Antonella Motta
Research interests
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Intereststissue engineering and regenerative medicine
Publications
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5.53Impact points
Nuclear magnetic resonance-based metabolomics of exhaled breath condensate: methodological aspects.
The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology. 02/2012; 39(2):498-500.
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2.14Impact points
Altered and asymmetric default mode network activity in a "hypnotic virtuoso": An fMRI and EEG study.
Consciousness and cognition. 12/2011; 21(1):393-400.
Very highly hypnotizable subjects are rare, easily induced, and able to manifest the whole spectrum of hypnotic phenomena, including post-hypnotic amnesia. The aim of this study was to detect and localize by means of quantitative functional MRI and EEG changes in cortical activity during hypnosis in... [more] Very highly hypnotizable subjects are rare, easily induced, and able to manifest the whole spectrum of hypnotic phenomena, including post-hypnotic amnesia. The aim of this study was to detect and localize by means of quantitative functional MRI and EEG changes in cortical activity during hypnosis induction and deep "pure hypnosis" in a hypnotic "virtuoso" subject. We focused on areas forming the default mode network (DMN), since previous studies found that very highly suggestible subjects in hypnosis showed decreased activity in anterior DMN. During undisturbed hypnosis, our "virtuoso" subject showed not only detectable changes in DMN, but also peculiar activations of non-DMN areas and hemispheric asymmetries of frontal lobe connectivity. Our findings confirm that hypnosis is associated with significant modulation of connectivity and activity which involve the DMN but are not limited to it, depending on the depth of the hypnotic state, the type of mental content and emotional involvement.
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4.64Impact points
Fibroin Scaffold Repairs Critical-Size Bone Defects In Vivo Supported by Human Amniotic Fluid and Dental Pulp Stem Cells.
Tissue engineering. Part A. 12/2011;
The main aim of this study was the comparative evaluation of fibroin scaffolds combined with human stem cells, such as dental pulp stem cells (hDPSCs) and amniotic fluid stem cells (hAFSCs), used to repair critical-size cranial bone defects in immunocompromised rats. Two symmetric full-thickness cra... [more] The main aim of this study was the comparative evaluation of fibroin scaffolds combined with human stem cells, such as dental pulp stem cells (hDPSCs) and amniotic fluid stem cells (hAFSCs), used to repair critical-size cranial bone defects in immunocompromised rats. Two symmetric full-thickness cranial defects on each parietal region of rats have been replenished with silk fibroin scaffolds with or without preseeded stem cells addressed toward osteogenic lineage in vitro. Animals were euthanized after 4 weeks postoperatively and cranial tissue samples were taken for histological analysis. The presence of human cells in the new-formed bone was confirmed by confocal analysis with an antibody directed to a human mitochondrial protein. Fibroin scaffolds induced mature bone formation and defect correction, with higher bone amount produced by hAFSC-seeded scaffolds. Our findings demonstrated the strong potential of stem cells/fibroin bioengineered constructs for correcting large cranial defects in animal model and is likely a promising approach for the reconstruction of human large skeletal defects in craniofacial surgery.
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3.86Impact points
Functional role of scaffold geometries as a template for physiological ECM formation: evaluation of collagen 3D assembly.
Journal of tissue engineering and regenerative medicine. 12/2011;
Bone tissue regeneration involves different healing stages and the resulting final hard tissue is formed from natural templates such as fibrous collagen, soft and hard callus and capillary bed. This work aims to evaluate the efficiency of different scaffold geometries with a novel approach: explorin... [more] Bone tissue regeneration involves different healing stages and the resulting final hard tissue is formed from natural templates such as fibrous collagen, soft and hard callus and capillary bed. This work aims to evaluate the efficiency of different scaffold geometries with a novel approach: exploring the relationships among scaffold morphologies, cell activity and collagen 3D organization, which serves as a natural template for subsequent mineralization. Among the possible systems to fabricate scaffolds, solvent casting with particulate leaching and microfabrication were used to produce random vs ordered structures from poly( d, l-lactic acid). In vitro biological testing was carried out by culturing a human osteosarcoma-derived osteoblast cell line (MG63) and measuring material cytotoxicity, cell proliferation and migration. Assemblage of collagen fibres was evaluated. A preliminary study of collagen distribution over the two different matrices was performed by confocal laser microscopy after direct red 80 staining. Both of the scaffolds were seen to be a good substrate for cell attachment, growth and proliferation. However, it seems that random, rather than regular, well-ordered porosity induces a more proper collagen fibre distribution and organization, similar to the natural one formed in the early stages of bone repair. Copyright © 2011 John Wiley & Sons, Ltd.
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2.19Impact points
Porous poly(D,L-lactic acid) foams with tunable structure and mechanical anisotropy prepared by supercritical carbon dioxide.
Journal of biomedical materials research. Part B, Applied biomaterials. 09/2011; 99(2):338-49.
The design and tunability of tissue scaffolds, such as pore size and geometry, is crucial to the success of an engineered tissue replacement. Moreover, the mechanical nature of a tissue scaffold should display properties similar to the tissue of interest; therefore, tunability of the foam mechanical... [more] The design and tunability of tissue scaffolds, such as pore size and geometry, is crucial to the success of an engineered tissue replacement. Moreover, the mechanical nature of a tissue scaffold should display properties similar to the tissue of interest; therefore, tunability of the foam mechanical properties is desirable. Polymeric foams prepared using supercritical carbon dioxide as a blowing agent has emerged in recent years as a promising technique to prepare porous scaffolds. While a number of groups have reported on the tailoring of scaffold morphologies by using gas foaming techniques, few have considered the effects of such processing conditions on the physical and mechanical anisotropy achieved. The aim of this study was to demonstrate the tunability of the structure and mechanical anisotropy of foams prepared using a variety of different gas foaming conditions. Porous poly(D,L lactic acid) foams were prepared by the systematic adjustment of processing conditions, namely pressure, temperature and venting time, resulting in an extensive range of scaffold morphologies. Characterization of sample anisotropy was achieved by mechanical evaluation of foam specimens both longitudinal and transverse to the foaming direction. The obtained mechanical properties demonstrated a strong dependence of the processing conditions on mechanical anisotropy and performance. Furthermore, results indicate that factors other than pore geometry may be necessary to define the mechanical behavior of the foam specimens. The favorable compressive moduli, coupled with large degrees of anisotropy, suggests these foams may have suitable application as scaffolds for bone tissue engineering.
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4.64Impact points
Human amniotic fluid stem cells seeded in fibroin scaffold produce in vivo mineralized matrix.
Tissue engineering. Part A. 08/2011; 17(21-22):2833-43.
This study investigated the potential of amniotic fluid stem cells (AFSCs) to synthesize mineralized extracellular matrix (ECM) within different porous scaffolds of collagen, poly-D,L-lactic acid (PDLLA), and silk fibroin. The AFSCs were initially differentiated by using an osteogenic medium in two-... [more] This study investigated the potential of amniotic fluid stem cells (AFSCs) to synthesize mineralized extracellular matrix (ECM) within different porous scaffolds of collagen, poly-D,L-lactic acid (PDLLA), and silk fibroin. The AFSCs were initially differentiated by using an osteogenic medium in two-dimensional culture, and expression of specific bone proteins and the physiologic mineral production by the AFSCs were analyzed. In particular, during differentiation process, AFSCs expressed proteins like Runt-related transcription factor 2 (Runx2), Osterix, Osteopontin, and Osteocalcin with a sequential expression, analogous to those occurring during osteoblast differentiation, and produced extracellular calcium stores. AFSCs were then cultured on three-dimensional (3D) scaffolds and evaluated for their ability to differentiate into osteoblastic cells in vivo. Stem cells were cultured in vitro for 1 week in collagen, fibroin, and PDLLA scaffolds. The effect of predifferentiation of the stem cells in scaffolds on the subsequent bone formation in vivo was determined in a rat subcutaneous model. With the addition of a third dimension, osteogenic differentiation and mineralized ECM production by AFSCs were significantly higher. This study demonstrated the strong potential of AFSCs to produce 3D mineralized bioengineered constructs in vivo and suggests that fibroin may be an effective scaffold material for functional repair of critical size bone defects.
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7.37Impact points
Scaffold vascularization in vivo driven by primary human osteoblasts in concert with host inflammatory cells.
Biomaterials. 08/2011; 32(32):8150-60.
Successful cell-based tissue engineering requires a rapid and thorough vascularization in order to ensure long-term implant survival and tissue integration. The vascularization of a scaffold is a complex process, and is modulated by the presence of transplanted cells, exogenous and endogenous signal... [more] Successful cell-based tissue engineering requires a rapid and thorough vascularization in order to ensure long-term implant survival and tissue integration. The vascularization of a scaffold is a complex process, and is modulated by the presence of transplanted cells, exogenous and endogenous signaling proteins, and the host tissue reaction, among other influencing factors. This paper presents evidence for the significance of pre-seeded osteoblasts for the in vivo vascularization of a biodegradable scaffold. Human osteoblasts, cultured on silk fibroin micronets in vitro, migrated throughout the interconnected pores of the scaffold and produced extensive bone matrix. When these constructs were implanted in SCID mice, a rapid and thorough vascularization of the scaffold by the host blood capillaries occurred. This profound response was not seen for the silk fibroin scaffold alone. Moreover, when the pre-cultivation time of human osteoblasts was reduced from 14 days to only 24 h, the significant effect these cells exerted on vascularization rate in vivo was still detectable. From these studies, we conclude that matrix and soluble factors produced by osteoblasts can serve to instruct host endothelial cells to migrate, proliferate, and initiate the process of scaffold vascularization. This finding represents a potential paradigm shift for the field of tissue engineering, especially in bone, as traditional strategies to enhance scaffold vascularization have focused on endovascular cells and regarded osteoblasts primarily as cell targets for mineralization. In addition, the migration of host macrophages and multinucleated giant cells into the scaffold was also found to influence the vascularization of the biomaterial. Therefore, the robust effect on scaffold vascularization seen by pre-culturing with osteoblasts appears to occur in concert with the pro-angiogenic stimuli arising from host immune cells.
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3.86Impact points
Microfabrication of PDLLA scaffolds.
Journal of tissue engineering and regenerative medicine. 07/2011; 5(7):569-77.
This study aimed to comprehend the potentialities of the microfabrication to produce tissue-engineering scaffolds. Structures presenting homogeneously distributed pores of size 100 and 200 µm were fabricated through layer-by-layer deposition of filaments of poly(D,L-lactic acid) (PDLLA) prepared fro... [more] This study aimed to comprehend the potentialities of the microfabrication to produce tissue-engineering scaffolds. Structures presenting homogeneously distributed pores of size 100 and 200 µm were fabricated through layer-by-layer deposition of filaments of poly(D,L-lactic acid) (PDLLA) prepared from dichloromethane/dimethylformamide solutions. Rheological tests on the solution and molecular weight distributions of PDLLA, solvent cast films and microfabricated scaffolds were performed to determine which material conditions are optimal for the microfabricated system and to identify any possible material modification induced by the process. In vitro qualitative preliminary cell culture studies were conducted using MG63 osteoblast cell lines after assuring the non-cytotoxicity of the scaffold material by the lactate dehydrogenase in vitro toxicology assay; biological evaluations were initially performed using scaffolds with the smaller (100 µm) pore size. Scanning electron microscopy imaging was used to determine cell morphology distribution. A second cell culture test was performed, using the scaffold with the higher (200 µm) porosity. Confocal laser microscopy (CLM) was utilized to examine cell morphology and growth behaviour. Cellular metabolic activity and viability were also examined using Alamar Blue assay and further verifications were performed using CLM. Cell culture studies indicated homogeneous distribution, high viability and metabolic activity. Pore dimension affects cell distribution: pores < 100 µm acted as barrier structures for the MG63 osteoblast cell line; penetration inside the matrix was hindered and cells grew on the outer part. Increasing pore size resulted in a more homogeneous cell distribution and penetration of cells inside the structure was achieved.
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2.19Impact points
Biohybrid nanofiber constructs with anisotropic biomechanical properties.
Journal of biomedical materials research. Part B, Applied biomaterials. 02/2011; 96(2):276-86.
Synthetic implant materials often lack of the anisotropic mechanical properties and cell-interactive surface which are shown by natural tissues. For example, engineered vascular grafts need to be developed to address the mechanical and biological problems associated with the graft materials. This st... [more] Synthetic implant materials often lack of the anisotropic mechanical properties and cell-interactive surface which are shown by natural tissues. For example, engineered vascular grafts need to be developed to address the mechanical and biological problems associated with the graft materials. This study has demonstrated a double-electrospinning fabrication process to produce a poly(ε-caprolactone)-fibroin multilayer composite which shows well-integrated nanofibrous structure, endothelial-conducive surface and anisotropic mechanical property, suitable as engineered vascular constructs. Electrospinning parameters such as voltage, solution concentration, feed rate, and relative humidity were optimized to obtain defect-free, uniform nanofibers. To mimic the different mechanical properties of natural vessels in the circumferential and longitudinal directions, a rotating cylinder was used as collector, resulting in the production of constructs with anisotropic properties. The combination of the collector shape and the collector rotation allows us to produce a tubular structure with tunable anisotropic mechanical properties. Fourier transform infrared spectroscopy, differential scanning calorimetry, and uniaxial tensile tests were used to characterize the electrospun constructs. Cell cultures with primary endothelial cells demonstrated that cells showed spread morphology and strong adhesion on fibroin richer surfaces. The platform for producing robust multilayer scaffolds with intermixing nanofiber structure, tunable anisotropy ratio, and surface with specific compositions may hold great potential in tissue engineering applications.
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Scaffolds for tissue engineering and 3D cell culture.
Methods in molecular biology (Clifton, N.J.). 01/2011; 695:17-39.
In tissue engineering applications or even in 3D cell cultures, the biological cross talk between cells and the scaffold is controlled by the material properties and scaffold characteristics. In order to induce cell adhesion, proliferation, and activation, materials used for the fabrication of scaff... [more] In tissue engineering applications or even in 3D cell cultures, the biological cross talk between cells and the scaffold is controlled by the material properties and scaffold characteristics. In order to induce cell adhesion, proliferation, and activation, materials used for the fabrication of scaffolds must possess requirements such as intrinsic biocompatibility and proper chemistry to induce molecular biorecognition from cells. Materials, scaffold mechanical properties and degradation kinetics should be adapted to the specific tissue engineering application to guarantee the required mechanical functions and to accomplish the rate of the new-tissue formation. For scaffolds, pore distribution, exposed surface area, and porosity play a major role, whose amount and distribution influence the penetration and the rate of penetration of cells within the scaffold volume, the architecture of the produced extracellular matrix, and for tissue engineering applications, the final effectiveness of the regenerative process. Depending on the fabrication process, scaffolds with different architecture can be obtained, with random or tailored pore distribution. In the recent years, rapid prototyping computer-controlled techniques have been applied to the fabrication of scaffolds with ordered geometry. This chapter reviews the principal polymeric materials that are used for the fabrication of scaffolds and the scaffold fabrication processes, with examples of properties and selected applications.
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7.37Impact points
The rapid anastomosis between prevascularized networks on silk fibroin scaffolds generated in vitro with cocultures of human microvascular endothelial and osteoblast cells and the host vasculature.
Biomaterials. 09/2010; 31(27):6959-67.
The survival and functioning of a bone biomaterial upon implantation requires a rapidly forming and stably functioning vascularization that connects the implant to the recipient. We have previously shown that human microcapillary endothelial cells (HDMEC) and primary human osteoblast cells (HOS) in ... [more] The survival and functioning of a bone biomaterial upon implantation requires a rapidly forming and stably functioning vascularization that connects the implant to the recipient. We have previously shown that human microcapillary endothelial cells (HDMEC) and primary human osteoblast cells (HOS) in coculture on various 3-D bone biomaterial scaffolds rapidly distribute and self-assemble into a morphological structure resembling bone tissue. Endothelial cells form microcapillary-like structures containing a lumen and these were intertwined between the osteoblast cells and the biomaterial. This tissue-like self-assembly occurred in the absence of exogenously added angiogenic stimuli or artificial matrices. The purpose of this study was to determine whether this in vitro pre-formed microvasculature persists and functions in vivo and to determine how the host responds to the cell-containing scaffolds. The scaffolds with cocultures were implanted into immune-deficient mice and compared to scaffolds without cells or with HDMEC alone. Histological evaluation and immunohistochemical staining with human-specific antibodies of materials removed 14 days after implantation demonstrated that the in vitro pre-formed microcapillary structures were present on the silk fibroin scaffolds and showed a perfused lumen that contained red blood cells. This proved anastomosis with the host vasculature. Chimeric vessels in which HDMEC were integrated with the host's ingrowing (murine) capillaries were also observed. No HDMEC-derived microvessel structures or chimeric vessels were observed on implanted silk fibroin when precultured with HDMEC alone. In addition, there was migration of the host (murine) vasculature into the silk fibroin scaffolds implanted with cocultures, whereas silk fibroin alone or silk fibroin precultured only with HDMEC were nearly devoid of ingrowing host microcapillaries. Therefore, not only do the in vitro pre-formed microcapillaries in a coculture survive and anastomose with the host vasculature to become functioning microcapillaries after implantation, the coculture also stimulates the host capillaries to rapidly grow into the scaffold to vascularize the implanted material. Thus, this coculture-based pre-vascularization of a biomaterial implant may have great potential in the clinical setting to treat large bone defects.
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3.86Impact points
Fine-tuning scaffolds for tissue regeneration: effects of formic acid processing on tissue reaction to silk fibroin.
Journal of tissue engineering and regenerative medicine. 08/2010; 4(6):464-72.
Formic acid (FA) plays a key role in the preparation of silk fibroin (SF) scaffolds from cocoons of Bombyx mori and is used for fibre distribution. In this study, we used a subcutaneous implantation model in Wistar rats to examine SF scaffolds prepared by treating the degummed cocoon with FA for eit... [more] Formic acid (FA) plays a key role in the preparation of silk fibroin (SF) scaffolds from cocoons of Bombyx mori and is used for fibre distribution. In this study, we used a subcutaneous implantation model in Wistar rats to examine SF scaffolds prepared by treating the degummed cocoon with FA for either 30 or 60 min. The tissue reaction and inflammatory response to SF was assessed by qualitative histology at intervals from 3 to 180 days. Additionally, dynamic biomaterial-induced vascularization and biomaterial degradation were quantified using a technique for analysing an image of the entire implanted biomaterial. Varying the FA treatment time led to different scaffold morphologies and resulted in two distinct peri-implant tissue reactions. The 30 min-treated scaffold was integrated into the surrounding tissue beginning at day 3 after implantation and vascularization increased 10-fold from 15 to 180 days, while the scaffold was continuously degraded throughout the first 90 days. In contrast, the 60 min-treated SF scaffold appeared as bulk for the first 90 days after implantation, after which a rapid degradation and vascularization process began. After 180 days, the tissue response was similar for both scaffolds, with eventual formation of a well vascularized connective tissue integrating the SF fibres. This study indicates that by modifying the FA treatment time, the tissue reaction to SF scaffolds can be tailored for different tissue-engineering applications. The tunability and biocompatibility of SF make it an attractive scaffold for exploration in regenerative medicine and clinical tissue engineering.
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7.37Impact points
The synergistic effects of 3-D porous silk fibroin matrix scaffold properties and hydrodynamic environment in cartilage tissue regeneration.
Biomaterials. 03/2010; 31(17):4672-81.
Autologous cell-based tissue engineering using three-dimensional porous scaffolds has provided a good option for the repair of cartilage defects. Silk fibroin-based scaffolds are naturally degradable materials with excellent biocompatibility and robust mechanical properties, indicating potential app... [more] Autologous cell-based tissue engineering using three-dimensional porous scaffolds has provided a good option for the repair of cartilage defects. Silk fibroin-based scaffolds are naturally degradable materials with excellent biocompatibility and robust mechanical properties, indicating potential applications in cartilage tissue engineering. In this study, silk fibroin scaffolds prepared by freeze-drying (FD) and salt-leaching (SL300 and SL500) were fully characterized and used to study the effects of silk fibroin scaffold properties on chondrocyte attachment, proliferation and differentiation. The synergistic effects of scaffold properties and hydrodynamic environment generated by in vitro rocking culture were also investigated using static cultures as control. FD scaffolds with small pore size and lower porosity increased cell attachment but inhibited cell penetration and limited cell proliferation and differentiation. In contrast, SL scaffolds displaying a bigger pore size, higher porosity and crystallinity resulted in homogenous cell distribution, increasing cell proliferation and advanced chondrocyte differentiation in terms of their spherical morphology, predominant chondrogenic gene expression and abundant cartilaginous extracellular matrix production. A hydrodynamic environment was beneficial to chondrocyte proliferation, differentiation, and integrin gene expression in a pore size dependent manner with superior cartilage matrix production but limited hypertrophic differentiation obtained using chondrocyte-seeded SL500 scaffolds. Integrin alpha5beta1 might mediate these effects. Chondrocyte/SL500 silk fibroin constructs obtained under in vitro rocking culture might serve as an excellent implant for in vivo cartilage defect reparation.
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1.91Impact points
Carbon Coatings for Cardiovascular Applications: Physico-Chemical Properties and Blood Compatibility.
Journal of biomaterials applications. 10/2009;
Two different types of carbon coatings for cardiovascular applications were characterized both as regards to their physico-chemical properties and blood compatibility upon contact with human plasma and platelets. The samples were analyzed by means of a wide range of techniques, including scanning el... [more] Two different types of carbon coatings for cardiovascular applications were characterized both as regards to their physico-chemical properties and blood compatibility upon contact with human plasma and platelets. The samples were analyzed by means of a wide range of techniques, including scanning electron microscopy (SEM) and atomic force microscopy (AFM), contact angle goniometry, Raman spectroscopy and X-ray Diffraction (XRD). Multiple tests have been performed to evaluate plasma protein adsorption and platelets adhesion and activation, and to investigate possible correlations between the surface properties of the materials and their blood compatibility. We proposed a similar mechanism of blood/material interaction for the carbon-based materials tested. It has been suggested that the characteristic wettability and surface heterogeneity of the coatings guide protein adsorption and retention onto the carbon surfaces, promoting a preferential, extensive and tight adsorption of albumin molecules, that in turn leads to surface passivation and inhibits subsequent platelets adhesion and activation.
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6.43Impact points
Differential Dose Adjustments of Immunosuppressants after Resuming Boosted versus Unboosted HIV-Protease Inhibitors Postliver Transplant.
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 08/2009;
Pharmacokinetic (PK) interactions between protease inhibitors (PI(s)) and immunosuppressive agents (IS) are critical elements in the management of HIV-infected patients who undergo liver transplantation (LT(x)). The primary objective of this study was to evaluate the decreases in IS dosages necessar... [more] Pharmacokinetic (PK) interactions between protease inhibitors (PI(s)) and immunosuppressive agents (IS) are critical elements in the management of HIV-infected patients who undergo liver transplantation (LT(x)). The primary objective of this study was to evaluate the decreases in IS dosages necessary to maintain an appropriate therapeutic window (TW) after initiating PI-based antiretroviral therapy regimens post-LT(x). Single-center, PK cross-sectional study of consecutive HIV-infected adult patients who underwent LT(x) was done. Blood trough concentrations (C(t)) of IS were obtained using a commercial MEIA test; plasma C(t) of PI(s) were measured using HPLC. Twelve consecutive HIV-infected adult patients (11 males, 1 female) were enrolled. More rapid increases in IS plasma C(t) were observed 48 h after initiating ritonavir (RTV)-boosted PI therapy post-LT(x) than when using unboosted PI(s). Seven patients developed acute renal failure. The median fold decrease in IS dosages required to regain IS concentrations that were in the TW was 7.5 (range 6-14) after resuming boosted PI(s) and 2.9 (range 2-4) after unboosted PI(s). The overall median time necessary to reach IS TW after dose adjustment was 3.5 days (range 0-15). Unboosted PI(s) exhibited lesser PK interactions with IS than did RTV-boosted PI(s) and were thus more amenable to use in the post-LT(x) setting.
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2.05Impact points
Efficacy and safety of atazanavir in patients with end-stage liver disease.
Infection. 07/2009; 37(3):250-5.
BACKGROUND: No data are available on the use of atazanavir (ATV) in patients with end-stage liver disease (ESLD), and guidelines discourage its use in this setting. The objective of our study was to evaluate the efficacy and safety of unboosted ATV in patients infected with HIV and suffering from ES... [more] BACKGROUND: No data are available on the use of atazanavir (ATV) in patients with end-stage liver disease (ESLD), and guidelines discourage its use in this setting. The objective of our study was to evaluate the efficacy and safety of unboosted ATV in patients infected with HIV and suffering from ESLD who had been screened for orthotopic liver transplantation (OLT(x)). PATIENTS AND METHODS: This was a single-arm, 24-week pilot study. Atazanavir-naïve patients undergoing a highly active antiretroviral therapy were switched to ATV 400 mg daily plus two non-thymidine nucleoside reverse transcriptase inhibitors. RESULTS: Fifteen patients (ten males and five females, age range 36-59 years) were enrolled in the study. Of these, 11 (73%) had a baseline CD4 cell count > 200 microl(-1), and 12 had undetectable plasma HIV-RNA. 12 subjects (80%) were able to remain on ATV until week 24 (n = 10) or transplantation (n = 2). At the end of the study, the median CD4 cell count was 340 microl(-1) , and nine of the ten patients had undetectable RNA. During the study period, two patients received a transplant, two died of intracerebral hemorrhage and lactic acidosis, respectively, and one discontinued ATV. Among the ten patients completing the 24-week study, no significant changes from baseline were observed for most of the liver function markers, with the exception of unconjugated bilirubin (from 1.15 mg/dl to 1.32 mg/dl, p = 0.047). CONCLUSIONS: Unboosted ATV treatment did not worsen liver disease and was able to maintain or gain immunovirological eligibility for OLT(x) in all patients, with a limited effect on unconjugated bilirubin. These results suggest that ATV is an easy-to-use drug in patients with ESLD.
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3.11Impact points
Comparative Methods for the Evaluation of Protein Adsorption.
Macromolecular bioscience. 03/2009;
AFM, Immunogold labeling and SPR have been successfully applied to the analysis of protein adsorption on fibroin substrates, chosen as a paradigmatic biomaterial. The process was evaluated both under static and dynamic conditions, also considering the effect of protein competition. AFM via antibody-... [more] AFM, Immunogold labeling and SPR have been successfully applied to the analysis of protein adsorption on fibroin substrates, chosen as a paradigmatic biomaterial. The process was evaluated both under static and dynamic conditions, also considering the effect of protein competition. AFM via antibody-modified tips provided maps of protein adsorption and information on protein-protein interactions. Double labeling Immunogold imaged protein distribution upon competitive adsorption. SPR described the dynamics of the process, offering also quantitative data both from individual and two-component protein solutions. The integration of these analytical techniques and the critical evaluation of the results can provide a detailed description of protein adsorption.
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7.37Impact points
Dynamic processes involved in the pre-vascularization of silk fibroin constructs for bone regeneration using outgrowth endothelial cells.
Biomaterials. 01/2009;
For successful bone regeneration tissue engineered bone constructs combining both aspects, namely a high osteogenic potential and a rapid connection to the vascular network are needed. In this study we assessed the formation of pre-vascular structures by human outgrowth endothelial cells (OEC) from ... [more] For successful bone regeneration tissue engineered bone constructs combining both aspects, namely a high osteogenic potential and a rapid connection to the vascular network are needed. In this study we assessed the formation of pre-vascular structures by human outgrowth endothelial cells (OEC) from progenitors in the peripheral blood and the osteogenic differentiation of primary human osteoblasts (pOB) on micrometric silk fibroin scaffolds. The rational was to gain more insight into the dynamic processes involved in the differentiation and functionality of both cell types depending on culture time in vitro. Vascular tube formation by OEC was assessed quantitatively at one and 4 weeks of culture. In parallel, we assessed the temporal changes in cell ratios by flow cytometry and in the marker profiles of endothelial and osteogenic markers by quantitative real-time PCR. In terms of OEC, we observed an increase in tube length, tube area, number of nodes and number of vascular meshes within a culture period of 4 weeks, but a decrease in endothelial markers in real-time PCR. At the same time early osteogenic markers were downregulated, while marker expression associated with progressing mineralized matrix was upregulated in later stages of the culture. In addition, deposition of matrix components, such as collagen type I, known as a pro-angiogenic substrate for endothelial cells, appeared to increase with time indicated by immunohistochemistry. In summary, the study suggests a progressing maturation of the tissue construct with culture time which seems to be not effected by culture conditions mainly designed for outgrowth endothelial cells.
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2.19Impact points
Surface properties and blood compatibility of commercially available diamond-like carbon coatings for cardiovascular devices.
Journal of biomedical materials research. Part B, Applied biomaterials. 01/2009;
The aim of this study was to determine the relationships between the surface properties and blood compatibility of in-use diamond-like carbon (DLC) coatings for cardiovascular components. Commercially available DLC films were characterized with respect to surface topography and wettability, protein ... [more] The aim of this study was to determine the relationships between the surface properties and blood compatibility of in-use diamond-like carbon (DLC) coatings for cardiovascular components. Commercially available DLC films were characterized with respect to surface topography and wettability, protein adsorption from human plasma, and platelets adhesion/activation. Fibrinogen (Fng) and human serum albumin (HSA) adsorbed onto the sample surfaces were in particular quantified as two of the main proteins involved in blood compatibility. A low tendency of platelets to spread and form aggregates onto the DLC-coated surfaces has been described and related to a low Fng-to-HSA adsorption ratio. This study provides evidence that the rapid and tenacious binding of albumin molecules to DLC materials tends to passivate the surfaces and to inhibit Fng adsorption, thus imparting thromboresistance to the carbon coatings by rendering the surfaces less adhesive and activating for platelets. Albumin preferential adsorption was ascribed to high chemical heterogeneity of the DLC sample surfaces. The DLC films tested present a favorable behavior as regards blood compatibility with respect to platelet thrombus formation by reason of their surface properties. (c) 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009.
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2.51Impact points
Silk fibroin processing and thrombogenic responses.
Journal of biomaterials science. Polymer edition. 01/2009; 20(13):1875-97.
Silkworm-derived fibroin, which constitutes the core of the silk filament, is an attractive protein-polymer for biomedical applications. Fibroin can also be processed into a variety of 2-D and 3-D formats to match morphological and structural features to specific applications. The focus of the prese... [more] Silkworm-derived fibroin, which constitutes the core of the silk filament, is an attractive protein-polymer for biomedical applications. Fibroin can also be processed into a variety of 2-D and 3-D formats to match morphological and structural features to specific applications. The focus of the present research was to correlate the structure of silk fibroin-derived biomaterials with plasma protein adsorption, platelet activation and inflammatory cell (THP-1 cell line) adhesion and activation. The amino-acid composition of the two types of silk studied influenced the crystallinity of the films, hydrophobicity, surface roughness and biological interactions. Protein adsorption was lower on samples with the higher crystallinity and hydrophobicity, in particular the chemotactic factors (C3a, C5a, C3b), while other proteins such as fibrinogen were comparable in terms of adsorption. As a consequence, platelets and immune cells responded differently to the various films obtained by following different processing protocols and stabilized by different methods (methanol or water vapour) in terms of their adherence, activation, and the secretion of inflammatory mediators by monocytes. The data presented here demonstrate that bioactivity can be influenced by changing the chemistry, such as the source of silk protein, or by the specific process used in the preparation of the materials used to assess biological responses.
Following (17)
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Imad Sheiban
univbersity of torino -
Mike Barbeck
Johannes Gutenberg-University -
Piero Andrea Temussi
MRC National Institute for Medical Research -
Shahram Ghanaati
REPAIR-Lab, Institute of Pathology, Johannes Gutenberg University, Mainz, Germany and Clinic for Maxillofacial and Plastic Surgery, Johann Wolfgang Goethe University, Frankfurt/Main, Germany -
Paola Petrini
Politecnico di Milano
