The effect of combining bone morphogenetic proteins -2 and -6 on osteoblastic differentiation and bone

Bone morphogenetic proteins-2 and -7 (BMP-2 and -7) are the only two members of the BMP subfamily approved to date to be used in combination with collagen type I in orthopedic surgery, although other BMPs have proven to also be highly osteoinductive. All the osteogenic BMPs signal through Smad-1/-5/-8 phosphorylation, but they have different preferences for the BMP receptors they use. Very high supraphysiological doses of BMPs have been used in the clinics for the treatment of non-union fractures and spinal fusions. Besides the high cost of these treatments, safety concerns have been recently raised. Hence there is an active field in finding alternatives to the most classical collagen + BMP-2 system. The aim of this work was to study the effect of combining two osteogenic BMPs (-2 and -6) belonging to different groups within the subfamily, and with different affinities to the existing BMP receptors. Both the growth and osteoblastic differentiation of MC3T3-E1 mouse preosteoblasts and rat bone marrow-derived mesenchymal stem cells (MSCs) under these conditions were studied, as well as in vivo ectopic bone formation when the BMPs were combined with collagen type I sponges. We show that the effect of these two growth factors is additive and that their combination might be helpful to accelerate in vivo osteogenesis while reducing the amount of each individual BMP used.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Room temperature ferromagnetic-like behavior in Mn-implanted and post-annealed InAs layers deposited by Molecular Beam Epitaxy

We report on the magnetic and structural properties of Ar and Mn implanted InAs epitaxial films grown on GaAs (100) by Molecular Beam Epitaxy (MBE) and the effect of Rapid Thermal Annealing (RTA) for 30 seconds at 750C. Channeling Particle Induced X- ray Emission (PIXE) experiments reveal that after Mn implantation almost all Mn atoms are subsbtitutional in the In-site of the InAs lattice, like in a diluted magnetic semiconductor (DMS). All of these samples show diamagnetic behavior. But, after RTA treatment the Mn-InAs films exhibit room-temperature magnetism. According to PIXE measurements the Mn atoms are no longer substitutional. When the same set of experiments were performed with As as implantation ion all of the layers present diamagnetism without exception. This indicates that the appearance of room-temperature ferromagnetic-like behavior in the Mn-InAs-RTA layer is not related to lattice disorder produce during implantation, but to a Mn reaction produced after a short thermal treatment. X-ray diffraction patterns (XRD) and Rutherford Back Scattering (RBS) measurements evidence the segregation of an oxygen deficient-MnO2 phase (nominally MnO1.94) in the Mn-InAs-RTA epitaxial layers which might be on the origin of room temperature ferromagnetic-like response observed.Comment: 16 pages, 5 figures. Acepted in J. Appl. Phy

The role of spatial and temporal radiation deposition in inertial fusion chambers: the case of HiPER¿

The first wall armour for the reactor chamber of HiPER will have to face short energy pulses of 5 to 20 MJ mostly in the form of x-rays and charged particles at a repetition rate of 5–10 Hz. Armour material and chamber dimensions have to be chosen to avoid/minimize damage to the chamber, ensuring the proper functioning of the facility during its planned lifetime. The maximum energy fluence that the armour can withstand without risk of failure, is determined by temporal and spatial deposition of the radiation energy inside the material. In this paper, simulations on the thermal effect of the radiation–armour interaction are carried out with an increasing definition of the temporal and spatial deposition of energy to prove their influence on the final results. These calculations will lead us to present the first values of the thermo-mechanical behaviour of the tungsten armour designed for the HiPER project under a shock ignition target of 48 MJ. The results will show that only the crossing of the plasticity limit in the first few micrometres might be a threat after thousands of shots for the survivability of the armour

Industrial Applications of Laser Neutron Source

The industrial applications of the intense neutron source have been widely explored because of the unique features of the neutron-matter interaction. Usually, intense neutron sources are assembled with fission reactors or high energy ion accelerators. The big size and high cost of these systems are the bottle neck to promote the industrial applications of intense neutrons. In this paper, we propose the compact laser driven neutron source for the industrial application. As the first step of our project for the versatile applications of laser driven neutron source, Li-neutron and/or Li-proton interactions have been investigated for the application to the development of Li battery

A model of maxilla resection to test new hybrid implants:macroporous titanium and tissue engineering elements

Maxillary bone loss in commonly found in humans, due to bone ageing, tooth loos, periodontal disease and, more severely, to trauma, radiotherapy and tumor resection. Masillofacial reconstructive surgery is a still unmet clinical demand, available therapies include grafting of autologous or heterologous bone tissue and/or the implantation of metallic plates, buy these treatments are still unable to resume form and function. The emrgence of 3D-printing technology applied to metal alloys now allows the manufacturing of customized, patient-tailored prosthetic implants. However, poor bone quiality at the implant site due to ageing or disease still hamper proper osseointegration. By combining Electron Beam Melting metal sintering and tissue engineering, we are developing hybrid maxillofacial implants, wher a metal framework of Ti6Al4V alloy confers both and appropiaate shape and mechanical stabilty, while stem cells and osteogenic molecules stimulate bone growth into the metal framework, thus pormoting osseointegration. We hereby present the in vitro work driving to the development of our hybrid maxillofacial prostheses, as well as the setting up of an in vivo model of complete maxilla full resection, created in order to test the prostheses in a preclinical studyUniversidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Ion Beam Analysis of He-implanted fusion solid breedes

Introduction Lithium-based ceramics (silicates, titanates, ?) possess a series of advantages as alternative over liquid lithium and lithium-lead alloys for fusion breeders. They have a sufficient lithium atomic density (up to 540 kg*m-3), high temperature stability (up to 1300 K), and good chemical compatibility with structural materials. Nevertheless, few research is made on the diffusion behavior of He and H isotopes through polycrystalline structures of porous ceramics which is crucial in order to understand the mobility of gas coolants as well as, the release of tritium. Moreover, in the operating conditions of actual breeder blanket concepts, the extraction rate of the helium produced during lithium transmutation can be affected by the composition and the structure of the near surface region modifying the performance of BB material

Bone marrow mesenchymal stem cells, collagen scaffold and BMP-2 for rat spinal fusio

The use of autograft for posterolateral spinal fusion, continue being considered the gold standard for the treatment of spine pathologies. However, due to complications such as donor site morbidity, increased operating time, and limited supply, the use of allograft has become an acceptable practice especially in multisegment arthrodesis or in patients with previous graft harvests. Since their use involves the risk of immune response or disease transmission and fusion rates are not as good as with autogenous bone, a variety of bone graft substitutes are being studied to obtain a better alternative. Osteoinductive growth factors, which initiate the molecular cascade of bone formation and play a key role in the development and regeneration of the skeletal system, have been shown to be effective in numerous animal studies. These molecules must be used in combination with a biomaterial to avoid their dispersion from the application site. On the other hand, it is well known that cultured bone marrow cells, harvested from adult bone marrow, may contribute to the regeneration of bone. Thus, hybrid constructs can be used as alternatives to autologous and allogenic grafts. In this study, we have evaluated different combination of cultured bone marrow cells with recombinant human osteoinductive growth factors, all of them in combination with a natural polimeric carrier, for the promotion of posterolateral spinal fusion in rats. Supported by grants from the Red de Terapia Celular (RD12/0019/0032), Spanish Government BIO2012-34960, and the Andalusian Government (P11-CVI 07245).Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

A synthetic collagen-binding arg-gly-asp (rgd) biomimetic peptide enhances bone cell differentiation

RGD (arginine-glycine-aspartic acid) peptides have shown some promising abilities to promote the attachment of cells to biomaterials and to direct their differentiation. However, anchoring these peptides to the biomaterial’s surface is mandatory and usually implies several chemical linking steps. The aim of this work was to design and characterize a synthetic RGD biomimetic peptide that includes a collagen-binding domain for easy one-step functionalization of absorbable collagen sponges (ACSs), which are of frequent use in orthopaedic surgery. The stable binding of biotinylated CBD-RGD peptide loaded onto ACSs was confirmed using chemiluminisence detection after washing of the sponges. Furthermore, the effect of the peptide on MC3T3-E1 mouse preosteoblasts and rat bone marrow-derived mesenchymal stem cells (MSCs) in vitro was characterized in terms of caspase activity, proliferation, alkaline phosphatase (ALP) activity, matrix mineralization and formation of focal adhesions. Finally, a rat ectopic osteogenesis model was used to determine if the co-administration of CBD-RGD could lower the dose of BMP-2 necessary to induce bone formation. The CBD-RGD peptide was demonstrated to bind stable to ACSs, even after extensive washing. In vitro, the peptide did not induce apoptosis of the cells, but positively affected both cell growth and differentiation. It also seemed to affect the cytoskeleton arrangement of MC3T3-E1 cells, favoring the establishment of focal adhesions. At last, the in vivo experiments showed that ACSs functionalized with this peptide and loaded with a subfunctional dose of BMP-2 gave rise to ectopic bone. In conclusion. the combination of CBD-RGD with the currently used collagen/BMP system might be a promising approach to improve osteogenesis and to reduce the doses of BMPs needed in clinical orthopaedics.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech