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Insufficient angiogenesis remains a major hurdle in current bone tissue engineering strategies. An extensive body of work has focused on the use of angiogenic factors or endothelial progenitor cells. However, these approaches are inherently complex, in terms of regulatory and methodologic implementation, and present a high cost. We have recently demonstrate the potential of electrospun poly(lactic acid) (PLA) fiber-based membranes, containing calcium phosphate (CaP) ormoglass particles, to elicit angiogenesis in vivo , in a subcutaneous model in mice. Here we have devised an injectable composite, containing CaP glass-ceramic particles, dispersed within a (Hydroxypropyl)methyl cellulose (HPMC) matrix, with the capacity to release calcium in a more sustained fashion. We show that by tuning the release of calcium in vivo , in a rat bone defect model, we could improve both bone formation and increase angiogenesis. The bone regeneration kinetics was dependent on the Ca 2+ release rate, with the faster Ca 2+ release composite gel showing improved bone repair at 3 weeks, in relation to control. In the same line, improved angiogenesis could be observed for the same gel formulation at 6 weeks post implantation. This methodology allows to integrate two fundamental processes for bone tissue regeneration while using a simple, cost effective, and safe approach. Statement of Significance In current bone tissue engineering approaches the achievement of sufficient angiogenesis, during tissue regeneration, is a major limitation in order to attain full tissue functionality. Recently, we have shown that calcium ions, released by the degradation of calcium phosphate ormoglasses (CaP), are effective angiogenic promoters, in both in vitro and in a subcutaneous implantation model. Here, we devised an injectable composite, containing CaP glass-ceramic particles, dispersed within a HPMC matrix, enabling the release of calcium in a more sustained fashion. We show that by tuning the release of calcium in vivo , in a rat bone defect model, we could improve both bone formation and increase angiogenesis. This simple and cost effective approach holds great promise to translate to the clinics. more...

Adhesion of tissue cells is a prerequisite for their growth and differentiation but prevents also apoptosis. Here the layer-by-layer technique (LbL) was used to design multilayer structures of poly(ethylene imine) (PEI) and heparin (HEP) on glass as model biomaterial to control the adhesion of primary human dermal fibroblasts. Distinct surface features like wettability, charge and lateral structures were controlled by changing the pH value of the HEP solution during multilayer assembly to acidic, neutral or alkaline values. While plain terminal layers were rather cytophobic, the pre-adsorption of serum or fibronectin (FN) caused a distinct change in cell morphology in dependence on the pH setup. The effect of serum was more prominent on PEI layers probably due to their positive surface charge, whereas the effect of FN was more pronounced on HEP terminated multilayers possibly due to its ability to bind FN specifically. Those layers which hampered cell adhesion also inhibited growth of human fibroblasts under serum conditions. Conversely, on layers where cell adhesion was increased also an elevated growth and, thus, metabolic activity was observed. more...

International audience; In current bone tissue engineering strategies the achievement of sufficient angiogenesis during tissue regeneration is still a major limitation in order to attain full functionality. Several strategies have been described to tackle this problem, mainly by the use of angiogenic factors or endothelial progenitor cells. However, when facing a clinical scenario these approaches are inherently complex and present a high cost. As such, more cost effective alternatives are awaited. Here, we demonstrate the potential of electrospun poly(lactic acid) (PLA) fiber-based membranes, containing calcium phosphate ormoglass (CaP) particles, to elicit angiogenesis in vivo, in a subcutaneous model in mice. We show that the current approach elicited the local expression of angiogenic factors, associated to a chemotactic effect on macrophages, and sustained angiogenesis into the biomaterial. As both PLA and CaP are currently accepted for clinical application these off-the-shelf novel membranes have great potential for guided bone regeneration applications.Statement of significance: In current bone tissue engineering approaches the achievement of sufficient angiogenesis, during tissue regeneration, is a major limitation in order to attain full tissue functionality. Recently, our group has found that calcium ions released by the degradation of calcium phosphate ormoglasses (CaP) are effective angiogenic promoters. Based on this, in this work we successfully produced hybrid fibrous mats with different contents of CaP nanoparticles and thus with different calcium ion release rates, using an ormoglass - poly(lactic acid) blend approach. We show that these matrices, upon implantation in a subcutaneous site, could elicit the local expression of angiogenic factors, associated to a chemotactic effect on macrophages, and sustained angiogenesis into the biomaterial, in a CaP dose dependent manner. This off-the-shelf cost effective approach presents great potential to translate to the clinics. more...

Purpose To study the biomechanical performance of various allografts and the effects of endplate treatment on a lumbar corporectomy model. Methods A modified non-lineal tri-dimensional finite-element model of the lumbar spine was used, to which a set of transpedicular instruments was adapted. By means of a finite- element analysis, modeling was carried out of diaphyseal fragments of the femur, the tibia and the fibula. Four configurations were analyzed: with one femur, with one tibia, with three fibulas and with six fibulas. Four surfaces were evaluated that gave support to the graft according to the resection of the various components. Compression loads of 1,000 N were applied, as well as flexion, extension and rotation of 15 Nm respectively. The stresses and displacements caused were calculated. Results Full cartilage and subchondral bone resection is the configuration that least disrupts stresses within the adjacent vertebrae whereas the use of fibular fragments causes the greatest disruption. The use of the tibial bone gives rise to an asymmetry in the displacement area because of the shape of the said graft. The femur does not bring about a significant disruption of stresses in the adjacent vertebrae thereby constituting a more physiological construct. Conclusions Preservation of the endplate's cortical bone does not lead to any biomechanical advantage in the reconstruction of the anterior spine. Femoral allografts are the most appropriate ones to replace the vertebral body, compared with the tibia or the fibula. more...

Objetivos Comparar la rigidez y la distribucion de tensiones en los implantes de dos modelos experimentales: un humero con pseudoartrosis diafisaria estabilizado con placa y un humero con pseudoartrosis diafisaria estabilizado con clavo encerrojado. Material y metodo Con un humero de cadaver y los dos dispositivos de fijacion se crearon las geometrias con el programa de diseno CATIA v4.2 ® (IBM, Armonk, USA). Posteriormente estas geometrias se modelaron con el preprocesador informatico MSC-PATRAN ® (IBM, Armonk, USA). Finalmente se establecieron las propiedades mecanicas de los materiales, las condiciones de contorno y las cargas a las que fueron sometidos los modelos. Resultados El modelo con clavo fue mas rigido que el modelo con placa a compresion, traccion y torsion, sin embargo, el modelo con placa fue mas rigido que el modelo con clavo en flexion anteroposterior, lateromedial y cizallamiento lateromedial. La distribucion de tensiones ha sido mas heterogenea en el clavo que en la placa, siendo esta ultima el implante que soporta los mayores valores tensionales en todos los estados de carga estudiados. Conclusiones La rigidez del modelo experimental depende no solo del implante sino del estado de carga aplicado, siendo superior el clavo en unas condiciones de carga y la placa en otras. El clavo sin embargo, absorbe menos tension que la placa en todos los estados de carga estudiados. more...

Purpose To compare the firmess and stress distribution patterns in the implants of two experimental models: a humerus with shaft pseudoarthrosis stabilized with a plate, and a humerus with shaft nonunions stabilized with a locking nail. Materials and methods The two fixation devices are attached to cadaver humerus bones; geometries are created with the CATIA 4.2 design software (IBM, Armonk, USA). Subsequently, these geometries were modelled with the MSC PATRAN ® computer processor (IBM, Armonk, USA). Finally, the mechanical properties of the materials were established as well as the contour properties and the loads the models were subjected to. Results The nailed model was firmer that the plated model as regards compression, traction and torsion. Nonetheless, as far as A/P and lateral-medial flexion and lateral-medial shear stresses were concerned, the plated model was firmer than the nailed model. Stress distribution was more heterogeneous in the nail than in the plate, the latter being the implant type supporting the highest stress levels in all the loading phases studied. Conclusions For some stress levels, the nail proved to be more stable than the plate, although for other stress levels the opposite was the case. In any case, the nail provides a better stress distribution than the plate. more...

The main objective of this work has been the characterisation and correlation of the wear behaviour of the NiTi and CuZnAl shape memory alloys in their different phases. The weight losses for the different alloys in function of the present phase, and of the M s transformation temperature are studied. Adhesive wear tests, Pin-on-Disk, according to the ASTM-G99 standard have been carried out. The thermoelastic martensitic transformations that cause the superelastic effect, the reorientation and coalescence of martensitic plates and the damping effect promotes a high ability to accommodate large deformations without generating permanent damages that causes the wear. The resulting plastic deformation may be accumulated during wear process without generating fracture. The results show that the wear resistance is mainly dependent of the M s transformation temperature for both alloys. For the NiTi alloys also the Ni atomic percentage and the hardness of the alloys are important parameters in the wear behavior. more...

The coarseness of the transformed β plate structure of β-heat treated Ti–6Al–4V has a strong influence on its properties. A systematic study of the effects of cooling rate on tensile and cyclic deformation properties in air was performed. The properties are correlated to the cooling rates and the controlling microstructural features. The tensile strength can be reduced by about 70 MPa with the slower cooling rate from the β transus temperature when comparing air cooling to water quenching for thinner section sizes. The cooling rate also affects the cyclic deformation behaviour. more...

Producción Científica, Bone tissue engineering demands alternatives overcoming the limitations of traditional approaches in the context of a constantly aging global population. In the present study, elastin-like recombinamers hydrogels were produced by means of carbodiimide-catalyzed crosslinking with citric acid, a molecule suggested to be essential for bone nanostructure. By systematically studying the effect of the relative abundance of reactive species on gelation and hydrogel properties such as functional groups content, degradation and structure, we were able to understand and to control the crosslinking reaction to achieve hydrogels mimicking the fibrillary nature of the extracellular matrix. By studying the effect of polymer concentration on scaffold mechanical properties, we were able to produce hydrogels with a stiffness value of 36.13 ± 10.72 kPa, previously suggested to be osteoinductive. Microstructured and mechanically-tailored hydrogels supported the growth of human mesenchymal stem cells and led to higher osteopontin expression in comparison to their non-tailored counterparts. Additionally, tailored hydrogels were able to rapidly self-mineralize in biomimetic conditions, evidencing that citric acid was successfully used both as a crosslinker and a bioactive molecule providing polymers with calcium phosphate nucleation capacity., Junta de Castilla y León (programa de apoyo a proyectos de investigación – Ref. VA244U13) more...

Cette etude s'interesse a la composition chimique, a l'ultrastructure, aux temperatures de changement d'etat et aux forces therapeutiques qui caracterisent les fils orthodontiques NiTi les plus couramment employes.La connaissance de ces nouveaux materiaux doit permettre une optimisation de leur utilisation clinique. more...

La caracterización de biomateriales se sirve cada vez más técnicas no destructivas de obtención de imágenes. Estás técnicas pueden ser aplicadas tanto in vitro como in vivo con una resolución que depende del tamaño de la muestra y de la técnica utilizada. Una de las técnicas más utilizadas, por su alta resolución, es la micro tomografía axial computerizada (μ-TAC). El objetivo de este estudio fue caracterizar andamios para ingeniería de tejidos óseos en términos de su arquitectura y porosidad usando reconstrucciones computacionales a partir de microtomografía y generar mallas tridimensionales para modelos de elementos finitos. Imágenes de dos materiales con morfología diferente fueron utilizadas. Un andamio de cemento de fosfato de calcio y un andamio de vidrio biodegradable poroso fueron escaneados con una resolución de 7,8 x 7,8 x 12,2 μm, para realizar posteriormente una recontrucción informática tridimensional y un mallado para análisis con el método de los elementos finitos. Se calculó la porosidad y se evaluó la interconectividad visualmente. No se encontraron grandes diferencias entre los dos andamios al calcular la porosidad y la interconectividad (18% para el cemento y 23% para el vidrio), sin embargo en las reconstrucciones tridimensionales se observaron grandes diferencias en la distribución de los poros dentro de los andamios. The characterization of biomaterials employs increasingly non-destructive imaging techniques. These techniques can be applied both in vitro and in vivo, with a resolution dependent on the size of the sample and the employed technique. One of the most used techniques, due to its high resolution, is the axial computer microtomography (μ-CT). The objective of this study was to characterize scaffolds for tissue engineering in terms of its architecture and porosity using computer reconstructions from microtomography and to generate 3D meshes for finite element modeling. Images of two materials with different morphology were utilized. A scaffold of calcium phosphate cement and a scaffold of porous biodegradable glass were scanned with a resolution of 7.8 x 7.8 x 12.2 μm, to carry out subsequently a 3D computer reconstruction and meshing. The porosity was calculated and the interconnectivity was evaluated visually. No relevant differences were found between the two scaffolds upon calculating the porosity and the interconnectivity (18% for the cement and 23% for the glass), nevertheless in the three-dimensional reconstructions large differences in the distribution of the pores inside the scaffolds were observed. more...

Musculoskeletal problems, including bone and joint pathologies are among the main causes of chronic pain, physical disability, and work absenteeism in both developed and developing countries, and they affect millions of people worldwide. This is the reason why biomaterials play a key role in bone repair and regeneration. In this chapter, the societal impact of musculoskeletal diseases, as well as other bone problems is discussed in terms of their costs and the degree of physical disability that they generate. In addition, some of the most relevant clinical challenges in bone repair are presented. more...

This paper reports that one of the reasons usually stated for avoiding annealing treatments and hot working of Ti-6Al-4V alloy at temperatures over the {beta} transus is the large grain growth which takes place at such temperatures. The aim of the present work is to quantify the grain growth kinetics when the alloy is heat treated in its {beta} phase. It is well known that the driving force for grain growth comes from the surface energy of the grain boundaries. When thermal energy is given to the material, diffusion takes place which leads to grain selection. This means that the number of grains decreases, their size increases, the area of the grain boundaries decreases with the total energy stored in them and consequently a state of higher thermodynamic stability is reached. more...

The large number of orthopaedic procedure performed arthoscopically each year has led to a great interest in injectable biodegradable materials for bone regeneration. In this study a composite hydrogel has been prepared with Calcium Phosphate particle (H-cement) reinforcong tha matrix of poly-vinylalcohol (PVA). The composite has demonstrated good mechanical properties in the range of spongious bone and easy injectable. more...

A novel iodine-containing methacrylate, 2,5-diiodo-8-quinolyl methacrylate, has been synthesized and used in the preparation of acrylic radiopaque cements. The e!ect of incorporation of this monomer to the self-curing resins, on the curing parameters, swelling behaviour and mechanical properties was studied. The incorporation of the radiopaque compound 2,5-diiodo-8-hydroxyquinoline to the solid phase was also carried out for comparative experiments. A decrease in the peak temperature and an increase in the setting time was observed with the addition of the radiopaque monomer, however, the curing parameters did not appreciably change with the addition of the radiopaque compound to the solid phase. Swelling of the modi"ed cements was in the same range as that of the radiolucent cement; however, the di!usion coe$cients calculated according to the Fick's law were higher for the iodine-containing materials. The addition of 5 wt% of the iodine-containing methacrylate provided a signi"cant increase in the tensile properties with respect to either control radiolucent formulations or BaSO 4 -containing formulations. Biocompatibility of the modi"ed cements was studied by implantation of rods of the cements into rats and histological analysis of the surrounding tissue., Financial support from the ComisioH n Interministerial de Ciencia y TecnologmH a (CICYT, Grant Mat 96-0981) is gratefully acknowledged. more...

Fibre and particle hydroxyapatite-zircona composites have been prepared by uniaxial pressing and sintering at different temperatures, and their mechanical properties have been measured and related with their texture and mineral dynamics. The products obtained are porous, with densities ranging from 46% to 78% of the theoretical density. A good correlation has been found between the increase in density and the Klc increase at sintering temperatures below 1200°C. At higher temperatures, the densification process of the material continues, but Klc decreases. This decrease is related with the reaction of the zircona material, with the nucleation and growth of CaZrO3 crystals and with the formation of defects or weakness points in the composite. more...