scholarly journals Layer-By-Layer Fabrication of Thicker and Larger Human Cardiac Muscle Patches for Cardiac Repair in Mice

2022 ◽  
Vol 8 ◽  
Author(s):  
Lu Wang ◽  
Jianyi Zhang

The engineered myocardial tissues produced via most manufacturing techniques are typically just a few dozen micrometers thick, which is too thin for therapeutic applications in patients. Here, we used a modified layer-by-layer (LBL) fabrication protocol to generate thick human cardiac muscle patches (hCMPs) with thicknesses of ~3.75 mm. The LBL-hCMPs were composed of a layer of endothelial cells (ECs) sandwiched between two layers of cardiomyocytes (CMs): both cell populations were differentiated from the same human induced pluripotent stem cell line (hiPSCs) and suspended in a fibrin matrix, and the individual layers were sutured together, leaving channels that allowed the culture medium to access the internal cell layer. The LBL-hCMPs were cultured on a dynamic culture platform with electrical stimulation, and when compared to Control-hCMPs consisting of the same total number of hiPSC-ECs and -CMs suspended in a single layer of fibrin, hiPSC-CMs in the LBL-hCMPs were qualitatively more mature with significantly longer sarcomeres and expressed significantly higher levels of mRNA transcripts for proteins that participate in cardiomyocyte contractile activity and calcium handing. Apoptotic cells were also less common in LBL- than in Control-hCMPs. The thickness of fabricated LBL-hCMP gradually decreased to 0.8 mm by day 28 in dynamic culture. When the hCMP constructs were compared in a mouse model of myocardial infarction, the LBL-hCMPs were associated with significantly better measurements of engraftment, cardiac function, infarct size, hypertrophy, and vascularity. Collectively these observations indicate that our modified LBL fabrication protocol produced thicker hCMPs with no decline in cell viability, and that LBL-hCMPs were more potent than Control-hCMPs for promoting myocardial repair in mice.

2021 ◽  
Vol 11 (12) ◽  
pp. 5656
Author(s):  
Yufan Zeng ◽  
Jiashan Tang

Graph neural networks (GNNs) have been very successful at solving fraud detection tasks. The GNN-based detection algorithms learn node embeddings by aggregating neighboring information. Recently, CAmouflage-REsistant GNN (CARE-GNN) is proposed, and this algorithm achieves state-of-the-art results on fraud detection tasks by dealing with relation camouflages and feature camouflages. However, stacking multiple layers in a traditional way defined by hop leads to a rapid performance drop. As the single-layer CARE-GNN cannot extract more information to fix the potential mistakes, the performance heavily relies on the only one layer. In order to avoid the case of single-layer learning, in this paper, we consider a multi-layer architecture which can form a complementary relationship with residual structure. We propose an improved algorithm named Residual Layered CARE-GNN (RLC-GNN). The new algorithm learns layer by layer progressively and corrects mistakes continuously. We choose three metrics—recall, AUC, and F1-score—to evaluate proposed algorithm. Numerical experiments are conducted. We obtain up to 5.66%, 7.72%, and 9.09% improvements in recall, AUC, and F1-score, respectively, on Yelp dataset. Moreover, we also obtain up to 3.66%, 4.27%, and 3.25% improvements in the same three metrics on the Amazon dataset.


1995 ◽  
Vol 401 ◽  
Author(s):  
L. Ryen ◽  
E. Olssoni ◽  
L. D. Madsen ◽  
C. N. L. Johnson ◽  
X. Wang ◽  
...  

AbstractEpitaxial single layer (001) SrTiO3 films and an epitaxial Yba2Cu3O7-x/SrTiO3 multilayer were dc and rf sputtered on (110)rhombohedral LaAIO3 substrates. The microstructure of the films was characterised using transmission electron microscopy. The single layer SrTiO3 films exhibited different columnar morphologies. The column boundaries were due to the lattice mismatch between film and substrate. The boundaries were associated with interfacial dislocations at the film/substrate interface, where the dislocations relaxed the strain in the a, b plane. The columns consisted of individual subgrains. These subgrains were misoriented with respect to each other, with different in-plane orientations and different tilts of the (001) planes. The subgrain boundaries were antiphase or tilt boundaries.The individual layers of the Yba2Cu3O7-x/SrTiO3 multilayer were relatively uniform. A distortion of the SrTiO3 unit cell of 0.9% in the ‘001’ direction and a Sr/Ti ratio of 0.62±0.04 was observed, both in correspondence with the single layer SrTiO3 films. Areas with different tilt of the (001)-planes were also present, within each individual SrTiO3 layer.


2018 ◽  
Vol 20 (2) ◽  
pp. 40-47
Author(s):  
V G Suslyaev ◽  
O N Vladimirova ◽  
K K Shcherbina ◽  
A V Sokurov ◽  
Yu I Zhdanov ◽  
...  

The role and the place of early use of technical means of rehabilitation in the system of complex rehabilitation of patients and disabled people owing to a military trauma is considered. Need of early providing the needing persons with technical means of rehabilitation is proved during recovery treatment, including before establishment by him of disability and formation of the individual program of rehabilitation and an abilitation of disabled people. The efficiency of the developed non-plaster technology of prosthetics manufacturing techniques of artificial limbs of the lower extremities is proved by express method, options of her execution are offered. The first option of production of products on this technology consists in use of polymeric silicone covers and the water-hardening polymeric bandage directly on the patient’s stump. The second option of prosthetics is applied at some defects and diseases of a stump excluding application of silicone covers and full contact individual reception sleeves. For this purpose at production of medical and training artificial limbs of a shin and hip adjustable demountable reception sleeves from thermolayers for right-and left-side amputating defects are used. These options of prosthetics by express method are innovative, are aimed at early rendering the prosthetic and orthopedic help to patients with amputating defects. At production of artificial limbs on these technology domestic materials, modular and not modular accessories are used. The modular complete set of medical and training artificial limbs provides fast and individual setting up the scheme of construction, the individual choice of combinations of functional elements taking into account group of physical activity of the patient, a possibility of replacement of a reception sleeve and any of product elements without withdrawal of an artificial limb at the user. In need of service of a product, for example repair, replacement of the module (artificial foot, a knee) there is no requirement of urgent production of a similar design. Adjustable reception sleeves for primary artificial limbs of a shin and hip in the form of a standard series and moisture-curing bandage can add the list of products of medical appointment in laying for expansion of medical institutions during the special period.


Author(s):  
Shubhra Kamal Nandi ◽  
Rakesh Kumar ◽  
Anubhav ◽  
Anupam Agrawal

Abstract Selective Laser Melting (SLM) is a powder-based layer-by-layer manufacturing technique to produce metallic customized shape components. The exceptionally high thermal gradient induces residual stress and distorts the part geometry affecting the yield quality. Computational models are instrumental in optimizing the process controls to fabricate high-quality components, and hence several such methods have been explored to simulate the thermal behavior of the process and the heat transfer in the melt-pool. Most of the practiced techniques are computationally expensive, making it infeasible to perform a parametric study. Based on closed-form exact heat conduction solution and Finite Volume Method (FVM), a pseudo-analytical thermal modeling approach has been employed to estimate the melt-pool characteristics and temperature distribution of the SLM process. A moving volumetric Gaussian heat source laser model and Green’s function have been adopted to model the heat input by conduction. The heat loss by conduction and convection has been calculated by implementing Finite Volume discretized equations on a 2-dimensional thin-walled domain with appropriate part boundary conditions. Additionally, the Alternating Direction Implicit iterative technique has been implemented for the fast convergence of the simulation. The model is used to demonstrate the influence of the process parameters and non-linear material phase change for a single-line single layer and multilayer part fabrication. The computed melt-pool dimensions and temperature distribution for varying laser-power, scanning velocity, and layer thickness for Ti6Al4V are validated with the experimental data from the literature with fair agreements.


2018 ◽  
Vol 28 (12) ◽  
pp. 2313-2366 ◽  
Author(s):  
Grégoire Allaire ◽  
Lukas Jakabčin

We introduce a model and several constraints for shape and topology optimization of structures, built by additive manufacturing techniques. The goal of these constraints is to take into account the thermal residual stresses or the thermal deformations, generated by processes like Selective Laser Melting, right from the beginning of the structural design optimization. In other words, the structure is optimized concurrently for its final use and for its behavior during the layer-by-layer production process. It is well known that metallic additive manufacturing generates very high temperatures and heat fluxes, which in turn yield thermal deformations that may prevent the coating of a new powder layer, or thermal residual stresses that may hinder the mechanical properties of the final design. Our proposed constraints are targeted to avoid these undesired effects. Shape derivatives are computed by an adjoint method and are incorporated into a level set numerical optimization algorithm. Several 2D and 3D numerical examples demonstrate the interest and effectiveness of our approach.


2020 ◽  
Vol 13 (11) ◽  
pp. 335
Author(s):  
Hazem Choukaife ◽  
Abd Almonem Doolaanea ◽  
Mulham Alfatama

Nanocarriers are defined as structures and devices that are constructed using nanomaterials which add functionality to the encapsulants. Being small in size and having a customized surface, improved solubility and multi-functionality, it is envisaged that nanoparticles will continue to create new biomedical applications owing to their stability, solubility, and bioavailability, as well as controlled release of drugs. The type and physiochemical as well as morphological attributes of nanoparticles influence their interaction with living cells and determine the route of administration, clearance, as well as related toxic effects. Over the past decades, biodegradable polymers such as polysaccharides have drowned a great deal of attention in pharmaceutical industry with respect to designing of drug delivery systems. On this note, biodegradable polymeric nanocarrier is deemed to control the release of the drug, stabilize labile molecules from degradation and site-specific drug targeting, with the main aim of reducing the dosing frequency and prolonging the therapeutic outcomes. Thus, it is essential to select the appropriate biopolymer material, e.g., sodium alginate to formulate nanoparticles for controlled drug delivery. Alginate has attracted considerable interest in pharmaceutical and biomedical applications as a matrix material of nanocarriers due to its inherent biological properties, including good biocompatibility and biodegradability. Various techniques have been adopted to synthesize alginate nanoparticles in order to introduce more rational, coherent, efficient and cost-effective properties. This review highlights the most used and recent manufacturing techniques of alginate-based nanoparticulate delivery system, including emulsification/gelation complexation, layer-by-layer, spray drying, electrospray and electrospinning methods. Besides, the effects of the main processing and formulation parameters on alginate nanoparticles are also summarized.


2020 ◽  
Vol 127 (2) ◽  
pp. 207-224 ◽  
Author(s):  
Molly E. Kupfer ◽  
Wei-Han Lin ◽  
Vasanth Ravikumar ◽  
Kaiyan Qiu ◽  
Lu Wang ◽  
...  

Rationale: One goal of cardiac tissue engineering is the generation of a living, human pump in vitro that could replace animal models and eventually serve as an in vivo therapeutic. Models that replicate the geometrically complex structure of the heart, harboring chambers and large vessels with soft biomaterials, can be achieved using 3-dimensional bioprinting. Yet, inclusion of contiguous, living muscle to support pump function has not been achieved. This is largely due to the challenge of attaining high densities of cardiomyocytes—a notoriously nonproliferative cell type. An alternative strategy is to print with human induced pluripotent stem cells, which can proliferate to high densities and fill tissue spaces, and subsequently differentiate them into cardiomyocytes in situ. Objective: To develop a bioink capable of promoting human induced pluripotent stem cell proliferation and cardiomyocyte differentiation to 3-dimensionally print electromechanically functional, chambered organoids composed of contiguous cardiac muscle. Methods and Results: We optimized a photo-crosslinkable formulation of native ECM (extracellular matrix) proteins and used this bioink to 3-dimensionally print human induced pluripotent stem cell–laden structures with 2 chambers and a vessel inlet and outlet. After human induced pluripotent stem cells proliferated to a sufficient density, we differentiated the cells within the structure and demonstrated function of the resultant human chambered muscle pump. Human chambered muscle pumps demonstrated macroscale beating and continuous action potential propagation with responsiveness to drugs and pacing. The connected chambers allowed for perfusion and enabled replication of pressure/volume relationships fundamental to the study of heart function and remodeling with health and disease. Conclusions: This advance represents a critical step toward generating macroscale tissues, akin to aggregate-based organoids, but with the critical advantage of harboring geometric structures essential to the pump function of cardiac muscle. Looking forward, human chambered organoids of this type might also serve as a test bed for cardiac medical devices and eventually lead to therapeutic tissue grafting.


2010 ◽  
Vol 426-427 ◽  
pp. 151-155 ◽  
Author(s):  
Ming Di Wang ◽  
Shi Hong Shi ◽  
Dun Wen Zuo

For the disadvantages of the lateral powder feeding and multi-lateral coaxial powder feeding process in laser cladding rapid prototyping process, a new process of hollow focusing laser, powder tube being middle and inside-beam powder feeding is put forward, which can be especially apply in laser cladding. In this paper, the finite element analysis model of temperature of the laser cladding using inside-beam powder feeding is established, temperature distribution of the single-layer in laser cladding is researched, which is theoretically useful for controlling the quality of microstructure and to prevent the cracks. When adopting finite element analysis software, Ansys, the layer unit is acted layer-by-layer, the full simulation of real cladding deposition process will be realized if moving boundary. Finally, some experiments validate the simulation results. Compared with the original mode, it can be found that if adopting the system of the laser cladding rapid manufacturing using inside-beam powder feeding, the temperature distribution is different and it will lead to a denser microstructure.


1990 ◽  
Vol 192 ◽  
Author(s):  
A. Banerjee ◽  
S. Guha

ABSTRACTA two-layer MgF2/ITO antireflection (AR) coating has been used to reduce the reflection losses from the surface of a hydrogenated amorphous silicon alloy solar cell. This has resulted in a higher efficiency device primarily due to an improved blue response. The relative thicknesses of the MgF2 and ITO layers have been tailored to give the highest overall quantum efficiency (Q) values, which are higher than that obtained with a single-layer antireflection coating. Typically, the 0 value at 400 nm (Q400) has been increased from 0.58 to 0.68 for a single a:SiH cell. Incorporation of the double-layer AR coating in conjunction with μc-SiC p-layer has yielded Q400 value of 0.77. The total current density obtained by adding the individual contribution of the component cells of a dual bandgap triple amorphous silicon alloy solar cell has been increased from 21.90 to 23.27 mA/cm2 using the double-layer AR coating.


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