Abstract Engineering cardiac tissues and organ models remains a great challenge due to the hierarchical structure of the native myocardium. The need of integrating blood vessels brings additional ...complexity, limiting the available approaches that are suitable to produce integrated cardiovascular organoids. In this work we propose a novel hybrid strategy based on 3D bioprinting, to fabricate endothelialized myocardium. Enabled by the use of our composite bioink, endothelial cells directly bioprinted within microfibrous hydrogel scaffolds gradually migrated towards the peripheries of the microfibers to form a layer of confluent endothelium. Together with controlled anisotropy, this 3D endothelial bed was then seeded with cardiomyocytes to generate aligned myocardium capable of spontaneous and synchronous contraction. We further embedded the organoids into a specially designed microfluidic perfusion bioreactor to complete the endothelialized-myocardium-on-a-chip platform for cardiovascular toxicity evaluation. Finally, we demonstrated that such a technique could be translated to human cardiomyocytes derived from induced pluripotent stem cells to construct endothelialized human myocardium. We believe that our method for generation of endothelialized organoids fabricated through an innovative 3D bioprinting technology may find widespread applications in regenerative medicine, drug screening, and potentially disease modeling.
Bioprinted thrombosis-on-a-chip Zhang, Yu Shrike; Davoudi, Farideh; Walch, Philipp ...
Lab on a chip,
01/2016, Letnik:
16, Številka:
21
Journal Article
Recenzirano
Odprti dostop
Pathologic thrombosis kills more people than cancer and trauma combined; it is associated with significant disability and morbidity, and represents a major healthcare burden. Despite advancements in ...medical therapies and imaging, there is often incomplete resolution of the thrombus. The residual thrombus can undergo fibrotic changes over time through infiltration of fibroblasts from the surrounding tissues and eventually transform into a permanent clot often associated with post-thrombotic syndrome. In order to understand the importance of cellular interactions and the impact of potential therapeutics to treat thrombosis, an in vitro platform using human cells and blood components would be beneficial. Towards achieving this aim, there have been studies utilizing the capabilities of microdevices to study the hemodynamics associated with thrombosis. In this work, we further exploited the utilization of 3D bioprinting technology, for the construction of a highly biomimetic thrombosis-on-a-chip model. The model consisted of microchannels coated with a layer of confluent human endothelium embedded in a gelatin methacryloyl (GelMA) hydrogel, where human whole blood was infused and induced to form thrombi. Continuous perfusion with tissue plasmin activator led to dissolution of non-fibrotic clots, revealing clinical relevance of the model. Further encapsulating fibroblasts in the GelMA matrix demonstrated the potential migration of these cells into the clot and subsequent deposition of collagen type I over time, facilitating fibrosis remodeling that resembled the in vivo scenario. Our study suggests that in vitro 3D bioprinted blood coagulation models can be used to study the pathology of fibrosis, and particularly, in thrombosis. This versatile platform may be conveniently extended to other vascularized fibrotic disease models.
To develop biomimetic three-dimensional (3D) tissue constructs for drug screening and biological studies, engineered blood vessels should be integrated into the constructs to mimic the drug ...administration process in vivo. The development of perfusable vascularized 3D tissue constructs for studying the drug administration process through an engineered endothelial layer remains an area of intensive research. Here, we report the development of a simple 3D vascularized liver tissue model to study drug toxicity through the incorporation of an engineered endothelial layer. Using a sacrificial bioprinting technique, a hollow microchannel was successfully fabricated in the 3D liver tissue construct created with HepG2/C3A cells encapsulated in a gelatin methacryloyl hydrogel. After seeding human umbilical vein endothelial cells (HUVECs) into the microchannel, we obtained a vascularized tissue construct containing a uniformly coated HUVEC layer within the hollow microchannel. The inclusion of the HUVEC layer into the scaffold resulted in delayed permeability of biomolecules into the 3D liver construct. In addition, the vascularized construct containing the HUVEC layer showed an increased viability of the HepG2/C3A cells within the 3D scaffold compared to that of the 3D liver constructs without the HUVEC layer, demonstrating a protective role of the introduced endothelial cell layer. The 3D vascularized liver model presented in this study is anticipated to provide a better and more accurate in vitro liver model system for future drug toxicity testing.
The heart is one of the most vital organs in the human body, which actively pumps the blood through the vascular network to supply nutrients to as well as to extract wastes from all other organs, ...maintaining the homeostasis of the biological system. Over the past few decades, tremendous efforts have been exerted in engineering functional cardiac tissues for heart regeneration via biomimetic approaches. More recently, progress has been made toward the transformation of knowledge obtained from cardiac tissue engineering to building physiologically relevant microfluidic human heart models (i.e. heart-on-chips) for applications in drug discovery. The advancement in stem cell technologies further provides the opportunity to create personalized in vitro models from cells derived from patients. Here, starting from heart biology, we review recent advances in engineering cardiac tissues and heart-on-a-chip platforms for their use in heart regeneration and cardiotoxic/cardiotherapeutic drug screening, and then briefly conclude with characterization techniques and personalization potential of the cardiac models.
To compare in-hospital outcome of Evolut-R 34 mm vs. smaller Evolut-R devices and to identify predictors of paravalvular leak (PVL) and deep implantation specific for Evolut-R 34 mm.
This ...single-center retrospective study included 359 consecutive patients undergoing transcatheter aortic valve replacement (TAVR) with Evolut-R 34 mm (N = 84,23.4%) and Evolut-R 23/26/29 mm (N = 275,76.6%) between 2016 and 2019.
Patients in Evolut-R 34 mm group were more frequently males, had lower STS score, ejection fraction, and mean aortic gradient compared to the Evolut-R 23/26/29 mm group. Horizontal aorta and large LVOT were more frequent findings in the Evolut-R 34 mm group, whereas calcium volume was comparable among the groups.
During TAVR, mean implantation depth and contrast volume were greater in the Evolut-R 34 mm group, compared to the Evolut 23/26/29 mm group. Post-procedurally, 30-day mortality, ≥moderate PVL, device success and pacemaker implantation (PM) rates were comparable between groups. Among independent predictors of ≥moderate PVL, calcium volume (OR:1.04; p < 0.001) was predictive with different thresholds in both groups, whereas aortic angulation (OR:1.40; p = 0.005) was predictive only in Evolut-R 34 mm group at a cutoff of 60° (AUC:0.73; p = 0.043).
Body weight (OR:1.03; p = 0.027), left ventricular outflow tract (LVOT) diameter (OR:1.34; p = 0.001), and mean aortic gradient (OR:0.96; p = 0.006) were independent predictors of deep implantation (mean depth ≥ 6 mm), with LVOT>27 mm being predictive specifically for Evolut-R 34 mm (AUC:0.66; p = 0.024).
TAVR with Evolut-R 34 mm and Evolut-R 23/26/29 mm showed comparable in-hospital outcome. Aortic angulation >60° and LVOT >27 mm were predictive respectively of ≥moderate PVL and deep implantation specifically in Evolut-R 34 mm patients.
•Evolut-R 34mm showed good device success rate (90.5%), similarly to smaller Evolut-Rs.•Paravalvular leak, need for permanent pacemaker, and complication rate were comparable to the smaller Evolut-R sizes.•Implantation of Evolut-R 34mm may require greater operator experience than other Evolut-Rs, given the large aortic annulus.•Aortic angle >60° and LVOT diameter >27mm were specific predictors for Evolut-R 34mm of >moderate PVL and deep implantation.
Pathologic thrombosis kills more people than cancer and trauma combined; it is associated with significant disability and morbidity, and represents a major healthcare burden. Despite advancements in ...medical therapies and imaging, there is often incomplete resolution of the thrombus. The residual thrombus can undergo fibrotic changes over time through infiltration of fibroblasts from the surrounding tissues and eventually transform into a permanent clot often associated with post-thrombotic syndrome. In order to understand the importance of cellular interactions and the impact of potential therapeutics to treat thrombosis, an
in vitro
platform using human cells and blood components would be beneficial. Towards achieving this aim, there have been studies utilizing the capabilities of microdevices to study the hemodynamics associated with thrombosis. In this work, we further exploited the utilization of 3D bioprinting technology, for the construction of a highly biomimetic thrombosis-on-a-chip model. The model consisted of microchannels coated with a layer of confluent human endothelium embedded in a gelatin methacryloyl (GelMA) hydrogel, where human whole blood was infused and induced to form thrombi. Continuous perfusion with tissue plasmin activator led to dissolution of non-fibrotic clots, revealing clinical relevance of the model. Further encapsulating fibroblasts in the GelMA matrix demonstrated the potential migration of these cells into the clot and subsequent deposition of collagen type I over time, facilitating fibrosis remodeling that resembled the
in vivo
scenario. Our study suggests that
in vitro
3D bioprinted blood coagulation models can be used to study the pathology of fibrosis, and particularly, in thrombosis. This versatile platform may be conveniently extended to other vascularized fibrotic disease models.
A novel bioprinted model of thrombosis was developed to study thrombosis and thrombolysis
in vitro
.
Abundance and distribution of commercial marine resources are influenced by environmental variables, which together with fishery patterns may also influence their catchability. However, Catch Per ...Unit Effort (CPUE) can be standardized in order to remove most of the variability not directly attributable to fish abundance. In the present study, Generalized Additive Models (GAMs) were used to investigate the effect of some environmental and fishery covariates on the spatial distribution and abundance of the Norway lobster Nephrops norvegicus within the Pomo/Jabuka Pits (Central Adriatic Sea) and to include those that resulted significant in a standardization process. N. norvegicus is a commercially important demersal crustacean, altering its catchability over the 24-h cycle and seasons according to its burrowing behavior. A historically exploited fishing ground for this species, since 2015 subject to specific fisheries management measures, is represented by the meso-Adriatic depressions, which are also characterized by particular oceanographic conditions. Both the species behaviour and the features of this study area influence the dynamics of the population offering a challenging case study for a standardization modelling approach. Environmental and catch data were obtained during scientific trawl surveys properly designed to catch N. norvegicus, thus improving the quality of the model input data. Standardization of CPUE from 2 surveys from 2012 to 2019 was conducted building two GAMs for both biomass and density indices. Bathymetry, fishing pressure, dissolved oxygen and salinity proved to be significant drivers influencing catch distribution. After cross validations, the tuned models were then used to predict new indices for the study area and the two survey series by means of informed spatial grids, composed by constant surface cells, to each of which are associated average values of environmental parameters and specific levels of fishing pressure, depending on the management measures in place. The predictions can be used to better describe the structure and the spatio-temporal distribution of the population providing valuable information to evaluate the status of such an important marine resource.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
It is well known that temporal fluctuations in small populations deeply influence evolutionary potential. Less well known is whether fluctuations can influence the evolutionary potentials of species ...with large census sizes. Here, we estimated genetic population parameters from as survey of polymorphic microsatellite DNA loci in archived otoliths from Adriatic European anchovy (Engraulis encrasicolus), a fish with large census sizes that supports numerous local fisheries. Stocks have fluctuated greatly over the past few decades, and the Adriatic fishery collapsed in 1987. Our results show a significant reduction of mean genetic parameters as a consequence of the population collapse. In addition, estimates of effective population size (Ne) are much smaller than those expected in a fishes with large population census sizes (Nc). Estimates of Ne indicate low effective population sizes, even before the population collapse. The ratio Ne/Ne ranged between 10-6 and 10-8, indicating a large discrepancy between the anchovy gene pool and population census size. Therefore, anchovy populations may be more vulnerable to fishery effort and environmental change than previously thought.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The sustained exploitation of marine populations requires an understanding of a species' adaptive seascape so that populations can track environmental changes from short- and long-term climate cycles ...and from human development. The analysis of the distributions of genetic markers among populations, together with correlates of life-history and environmental variability, can provide insights into the extent of adaptive variation. Here, we examined genetic variability among populations of mature European anchovies (n = 531) in the Adriatic (13 samples) and Tyrrhenian seas (2 samples) with neutral and putative non-neutral microsatellite loci. These genetic markers failed to confirm the occurrence of two anchovy species in the Adriatic Sea, as previously postulated. However, we found fine-scale population structure in the Adriatic, especially in northern areas, that was associated with four of the 13 environmental variables tested. Geographic gradients in sea temperature, salinity and dissolved oxygen appear to drive adaptive differences in spawning time and early larval development among populations. Resolving adaptive seascapes in Adriatic anchovies provides a means to understand mechanisms underpinning local adaptation and a basis for optimizing exploitation strategies for sustainable harvests.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The Adriatic stock of European sardine (
Sardina pilchardus
) has experienced large interannual demographic fluctuations over the last 30 years, with a severe decline beginning in 1991 and continuing ...until 1997. In the present study, six microsatellite loci were used on a time series collection of otoliths and scales from sampling locations of northern (Chioggia) and southern (Vieste) Adriatic Sea, with the aim to investigate the genetic effects of these stock biomass fluctuations. The northern samples showed significant reduction in observed heterozygosity (H
O
) and mean number of alleles (N
a
) that explain the genetic diversity variation, while the same parameters turned out to be more stable in the southern samples. In addition, we detected the presence of a genetic bottleneck and low effective population size (N
e
) values in several northern samples. Even if the northern and southern Adriatic sardine samples belong to the same genetic stock, the more pronounced decrease in genetic variability recorded in the northern sample led us to speculate that a more intensive fishing pressure and a more pronounced oceanographic isolation of this area could have accentuated the effects of the genetic bottleneck.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
