Multiscale Characterization of Acrylic Bone Cement Modified with Functionalized Mesoporous Silica Nanoparticles

Acrylic bone cement is widely used to anchor orthopedic implants to bone and mechanical failure of the cement mantle surrounding an implant can contribute to aseptic loosening. In an effort to enhance the mechanical properties of bone cement, a variety of nanoparticles and fibers can be incorporated into the cement matrix. Mesoporous silica nanoparticles (MSNs) are a class of particles that display high potential for use as reinforcement within bone cement. Therefore, the purpose of this study was to quantify the impact of modifying an acrylic cement with various low-loadings of mesoporous silica. Three types of MSNs (one plain variety and two modified with functional groups) at two loading ratios (0.1 and 0.2 wt/wt) were incorporated into a commercially available bone cement. The mechanical properties were characterized using four-point bending, microindentation and nanoindentation (static, stress relaxation, and creep) while material properties were assessed through dynamic mechanical analysis, differential scanning calorimetry, thermogravimetric analysis, FTIR spectroscopy, and scanning electron microscopy. Four-point flexural testing and nanoindentation revealed minimal impact on the properties of the cements, except for several changes in the nano-level static mechanical properties. Conversely, microindentation testing demonstrated that the addition of MSNs significantly increased the microhardness. The stress relaxation and creep properties of the cements measured with nanoindentation displayed no effect resulting from the addition of MSNs. The measured material properties were consistent among all cements. Analysis of scanning electron micrographs images revealed that surface functionalization enhanced particle dispersion within the cement matrix and resulted in fewer particle agglomerates. These results suggest that the loading ratios of mesoporous silica used in this study were not an effective reinforcement material. Future work should be conducted to determine the impact of higher MSN loading ratios and alternative functional groups. (C) 2014 Elsevier Ltd. All rights reserved.

Wear particles and surface topographies are modulators of osteoclastogenesis in vitro

Prosthetic and osteosynthetic implants from metal alloys will be indispensable in orthopedic surgery, as long as tissue engineering and biodegradable bone substitutes do not lead to products that will be applied in clinical routine for the repair of bone, cartilage, and joint defects. Therefore, the elucidation of the interactions between the periprosthetic tissues and the implant remains of clinical relevance and several factors are known to affect the longevity of implants. Within this study, the effects of metal particles and surface topography on the recruitment of osteoclasts was investigated in vitro in a coculture of osteoblasts and bone marrow cells. The cells were grown in the presence of particles of different sizes and chemical composition or on metal discs with polished or sandblasted surfaces, respectively. At the end of the culture, newly formed osteoclasts were counted. Osteoclastogenesis was reduced when particles were added directly to the coculture. The effect depended on the size of the particles, small particles exerting stronger effects than larger ones. The chemical composition of the particles, however, did not affect the development of osteoclasts. In cocultures grown on sandblasted surfaces, osteoclasts developed at higher rates than they did in cultures on polished surfaces. The data demonstrate that wear particles and implant surfaces affect osteoclastogenesis and thus may be involved in the induction of local bone resorption and the formation of osteolytic lesions, leading eventually to the loosening of orthopedic implants.

BMP-2 liberated from biomimetic implant coatings induces and sustains direct ossification in an ectopic rat model

INTRODUCTION: Using a rat model, we evaluated the kinetics and histomorphometry of ectopic bone formation in association with biomimetic implant coatings containing BMP-2. MATERIALS AND METHODS: One experimental and three control groups were set up: titanium-alloy discs coated with a biomimetically co-precipitated layer of calcium phosphate and BMP-2 [1.7 microg per disc (incorporated-BMP group)]; uncoated discs (control); discs biomimetically coated with a layer of calcium phosphate alone (control); and discs biomimetically coated with a layer of calcium phosphate bearing superficially adsorbed BMP-2 [0.98 microg per disc (control)]. Discs (n = 6 per group) were implanted subcutaneously in rats and retrieved at 7-day intervals over a period of 5 weeks for kinetic, histomorphometrical, morphological and histochemical analyses. RESULTS: In the incorporated-BMP-2 group, osteogenic activity was first observed 2 weeks after implantation and thereafter continued unabated until the end of the monitoring period. The net weekly rates of bone formation per disc were 5.8 mm3 at 2 weeks and 3.64 mm3 at 5 weeks. The total volumes of bone formed per disc at these junctures were 5.8 mm3 and 10.3 mm3, respectively. Bone tissue, which was formed by a direct ossification mechanism, was deposited at distances of up to 340 microm from the implant surfaces. The biomimetic coatings were degraded gradually, initially by foreign body giant cells alone and then also by osteoclasts. Forty percent of the coating material (and thus presumably of the incorporated BMP-2) remained at the end of the monitoring period. Hence, 60% of the incorporated BMP-2 had been released. At this 5-week juncture, no bone tissue was associated with any of the control implants. CONCLUSION: BMP-2 incorporated into biomimetic calcium phosphate coatings is capable not only of inducing bone formation at an ectopic site in vivo but also of doing so with a very high potency at a low pharmacological level, and of sustaining this activity for a considerable period of time. The sustainment of osteogenic activity is of great clinical importance for the osseointegration of dental and orthopedic implants.

OsteoMacs: Key players around bone biomaterials.

Osteal macrophages (OsteoMacs) are a special subtype of macrophage residing in bony tissues. Interesting findings from basic research have pointed to their vast and substantial roles in bone biology by demonstrating their key function in bone formation and remodeling. Despite these essential findings, much less information is available concerning their response to a variety of biomaterials used for bone regeneration with the majority of investigation primarily focused on their role during the foreign body reaction. With respect to biomaterials, it is well known that cells derived from the monocyte/macrophage lineage are one of the first cell types in contact with implanted biomaterials. Here they demonstrate extremely plastic phenotypes with the ability to differentiate towards classical M1 or M2 macrophages, or subsequently fuse into osteoclasts or multinucleated giant cells (MNGCs). These MNGCs have previously been characterized as foreign body giant cells and associated with biomaterial rejection, however more recently their phenotypes have been implicated with wound healing and tissue regeneration by studies demonstrating their expression of key M2 markers around biomaterials. With such contrasting hypotheses, it becomes essential to better understand their roles to improve the development of osteo-compatible and osteo-promotive biomaterials. This review article expresses the necessity to further study OsteoMacs and MNGCs to understand their function in bone biomaterial tissue integration including dental/orthopedic implants and bone grafting materials.

Análisis de distribución de tensiones asociada a la utilización de implantes ortopédicos de materiales superelásticos en el tratamiento de deficiencias óseas.

Durante el desarrollo de un niño pueden ocurrir diversas anomalías y distorsiones en el crecimiento de los huesos que resultan en distintos problemas. Independientemente de las razones por las que ocurren, si son detectadas y tratadas con tiempo sus secuelas pueden ser minimizadas o eliminadas. Este trabajo continúa el proyecto integrador de ingeniería mecánica del ingeniero Matías Korten. En ese trabajo se realizaron ensayos termomecánicos a alambres de NiTi para caracterizar las fuerzas desarrolladas y la influencia de diferentes parámetros geométricos y físicos en las mismas. El Dr. J. Groiso propone la fabricación de un dispositivo pseudoelástico y biocompatible de NiTi para corregir deformaciones angulares en huesos. En este trabajo, se buscó caracterizar nuevamente el material NiTi, validar los resultados obtenidos en ese trabajo y diseñar un dispositivo que permita la caracterización del material de forma más confiable. Se desarrolló un modelo computacional de un hueso en 3D que permite obtener el campo de tensiones sobre la placa de crecimiento al aplicar una fuerza superficial sobre los tornillos. Se analizaron los resultados con distintas formas de aplicación de la fuerza, la zona afectada por la prótesis al cambiar la posición de los tornillos y se hizo un análisis de sensibilidad en el rango (según bibliografía) del módulo de elasticidad de la placa de crecimiento. Se concluye que la aplicación de un dispositivo de NiTi puede generar las tensiones necesarias para impulsar el crecimiento del hueso en la dirección correcta.

Análisis de distribución de tensiones asociada a la utilización de implantes ortopédicos de materiales superelásticos en el tratamiento de deficiencias óseas.

Durante el desarrollo de un niño pueden ocurrir diversas anomalías y distorsiones en el crecimiento de los huesos que resultan en distintos problemas. Independientemente de las razones por las que ocurren, si son detectadas y tratadas con tiempo sus secuelas pueden ser minimizadas o eliminadas. Este trabajo continúa el proyecto integrador de ingeniería mecánica del ingeniero Matías Korten. En ese trabajo se realizaron ensayos termomecánicos a alambres de NiTi para caracterizar las fuerzas desarrolladas y la influencia de diferentes parámetros geométricos y físicos en las mismas. El Dr. J. Groiso propone la fabricación de un dispositivo pseudoelástico y biocompatible de NiTi para corregir deformaciones angulares en huesos. En este trabajo, se buscó caracterizar nuevamente el material NiTi, validar los resultados obtenidos en ese trabajo y diseñar un dispositivo que permita la caracterización del material de forma más confiable. Se desarrolló un modelo computacional de un hueso en 3D que permite obtener el campo de tensiones sobre la placa de crecimiento al aplicar una fuerza superficial sobre los tornillos. Se analizaron los resultados con distintas formas de aplicación de la fuerza, la zona afectada por la prótesis al cambiar la posición de los tornillos y se hizo un análisis de sensibilidad en el rango (según bibliografía) del módulo de elasticidad de la placa de crecimiento. Se concluye que la aplicación de un dispositivo de NiTi puede generar las tensiones necesarias para impulsar el crecimiento del hueso en la dirección correcta.

Caracterização elementar de ligas metálicas em implantes dentários

An ideal biomaterial for dental implants must have very high biocompatibility, which means that such materials should not provoke any serious adverse tissue response. Also, used metal alloys must have high fatigue resistance due the masticatory force and good corrosion resistance. These properties are rendered by using alpha and beta stabilizers, such as Al, V, Ni, Fe, Cr, Cu, Zn. Commercially pure titanium (TiCP) is used often for dental and orthopedic implants manufacturing. However, sometimes other alloys are employed and consequently it is essential to research the chemical elements present in those alloys that could bring prejudice for the health. Present work investigated TiCP metal alloys used for dental implant manufacturing and evaluated the presence of stabilizing elements within existing limits and standards for such materials. For alloy characterization and identification of stabilizing elements it was used EDXRF technique. This method allows to perform qualitative and quantitative analysis of the materials using the spectra of the characteristic X-rays emitted by the elements present in the metal samples. The experimental setup was based on two X- rays tubes (AMPTEK Mini X model with Ag and Au targets), a X-123SDD detector (AMPTEK) and a 0.5mm Cu collimator, developed due to the sample characteristics. The other experimental setup used as a complementary technique is composed of an X-ray tube with a Mo target, collimator 0.65mm and XFlash (SDD) detector - ARTAX 200 (BRUKER). Other method for elemental characterization by energy dispersive spectroscopy (EDS) applied in present work was based on Scanning Electron Microscopy (SEM) EVO® (Zeeis). This method also was used to evaluate the surface microstructure of the sample. The percentual of Ti obtained in the elementary characterization was among 93.35 ± 0.17% and 95.34 ± 0.19 %. These values are considered below the reference limit of 98.635% to 99.5% for TiCP, established by Association of metals centric materials engineers and scientists Society (ASM). The presence of elements Al and V in all samples also contributed to underpin the fact that are not TiCP implants. The values for Al vary between 6.3 ± 1.3% and 3.7 ± 2.0% and for V, between 0.26 ± 0.09% and 0.112 ± 0.048%. According to the American Society for Testing and Materials (ASTM), these elements should not be present in TiCP and in accordance with the National Institute of Standards and Technology (NIST), the presence of Al should be <0.01% and V should be of 0.009 ± 0.001%. Obtained results showed that implant materials are not exactly TiCP but, were manufactured using Ti-Al-V alloy, which contained Fe, Ni, Cu and Zn. The quantitative analysis and elementary characterization of experimental results shows that the best accuracy and precision were reached with X-Ray tube with Au target and collimator of 0.5 mm. Use of technique of EDS confirmed the results of EDXRF for Ti-Al-V alloy. Evaluating the surface microstructure by SEM of the implants, it was possible to infer that ten of the thirteen studied samples are contemporaneous, rough surface and three with machined surface.

Effects of zirconium and strontium on the biocorrosion of Mg-Zr-Sr alloys for biodegradable implant applications

The successful applications of magnesium (Mg) alloys as biodegradable orthopedic implants are mainly restricted due to their rapid degradation rate in the physiological environment, leading to a loss of mechanical integrity. This study systematically investigated the degradation behaviors of novel Mg-Zr-Sr alloys using electrochemical techniques, hydrogen evolution, and weight loss in simulated body fluid (SBF). The microstructure and degradation behaviors of the alloys were characterized using optical microscopy, XRD, SEM, and EDX. The results indicate that Zr and Sr concentrations in Mg alloys strongly affected the degradation rate of the alloys in SBF. A high concentration of 5 wt% Zr led to acceleration of anodic dissolution, which significantly decreased the biocorrosion resistance of the alloys and their biocompatibility. A high volume fraction of Mg17Sr2 phases due to the addition of excessive Sr (over 5 wt%) resulted in enhanced galvanic effects between the Mg matrix and Mg17Sr2 phases, which reduced the biocorrosion resistance. The average Sr release rate is approximately 0.15 mg L^-1 day^-1, which is much lower than the body burden and proves its good biocompatibility. A new biocorrosion model has been established to illustrate the degradation of alloys and the formation of degradation products on the surface of the alloys. It can be concluded that the optimal concentration of Zr and Sr is less than 2 wt% for as-cast Mg-Zr-Sr alloys used as biodegradable orthopedic implants.

Biomaterials in orthopedic bone plates : a review

This paper aims to review biomaterials used in manufacturing bone plates including advances in recent years and prospect in the future. It has found among all biomaterials, currently titanium and stainless steel alloys are the most common in production of bone plates. Other biomaterials such as Mg alloys, Ta alloys, SMAs, carbon fiber composites and bioceramics are potentially suitable for bone plates because of their advantages in biocompatibility, bioactivity and biodegradability. However, today either they are not used in bone plates or have limited applications in only some flexible small-size implants. This problem is mainly related to their poor mechanical properties. Additionally, production processes play an effective role. Therefore, in the future, further studies should be conducted to solve these problems and make them feasible for heavy-duty bone plates.

Bacterial adherence and biofilm formation on medical implants : a review

Biofilms are a complex group of microbial cells that adhere to the exopolysaccharide matrix present on the surface of medical devices. Biofilm-associated infections in the medical devices pose a serious problem to the public health and adversely affect the function of the device. Medical implants used in oral and orthopedic surgery are fabricated using alloys such as stainless steel and titanium. The biological behavior, such as osseointegration and its antibacterial activity, essentially depends on both the chemical composition and the morphology of the surface of the device. Surface treatment of medical implants by various physical and chemical techniques are attempted in order to improve their surface properties so as to facilitate bio-integration and prevent bacterial adhesion. The potential source of infection of the surrounding tissue and antimicrobial strategies are from bacteria adherent to or in a biofilm on the implant which should prevent both biofilm formation and tissue colonization. This article provides an overview of bacterial biofilm formation and methods adopted for the inhibition of bacterial adhesion on medical implants

The importance of crystallographic texture in the use of titanium as an orthopedic biomaterial

Crystallographic texture is perceived to play an important role in controlling material properties. However, the influence of texture in modulating the properties of biomedical materials has not been well investigated. In this work, commercially pure titanium (cp-Ti) was processed through six different routes to generate a variety of textures. The effect of texture on mechanical properties, corrosion behavior, cell proliferation and osteogenesis was characterized for potential use in orthopedic applications. The presence of closely packed, low-energy crystallographic planes at the material surface was influenced by the volume fraction of the components in the overall texture, thereby influencing surface energy and corrosion behavior. Texture modulated osteoblast proliferation through variations in surface water wettability. It also affected mineralization by possibly influencing the coherency between the substrate and calcium phosphate deposits. This study demonstrates that crystallographic texture can be an important tool in improving the properties of biomaterials to achieve the enhanced performance of biomedical implants.

Advantages and pitfalls in computer assisted orthopedic surgery planning using rapid-prototyped guides

Durch die von Rapid Prototyping gebotenen Möglichkeiten können computergestützte 3D Operationsplanungen präzise in der Operation umgesetzt werden. An der Universitätsklinik Balgrist wurden in den letzten 3 Jahren nahezu 100 Patienten erfolgreich behandelt, deren Operation in 3D geplant und mit patienten-spezifischen Schablonen umgesetzt wurde. Wir beschreiben die Genauigkeit dieser Methode und berichten über die hierbei gesammelten Erfahrungen. Aufgrund der Flexibilität der Rapid Prototyping Technologie, gibt es nicht immer nur einen Weg wie eine 3D geplante Operation umgesetzt werden kann. Wir zeigen daher anhand von Fallbeispielen unterschiedliche Strategien auf und beschreiben deren Vor- und Nachteile. Ausserdem präsentieren wir die Weiterentwicklung der Methode zur Anwendung an kleinerer Anatomie wie Knochen des Handgelenkes oder der Finger.

CT Image Electron Density Quantification in Regions with Metal Implants: Implications for Radiotherapy Treatment Planning

In radiotherapy planning, computed tomography (CT) images are used to quantify the electron density of tissues and provide spatial anatomical information. Treatment planning systems use these data to calculate the expected spatial distribution of absorbed dose in a patient. CT imaging is complicated by the presence of metal implants which cause increased image noise, produce artifacts throughout the image and can exceed the available range of CT number values within the implant, perturbing electron density estimates in the image. Furthermore, current dose calculation algorithms do not accurately model radiation transport at metal-tissue interfaces. Combined, these issues adversely affect the accuracy of dose calculations in the vicinity of metal implants. As the number of patients with orthopedic and dental implants grows, so does the need to deliver safe and effective radiotherapy treatments in the presence of implants. The Medical Physics group at the Cancer Centre of Southeastern Ontario and Queen's University has developed a Cobalt-60 CT system that is relatively insensitive to metal artifacts due to the high energy, nearly monoenergetic Cobalt-60 photon beam. Kilovoltage CT (kVCT) images, including images corrected using a commercial metal artifact reduction tool, were compared to Cobalt-60 CT images throughout the treatment planning process, from initial imaging through to dose calculation. An effective metal artifact reduction algorithm was also implemented for the Cobalt-60 CT system. Electron density maps derived from the same kVCT and Cobalt-60 CT images indicated the impact of image artifacts on estimates of photon attenuation for treatment planning applications. Measurements showed that truncation of CT number data in kVCT images produced significant mischaracterization of the electron density of metals. Dose measurements downstream of metal inserts in a water phantom were compared to dose data calculated using CT images from kVCT and Cobalt-60 systems with and without artifact correction. The superior accuracy of electron density data derived from Cobalt-60 images compared to kVCT images produced calculated dose with far better agreement with measured results. These results indicated that dose calculation errors from metal image artifacts are primarily due to misrepresentation of electron density within metals rather than artifacts surrounding the implants.

Physiological investigation of periosteum structure and its application in periosteum tissue engineering

Although many different materials, techniques and methods, including artificial or engineered bone substitutes, have been used to repair various bone defects, the restoration of critical-sized bone defects caused by trauma, surgery or congenital malformation is still a great challenge to orthopedic surgeons. One important fact that has been neglected in the pursuit of resolutions for large bone defect healing is that most physiological bone defect healing needs the periosteum and stripping off the periosteum may result in non-union or non-healed bone defects. Periosteum plays very important roles not only in bone development but also in bone defect healing. The purpose of this project was to construct a functional periosteum in vitro using a single stem cell source and then test its ability to aid the repair of critical-sized bone defect in animal models. This project was designed with three separate but closely-linked parts which in the end led to four independent papers. The first part of this study investigated the structural and cellular features in periostea from diaphyseal and metaphyseal bone surfaces in rats of different ages or with osteoporosis. Histological and immunohistological methods were used in this part of the study. Results revealed that the structure and cell populations in periosteum are both age-related and site-specific. The diaphyseal periosteum showed age-related degeneration, whereas the metaphyseal periosteum is more destructive in older aged rats. The periosteum from osteoporotic bones differs from normal bones both in terms of structure and cell populations. This is especially evident in the cambial layer of the metaphyseal area. Bone resorption appears to be more active in the periosteum from osteoporotic bones, whereas bone formation activity is comparable between the osteoporotic and normal bone. The dysregulation of bone resorption and formation in the periosteum may also be the effect of the interaction between various neural pathways and the cell populations residing within it. One of the most important aspects in periosteum engineering is how to introduce new blood vessels into the engineered periosteum to help form vascularized bone tissues in bone defect areas. The second part of this study was designed to investigate the possibility of differentiating bone marrow stromal cells (BMSCs) into the endothelial cells and using them to construct vascularized periosteum. The endothelial cell differentiation of BMSCs was induced in pro-angiogenic media under both normoxia and CoCl2 (hypoxia-mimicking agent)-induced hypoxia conditions. The VEGF/PEDF expression pattern, endothelial cell specific marker expression, in vitro and in vivo vascularization ability of BMSCs cultured in different situations were assessed. Results revealed that BMSCs most likely cannot be differentiated into endothelial cells through the application of pro-angiogenic growth factors or by culturing under CoCl2-induced hypoxic conditions. However, they may be involved in angiogenesis as regulators under both normoxia and hypoxia conditions. Two major angiogenesis-related growth factors, VEGF (pro-angiogenic) and PEDF (anti-angiogenic) were found to have altered their expressions in accordance with the extracellular environment. BMSCs treated with the hypoxia-mimicking agent CoCl2 expressed more VEGF and less PEDF and enhanced the vascularization of subcutaneous implants in vivo. Based on the findings of the second part, the CoCl2 pre-treated BMSCs were used to construct periosteum, and the in vivo vascularization and osteogenesis of the constructed periosteum were assessed in the third part of this project. The findings of the third part revealed that BMSCs pre-treated with CoCl2 could enhance both ectopic and orthotopic osteogenesis of BMSCs-derived osteoblasts and vascularization at the early osteogenic stage, and the endothelial cells (HUVECs), which were used as positive control, were only capable of promoting osteogenesis after four-weeks. The subcutaneous area of the mouse is most likely inappropriate for assessing new bone formation on collagen scaffolds. This study demonstrated the potential application of CoCl2 pre-treated BMSCs in the tissue engineering not only for periosteum but also bone or other vascularized tissues. In summary, the structure and cell populations in periosteum are age-related, site-specific and closely linked with bone health status. BMSCs as a stem cell source for periosteum engineering are not endothelial cell progenitors but regulators, and CoCl2-treated BMSCs expressed more VEGF and less PEDF. These CoCl2-treated BMSCs enhanced both vascularization and osteogenesis in constructed periosteum transplanted in vivo.