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PURPOSE: To examine predictive value of apparent diffusion coefficient (ADC) in diffusion-weighted imaging (DWI) for response of patients with primary and secondary lung neoplasms undergoing transpulmonary chemoembolization (TPCE) and transarterial chemoperfusion (TACP) treatment. MATERIALS AND METHODS: Thirty-one patients (mean age ± SD 64 ± 12.4 y) with 42 lung target lesions (13 primary and 29 secondary) underwent DWI and subsequent ADC analysis on a 1.5T MR imaging scanner before and 30.3 days ± 6.4 after first session of TPCE or TACP. After 3.1 treatment sessions ± 1.4 performed in 2- to 4-week intervals, morphologic response was analyzed by comparing tumor diameter and volume before and after treatment on unenhanced T1-weighted MR images. On a per-lesion basis, response was classified according to Response Evaluation Criteria In Solid Tumors. RESULTS: Threshold ADC increase of 20.7% indicated volume response with 88% sensitivity and 78% specificity (area under the curve [AUC] = 0.84). Differences between ADC changes in volume response groups were significant (P = .002). AUC for volume response predicted by ADC before treatment was 0.77. Median ADC before treatment and mean ADC change were 1.09 × 10-3 mm2/second and 0.36 × 10-3 mm2/second ± 0.23, 1.45 × 10-3 mm2/second and 0.14 × 10-3 mm2/second ± 0.16, and 1.30 × 10-3 mm2/second and 0.06 × 10-3 mm2/second ± 0.19 in partial response, stable disease, and progressive disease groups. In primary lung cancer lesions, strong negative correlation of ADC change with change in diameter (ρ = -.87, P < .001) and volume (ρ = -.66, P = .016) was found. In metastases, respective correlation coefficients were ρ = -.18 (P = .356) and ρ = -.35 (P = .061). CONCLUSIONS: ADC quantification shows considerable diagnostic value for predicting response and monitoring TPCE and TACP treatment of patients with primary and secondary lung neoplasms.
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Quimioembolización Terapéutica , Quimioterapia del Cáncer por Perfusión Regional , Imagen de Difusión por Resonancia Magnética , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Toma de Decisiones Clínicas , Femenino , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/secundario , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
The aim of this study was to propose and validate a new unified method for testing dissolution rates of bioactive glasses and their variants, and the formation of calcium phosphate layer formation on their surface, which is an indicator of bioactivity. At present, comparison in the literature is difficult as many groups use different testing protocols. An ISO standard covers the use of simulated body fluid on standard shape materials but it does not take into account that bioactive glasses can have very different specific surface areas, as for glass powders. Validation of the proposed modified test was through round robin testing and comparison to the ISO standard where appropriate. The proposed test uses fixed mass per solution volume ratio and agitated solution. The round robin study showed differences in hydroxyapatite nucleation on glasses of different composition and between glasses of the same composition but different particle size. The results were reproducible between research facilities. Researchers should use this method when testing new glasses, or their variants, to enable comparison between the literature in the future.
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Apatitas/química , Materiales Biomiméticos/química , Materiales Biomiméticos/normas , Líquidos Corporales/química , Cerámica/química , Vidrio/química , Ensayo de Materiales/normas , Apatitas/normas , Cerámica/análisis , Cerámica/normas , Vidrio/análisis , Vidrio/normas , Internacionalidad , Ensayo de Materiales/métodos , Tamaño de la Partícula , Estándares de Referencia , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: We evaluated the role of dual-energy computed tomography (DECT)-based collagen maps in assessing thoracic disc degeneration. METHODS: We performed a retrospective analysis of patients who underwent DECT and magnetic resonance imaging (MRI) of the thoracic spine within a 2-week period from July 2019 to October 2022. Thoracic disc degeneration was classified by three blinded radiologists into three Pfirrmann categories: no/mild (grade 1-2), moderate (grade 3-4), and severe (grade 5). The DECT performance was determined using MRI as a reference standard. Interreader reliability was assessed using intraclass correlation coefficient (ICC). Five-point Likert scales were used to assess diagnostic confidence and image quality. RESULTS: In total, 612 intervertebral discs across 51 patients aged 68 ± 16 years (mean ± standard deviation), 28 males and 23 females, were assessed. MRI revealed 135 no/mildly degenerated discs (22.1%), 470 moderately degenerated discs (76.8%), and 7 severely degenerated discs (1.1%). DECT collagen maps achieved an overall accuracy of 1,483/1,838 (80.8%) for thoracic disc degeneration. Overall recall (sensitivity) was 331/405 (81.7%) for detecting no/mild degeneration, 1,134/1,410 (80.4%) for moderate degeneration, and 18/21 (85.7%) for severe degeneration. Interrater agreement was good (ICC = 0.89). Assessment of DECT-based collagen maps demonstrated high diagnostic confidence (median 4; interquartile range 3-4) and good image quality (median 4; interquartile range 4-4). CONCLUSION: DECT showed an overall 81% accuracy for disc degeneration by visualizing differences in the collagen content of thoracic discs. RELEVANCE STATEMENT: Utilizing DECT-based collagen maps to distinguish various stages of thoracic disc degeneration could be clinically relevant for early detection of disc-related conditions. This approach may be particularly beneficial when MRI is contraindicated. KEY POINTS: A total of 612 intervertebral discs across 51 patients were retrospectively assessed with DECT, using MRI as a reference standard. DECT-based collagen maps allowed thoracic disc degeneration assessment achieving an overall 81% accuracy with good interrater agreement (ICC = 0.89). DECT-based collagen maps could be a good alternative in the case of contraindications to MRI.
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Colágeno , Degeneración del Disco Intervertebral , Imagen por Resonancia Magnética , Vértebras Torácicas , Tomografía Computarizada por Rayos X , Humanos , Masculino , Femenino , Degeneración del Disco Intervertebral/diagnóstico por imagen , Anciano , Estudios Retrospectivos , Vértebras Torácicas/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Reproducibilidad de los ResultadosRESUMEN
Novel multifunctional nanocomposite scaffolds made of nanobioactive glass and alginate crosslinked with therapeutic ions such as calcium and copper were developed for delivering therapeutic agents, in a highly controlled and sustainable manner, for bone tissue engineering. Alendronate, a well-known antiresorptive agent, was formulated into microspheres under optimized conditions and effectively loaded within the novel multifunctional scaffolds with a high encapsulation percentage. The size of the cation used for the alginate crosslinking impacted directly on porosity and viscoelastic properties, and thus, on the degradation rate and the release profile of copper, calcium and alendronate. According to this, even though highly porous structures were created with suitable pore sizes for cell ingrowth and vascularization in both cases, copper-crosslinked scaffolds showed higher values of porosity, elastic modulus, degradation rate and the amount of copper and alendronate released, when compared with calcium-crosslinked scaffolds. In addition, in all cases, the scaffolds showed bioactivity and mechanical properties close to the endogenous trabecular bone tissue in terms of viscoelasticity. Furthermore, the scaffolds showed osteogenic and angiogenic properties on bone and endothelial cells, respectively, and the extracts of the biomaterials used promoted the formation of blood vessels in an ex vivo model. These new bioactive nanocomposite scaffolds represent an exciting new class of therapeutic cell delivery carrier with tunable mechanical and degradation properties; potentially useful in the controlled and sustainable delivery of therapeutic agents with active roles in bone formation and angiogenesis, as well as in the support of cell proliferation and osteogenesis for bone tissue engineering.
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Huesos/fisiología , Nanocompuestos/química , Ingeniería de Tejidos/métodos , Andamios del Tejido/química , Alendronato/química , Alginatos/química , Animales , Materiales Biocompatibles/química , Células de la Médula Ósea/citología , Resorción Ósea , Calcio/química , Supervivencia Celular , Membrana Corioalantoides/metabolismo , Fuerza Compresiva , Cobre/química , Coturnix , Reactivos de Enlaces Cruzados/química , Elasticidad , Ácido Glucurónico/química , Ácidos Hexurónicos/química , Células Madre Mesenquimatosas/citología , Microesferas , Osteogénesis , Porosidad , Ratas , Ratas Sprague-Dawley , Estrés Mecánico , ViscosidadRESUMEN
For many years, bioactive glasses (BGs) have been widely considered for bone tissue engineering applications due to their ability to bond to hard as well as soft tissue (a property termed bioactivity) and for their stimulating effects on bone formation. Ionic dissolution products released during the degradation of the BG matrix induce osteogenic gene expression leading to enhanced bone regeneration. Recently, adding bioactive metallic ions (e.g. boron, copper, cobalt, silver, zinc and strontium) to silicate (or phosphate and borate) glasses has emerged as a promising route for developing novel BG formulations with specific therapeutic functionalities, including antibacterial, angiogenic and osteogenic properties. The degradation behaviour of BGs can be tailored by adjusting the glass chemistry making these glass matrices potential carrier systems for controlled therapeutic ion release. This book chapter summarises the fundamental aspects of the effect of ionic dissolution products from BGs on osteogenesis and angiogenesis, whilst discussing novel BG compositions with controlled therapeutic ion release.
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Materiales Biocompatibles/química , Sustitutos de Huesos/química , Vidrio/química , Química Farmacéutica , Preparaciones de Acción Retardada , Sistemas de Liberación de Medicamentos , Humanos , Neovascularización Fisiológica/fisiología , Osteogénesis/fisiología , SolubilidadRESUMEN
Both silicate-based bioactive glasses and copper ions have demonstrated angiogenic activity and therefore represent promising bioinorganic agents for the promotion of vascularization in tissue-engineered scaffolds. This study examined the effect of ionic release products from 45S5 Bioglass® doped with 0 and 2.5 wt.% CuO (BG and Cu-BG respectively) on the formation of capillary-like networks by SVEC4-10 endothelial cells (ECs) seeded in a three-dimensional (3D) type I collagen matrix. Copper and silicon release following 24h dissolution increased non-proportionally with Cu-BG concentration in cell culture medium, while calcium levels were decreased below the initial medium concentration. EC network length, connectivity, branching, quantified by means of a 3D morphometric image analysis method, as well as proliferation and metabolic activity were reduced in a dose-dependent fashion by BG and Cu-BG ionic release products. This reduction was less prominent for BG compared to an equivalent concentration of Cu-BG, which was attributed to a lower extent of silicon release and calcium consumption. Moreover, a CuCl2 dose equivalent to the highest concentration of Cu-BG exhibited no effect on ECs. In conclusion, while the previously reported pro-angiogenic activity of both Bioglass® and copper may not be reflected in a direct response of ECs, this study provides a maximum glass concentration for non-harmful angiogenic stimulation to be examined in future work.
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Cerámica/química , Cerámica/farmacología , Cobre/química , Cobre/farmacología , Células Endoteliales/fisiología , Vidrio/química , Morfogénesis/fisiología , Animales , Línea Celular , Proliferación Celular/efectos de los fármacos , Proliferación Celular/fisiología , Células Endoteliales/citología , Células Endoteliales/efectos de los fármacos , Iones/farmacología , Ensayo de Materiales , Ratones , Morfogénesis/efectos de los fármacos , Andamios del TejidoRESUMEN
Cobalt ions are known to stimulate angiogenesis via inducing hypoxic conditions and hence are interesting agents to be used in conjunction with bioactive glasses (BGs) in bone tissue engineering approaches. In this work we investigated in vitro cell biocompatibility of Co releasing 1393 BG composition (in wt.%: 53SiO2, 6Na2O, 12K2O, 5MgO, 20CaO, and 4P2O5) derived scaffolds with osteoblast-like cells (MG-63) and human dermal microvascular endothelial cells (hDMECs). Cell viability, cell number and cell morphology of osteoblast-like cells in contact with particulate glass and 3D scaffolds were assessed showing good biocompatibility of 1393 reference material and with 1 wt.% CoO addition whereby 5 wt.% of CoO in the glass showed cytotoxicity. Furthermore for 1393 with 1 wt.% of CoO increased mitochondrial activity was measured. Similar observations were made with hDMECs: while 1393 and 1393 with 1 wt.% CoO were biocompatible and the endothelial phenotype was retained, 5 wt.% CoO containing BG showed cytotoxic effects after 1 week of cell culture. In conclusion, 1 wt.% Co containing BG was biocompatible with osteoblast like cells and endothelial cells and showed slightly stimulating effects on osteoblast-like cells whereas the addition of 5 wt.% CoO seems to exceed the vital therapeutic ranges of Co ions being released in physiological fluids.
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Sustitutos de Huesos/química , Cobalto/química , Cobalto/toxicidad , Células Endoteliales/efectos de los fármacos , Vidrio/química , Osteoblastos/efectos de los fármacos , Óxidos/química , Óxidos/toxicidad , Línea Celular , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Ensayo de MaterialesRESUMEN
Carbon derived materials such as pyrolytic carbon or carbon-carbon composites (CCCs) exhibit excellent mechanical properties making them promising candidates for bone replacement. However, these materials are considered bioinert and not to induce bone formation in vivo. In this study, a two-step chemical surface treatment including etching with HCl/HNO3 solution and subsequent soaking in CaCl2 solution was applied to carbon substrates in order to activate the materials surface towards bioactive behavior. The bioactivity was proven by soaking the samples in simulated body fluid (SBF) and formation of carbonated hydroxyapatite layer (HCA), which indicates the ability of the material to bond to bone in vivo. The materials surface is shown to be functionalized through the chemical etching creating COO(-)Ca(2+) complexes on the surface as confirmed by FTIR and XPS analyses. These ionic complexes provide nucleation sites for HAp precipitation. After similar immersion time in SBF under the condition of local supersaturation the thickness and homogeneity of the HAp layer were found to depend on the chemical pretreatment with HCl/HNO3. Homogenous HAp layers with a thickness ranging from â¼ 6 to â¼ 17 µm were achieved. The proposed bioactivating treatment of carbon stimulates HAp formation in vivo and can be considered an easy biomimetic approach for coating carbon derived materials with bone-like hydroxyapatite. In vitro cell assay with osteosarcoma cells (MG-63) showed increased cell viability (+70%) on HAp coated carbon substrates as compared to uncoated reference while both materials induced ALP expression in MG-63 cells confirming the osteoblastic phenotype.
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Materiales Biomiméticos , Carbono , Materiales Biocompatibles Revestidos , Durapatita , Ensayo de Materiales , Osteogénesis/efectos de los fármacos , Fosfatasa Alcalina/biosíntesis , Animales , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Carbono/química , Carbono/farmacología , Línea Celular Tumoral , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Durapatita/química , Durapatita/farmacología , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , RatonesRESUMEN
Bioactive glass (BG) is a highly attractive material, exhibiting both osteoinductive and osteoconductive properties, which is known to provide a growth enhancing surface for bone cells. Previous studies have shown that lipid peroxidation and in particular generation of 4-hydroxynonenal (HNE) is involved in the growth of human osteoblast-like cells, HOS, on BG. Copper (Cu), which is an essential cofactor of several enzymes as well as a proangiogenic and an antimicrobial agent, is known to induce lipid peroxidation. Therefore, the enrichment of BG with Cu could potentially have beneficial effects on the growth of the bone cells. In this study, we investigated the effects of copper-doped 45S5 BG on the growth of HOS cells and the generation of HNE. Our results confirmed the association of HNE with the growth of HOS cells. The effects of added Cu were dose-dependent. Specifically, low concentrations (i.e., 0.1% w/w) of Cu improved viability and enhanced HOS cell growth, whereas higher Cu concentrations [i.e., 2.5% and 1% (w/w)] were cytotoxic. The observed effects of Cu concentration on cell growth correlated with the level of HNE production. Therefore, Cu containing BG may represent a useful biomaterial for research and development studies of bone regeneration.
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Cerámica/farmacología , Cobre/farmacología , Peroxidación de Lípido/efectos de los fármacos , Osteoblastos/citología , Aldehídos/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Vidrio , Humanos , Immunoblotting , Indoles/metabolismo , Osteoblastos/efectos de los fármacos , Osteoblastos/ultraestructura , Espectrometría por Rayos XRESUMEN
Loading biomaterials with angiogenic therapeutics has emerged as a promising approach for developing superior biomaterials for engineering bone constructs. In this context, cobalt-releasing materials are of interest as Co is a known angiogenic agent. In this study, we report on cobalt-releasing three-dimensional (3D) scaffolds based on a silicate bioactive glass. Novel melt-derived "1393" glass (53 wt % SiO2, 6 wt % Na2O, 12 wt % K2O, 5 wt % MgO, 20 wt % CaO, and 4 wt % P2O5) with CoO substituted for CaO was fabricated and was used to produce a 3D porous scaffold by the foam replica technique. Glass structural and thermal properties as well as scaffold macrostructure, compressive strength, acellular bioactivity, and Co release in simulated body fluid (SBF) were investigated. In particular, detailed insights into the physicochemical reactions occurring at the scaffold-fluid interface were derived from advanced micro-particle-induced X-ray emission/Rutherford backscattering spectrometry analysis. CoO is shown to act in a concentration-dependent manner as both a network former and a network modifier. At a concentration of 5 wt % CoO, the glass transition point (Tg) of the glass was reduced because of the replacement of stronger Si-O bonds with Co-O bonds in the glass network. Compressive strengths of >2 MPa were measured for Co-containing 1393-derived scaffolds, which are comparable to values of human spongy bone. SBF studies showed that all glass scaffolds form a calcium phosphate (CaP) layer, and for 1393-1Co and 1393-5Co, CaP layers with incorporated traces of Co were observed. The highest Co concentrations of â¼12 ppm were released in SBF after reaction for 21 days, which are known to be within therapeutic ranges reported for Co(2+) ions.
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Materiales Biocompatibles , Desarrollo Óseo , Cobalto/química , Vidrio , Ingeniería de Tejidos , Andamios del Tejido , Microscopía Electrónica de RastreoRESUMEN
Bioactive glass (BG) scaffolds are being investigated for bone tissue engineering applications because of their osteoconductive and angiogenic nature. However, to increase the in vivo performance of the scaffold, including enhancing the angiogenetic growth into the scaffolds, some researchers use different modifications of the scaffold including addition of inorganic ionic components to the basic BG composition. In this study, we investigated the in vitro biocompatibility and bioactivity of Cu2+-doped BG derived scaffolds in either BMSC (bone-marrow derived mesenchymal stem cells)-only culture or co-culture of BMSC and human dermal microvascular endothelial cells (HDMEC). In BMSC-only culture, cells were seeded either directly on the scaffolds (3D or direct culture) or were exposed to ionic dissolution products of the BG scaffolds, kept in permeable cell culture inserts (2D or indirect culture). Though we did not observe any direct osteoinduction of BMSCs by alkaline phosphatase (ALP) assay or by PCR, there was increased vascular endothelial growth factor (VEGF) expression, observed by PCR and ELISA assays. Additionally, the scaffolds showed no toxicity to BMSCs and there were healthy live cells found throughout the scaffold. To analyze further the reasons behind the increased VEGF expression and to exploit the benefits of the finding, we used the indirect method with HDMECs in culture plastic and Cu2+-doped BG scaffolds with or without BMSCs in cell culture inserts. There was clear observation of increased endothelial markers by both FACS analysis and acetylated LDL (acLDL) uptake assay. Only in presence of Cu2+-doped BG scaffolds with BMSCs, a high VEGF secretion was demonstrated by ELISA; and typical tubular structures were observed in culture plastics. We conclude that Cu2+-doped BG scaffolds release Cu2+, which in turn act on BMSCs to secrete VEGF. This result is of significance for the application of BG scaffolds in bone tissue engineering approaches.
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Sustitutos de Huesos/farmacología , Cobre/farmacología , Células Endoteliales/metabolismo , Células Madre Mesenquimatosas/metabolismo , Andamios del Tejido/química , Sustitutos de Huesos/química , Diferenciación Celular , Técnicas de Cocultivo , Cobre/química , Células Endoteliales/citología , Vidrio/química , Humanos , Células Madre Mesenquimatosas/citología , Microvasos/citología , Osteogénesis , Ingeniería de Tejidos/métodos , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
A highly selective and efficient cancer therapy can be achieved using magnetically directed superparamagnetic iron oxide nanoparticles (SPIONs) bearing a sufficient amount of the therapeutic agent. In this project, SPIONs with a dextran and cisplatin-bearing hyaluronic acid coating were successfully synthesized as a novel cisplatin drug delivery system. Transmission electron microscopy images as well as X-ray diffraction analysis showed that the individual magnetite particles were around 4.5 nm in size and monocrystalline. The small crystallite sizes led to the superparamagnetic behavior of the particles, which was exemplified in their magnetization curves, acquired using superconducting quantum interference device measurements. Hyaluronic acid was bound to the initially dextran-coated SPIONs by esterification. The resulting amide bond linkage was verified using Fourier transform infrared spectroscopy. The additional polymer layer increased the vehicle size from 22 nm to 56 nm, with a hyaluronic acid to dextran to magnetite weight ratio of 51:29:20. A maximum payload of 330 µg cisplatin/mL nanoparticle suspension was achieved, thus the particle size was further increased to around 77 nm with a zeta potential of -45 mV. No signs of particle precipitation were observed over a period of at least 8 weeks. Analysis of drug-release kinetics using the dialysis tube method revealed that these were driven by inverse ligand substitution and diffusion through the polymer shell as well as enzymatic degradation of hyaluronic acid. The biological activity of the particles was investigated in a nonadherent Jurkat cell line using flow cytometry. Further, cell viability and proliferation was examined in an adherent PC-3 cell line using xCELLigence analysis. Both tests demonstrated that particles without cisplatin were biocompatible with these cells, whereas particles with the drug induced apoptosis in a dose-dependent manner, with secondary necrosis after prolonged incubation. In conclusion, combination of dextran-coated SPIONs with hyaluronic acid and cisplatin represents a promising approach for magnetic drug targeting in the treatment of cancer.
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Cisplatino/química , Dextranos/química , Portadores de Fármacos/química , Ácido Hialurónico/química , Nanopartículas de Magnetita/química , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Cisplatino/farmacocinética , Cisplatino/farmacología , Sistemas de Liberación de Medicamentos , Humanos , Células Jurkat , Tamaño de la PartículaRESUMEN
Bioactive glasses (BG) are being widely used for bone tissue engineering applications due to their bioactivity (ability to form strong bonds to bone) and their stimulating effects on bone formation. Recently, progress has been made to enhance the biological impact of BGs by incorporating specific metallic ions in silicate (or phosphate) glasses, including boron, copper, cobalt, silver, zinc and strontium. This review summarizes the newest developments on novel compositions of bioactive glasses in the field of bone tissue engineering related to osteogenesis and angiogenesis. Furthermore, new applications areas for bioactive glasses, including nerve regeneration and cancer treatment, are highlighted.
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In this study, the angiogenetic effect of sintered 45S5 Bioglass® was quantitatively assessed for the first time in the arteriovenous loop (AVL) model. An AVL was created by interposition of a venous graft from the contralateral side between the femoral artery and vein in the medial thigh of eight rats. The loop was placed in a Teflon isolation chamber and was embedded in a sintered 45S5 Bioglass® granula matrix filled with fibrin gel. Specimens were investigated 3 weeks postoperatively by means of microcomputed tomography, histological, and morphometrical techniques. All animals tolerated the operations well. At 3 weeks, both microcomputed tomography and histology demonstrated a dense network of newly formed vessels originating from the AVL. All constructs were filled with cell-rich, highly vascularized connective tissue around the vascular axis. Analysis of vessel diameter revealed constant small vessel diameters, indicating immature new vessel sprouts. This study shows for the first time axial vascularization of a sintered 45S5 Bioglass® granula matrix. After 3 weeks, the newly generated vascular network already interfused most parts of the scaffolds and showed signs of immaturity. The intrinsic type of vascularization allows transplantation of the entire construct using the AVL pedicle.
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Fístula Arteriovenosa , Cerámica/farmacología , Neovascularización Fisiológica/efectos de los fármacos , Animales , Modelos Animales de Enfermedad , Vidrio , Masculino , Ratas , Ratas Endogámicas Lew , Factores de TiempoRESUMEN
Cu-doped 45S5 bioactive glasses with varying Cu contents were fabricated and used to process 3D porous scaffolds via the foam replica technique. Cu-doping results in the weakening of the glass network and a decrease in its glass transition temperature. Acellular in vitro studies revealed very high bioactivity independent of Cu doping as indicated by the fast formation of a carbonated hydroxyapatite layer (CHA) on scaffold surfaces after immersion in simulated body fluid (SBF). The kinetics of the glass-ceramic scaffold's transition to an amorphous calcium phosphate layer (ACP) and the crystallisation of CHA were explored by FT-IR and SEM analyses. The elemental distribution in the scaffold/fluid interface region was monitored by the advanced micro-PIXE-RBS (particle induced X-ray emission/Rutherford backscattering spectrometry) method. Cu-containing glasses showed slower release of Si, Ca and P from the scaffold periphery, whereas traces of Cu were found incorporated in the CaP layer on the scaffold surface. Cu release kinetics from the scaffolds in SBF were found to depend on culturing conditions while highest Cu concentrations of â¼3.1 ppm and â¼4.6 ppm under static and quasi-dynamic conditions, respectively, were observed. Since Cu exhibits potential angiogenic and osteogenic properties, the Cu-containing scaffolds are suggested as promising materials for bone tissue engineering applications.
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Several inorganic materials such as special compositions of silicate glasses, glass-ceramics and calcium phosphates have been shown to be bioactive and resorbable and to exhibit appropriate mechanical properties which make them suitable for bone tissue engineering applications. However, the exact mechanism of interaction between the ionic dissolution products of such inorganic materials and human cells are not fully understood, which has prompted considerable research work in the biomaterials community during the last decade. This review comprehensively covers literature reports which have investigated specifically the effect of dissolution products of silicate bioactive glasses and glass-ceramics in relation to osteogenesis and angiogenesis. Particularly, recent advances made in fabricating dense biomaterials and scaffolds doped with trace elements (e.g. Zn, Sr, Mg, and Cu) and investigations on the effect of these elements on the scaffold biological performance are summarized and discussed in detail. Clearly, the biological response to artificial materials depends on many parameters such as chemical composition, topography, porosity and grain size. This review, however, focuses only on the ion release kinetics of the materials and the specific effect of the released ionic dissolution products on human cell behaviour, providing also a scope for future investigations and identifying specific research needs to advance the field. The biological performance of pure and doped silicate glasses, phosphate based glasses with novel specific compositions as well as several other silicate based compounds are discussed in detail. Cells investigated in the reviewed articles include human osteoblastic and osteoclastic cells as well as endothelial cells and stem cells.
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Materiales Biocompatibles/química , Materiales Biocompatibles/metabolismo , Cerámica/química , Vidrio/química , Humanos , Iones/química , Iones/metabolismo , Ingeniería de TejidosRESUMEN
Wood-derived silicon carbide (SiC) offers a specific biomorphous microstructure similar to the cellular pore microstructure of bone. Compared with bioactive ceramics such as calcium phosphate, however, silicon carbide is considered not to induce spontaneous interface bonding to living bone. Bioactivation by chemical treatment of biomorphous silicon carbide was investigated in order to accelerate osseointegration and improve bone bonding ability. Biomorphous SiC was processed from sipo (Entrandrophragma utile) wood by heating in an inert atmosphere and infiltrating the resulting carbon replica with liquid silicon melt at 1450°C. After removing excess silicon by leaching in HF/HNO3 the biomorphous preform consisted of ß-SiC with a small amount (approximately 6wt.%) of unreacted carbon. The preform was again leached in HCl/HNO3 and finally exposed to CaCl2 solution. X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared analyses proved that oxidation of the residual carbon at the surface induced formation of carboxyl [COOâ»] groups, which triggered adsorption of Ca(2+), as confirmed by XPS and inductively coupled plasma optical emission spectroscopy measurements. A local increase in Ca(2+) concentration stimulated in vitro precipitation of Ca5(PO4)3OH (HAP) on the silicon carbide preform surface during exposure to simulated body fluid, which indicates a significantly increased bone bonding activity compared with SiC.
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Materiales Biocompatibles/metabolismo , Huesos/metabolismo , Compuestos Inorgánicos de Carbono/metabolismo , Prótesis e Implantes , Compuestos de Silicona/metabolismo , Líquidos Corporales/metabolismo , Durapatita/metabolismo , Microscopía Electrónica de Rastreo , Espectroscopía de Fotoelectrones , Porosidad , Espectroscopía Infrarroja por Transformada de Fourier , Espectrometría Raman , Propiedades de Superficie , Difracción de Rayos XRESUMEN
Data management in post-genomic clinical trials is the process of collecting and validating clinical and genomic data with the goal to answer research questions and to preserve it for future scientific investigation. Comprehensive metadata describing the semantics of the data are needed to leverage it for further research like cross-trial analysis. Current clinical trial management systems mostly lack sufficient metadata and are not semantically interoperable. This paper outlines our approach to develop an application that allows trial chairmen to design their trial and especially the required data management system with comprehensive metadata according to their needs, integrating a clinical trial ontology into the design process. To demonstrate the built-in interoperability of data management systems developed in this way, we integrate these applications into a European biomedical Grid for cancer research in a way that the research data collected in the data management systems can be seamlessly analyzed and mined by researchers.
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Ensayos Clínicos como Asunto , Sistemas de Administración de Bases de Datos , Europa (Continente) , Genómica , Humanos , Almacenamiento y Recuperación de la Información/métodos , Neoplasias , InvestigaciónRESUMEN
The "Oncosimulator" is at the same time a concept of multilevel integrative cancer and (treatment affected) normal tissue biology, an algorithmic construct and a software tool which aims at supporting the clinician in the process of optimizing cancer treatment on the patient individualized basis. Additionally it is a platform for better understanding and exploring the natural phenomenon of cancer as well as training doctors and interested patients alike. In order to achieve all of these goals it has to undergo a thorough clinical optimization and validation process. This is one of the goals of the European Commission funded integrated project "ACGT: Advancing Clinicogenomic Trials on Cancer". Nephroblastoma (Wilms' tumor) and breast cancer have been selected to serve as two paradigms to clinically specify and evaluate the "Oncosimulator" as well as the emerging domain of in silico oncology.