonectin, indicating efficient inhibitor delivery. These cells also displayed increased Igf1 and Tgfb1 mRNA. Moreover, primary bone marrow stromal cells from transgenic pOBCol3.6cyan reporter mice, grown on miR-29a inhibitor scaffolds, displayed increased col3.6 cyan expression as well as collagen production. This study demonstrated that ECM mimicking nanostructured scaffolds, in conjunction with bioactive miRNA-based therapeutics, may serve as a novel platform for developing biologically active localized cell delivery systems.
The corrosion behavior of Ti-48Al-2Cr-2Nb (at.%) in Ringer's solution was studied to evaluate its potential as a biocompatible material. Corrosion properties of Ti-6Al-4V were determined under the same conditions for comparison. Two electrochemical techniques, potentiodynamic anodic polarization and electrochemical impedance spectroscopy, were employed to test Ti-48Al-2Cr-2Nb and Ti-6Al-4V. Surface modifications to the samples were made by autoclaving and by oxidation in air at 500 degrees C and 800 degrees C. The results show excellent corrosion resistance for unmodified Ti-48Al-2Cr-2Nb, corroborated by the high values of polarization resistance and corrosion potential and low values of corrosion current and corrosion rate. Ti-48Al-2Cr-2Nb appears to possess corrosion characteristics similar to Ti-6Al-4V. Surface modification rendered the Ti-48Al-2Cr-2Nb material extremely corrosion resistant.
This study concerns the preparation and in vitro characterization of an apatite-wollastonite-2M bioactive glass ceramic which is intended to be used for the regeneration of hard tissue (i.e. in dental and craniomaxillofacial surgery). This bioglass ceramic has been obtained by appropriate thermal treatment through the devitrification (crystallization) of a glass with a stoichiometric eutectic composition within the Ca(3)(PO(4))(2)-CaSiO(3) binary system. Crack-free specimens of the bioglass ceramic were immersed in human bone marrow cell cultures for 3, 7, 14 and 21days, in order to study biocompatibility. Cell morphology, proliferation and colonization were assessed by scanning electron microscopy and confocal laser scanning microscopy. A total protein content assay was used to evaluate the viability and proliferation of cultured bone marrow cells. The results showed that the cells were able to adhere and proliferate on the designed material due to the essentiality of silicon and calcium as accessory factors for cell activity stimulation.
Top-cited authors
Susmita Bose
  • Washington State University
Amit Bandyopadhyay
  • Washington State University
Aldo R. Boccaccini
  • Friedrich-Alexander-University of Erlangen-Nürnberg
Yufeng Zheng
  • Peking University
R.D.K. Misra