Biomimetic modification of porous TiNbZr alloy scaffold for bone tissue engineering

Porous titanium (Ti) and Ti alloys are important scaffold materials for bone tissue engineering. In the present study, a new type of porous Ti alloy scaffold with biocompatible alloying elements, that is, niobium (Nb) and zirconium (Zr), was prepared by a space-holder sintering method. This porous TiNbZr scaffold with a porosity of 69% exhibits a mechanical strength of 67MPa and an elastic modulus of 3.9GPa, resembling the mechanical properties of cortical bone. To improve the osteoconductivity, a calcium phosphate (Ca/P) coating was applied to the surface of the scaffold using a biomimetic method. The biocompatibility of the porous TiNbZr alloy scaffold before and after the biomimetic modification was assessed using the SaOS2 osteoblast&ndash;like cells. Cell culture results indicated that the porous TiNbZr scaffold is more favorable for cell adhesion and proliferation than its solid counterpart. By applying a Ca/P coating, the cell proliferation rate on the Ca/P-coated scaffold was significantly improved. The results suggest that high-strength porous TiNbZr scaffolds with an appropriate osteoconductive coating could be potentially used for bone tissue engineering application.<br /

Caracterización de la microestructura de una aleación de Ti libre de Ni con memoria de forma y bajo módulo para aplicaciones biomédicas ante diferentes velocidades de enfriamiento

En aquest projecte s’ha caracteritzat una aleació de titani sense níquel disenyada per tenir un baix mòdul elàstic i/o memòria de forma, destinada a ser utilitzada per la creació d’implants biomèdics. La aleació va ser dissenyada per Marta González per una tesis actualment en curs. S’ha realitzat un estudi de l’art sobre materials similars ja estudiats al llarg de la história en implantología, amb l’objectiu d’entendre i justificar l’efecte de la transformació martensítica en les propietats del material, així com la influència de la fase ω en aquestes propietats i transformacions. Asociada a aquesta justificació de les propietats del materia es planteja també la validació del mètode amb el que s’ha dissenyat el material i els diferents mètodes experimentals utilitzats al laboratori per la caracterització del material. Finalment, els resultats de cadascun dels mètodes realitzats, entre els que destaquen la nanoindentació instrumentada i la microscopia de transmissió electrònica, a través de la seva discusió i validació mostren que la aleació objecte d’estudi es una aleació amb gran potencial en el sector biomèdic degut al seu baix módul elàstic i el seu aparent apantallament de carregues

Design and testing of additively manufactured lattice structures for musculoskeletal applications

Additive manufacturing (AM) methods present a new frontier in engineering, allowing the fabrication of porous lattice structures with tailored mechanical properties. AM structures can be made using bio-inert metals, creating controlled stiffness biomaterials. As bone formation is strain dependent, these AM biomaterials can be used in implants to optimise the strain in surrounding trabecular bone for peak bone formation. However, the behaviour of AM lattices varies and is subject to manufacturing constraints. The aim of this PhD was to investigate the mechanical behaviour of AM lattices, and maximise the clinical benefits of AM for musculoskeletal applications. Lattice architecture was shown to affect the anisotropy of an AM lattice biomaterial, increasing the stiffness in directions not often tested in the literature. The mechanical and morphological properties of individual struts within powder bed fusion (PBF) lattices were also shown to vary depending on the orientation of the struts to the build direction. The ultimate tensile strength of titanium alloy (Ti6Al4V) struts more than doubled when built at a low angle versus perpendicular to the build platform, and other properties were substantially lower than for the bulk material. Geometric imperfections were found for struts built at low angles. As such, a low stiffness modified stochastic lattice was designed and tested which avoided the problems found with struts built at low angles. The resulting lattice had improved stiffness isotropy and could be used for musculoskeletal applications, tuned to match the mechanical properties in local trabecular bone and enhancing bone formation.Open Acces

Validation of numerical prediction of bone ingrowth into cementless implants

Total joint replacement was pioneered by John Charnley in the late 1950's, and has since revolutionised the management of arthritis sufferers. By 1991, an estimated 5 million people had undergone hip replacements. Although relatively successful, the cemented components had some problems, and this led to the development of cementless implants. These implants depend on the ingrowth of bone into a porous coating, to produce a durable method of implant fixation which the normal bone turnover process will maintain. One of the problems with cementless implants is that the type and extent of tissue ingrowth into the porous coating is unpredictable. Movement of the implant relative to the surrounding bone may result in the formation of an interfacial fibrous tissue layer. Hence, numerical modelling has been used to predict tissue ingrowth into such implants. Numerical simulation has the advantage that comprehensive data can be extracted relatively quickly. The finite element method is a powerful tool that has become the preferred method of analysis, and takes into account critical factors such as implant design, bone properties, and loading conditions. However, these models have not been tested extensively. Little attention has been given to comparing numerical models with the actual findings of retrieval studies or radiological imaging studies. This study thus evaluates the potential of one such numerical model. Most numerical models analyse the stress patterns of a particular state of bone ingrowth (i.e. a static case). This model considered the development of the ingrowing material - a dynamic analysis of tissue changes over a period of time. A 2-dimensional, plane stress finite element model was used to predict the ingrowth of bone into the porous coating of the femoral stem of a hip implant. A side plate was incorporated to mimic 3-dimensional characteristics. The evaluation was achieved by comparing the predictions of the numerical model with plane X-ray images of seven patients with Zimmer Anatomic cementless hip implants. The X-rays were scanned at a high resolution, so as to be able to "magnify" the regions to be examined. Several algorithms were developed to analyse the images, and provide a quantitative assessment of the X-ray images. The algorithms were designed to identify regions of bony and fibrous tissue. This involved the identification of the interface between the implant and the surrounding bone, and the extraction of the grayscale values of the X-rays at this interface. Thereafter, various radiographic signs that indicate the presence of fibrous tissue or bony tissue were identified, and these were used to enhance the original grayscale plot. The resulting graph was then modified slightly so as to make its presentation comparable with the numerical model. Plane X-rays proved to be suitable for the task of identifying tissue types. These data were then compared with the predictions of the numerical model. A qualitative correlation was used, as this was deemed to be most appropriate. Several authors in the literature also found a quantitative approach to have limitations. Some agreement between the experimental findings and the numerical simulation was found to exist, although this was limited. The agreement was judged to be less than the "reasonable agreement'' that several studies in the literature concluded. The correlation is better described by "some agreement". Nevertheless, the finite element method was assessed as being a tool with great potential, and modifications to the present model may provide more reliable results. A time study was also undertaken, whereby the tissue density was evaluated at various periods after the operation. The study provided insight into the evolution of the implant-bone interface after surgery, and correlated well with the literature. The phases of repair and remodelling were evident, and it was assessed as being a valuable contribution to this work. The time study may prove to be a more useful method than those used in assessing the "static" images, and could even provide a prognostic tool in assessing implant stability over time

On the design evolution of hip implants: A review

This manuscript reviews the development of femoral stem prostheses in the biomedical field. After a brief introduction on the development of these prostheses and the associated problems, we describe the standard design of these systems. We review the different materials, constructions, and surfaces used in the development of femoral stems, in order to solve and avoid various problems associated with their use. Femoral stem prostheses have undergone substantial changes and design optimizations since their introduction. Common materials include stainless steel, cobalt–chromium alloy, titanium alloy, and composites. The structural development of femoral stem prostheses, including their length, shape, porosity, and functional gradient construction, is also reviewed. The performance of these prostheses is affected not only by individual factors, but also by the synergistic combination of multiple effects; therefore, several aspects need to be optimized. The main purpose of this study is to summarize various strategies for the material and construction optimization of femoral stem prostheses, and to provide a reference for the combined optimization of their performance. Substantial research is still needed to develop prostheses emulating the behavior of a real human femoral stem

Modelling and in vitro evaluation of customised Ti6Al4V and PEEK hip implants for improving osseointegration and reducing stress shielding

Following total hip arthroplasty (THA), a considerable level of natural mechanical loading is shielded from the cortical bone and is transferred to the hip stem. This stress shielding effect caused by the underloaded femur post THA, over time, lead to bone loss. This consequently weakens the implant support and increases the risk of elevated micromotion at the bone-implant interface, leading to aseptic loosening and potentially femoral fracture, requiring a revision surgery. Many studies have investigated the development of different types of hip stems with various geometrical/structural designs and material properties to reduce the stress shielding. However, current approaches in the literature do not show a significant reduction in stress shielding and bone resorption, and often do not evaluate these parameters in Gruen zones, where such considerations are very important for clinicians when evaluating the performance of a hip implant. Furthermore, no fatigue performance has been performed on any of the suggested low stiffness hip stems in the literature. The overall aim of this thesis was to design and develop a low stiffness hip stem that can simultaneously minimize bone resorption and implant instability. Two custom tailored stems were developed and evaluated. One had a low material stiffness made from polyether ether ketone (PEEK) and one had a variable stiffness based on graded lattice structures made from 3D printed titanium (i.e. Ti6Al4V). In this study, stress shielding and bone resorption were evaluated across the Gruen zones using experimental and validated computational models. The overall stiffness and fatigue life of the developed hip stems were measured. Results demonstrated that the developed low stiffness porous Ti6Al4V and PEEK hip stems considerably reduced the level of stress shielding and bone resorption compared to a solid Ti6Al4V hip stem with identical geometry. This reduction was more evidenced in the proximal femur

Finite element simulation of hip joint replacement under static and dynamic loading

The objective of this work is to develop methods for the structural analysis of orthopaedic implants. The central argument is that, if stress distributions are interpreted in the context of failure models of the component materials, significant advantages can be made in our ability to design these devices. The artificial hip joint is used throughout as an example. The finite element method was used as a structural analysis tool and its pplicability was discussed. Validity and accuracy were assessed and results were ompared with previous experimental and finite element studies. By comparing tress distributions with failure criteria for prosthesis and cement, the suitability of roposed design changes were assessed and guidelines for materials selection were resented. Prediction of bone stresses were also given for different prosthesis designs n the region of the artificial hip joint where bone adaption contributes to failure. hereafter the focus was on utilizing a new technique to develop a new hip prosthesis model. This study was divided into two parts according to the loading type. In this regard the stress field in the artificial hip components (prostheses, cement mantle, and bone) is analysed statically and dynamically to assess the implant longevity. In this static analysis all the simulations were conducted by assuming the peak loads during the normal gait at a particular time (static loads). The aim was to study the effects of a set of variables within which an optimal prosthesis design can be made by means of finite element analysis to qualify and quantify the stresses and the strains in natural and treated human femur for different cases of implantation. Until now, models developed to predict stresses in total hip replacements have been generally poorly validated. This could be because all the pre-clinical simulations were performed statically, that is by selecting the greatest load at a particular time of the activity cycle. The second part of the study was aimed to take into consideration, in designing total hip replacement, another factor belongs to the patient activity (stamping, jumping, walking, etc) and the effect of impact over the prosthesis head during these activity into the prosthesis performance. This study considered the prosthesis hip deformation with time, dynamic loads study. The elimination of impact cracking was considered by studying the effect of using “damper” trapped between the grooved prosthesis collar and the bone. Material selection of the total hip replacements was also investigated under the dynamic loading. The approaches of prosthesis fixation have been studied, too. This study was conducted by onstructing three-dimensional finite element model for a femur implanted with a cemented prosthesis with a representative physiological loading condition by using he LS-DYNA3D software

Electrophoretic deposition of organic/inorganic composite coatings on metallic substrates for bone replacement applications: mechanisms and development of new bioactive materials based on polysaccharides

Regarding the need to improve the usually encountered osteointegration of metallic implants with the surrounding body tissue in bone replacement applications, bioactive organic/inorganic composite coatings on metallic substrates were developed in this work using electrophoretic deposition (EPD) as coating technology. In the present work three polysaccharides, namely alginate, chondroitin sulfate and chitosan were used as the organic part, acting as the matrix of the coating and enabling the coating attachment to the metallic substrates (stainless steel AISI 316L, titanium alloy TI6Al4V and magnesium alloy AD91D). Different types of ceramic fillers were investigated as the inorganic phase of the coatings. Different bioactive glasses were used to impart osteoconductive and osteoinductive properties to the coating, while nanoparticles of titania and zinc oxide were used to bring antibacterial properties, improve the mechanical stability and control the degradation behavior of the coatings. In this work the possibility to develop stable suitable suspensions to produce coatings by EPD is shown, based in the three selected biopolymers and containing one or more types of ceramic particles in different size ranges from 20 nm to 30 µm. The investigation of different solvents for EPD, namely water and ethanol, was carried out (single or in mixtures of both) to develop stable suspensions to reduce the negative effect of the water hydrolysis in the coating morphology. The suspension stability was studied via ζ–potential measurements finding that the suspension mechanism is controlled by the polymer, which, by esterification effect, suspends the ceramic particles in the liquid media. A variety of more than 20 coatings were studied and developed during this thesis. The major goal was to develop suitable EPD technology to produce coatings with: adequate (i) homogeneity, (ii) attachment to the substrate, (iii) ceramic/polymer ratio, (iv) wettability and morphology, (v) electrochemical behavior, (vi) bioactivity and (vi) degradation behavior. Other properties were also analyzed such as: antibacterial activity and drug delivery function (by incorporation of simvastatin). Alginate based coatings containing nanoparticles of TiO2 or ZnO were developed by anodic EPD. Bioactive glass 45S5® (BG) was successfully incorporated to those coatings with the aim to provide bioactivity to the coating by the formation of hydroxyapatite. However not all the coatings were able to show bioactivity, mainly by an interaction of the anodic alginate with the ions coming from the simulated body fluid (SBF) and the BG particles. It was confirmed that all coatings imparted corrosion protection to the substrate when evaluated via potentiostatic polarization curves by immersion in Dulbecco´s MEM, also to the highly reactive magnesium alloy AZ91D, in the initial immersion stages. For the first time, in this project chondroitin sulfate (CS) was deposited by EPD. Even when the deposition was successful the coating degraded considerably fast when immersed in water based fluids. To tackle the fast degradation and impart bioactivity to CS coatings, a multilayer approach was chosen, where chitosan was used in the production of sandwich-type multilayers with the presence of BG in some of the layers. By this method the coating degradation was considerable reduced and the development of a bioactive composite coating was possible. The most successful coatings, in terms of degradation behavior and bioactivity, were the chitosan based coatings. The bioactive glass/chitosan (BG/Ch) system was studied in a comparative study using three different bioactive glasses. In this study all the coatings exhibited bioactivity, independently of the bioactive glass composition. The best coating in terms of homogeneity, degradability and bioactivity was produced using Bioglass 45S5®. For the system Bioglass/Chitosan considerable improvements were done compared with previous reported works, obtaining more stable suspensions and better coating homogeneity. To tailor the coating degradability and improve adhesion to the substrate, titania was added to the BG/Ch coating. In addition, simvastatin, a drug currently proposed to promote bone formation, was added to the system confirming the drug delivery potential of the coatings. Cell test studies with MG-63 human osteosarcoma cells were done on selected coatings to evaluate cell vitality and the effect of the simvastatin on cell behavior. In this work EPD has shown to be a highly versatile, low-cost and convenient method to produce organic/inorganic coatings on metallic substrates based on the chosen materials. Different approaches were studied: from single to multilayers, from coatings on flat surfaces to complex 3D structures, as well as the drug delivery potential. Coatings with tailored composition and thickness were successfully produced exhibiting the versatility of EPD as coating production technique