XanoMatrix surfaces as scaffolds for mesenchymal stem cell culture and growth

PubMed Central

Bhardwaj, Garima; Webster, Thomas J

2016-01-01

Stem cells are being widely investigated for a wide variety of applications in tissue engineering due to their ability to differentiate into a number of cells such as neurons, osteoblasts, and fibroblasts. This ability of stem cells to differentiate into different types of cells is greatly based on mechanical and chemical cues received from their three-dimensional environments. All organs are formed by a number of cells linked together via an extracellular matrix (ECM). The ECM is a complex network of proteins and carbohydrates, which occupies intercellular spaces and regulates cellular activity by controlling cell adhesion, migration, proliferation, and differentiation. The ECM is composed of two main types of macromolecules, namely, polysaccharide glycosaminoglycans, which are covalently attached to proteins in the form of proteoglycans and fibrous proteins belonging to two functional groups, structural (collagen and elastin) and adhesive (fibronectin, laminin, vitronectin, etc). Tissue engineering is a multidisciplinary field that aims to develop biomimetic scaffolds that emulate properties of the ECM to help repair or regenerate diseased or damaged tissue. This study introduces one of these matrices, XanoMatrix, as an optimal scaffold for tissue engineering applications, in particular, for stem cell research, based on its composition, nanofibrous structure, and porosity. Results of this study suggest that XanoMatrix scaffolds are promising for stem cell tissue engineering applications and as improved cell culture inserts for studying stem cell functions (compared to traditional Corning and Falcon cell culture plates) and, thus, should be further studied. PMID:27354795

Digital micromirror device projection printing system for meniscus tissue engineering.

PubMed

Grogan, Shawn P; Chung, Peter H; Soman, Pranav; Chen, Peter; Lotz, Martin K; Chen, Shaochen; D'Lima, Darryl D

2013-07-01

Meniscus degeneration due to age or injury can lead to osteoarthritis. Although promising, current cell-based approaches show limited success. Here we present three-dimensional methacrylated gelatin (GelMA) scaffolds patterned via projection stereolithography to emulate the circumferential alignment of cells in native meniscus tissue. Cultured human avascular zone meniscus cells from normal meniscus were seeded on the scaffolds. Cell viability was monitored, and new tissue formation was assessed by gene expression analysis and histology after 2weeks in serum-free culture with transforming growth factor β1 (10ngml(-1)). Light, confocal and scanning electron microscopy were used to observe cell-GelMA interactions. Tensile mechanical testing was performed on unseeded, fresh scaffolds and 2-week-old cell-seeded and unseeded scaffolds. 2-week-old cell-GelMA constructs were implanted into surgically created meniscus defects in an explant organ culture model. No cytotoxic effects were observed 3weeks after implantation, and cells grew and aligned to the patterned GelMA strands. Gene expression profiles and histology indicated promotion of a fibrocartilage-like meniscus phenotype, and scaffold integration with repair tissue was observed in the explant model. We show that micropatterned GelMA scaffolds are non-toxic, produce organized cellular alignment, and promote meniscus-like tissue formation. Prefabrication of GelMA scaffolds with architectures mimicking the meniscus collagen bundle organization shows promise for meniscal repair. Furthermore, the technique presented may be scaled up to repair larger defects. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Three-Dimensional Normal Human Neutral Progenitor Tissue-Like Assemblies: A Model for Persistent Varicella-Zoster Virus Infection and Platform to Study Oxidate Stress and Damage in Multiple Hit Scenarios

NASA Technical Reports Server (NTRS)

Goodwin, Thomas J.; McCarthy, M.; Osterrieder, N.; Cohrs, R. J.; Kaufer, B. B.

2014-01-01

The environment of space results in a multitude of challenges to the human physiology that present barriers to extended habitation and exploration. Over 40 years of investigation to define countermeasures to address space flight adaptation has left gaps in our knowledge regarding mitigation strategies partly due to the lack of investigative tools, monitoring strategies, and real time diagnostics to understand the central causative agent(s) responsible for physiologic adaptation and maintaining homeostasis. Spaceflight-adaptation syndrome is the combination of space environmental conditions and the synergistic reaction of the human physiology. Our work addresses the role of oxidative stress and damage (OSaD) as a negative and contributing Risk Factor (RF) in the following areas of combined spaceflight related dysregulation: i) radiation induced cellular damage [1], [2] ii) immune impacts and the inflammatory response [3], [4] and iii) varicella zoster virus (VZV) reactivation [5]. Varicella-zoster (VZV)/Chicken Pox virus is a neurotropic human alphaherpes virus resulting in varicella upon primary infection, suppressed by the immune system becomes latent in ganglionic neurons, and reactivates under stress events to re-express in zoster and possibly shingles. Our laboratory has developed a complex three-dimensional (3D) normal human neural tissue model that emulates several characteristics of the human trigeminal ganglia (TG) and allows the study of combinatorial experimentation which addresses, simultaneously, OSaD associated with Spaceflight adaptation and habitation [6]. By combining the RFs of microgravity, radiation, and viral infection we will demonstrate that living in the space environment leads to significant physiological consequences for the peripheral and subsequently the central nervous system (PNS, CNS) associated with OSaD generation and consequentially endangers long-duration and exploration-class missions.

Surrogate modelling for the prediction of spatial fields based on simultaneous dimensionality reduction of high-dimensional input/output spaces.

PubMed

Crevillén-García, D

2018-04-01

Time-consuming numerical simulators for solving groundwater flow and dissolution models of physico-chemical processes in deep aquifers normally require some of the model inputs to be defined in high-dimensional spaces in order to return realistic results. Sometimes, the outputs of interest are spatial fields leading to high-dimensional output spaces. Although Gaussian process emulation has been satisfactorily used for computing faithful and inexpensive approximations of complex simulators, these have been mostly applied to problems defined in low-dimensional input spaces. In this paper, we propose a method for simultaneously reducing the dimensionality of very high-dimensional input and output spaces in Gaussian process emulators for stochastic partial differential equation models while retaining the qualitative features of the original models. This allows us to build a surrogate model for the prediction of spatial fields in such time-consuming simulators. We apply the methodology to a model of convection and dissolution processes occurring during carbon capture and storage.

Tunneling Conductivity and Piezoresistivity of Composites Containing Randomly Dispersed Conductive Nano-Platelets

PubMed Central

Oskouyi, Amirhossein Biabangard; Sundararaj, Uttandaraman; Mertiny, Pierre

2014-01-01

In this study, a three-dimensional continuum percolation model was developed based on a Monte Carlo simulation approach to investigate the percolation behavior of an electrically insulating matrix reinforced with conductive nano-platelet fillers. The conductivity behavior of composites rendered conductive by randomly dispersed conductive platelets was modeled by developing a three-dimensional finite element resistor network. Parameters related to the percolation threshold and a power-low describing the conductivity behavior were determined. The piezoresistivity behavior of conductive composites was studied employing a reoriented resistor network emulating a conductive composite subjected to mechanical strain. The effects of the governing parameters, i.e., electron tunneling distance, conductive particle aspect ratio and size effects on conductivity behavior were examined. PMID:28788580

Multi-level emulation of complex climate model responses to boundary forcing data

NASA Astrophysics Data System (ADS)

Tran, Giang T.; Oliver, Kevin I. C.; Holden, Philip B.; Edwards, Neil R.; Sóbester, András; Challenor, Peter

2018-04-01

Climate model components involve both high-dimensional input and output fields. It is desirable to efficiently generate spatio-temporal outputs of these models for applications in integrated assessment modelling or to assess the statistical relationship between such sets of inputs and outputs, for example, uncertainty analysis. However, the need for efficiency often compromises the fidelity of output through the use of low complexity models. Here, we develop a technique which combines statistical emulation with a dimensionality reduction technique to emulate a wide range of outputs from an atmospheric general circulation model, PLASIM, as functions of the boundary forcing prescribed by the ocean component of a lower complexity climate model, GENIE-1. Although accurate and detailed spatial information on atmospheric variables such as precipitation and wind speed is well beyond the capability of GENIE-1's energy-moisture balance model of the atmosphere, this study demonstrates that the output of this model is useful in predicting PLASIM's spatio-temporal fields through multi-level emulation. Meaningful information from the fast model, GENIE-1 was extracted by utilising the correlation between variables of the same type in the two models and between variables of different types in PLASIM. We present here the construction and validation of several PLASIM variable emulators and discuss their potential use in developing a hybrid model with statistical components.

Three dimensional optic tissue culture and process

NASA Technical Reports Server (NTRS)

Spaulding, Glenn F. (Inventor); Prewett, Tacey L. (Inventor); Goodwin, Thomas J. (Inventor); Francis, Karen M. (Inventor); Cardwell, Delmar R. (Inventor); Oconnor, Kim (Inventor); Fitzgerald, Wendy S. (Inventor); Aten, Laurie A. (Inventor)

1994-01-01

A process for artificially producing three-dimensional optic tissue has been developed. The optic cells are cultured in a bioreactor at low shear conditions. The tissue forms normal, functional tissue organization and extracellular matrix.

Three Dimensional Optic Tissue Culture and Process

NASA Technical Reports Server (NTRS)

OConnor, Kim C. (Inventor); Spaulding, Glenn F. (Inventor); Goodwin, Thomas J. (Inventor); Aten, Laurie A. (Inventor); Francis, Karen M. (Inventor); Caldwell, Delmar R. (Inventor); Prewett, Tacey L. (Inventor); Fitzgerald, Wendy S. (Inventor)

1999-01-01

A process for artificially producing three-dimensional optic tissue has been developed. The optic cells are cultured in a bioireactor at low shear conditions. The tissue forms as normal, functional tissue grows with tissue organization and extracellular matrix formation.

Tissue engineering of fish skin: behavior of fish cells on poly(ethylene glycol terephthalate)/poly(butylene terephthalate) copolymers in relation to the composition of the polymer substrate as an initial step in constructing a robotic/living tissue hybrid.

PubMed

Pouliot, Roxane; Azhari, Rosa; Qanadilo, Hala F; Mahmood, Tahir A; Triantafyllou, Michael S; Langer, Robert

2004-01-01

This study presents the development of a biosynthetic fish skin to be used on aquatic robots that can emulate fish. Smoothness of the external surface is desired in improving high propulsive efficiency and maneuvering agility of autonomous underwater vehicles such as the RoboTuna (Triantafyllou, M., and Triantafyllou, G. Sci. Am. 272, 64, 1995). An initial step was to determine the seeding density and select a polymer for the scaffolds. The attachment and proliferation of chinook salmon embryo (CHSE-214) and brown bullhead (BB) cells were studied on different compositions of a poly(ethylene glycol terephthalate) (PEGT) and poly(butylene terephthalate) (PBT) copolymer (Polyactive). Polymer films were used, cast of three different compositions of PEGT/PBT (weight ratios of 55/45, 60/40, and 70/30) and two different molecular masses of PEGT (300 and 1000 Da). When a 55 wt% and a 300-Da molecular mass form of PEGT was used, maximum attachment and proliferation of CHSE-214 and BB cells were achieved. Histological studies and immunostaining indicate the presence of collagen and cytokeratins in the extracellular matrix formed after 14 days of culture. Porous scaffolds of PEGT/PBT copolymers were also used for three-dimensional tissue engineering of fish skin, using BB cells. Overall, our results indicate that fish cells can attach, proliferate, and express fish skin components on dense and porous Polyactive scaffolds.

The Use of Interactive Raster Graphics in the Display and Manipulation of Multidimensional Data

NASA Technical Reports Server (NTRS)

Anderson, D. C.

1981-01-01

Techniques for the review, display, and manipulation of multidimensional data are developed and described. Multidimensional data is meant in this context to describe scalar data associated with a three dimensional geometry or otherwise too complex to be well represented by traditional graphs. Raster graphics techniques are used to display a shaded image of a three dimensional geometry. The use of color to represent scalar data associated with the geometries in shaded images is explored. Distinct hues are associated with discrete data ranges, thus emulating the traditional representation of data with isarithms, or lines of constant numerical value. Data ranges are alternatively associated with a continuous spectrum of hues to show subtler data trends. The application of raster graphics techniques to the display of bivariate functions is explored.

A Three-dimensional Polymer Scaffolding Material Exhibiting a Zero Poisson's Ratio.

PubMed

Soman, Pranav; Fozdar, David Y; Lee, Jin Woo; Phadke, Ameya; Varghese, Shyni; Chen, Shaochen

2012-05-14

Poisson's ratio describes the degree to which a material contracts (expands) transversally when axially strained. A material with a zero Poisson's ratio does not transversally deform in response to an axial strain (stretching). In tissue engineering applications, scaffolding having a zero Poisson's ratio (ZPR) may be more suitable for emulating the behavior of native tissues and accommodating and transmitting forces to the host tissue site during wound healing (or tissue regrowth). For example, scaffolding with a zero Poisson's ratio may be beneficial in the engineering of cartilage, ligament, corneal, and brain tissues, which are known to possess Poisson's ratios of nearly zero. Here, we report a 3D biomaterial constructed from polyethylene glycol (PEG) exhibiting in-plane Poisson's ratios of zero for large values of axial strain. We use digital micro-mirror device projection printing (DMD-PP) to create single- and double-layer scaffolds composed of semi re-entrant pores whose arrangement and deformation mechanisms contribute the zero Poisson's ratio. Strain experiments prove the zero Poisson's behavior of the scaffolds and that the addition of layers does not change the Poisson's ratio. Human mesenchymal stem cells (hMSCs) cultured on biomaterials with zero Poisson's ratio demonstrate the feasibility of utilizing these novel materials for biological applications which require little to no transverse deformations resulting from axial strains. Techniques used in this work allow Poisson's ratio to be both scale-independent and independent of the choice of strut material for strains in the elastic regime, and therefore ZPR behavior can be imparted to a variety of photocurable biomaterial.

Method using in vivo quantitative spectroscopy to guide design and optimization of low-cost, compact clinical imaging devices: emulation and evaluation of multispectral imaging systems

NASA Astrophysics Data System (ADS)

Saager, Rolf B.; Baldado, Melissa L.; Rowland, Rebecca A.; Kelly, Kristen M.; Durkin, Anthony J.

2018-04-01

With recent proliferation in compact and/or low-cost clinical multispectral imaging approaches and commercially available components, questions remain whether they adequately capture the requisite spectral content of their applications. We present a method to emulate the spectral range and resolution of a variety of multispectral imagers, based on in-vivo data acquired from spatial frequency domain spectroscopy (SFDS). This approach simulates spectral responses over 400 to 1100 nm. Comparing emulated data with full SFDS spectra of in-vivo tissue affords the opportunity to evaluate whether the sparse spectral content of these imagers can (1) account for all sources of optical contrast present (completeness) and (2) robustly separate and quantify sources of optical contrast (crosstalk). We validate the approach over a range of tissue-simulating phantoms, comparing the SFDS-based emulated spectra against measurements from an independently characterized multispectral imager. Emulated results match the imager across all phantoms (<3 % absorption, <1 % reduced scattering). In-vivo test cases (burn wounds and photoaging) illustrate how SFDS can be used to evaluate different multispectral imagers. This approach provides an in-vivo measurement method to evaluate the performance of multispectral imagers specific to their targeted clinical applications and can assist in the design and optimization of new spectral imaging devices.

Speckle contrast optical tomography: A new method for deep tissue three-dimensional tomography of blood flow

PubMed Central

Varma, Hari M.; Valdes, Claudia P.; Kristoffersen, Anna K.; Culver, Joseph P.; Durduran, Turgut

2014-01-01

A novel tomographic method based on the laser speckle contrast, speckle contrast optical tomography (SCOT) is introduced that allows us to reconstruct three dimensional distribution of blood flow in deep tissues. This method is analogous to the diffuse optical tomography (DOT) but for deep tissue blood flow. We develop a reconstruction algorithm based on first Born approximation to generate three dimensional distribution of flow using the experimental data obtained from tissue simulating phantoms. PMID:24761306

THE MIRA–TITAN UNIVERSE: PRECISION PREDICTIONS FOR DARK ENERGY SURVEYS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heitmann, Katrin; Habib, Salman; Biswas, Rahul

2016-04-01

Large-scale simulations of cosmic structure formation play an important role in interpreting cosmological observations at high precision. The simulations must cover a parameter range beyond the standard six cosmological parameters and need to be run at high mass and force resolution. A key simulation-based task is the generation of accurate theoretical predictions for observables using a finite number of simulation runs, via the method of emulation. Using a new sampling technique, we explore an eight-dimensional parameter space including massive neutrinos and a variable equation of state of dark energy. We construct trial emulators using two surrogate models (the linear powermore » spectrum and an approximate halo mass function). The new sampling method allows us to build precision emulators from just 26 cosmological models and to systematically increase the emulator accuracy by adding new sets of simulations in a prescribed way. Emulator fidelity can now be continuously improved as new observational data sets become available and higher accuracy is required. Finally, using one ΛCDM cosmology as an example, we study the demands imposed on a simulation campaign to achieve the required statistics and accuracy when building emulators for investigations of dark energy.« less

The mira-titan universe. Precision predictions for dark energy surveys

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heitmann, Katrin; Bingham, Derek; Lawrence, Earl

2016-03-28

Large-scale simulations of cosmic structure formation play an important role in interpreting cosmological observations at high precision. The simulations must cover a parameter range beyond the standard six cosmological parameters and need to be run at high mass and force resolution. A key simulation-based task is the generation of accurate theoretical predictions for observables using a finite number of simulation runs, via the method of emulation. Using a new sampling technique, we explore an eight-dimensional parameter space including massive neutrinos and a variable equation of state of dark energy. We construct trial emulators using two surrogate models (the linear powermore » spectrum and an approximate halo mass function). The new sampling method allows us to build precision emulators from just 26 cosmological models and to systematically increase the emulator accuracy by adding new sets of simulations in a prescribed way. Emulator fidelity can now be continuously improved as new observational data sets become available and higher accuracy is required. Finally, using one ΛCDM cosmology as an example, we study the demands imposed on a simulation campaign to achieve the required statistics and accuracy when building emulators for investigations of dark energy.« less

Emulating Host-Microbiome Ecosystem of Human Gastrointestinal Tract in Vitro.

PubMed

Park, Gun-Seok; Park, Min Hee; Shin, Woojung; Zhao, Connie; Sheikh, Sameer; Oh, So Jung; Kim, Hyun Jung

2017-06-01

The human gut microbiome performs prodigious physiological functions such as production of microbial metabolites, modulation of nutrient digestion and drug metabolism, control of immune system, and prevention of infection. Paradoxically, gut microbiome can also negatively orchestrate the host responses in diseases or chronic disorders, suggesting that the regulated and balanced host-gut microbiome crosstalk is a salient prerequisite in gastrointestinal physiology. To understand the pathophysiological role of host-microbiome crosstalk, it is critical to recreate in vivo relevant models of the host-gut microbiome ecosystem in human. However, controlling the multi-species microbial communities and their uncontrolled growth has remained a notable technical challenge. Furthermore, conventional two-dimensional (2D) or 3D culture systems do not recapitulate multicellular microarchitectures, mechanical dynamics, and tissue-specific functions. Here, we review recent advances and current pitfalls of in vitro and ex vivo models that display human GI functions. We also discuss how the disruptive technologies such as 3D organoids or a human organ-on-a-chip microphysiological system can contribute to better emulate host-gut microbiome crosstalks in health and disease. Finally, the medical and pharmaceutical significance of the gut microbiome-based personalized interventions is underlined as a future perspective.

Yielding physically-interpretable emulators - A Sparse PCA approach

NASA Astrophysics Data System (ADS)

Galelli, S.; Alsahaf, A.; Giuliani, M.; Castelletti, A.

2015-12-01

Projection-based techniques, such as Principal Orthogonal Decomposition (POD), are a common approach to surrogate high-fidelity process-based models by lower order dynamic emulators. With POD, the dimensionality reduction is achieved by using observations, or 'snapshots' - generated with the high-fidelity model -, to project the entire set of input and state variables of this model onto a smaller set of basis functions that account for most of the variability in the data. While reduction efficiency and variance control of POD techniques are usually very high, the resulting emulators are structurally highly complex and can hardly be given a physically meaningful interpretation as each basis is a projection of the entire set of inputs and states. In this work, we propose a novel approach based on Sparse Principal Component Analysis (SPCA) that combines the several assets of POD methods with the potential for ex-post interpretation of the emulator structure. SPCA reduces the number of non-zero coefficients in the basis functions by identifying a sparse matrix of coefficients. While the resulting set of basis functions may retain less variance of the snapshots, the presence of a few non-zero coefficients assists in the interpretation of the underlying physical processes. The SPCA approach is tested on the reduction of a 1D hydro-ecological model (DYRESM-CAEDYM) used to describe the main ecological and hydrodynamic processes in Tono Dam, Japan. An experimental comparison against a standard POD approach shows that SPCA achieves the same accuracy in emulating a given output variable - for the same level of dimensionality reduction - while yielding better insights of the main process dynamics.

Two-Dimensional Versus Three-Dimensional Conceptualization in Astronomy Education

NASA Astrophysics Data System (ADS)

Reynolds, Michael David

Numerous science conceptual issues are naturally three-dimensional. Classroom presentations are often two -dimensional or at best multidimensional. Several astronomy topics are of this nature, e. g. mechanics of the phases of the moon. Textbooks present this three-dimensional topic in two-dimensions; such is often the case in the classroom. This study was conducted to examine conceptions exhibited by pairs of like-sex 11th grade standard physics students as they modeled the lunar phases. Student pairs, 13 male and 13 female, were randomly selected and assigned. Pairing comes closer to classroom emulation, minimizes needs for direct probes, and pair discussion is more likely to display variety and depth. Four hypotheses were addressed: (1) Participants who model three-dimensionally will more likely achieve a higher explanation score. (2) Students who experienced more earth or physical science exposure will more likely model three-dimensionally. (3) Pairs that exhibit a strong science or mathematics preference will more likely model three-dimensionally. (4) Males will model in three dimensions more than females. Students provided background information, including science course exposure and subject preference. Each pair laid out a 16-card set representing two complete lunar phase changes. The pair was asked to explain why the phases occur. Materials were provided for use, including disks, spheres, paper and pen, and flashlight. Activities were videotaped for later evaluation. Statistics of choice was a correlation determination between course preference and model type and ANOVA for the other hypotheses. It was determined that pairs who modeled three -dimensionally achieved a higher score on their phases mechanics explanation at p <.05 level. Pairs with earth science or physical science exposure, those who prefer science or mathematics, and male participants were not more likely to model three-dimensionally. Possible reasons for lack of significance was small sample size and in the case of course preferences, small differences in course preference means. Based on this study, instructors should be aware of dimensionality and student misconceptions. Whenever possible, three-dimensional concepts should be modeled as such. Authors and publishers should consider modeling suggestions and three-dimensional ancillaries.

Multi and mixed 3D-printing of graphene-hydroxyapatite hybrid materials for complex tissue engineering.

PubMed

Jakus, Adam E; Shah, Ramille N

2017-01-01

With the emergence of three-dimensional (3D)-printing (3DP) as a vital tool in tissue engineering and medicine, there is an ever growing need to develop new biomaterials that can be 3D-printed and also emulate the compositional, structural, and functional complexities of human tissues and organs. In this work, we probe the 3D-printable biomaterials spectrum by combining two recently established functional 3D-printable particle-laden biomaterial inks: one that contains hydroxyapatite microspheres (hyperelastic bone, HB) and another that contains graphene nanoflakes (3D-graphene, 3DG). We demonstrate that not only can these distinct, osteogenic, and neurogenic inks be co-3D-printed to create complex, multimaterial constructs, but that composite inks of HB and 3DG can also be synthesized. Specifically, the printability, microstructural, mechanical, electrical, and biological properties of a hybrid material comprised of 1:1 HA:graphene by volume is investigated. The resulting HB-3DG hybrid exhibits mixed characteristics of the two distinct systems, while maintaining 3D-printability, electrical conductivity, and flexibility. In vitro assessment of HB-3DG using mesenchymal stem cells demonstrates the hybrid material supports cell viability and proliferation, as well as significantly upregulates both osteogenic and neurogenic gene expression over 14 days. This work ultimately demonstrates a significant step forward towards being able to 3D-print graded, multicompositional, and multifunctional constructs from hybrid inks for complex composite tissue engineering. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 274-283, 2017. © 2016 Wiley Periodicals, Inc.

Ultracold few fermionic atoms in needle-shaped double wells: spin chains and resonating spin clusters from microscopic Hamiltonians emulated via antiferromagnetic Heisenberg and t-J models

NASA Astrophysics Data System (ADS)

Yannouleas, Constantine; Brandt, Benedikt B.; Landman, Uzi

2016-07-01

Advances with trapped ultracold atoms intensified interest in simulating complex physical phenomena, including quantum magnetism and transitions from itinerant to non-itinerant behavior. Here we show formation of antiferromagnetic ground states of few ultracold fermionic atoms in single and double well (DW) traps, through microscopic Hamiltonian exact diagonalization for two DW arrangements: (i) two linearly oriented one-dimensional, 1D, wells, and (ii) two coupled parallel wells, forming a trap of two-dimensional, 2D, nature. The spectra and spin-resolved conditional probabilities reveal for both cases, under strong repulsion, atomic spatial localization at extemporaneously created sites, forming quantum molecular magnetic structures with non-itinerant character. These findings usher future theoretical and experimental explorations into the highly correlated behavior of ultracold strongly repelling fermionic atoms in higher dimensions, beyond the fermionization physics that is strictly applicable only in the 1D case. The results for four atoms are well described with finite Heisenberg spin-chain and cluster models. The numerical simulations of three fermionic atoms in symmetric DWs reveal the emergent appearance of coupled resonating 2D Heisenberg clusters, whose emulation requires the use of a t-J-like model, akin to that used in investigations of high T c superconductivity. The highly entangled states discovered in the microscopic and model calculations of controllably detuned, asymmetric, DWs suggest three-cold-atom DW quantum computing qubits.

Cinematic camera emulation using two-dimensional color transforms

NASA Astrophysics Data System (ADS)

McElvain, Jon S.; Gish, Walter

2015-02-01

For cinematic and episodic productions, on-set look management is an important component of the creative process, and involves iterative adjustments of the set, actors, lighting and camera configuration. Instead of using the professional motion capture device to establish a particular look, the use of a smaller form factor DSLR is considered for this purpose due to its increased agility. Because the spectral response characteristics will be different between the two camera systems, a camera emulation transform is needed to approximate the behavior of the destination camera. Recently, twodimensional transforms have been shown to provide high-accuracy conversion of raw camera signals to a defined colorimetric state. In this study, the same formalism is used for camera emulation, whereby a Canon 5D Mark III DSLR is used to approximate the behavior a Red Epic cinematic camera. The spectral response characteristics for both cameras were measured and used to build 2D as well as 3x3 matrix emulation transforms. When tested on multispectral image databases, the 2D emulation transforms outperform their matrix counterparts, particularly for images containing highly chromatic content.

Weyl solitons in three-dimensional optical lattices

NASA Astrophysics Data System (ADS)

Shang, Ce; Zheng, Yuanlin; Malomed, Boris A.

2018-04-01

Weyl fermions are massless chiral quasiparticles existing in materials known as Weyl semimetals. Topological surface states, associated with the unusual electronic structure in the Weyl semimetals, have been recently demonstrated in linear systems. Ultracold atomic gases, featuring laser-assisted tunneling in three-dimensional optical lattices, can be used for the emulation of Weyl semimetals, including nonlinear effects induced by the collisional nonlinearity of atomic Bose-Einstein condensates. We demonstrate that this setting gives rise to topological states in the form of Weyl solitons at the surface of the underlying optical lattice. These nonlinear modes, being exceptionally robust, bifurcate from linear states for a given quasimomentum. The Weyl solitons may be used to design an efficient control scheme for topologically protected unidirectional propagation of excitations in light-matter-interaction physics. After the recently introduced Majorana and Dirac solitons, the Weyl solitons proposed in this work constitute the third (and the last) member in this family of topological solitons.

Rationalisation and Validation of an Acrylamide-Free Procedure in Three-Dimensional Histological Imaging

PubMed Central

Lai, Hei Ming; Liu, Alan King Lun; Ng, Wai-Lung; DeFelice, John; Lee, Wing Sang; Li, Heng; Li, Wen; Ng, Ho Man; Chang, Raymond Chuen-Chung; Lin, Bin; Wu, Wutian; Gentleman, Steve M.

2016-01-01

Three-dimensional visualization of intact tissues is now being achieved by turning tissues transparent. CLARITY is a unique tissue clearing technique, which features the use of detergents to remove lipids from fixed tissues to achieve optical transparency. To preserve tissue integrity, an acrylamide-based hydrogel has been proposed to embed the tissue. In this study, we examined the rationale behind the use of acrylamide in CLARITY, and presented evidence to suggest that the omission of acrylamide-hydrogel embedding in CLARITY does not alter the preservation of tissue morphology and molecular information in fixed tissues. We therefore propose a novel and simplified workflow for formaldehyde-fixed tissue clearing, which will facilitate the laboratory implementation of this technique. Furthermore, we have investigated the basic tissue clearing process in detail and have highlighted some areas for targeted improvement of technologies essential for the emerging subject of three-dimensional histology. PMID:27359336

Three-dimensional cell to tissue development process

NASA Technical Reports Server (NTRS)

Goodwin, Thomas J. (Inventor); Parker, Clayton R. (Inventor)

2008-01-01

An improved three-dimensional cell to tissue development process using a specific time varying electromagnetic force, pulsed, square wave, with minimum fluid shear stress, freedom for 3-dimensional spatial orientation of the suspended particles and localization of particles with differing or similar sedimentation properties in a similar spatial region.

Three-dimensional Cell Culture Devices for Cancer Migration and Drug Testing

NASA Astrophysics Data System (ADS)

Ma, Liang

Porous polymeric materials are widely used to mimic the extracellular matrix (ECM) environment for applications such as 3D cell culturing and tissue engineering. A series of comparative experiments on 3D cell cultures both in PLA porous scaffolds and alginate gels were conducted to create an in vitro tumor model. A novel 3D cell culture device based on porous polymeric material was developed to study cancer migration. Significant cell migration was observed through the porous channel within 1--2 weeks induced by 20% fetal bovine serum (FBS). A three-dimensional micro-scale perfusion-based two-chamber (3D-muPTC) tissue model system was developed to test the cytotoxicity of anticancer drugs by emulating liver metabolism effects in vitro. Hepatoma cells and glioblastoma multiforme (GBM) cancer cells were cultured in porous polymeric scaffolds in two separate chambers, representing the liver and tumor, respectively. The cytotoxic effect of temozolomide (TMZ) was first tested using this system. It was found that the GBM cells showed a much higher viability under the TMZ treatment with liver cells in the system, suggesting that the drug metabolism in liver is affecting the efficacy of the drug. The favorable metabolism effect of cytochrome P450 (CYP) was tested using a prodrug ifosfamide (IFO). Without the liver cells, IFO showed only slight toxicity to GBM cells. Moreover, it was shown that different expression levels of CYP 3A4, a major drug metabolizing enzyme, in liver cells caused significantly different levels of GBM cell viability. Simulation of the flow characteristics in the 3D-muPTC system was conducted using the finite-element analysis approach. The shear stress was predicted in the porous scaffolds under different flow rate conditions. The predicted shear stress effects agreed well with an experimental cell viability study. A low cost organic solvent free approach to fabricating tissue engineering scaffolds was developed by combining the twin-screw extrusion and particulate leaching. High porosity and interconnected porous PLA scaffolds with the pore size 50 to 200μm were fabricated with this immiscible polymer blending method. This combined extrusion and particulate leaching method provides a new technique to fabricate tissue engineering scaffolds that can be used in the 3D-muPTC device.

Media Compositions for Three Dimensional Mammalian Tissue Growth Under Microgravity Culture Conditions

NASA Technical Reports Server (NTRS)

Goodwin, Thomas J. (Inventor)

1998-01-01

Normal mammalian tissue and the culturing process has been developed for the three groups of organ, structural and blood tissue. The cells are grown in vitro under microgravity culture conditions and form three dimensional cells aggregates with normal cell function. The microgravity culture conditions may be microgravity or simulated microgravity created in a horizontal rotating wall culture vessel.

Media Compositions for Three-Dimensional Mammalian Tissue Growth under Microgravity Culture Conditions

NASA Technical Reports Server (NTRS)

Goodwin, Thomas J. (Inventor)

1998-01-01

Normal mammalian tissue and the culturing process has been developed for the three groups of organ, structural and blood tissue.The cells are grown in vitro under microgravity culture conditions and form three dimensional cells aggregates with normal cell function. The microgravity culture conditions may be microgravity or simulated microgravity created in a horizontal rotating wall culture vessel.

Three-Dimensional Co-Culture Process

NASA Technical Reports Server (NTRS)

Goodwin, Thomas J. (Inventor); Wolf, David A. (Inventor)

1997-01-01

By the process of the present invention a variety of cells may be co-cultured to produce tissue which has 3-dimensionality and had some of the characteristics of in vivo tissue. The process provides enhanced 3-dimensional tissue which creates a multicellular organoid differentiation model.

Three-dimensional organization of dermal fibroblasts by macromass culture.

PubMed

Deshpande, Manisha

2008-01-01

The three-dimensional organization of cells by high-cell-seeding-density culture, termed 'macromass culture', is described. By macromass culture, dermal fibroblasts can be made to organize themselves into a unified three-dimensional form without the aid of a scaffold, and macroscopic constructs, named macromasses, can be made wholly from cells. The sole factor causing three-dimensional organization is culture of cells at high cell seeding density per unit area. No scaffold or extraneous matrix is used for the generation of macromasses; they are of completely cellular origin. No other agents or external influences such as tissue-inducing chemicals, tissue-inducing growth factors, substratum with special properties, rotational culture, centrifugation etc. are employed for macromass formation, and all seeded cells become part of the cohesive construct. These three-dimensional constructs have the potential for use as in vitro tissue analogues, and a possible application for in vitro cytotoxicity testing is demonstrated.

Hydrofocusing Bioreactor for Three-Dimensional Cell Culture

NASA Technical Reports Server (NTRS)

Gonda, Steve R.; Spaulding, Glenn F.; Tsao, Yow-Min D.; Flechsig, Scott; Jones, Leslie; Soehnge, Holly

2003-01-01

The hydrodynamic focusing bioreactor (HFB) is a bioreactor system designed for three-dimensional cell culture and tissue-engineering investigations on orbiting spacecraft and in laboratories on Earth. The HFB offers a unique hydrofocusing capability that enables the creation of a low-shear culture environment simultaneously with the "herding" of suspended cells, tissue assemblies, and air bubbles. Under development for use in the Biotechnology Facility on the International Space Station, the HFB has successfully grown large three-dimensional, tissuelike assemblies from anchorage-dependent cells and grown suspension hybridoma cells to high densities. The HFB, based on the principle of hydrodynamic focusing, provides the capability to control the movement of air bubbles and removes them from the bioreactor without degrading the low-shear culture environment or the suspended three-dimensional tissue assemblies. The HFB also provides unparalleled control over the locations of cells and tissues within its bioreactor vessel during operation and sampling.

Naturally Engineered Maturation of Cardiomyocytes

PubMed Central

Scuderi, Gaetano J.; Butcher, Jonathan

2017-01-01

Ischemic heart disease remains one of the most prominent causes of mortalities worldwide with heart transplantation being the gold-standard treatment option. However, due to the major limitations associated with heart transplants, such as an inadequate supply and heart rejection, there remains a significant clinical need for a viable cardiac regenerative therapy to restore native myocardial function. Over the course of the previous several decades, researchers have made prominent advances in the field of cardiac regeneration with the creation of in vitro human pluripotent stem cell-derived cardiomyocyte tissue engineered constructs. However, these engineered constructs exhibit a functionally immature, disorganized, fetal-like phenotype that is not equivalent physiologically to native adult cardiac tissue. Due to this major limitation, many recent studies have investigated approaches to improve pluripotent stem cell-derived cardiomyocyte maturation to close this large functionality gap between engineered and native cardiac tissue. This review integrates the natural developmental mechanisms of cardiomyocyte structural and functional maturation. The variety of ways researchers have attempted to improve cardiomyocyte maturation in vitro by mimicking natural development, known as natural engineering, is readily discussed. The main focus of this review involves the synergistic role of electrical and mechanical stimulation, extracellular matrix interactions, and non-cardiomyocyte interactions in facilitating cardiomyocyte maturation. Overall, even with these current natural engineering approaches, pluripotent stem cell-derived cardiomyocytes within three-dimensional engineered heart tissue still remain mostly within the early to late fetal stages of cardiomyocyte maturity. Therefore, although the end goal is to achieve adult phenotypic maturity, more emphasis must be placed on elucidating how the in vivo fetal microenvironment drives cardiomyocyte maturation. This information can then be utilized to develop natural engineering approaches that can emulate this fetal microenvironment and thus make prominent progress in pluripotent stem cell-derived maturity toward a more clinically relevant model for cardiac regeneration. PMID:28529939

Multi-cellular, three-dimensional living mammalian tissue

NASA Technical Reports Server (NTRS)

Goodwin, Thomas J. (Inventor); Wolf, David A. (Inventor)

1994-01-01

The present invention relates to a multicellular, three-dimensional, living mammalian tissue. The tissue is produced by a co-culture process wherein two distinct types of mammalian cells are co-cultured in a rotating bioreactor which is completely filled with culture media and cell attachment substrates. As the size of the tissue assemblies formed on the attachment substrates changes, the rotation of the bioreactor is adjusted accordingly.

Uncertainty in modeled upper ocean heat content change

NASA Astrophysics Data System (ADS)

Tokmakian, Robin; Challenor, Peter

2014-02-01

This paper examines the uncertainty in the change in the heat content in the ocean component of a general circulation model. We describe the design and implementation of our statistical methodology. Using an ensemble of model runs and an emulator, we produce an estimate of the full probability distribution function (PDF) for the change in upper ocean heat in an Atmosphere/Ocean General Circulation Model, the Community Climate System Model v. 3, across a multi-dimensional input space. We show how the emulator of the GCM's heat content change and hence, the PDF, can be validated and how implausible outcomes from the emulator can be identified when compared to observational estimates of the metric. In addition, the paper describes how the emulator outcomes and related uncertainty information might inform estimates of the same metric from a multi-model Coupled Model Intercomparison Project phase 3 ensemble. We illustrate how to (1) construct an ensemble based on experiment design methods, (2) construct and evaluate an emulator for a particular metric of a complex model, (3) validate the emulator using observational estimates and explore the input space with respect to implausible outcomes and (4) contribute to the understanding of uncertainties within a multi-model ensemble. Finally, we estimate the most likely value for heat content change and its uncertainty for the model, with respect to both observations and the uncertainty in the value for the input parameters.

Three-dimensional epithelial tissues generated from human embryonic stem cells.

PubMed

Hewitt, Kyle J; Shamis, Yulia; Carlson, Mark W; Aberdam, Edith; Aberdam, Daniel; Garlick, Jonathan A

2009-11-01

The use of pluripotent human embryonic stem (hES) cells for tissue engineering may provide advantages over traditional sources of progenitor cells because of their ability to give rise to multiple cell types and their unlimited expansion potential. We derived cell populations with properties of ectodermal and mesenchymal cells in two-dimensional culture and incorporated these divergent cell populations into three-dimensional (3D) epithelial tissues. When grown in specific media and substrate conditions, two-dimensional cultures were enriched in cells (EDK1) with mesenchymal morphology and surface markers. Cells with a distinct epithelial morphology (HDE1) that expressed cytokeratin 12 and beta-catenin at cell junctions became the predominant cell type when EDK1 were grown on surfaces enriched in keratinocyte-derived extracellular matrix proteins. When these cells were incorporated into the stromal and epithelial tissue compartments of 3D tissues, they generated multilayer epithelia similar to those generated with foreskin-derived epithelium and fibroblasts. Three-dimensional tissues demonstrated stromal cells with morphologic features of mature fibroblasts, type IV collagen deposition in the basement membrane, and a stratified epithelium that expressed cytokeratin 12. By deriving two distinct cell lineages from a common hES cell source to fabricate complex tissues, it is possible to explore environmental cues that will direct hES-derived cells toward optimal tissue form and function.

Method for Producing Non-Neoplastic, Three Dimensional, Mammalian Tissue and Cell Aggregates Under Microgravity Culture Conditions and the Products Produced Therefrom

NASA Technical Reports Server (NTRS)

Goodwin, Thomas J. (Inventor); Wolf, David A. (Inventor); Spaulding, Glenn F. (Inventor); Prewett, Tracey L. (Inventor)

1996-01-01

Normal mammalian tissue and the culturing process has been developed for the three groups of organ, structural, and blood tissue. The cells are grown in vitro under microgravity culture conditions and form three dimensional cells aggregates with normal cell function. The microgravity culture conditions may be microgravity or simulated microgravity created in a horizontal rotating wall culture vessel.

Fabrication of three-dimensional scaffolds using precision extrusion deposition with an assisted cooling device.

PubMed

Hamid, Q; Snyder, J; Wang, C; Timmer, M; Hammer, J; Guceri, S; Sun, W

2011-09-01

In the field of biofabrication, tissue engineering and regenerative medicine, there are many methodologies to fabricate a building block (scaffold) which is unique to the target tissue or organ that facilitates cell growth, attachment, proliferation and/or differentiation. Currently, there are many techniques that fabricate three-dimensional scaffolds; however, there are advantages, limitations and specific tissue focuses of each fabrication technique. The focus of this initiative is to utilize an existing technique and expand the library of biomaterials which can be utilized to fabricate three-dimensional scaffolds rather than focusing on a new fabrication technique. An expanded library of biomaterials will enable the precision extrusion deposition (PED) device to construct three-dimensional scaffolds with enhanced biological, chemical and mechanical cues that will benefit tissue generation. Computer-aided motion and extrusion drive the PED to precisely fabricate micro-scaled scaffolds with biologically inspired, porosity, interconnectivity and internal and external architectures. The high printing resolution, precision and controllability of the PED allow for closer mimicry of tissues and organs. The PED expands its library of biopolymers by introducing an assisting cooling (AC) device which increases the working extrusion temperature from 120 to 250 °C. This paper investigates the PED with the integrated AC's capabilities to fabricate three-dimensional scaffolds that support cell growth, attachment and proliferation. Studies carried out in this paper utilized a biopolymer whose melting point is established to be 200 °C. This polymer was selected to illustrate the newly developed device's ability to fabricate three-dimensional scaffolds from a new library of biopolymers. Three-dimensional scaffolds fabricated with the integrated AC device should illustrate structural integrity and ability to support cell attachment and proliferation.

Fast neural network surrogates for very high dimensional physics-based models in computational oceanography.

PubMed

van der Merwe, Rudolph; Leen, Todd K; Lu, Zhengdong; Frolov, Sergey; Baptista, Antonio M

2007-05-01

We present neural network surrogates that provide extremely fast and accurate emulation of a large-scale circulation model for the coupled Columbia River, its estuary and near ocean regions. The circulation model has O(10(7)) degrees of freedom, is highly nonlinear and is driven by ocean, atmospheric and river influences at its boundaries. The surrogates provide accurate emulation of the full circulation code and run over 1000 times faster. Such fast dynamic surrogates will enable significant advances in ensemble forecasts in oceanography and weather.

Manufacture and characterization of breast tissue phantoms for emulating benign lesions

NASA Astrophysics Data System (ADS)

Villamarín, J. A.; Rojas, M. A.; Potosi, O. M.; Narváez-Semanate, J. L.; Gaviria, C.

2017-11-01

Phantoms elaboration has turned a very important field of study during the last decades due to its applications in medicine. These objects are capable of emulating or mimicking acoustically biological tissues in which parameters like speed of sound (SOS) and attenuation are successfully attained. However, these materials are expensive depending on their characteristics (USD 460.00 - 6000.00) and is difficult to have precise measurements because of their composition. This paper presents the elaboration and characterization of low cost ( USD $25.00) breast phantoms which emulate histological normality and pathological conditions in order to support algorithm calibration procedures in imaging diagnosis. Quantitative ultrasound (QUS) was applied to estimate SOS and attenuation values for breast tissue (background) and benign lesions (fibroadenoma and cysts). Results showed values of the SOS and attenuation for the background between 1410 - 1450 m/s and 0.40 - 0.55 dB/cm at 1 MHz sampling frequency, respectively. On the other hand, the SOS obtained for the lesions ranges from 1350 to 1700 m/s and attenuation values between 0.50 - 1.80 dB/cm at 1 MHz. Finally, the fabricated phantoms allowed for obtaining ultrasonograms comparable with real ones whose acoustic parameters are in agree with those reported in the literature.

Characterization and Clinical Implication of Th1/Th2/Th17 Cytokines Produced from Three-Dimensionally Cultured Tumor Tissues Resected from Breast Cancer Patients

PubMed Central

Kiyomi, Anna; Makita, Masujiro; Ozeki, Tomoko; Li, Na; Satomura, Aiko; Tanaka, Sachiko; Onda, Kenji; Sugiyama, Kentaro; Iwase, Takuji; Hirano, Toshihiko

2015-01-01

OBJECTIVES: Several cytokines secreted from breast cancer tissues are suggested to be related to disease prognosis. We examined Th1/Th2/Th17 cytokines produced from three-dimensionally cultured breast cancer tissues and related them with patient clinical profiles. METHODS: 21 tumor tissues and 9 normal tissues surgically resected from breast cancer patients were cultured in thermoreversible gelatin polymer–containing medium. Tissue growth and Th1/Th2/Th17 cytokine concentrations in the culture medium were analyzed and were related with hormone receptor expressions and patient clinical profiles. RESULTS: IL-6 and IL-10 were expressed highly in culture medium of both cancer and normal tissues. However, IFN-γ, TNF-α, IL-2, and IL-17A were not detected in the supernatant of the three-dimensionally cultured normal mammary gland and are seemed to be specific to breast cancer tissues. The growth abilities of hormone receptor–negative cancer tissues were significantly higher than those of receptor-positive tissues (P = 0.0383). Cancer tissues of stage ≥ IIB patients expressed significantly higher TNF-α levels as compared with those of patients with stage < IIB (P = 0.0096). CONCLUSIONS: The tumor tissues resected from breast cancer patients can grow in the three-dimensional thermoreversible gelatin polymer culture system and produce Th1/Th2/Th17 cytokines. Hormone receptor–positive cancer tissues showed less growth ability. TNF-α is suggested to be a biomarker for the cancer stage. PMID:26310378

Three-Dimensional Normal Human Neural Progenitor Tissue-Like Assemblies: A Model for Persistent Varicell-Zoster Virus Infection and Platform to Study Viral Infectivity and Oxidative Stress and Damage

NASA Technical Reports Server (NTRS)

Goodwin, T. J.; McCarthy, M.; Osterrieder, N.; Cohrs, R. J.; Kaufer, B. B.

2014-01-01

The environment of space results in a multitude of challenges to the human physiology that present barriers to extended habitation and exploration. Over 40 years of investigation to define countermeasures to address space flight adaptation has left gaps in our knowledge regarding mitigation strategies partly due to the lack of investigative tools, monitoring strategies, and real time diagnostics to understand the central causative agent(s) responsible for physiologic adaptation and maintaining homeostasis. Spaceflight-adaptation syndrome is the combination of space environmental conditions and the synergistic reaction of the human physiology. Our work addresses the role of oxidative stress and damage (OSaD) as a negative and contributing Risk Factor (RF) in the following areas of combined spaceflight related dysregulation: i) radiation induced cellular damage [1], [2] ii) immune impacts and the inflammatory response [3], [4] and iii) varicella zoster virus (VZV) reactivation [5]. Varicella-zoster (VZV)/Chicken Pox virus is a neurotropic human alphaherpesvirus resulting in varicella upon primary infection, suppressed by the immune system becomes latent in ganglionic neurons, and reactivates under stress events to re-express in zoster and possibly shingles. Our laboratory has developed a complex threedimensional (3D) normal human neural tissue model that emulates several characteristics of the human trigeminal ganglia (TG) and allows the study of combinatorial experimentation which addresses, simultaneously, OSaD associated with Spaceflight adaptation and habitation [6].

Evaluation of Electromechanical Systems Dynamically Emulating a Candidate Hydrokinetic Turbine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cavagnaro, Robert J.; Neely, Jason C.; Fay, Franois-Xavier

The use of controllable motor-generator sets to emulate the dynamics of a hydrokinetic turbine is evaluated as an alternative to field testing a prototype. The emulator control dynamic equations are presented, methods for scaling turbine parameters are examined, and experimental results are presented from three electromechanical emulation machines (EEMs) programmed to emulate the same vertical-axis fixed-pitch turbine. Although hardware platforms and control implementations varied, results show that each EEM is successful in emulating the turbine model, thus demonstrating the general feasibility of the approach. However, performance of motor control under torque command, current command or speed command differed. In onemore » of the EEMs evaluated, the power take off controller tracks the maximum power-point of the turbine in response to turbulence. Utilizing realistic inflow conditions and control laws, the emulator dynamic speed response is shown to agree well at low frequencies with numerical simulation but to deviate at high frequencies.« less

Evaluation of Electromechanical Systems Dynamically Emulating a Candidate Hydrokinetic Turbine

DOE PAGES

Cavagnaro, Robert J.; Neely, Jason C.; Fay, Franois-Xavier; ...

2016-11-06

The use of controllable motor-generator sets to emulate the dynamics of a hydrokinetic turbine is evaluated as an alternative to field testing a prototype. The emulator control dynamic equations are presented, methods for scaling turbine parameters are examined, and experimental results are presented from three electromechanical emulation machines (EEMs) programmed to emulate the same vertical-axis fixed-pitch turbine. Although hardware platforms and control implementations varied, results show that each EEM is successful in emulating the turbine model, thus demonstrating the general feasibility of the approach. However, performance of motor control under torque command, current command or speed command differed. In onemore » of the EEMs evaluated, the power take off controller tracks the maximum power-point of the turbine in response to turbulence. Utilizing realistic inflow conditions and control laws, the emulator dynamic speed response is shown to agree well at low frequencies with numerical simulation but to deviate at high frequencies.« less

MRI-based morphological modeling, synthesis and characterization of cardiac tissue-mimicking materials.

PubMed

Kossivas, Fotis; Angeli, S; Kafouris, D; Patrickios, C S; Tzagarakis, V; Constantinides, C

2012-06-01

This study uses standard synthetic methodologies to produce tissue-mimicking materials that match the morphology and emulate the in vivo murine and human cardiac mechanical and imaging characteristics, with dynamic mechanical analysis, atomic force microscopy (AFM), scanning electron microscopy (SEM) and magnetic resonance imaging. In accordance with such aims, poly(glycerol sebacate) (PGS) elastomeric materials were synthesized (at two different glycerol (G)-sebacic (S) acid molar ratios; the first was synthesized using a G:S molar ratio of 2:2, while the second from a 2:5 G:S molar ratio, resulting in PGS2:2 and PGS2:5 elastomers, respectively). Unlike the synthesized PGS2:2 elastomers, the PGS2:5 materials were characterized by an overall mechanical instability in their loading behavior under the three successive loading conditions tested. An oscillatory response in the mechanical properties of the synthesized elastomers was observed throughout the loading cycles, with measured increased storage modulus values at the first loading cycle, stabilizing to lower values at subsequent cycles. These elastomers were characterized at 4 °C and were found to have storage modulus values of 850 and 1430 kPa at the third loading cycle, respectively, in agreement with previously reported values of the rat and human myocardium. SEM of surface topology indicated minor degradation of synthesized materials at 10 and 20 d post-immersion in the PBS buffer solution, with a noted cluster formation on the PGS2:5 elastomers. AFM nanoindentation experiments were also conducted for the measurement of the Young modulus of the sample surface (no bulk contribution). Correspondingly, the PGS2:2 elastomer indicated significantly decreased surface Young's modulus values 20 d post-PBS immersion, compared to dry conditions (Young's modulus = 1160 ± 290 kPa (dry) and 200 ± 120 kPa (20 d)). In addition to the two-dimensional (2D) elastomers, an integrative platform for accurate construction of three-dimensional tissue-mimicking models of cardiac anatomy from 2D MR images using rapid prototyping manufacturing processes was developed. For synthesized elastomers, doping strategies with two different concentrations of the MRI contrast agent Dotarem allowed independent and concurrent control of the imaging characteristics (contrast and relaxivity) during the synthetic process for increased contrast agent absorption, with tremendous potential for non-destructive in vivo use and applications to cardiovascular and cerebrovascular diseases.

Formation of three-dimensional fetal myocardial tissue cultures from rat for long-term cultivation.

PubMed

Just, Lothar; Kürsten, Anne; Borth-Bruhns, Thomas; Lindenmaier, Werner; Rohde, Manfred; Dittmar, Kurt; Bader, Augustinus

2006-08-01

Three-dimensional cardiomyocyte cultures offer new possibilities for the analysis of cardiac cell differentiation, spatial cellular arrangement, and time-specific gene expression in a tissue-like environment. We present a new method for generating homogenous and robust cardiomyocyte tissue cultures with good long-term viability. Ventricular heart cells prepared from fetal rats at embryonic day 13 were cultured in a scaffold-free two-step process. To optimize the cell culture model, several digestion protocols and culture conditions were tested. After digestion of fetal cardiac ventricles, the resultant cell suspension of isolated cardiocytes was shaken to initialize cell aggregate formation. In the second step, these three-dimensional cell aggregates were transferred onto a microporous membrane to allow further microstructure formation. Autonomously beating cultures possessed more than 25 cell layers and a homogenous distribution of cardiomyocytes without central necrosis after 8 weeks in vitro. The cardiomyocytes showed contractile elements, desmosomes, and gap junctions analyzed by immunohistochemistry and electron microscopy. The beat frequency could be modulated by adrenergic agonist and antagonist. Adenoviral green fluorescent protein transfer into cardiomyocytes was possible and highly effective. This three-dimensional tissue model proved to be useful for studying cell-cell interactions and cell differentiation processes in a three-dimensional cell arrangement.

Viability of Bioprinted Cellular Constructs Using a Three Dispenser Cartesian Printer.

PubMed

Dennis, Sarah Grace; Trusk, Thomas; Richards, Dylan; Jia, Jia; Tan, Yu; Mei, Ying; Fann, Stephen; Markwald, Roger; Yost, Michael

2015-09-22

Tissue engineering has centralized its focus on the construction of replacements for non-functional or damaged tissue. The utilization of three-dimensional bioprinting in tissue engineering has generated new methods for the printing of cells and matrix to fabricate biomimetic tissue constructs. The solid freeform fabrication (SFF) method developed for three-dimensional bioprinting uses an additive manufacturing approach by depositing droplets of cells and hydrogels in a layer-by-layer fashion. Bioprinting fabrication is dependent on the specific placement of biological materials into three-dimensional architectures, and the printed constructs should closely mimic the complex organization of cells and extracellular matrices in native tissue. This paper highlights the use of the Palmetto Printer, a Cartesian bioprinter, as well as the process of producing spatially organized, viable constructs while simultaneously allowing control of environmental factors. This methodology utilizes computer-aided design and computer-aided manufacturing to produce these specific and complex geometries. Finally, this approach allows for the reproducible production of fabricated constructs optimized by controllable printing parameters.

Idols as Sunshine or Road Signs: Comparing Absorption-Addiction Idolatry With Identification-Emulation Idolatry.

PubMed

Cheung, Chau-Kiu; Yue, Xiao Dong

2018-01-01

This study seeks to contrast absorption-addiction idolatry and identification-emulation idolatry. Whereas absorption-addiction idolatry progresses from entertainment/socializing to personalizing and obsession about the idol, identification-emulation idolatry unfolds in terms of identification, attachment, romantization, idealization, and consumption about the idol or his or her derivatives. Based on a sample of 1310 secondary school and university students in Hong Kong, the study verified the original factor model composed of five first-order identification-emulation idolatry and three first-order absorption-addiction idolatry factors, with the latter more predictable by fans' club membership.

From Three-Dimensional Cell Culture to Organs-on-Chips

PubMed Central

Huh, Dongeun; Hamilton, Geraldine A.; Ingber, Donald E.

2014-01-01

Three-dimensional (3D) cell culture models have recently garnered great attention because they often promote levels of cell differentiation and tissue organization not possible in conventional two-dimensional (2D) culture systems. Here, we review new advances in 3D culture that leverage microfabrication technologies from the microchip industry and microfluidics approaches to create cell culture microenvironments that both support tissue differentiation and recapitulate the tissue-tissue interfaces, spatiotemporal chemical gradients, and mechanical microenvironments of living organs. These ‘organs-on-chips’ permit study of human physiology in an organ-specific context, enable development of novel in vitro disease models, and could potentially serve as replacements for animals used in drug development and toxin testing. PMID:22033488

Preparation of wholemount mouse intestine for high-resolution three-dimensional imaging using two-photon microscopy.

PubMed

Appleton, P L; Quyn, A J; Swift, S; Näthke, I

2009-05-01

Visualizing overall tissue architecture in three dimensions is fundamental for validating and integrating biochemical, cell biological and visual data from less complex systems such as cultured cells. Here, we describe a method to generate high-resolution three-dimensional image data of intact mouse gut tissue. Regions of highest interest lie between 50 and 200 mum within this tissue. The quality and usefulness of three-dimensional image data of tissue with such depth is limited owing to problems associated with scattered light, photobleaching and spherical aberration. Furthermore, the highest-quality oil-immersion lenses are designed to work at a maximum distance of

Emulating Simulations of Cosmic Dawn for 21 cm Power Spectrum Constraints on Cosmology, Reionization, and X-Ray Heating

NASA Astrophysics Data System (ADS)

Kern, Nicholas S.; Liu, Adrian; Parsons, Aaron R.; Mesinger, Andrei; Greig, Bradley

2017-10-01

Current and upcoming radio interferometric experiments are aiming to make a statistical characterization of the high-redshift 21 cm fluctuation signal spanning the hydrogen reionization and X-ray heating epochs of the universe. However, connecting 21 cm statistics to the underlying physical parameters is complicated by the theoretical challenge of modeling the relevant physics at computational speeds quick enough to enable exploration of the high-dimensional and weakly constrained parameter space. In this work, we use machine learning algorithms to build a fast emulator that can accurately mimic an expensive simulation of the 21 cm signal across a wide parameter space. We embed our emulator within a Markov Chain Monte Carlo framework in order to perform Bayesian parameter constraints over a large number of model parameters, including those that govern the Epoch of Reionization, the Epoch of X-ray Heating, and cosmology. As a worked example, we use our emulator to present an updated parameter constraint forecast for the Hydrogen Epoch of Reionization Array experiment, showing that its characterization of a fiducial 21 cm power spectrum will considerably narrow the allowed parameter space of reionization and heating parameters, and could help strengthen Planck's constraints on {σ }8. We provide both our generalized emulator code and its implementation specifically for 21 cm parameter constraints as publicly available software.

Atherosclerosis of the carotid artery: evaluation by magnetic resonance angiography.

PubMed

Wildy, K S; Yuan, C; Tsuruda, J S; Ferguson, M S; Wen, N; Subramaniam, D S; Strandness, D E

1996-01-01

Carotid artery atherosclerotic plaques (APs) can lead to brain ischemia, an event shown to correlate with both the degree of stenosis and the composition of the AP. Currently, accurate estimates of stenosis can be obtained by either x-ray angiography or three-dimensional time-of-flight (TOF) magnetic resonance angiography (MRA). Our purpose was to determine whether three-dimensional TOF MRA images could also provide information on plaque location, morphology, and composition. Seven pre-endarterectomy patients underwent three-dimensional TOF MRA. After endarterectomy, plaque histology was evaluated. Three-dimensional TOF MRA images contained sufficient soft tissue contrast to differentiate the plaques from the surrounding tissues in all cases. Estimation of plaque morphology had 80% correlation with histology. Finally, intraplaque hemorrhage and calcification were deplicted as regions of moderately high and very low intensity, respectively. These preliminary results suggest that three-dimensional TOF MRA may be useful in studying the development and progression of carotid atherosclerosis.

Mechanical stretching for tissue engineering: two-dimensional and three-dimensional constructs.

PubMed

Riehl, Brandon D; Park, Jae-Hong; Kwon, Il Keun; Lim, Jung Yul

2012-08-01

Mechanical cell stretching may be an attractive strategy for the tissue engineering of mechanically functional tissues. It has been demonstrated that cell growth and differentiation can be guided by cell stretch with minimal help from soluble factors and engineered tissues that are mechanically stretched in bioreactors may have superior organization, functionality, and strength compared with unstretched counterparts. This review explores recent studies on cell stretching in both two-dimensional (2D) and three-dimensional (3D) setups focusing on the applications of stretch stimulation as a tool for controlling cell orientation, growth, gene expression, lineage commitment, and differentiation and for achieving successful tissue engineering of mechanically functional tissues, including cardiac, muscle, vasculature, ligament, tendon, bone, and so on. Custom stretching devices and lab-specific mechanical bioreactors are described with a discussion on capabilities and limitations. While stretch mechanotransduction pathways have been examined using 2D stretch, studying such pathways in physiologically relevant 3D environments may be required to understand how cells direct tissue development under stretch. Cell stretch study using 3D milieus may also help to develop tissue-specific stretch regimens optimized with biochemical feedback, which once developed will provide optimal tissue engineering protocols.

Mechanical Stretching for Tissue Engineering: Two-Dimensional and Three-Dimensional Constructs

PubMed Central

Riehl, Brandon D.; Park, Jae-Hong; Kwon, Il Keun

2012-01-01

Mechanical cell stretching may be an attractive strategy for the tissue engineering of mechanically functional tissues. It has been demonstrated that cell growth and differentiation can be guided by cell stretch with minimal help from soluble factors and engineered tissues that are mechanically stretched in bioreactors may have superior organization, functionality, and strength compared with unstretched counterparts. This review explores recent studies on cell stretching in both two-dimensional (2D) and three-dimensional (3D) setups focusing on the applications of stretch stimulation as a tool for controlling cell orientation, growth, gene expression, lineage commitment, and differentiation and for achieving successful tissue engineering of mechanically functional tissues, including cardiac, muscle, vasculature, ligament, tendon, bone, and so on. Custom stretching devices and lab-specific mechanical bioreactors are described with a discussion on capabilities and limitations. While stretch mechanotransduction pathways have been examined using 2D stretch, studying such pathways in physiologically relevant 3D environments may be required to understand how cells direct tissue development under stretch. Cell stretch study using 3D milieus may also help to develop tissue-specific stretch regimens optimized with biochemical feedback, which once developed will provide optimal tissue engineering protocols. PMID:22335794

Role of cellular adhesions in tissue dynamics spectroscopy

NASA Astrophysics Data System (ADS)

Merrill, Daniel A.; An, Ran; Turek, John; Nolte, David

2014-02-01

Cellular adhesions play a critical role in cell behavior, and modified expression of cellular adhesion compounds has been linked to various cancers. We tested the role of cellular adhesions in drug response by studying three cellular culture models: three-dimensional tumor spheroids with well-developed cellular adhesions and extracellular matrix (ECM), dense three-dimensional cell pellets with moderate numbers of adhesions, and dilute three-dimensional cell suspensions in agarose having few adhesions. Our technique for measuring the drug response for the spheroids and cell pellets was biodynamic imaging (BDI), and for the suspensions was quasi-elastic light scattering (QELS). We tested several cytoskeletal chemotherapeutic drugs (nocodazole, cytochalasin-D, paclitaxel, and colchicine) on three cancer cell lines chosen from human colorectal adenocarcinoma (HT-29), human pancreatic carcinoma (MIA PaCa-2), and rat osteosarcoma (UMR-106) to exhibit differences in adhesion strength. Comparing tumor spheroid behavior to that of cell suspensions showed shifts in the spectral motion of the cancer tissues that match predictions based on different degrees of cell-cell contacts. The HT-29 cell line, which has the strongest adhesions in the spheroid model, exhibits anomalous behavior in some cases. These results highlight the importance of using three-dimensional tissue models in drug screening with cellular adhesions being a contributory factor in phenotypic differences between the drug responses of tissue and cells.

Solvent-free fabrication of three dimensionally aligned polycaprolactone microfibers for engineering of anisotropic tissues.

PubMed

An, Jia; Chua, Chee Kai; Leong, Kah Fai; Chen, Chih-Hao; Chen, Jyh-Ping

2012-10-01

Fabrication of aligned microfiber scaffolds is critical in successful engineering of anisotropic tissues such as tendon, ligaments and nerves. Conventionally, aligned microfiber scaffolds are two dimensional and predominantly fabricated by electrospinning which is solvent dependent. In this paper, we report a novel technique, named microfiber melt drawing, to fabricate a bundle of three dimensionally aligned polycaprolactone microfibers without using any organic solvent. This technique is simple yet effective. It has been demonstrated that polycaprolactone microfibers of 10 μm fiber diameter can be directly drawn from a 2 mm orifice. Orifice diameter, temperature and take-up speed significantly influence the final linear density and fiber diameter of the microfibers. Mechanical test suggests that mechanical properties such as stiffness and breaking force of microfiber bundles can be easily adjusted by the number of fibers. In vitro study shows that these microfibers are able to support the proliferation of human dermal fibroblasts over 7 days. In vivo result of Achilles tendon repair in a rabbit model shows that the microfibers were highly infiltrated by tendon tissue as early as in 1 month, besides, the repaired tendon have a well-aligned tissue structure under the guidance of aligned microfibers. However whether these three dimensionally aligned microfibers can induce three dimensionally aligned cells remains inconclusive.

Soft Tissue Augmentation Using Silk Gels: An In Vitro and In Vivo Study

PubMed Central

Etienne, Olivier; Schneider, Aurore; Kluge, Jonathan A.; Bellemin-Laponnaz, Claire; Polidori, Camille; Leisk, Gary G.; Kaplan, David L.; Garlick, Jonathan A.; Egles, Christophe

2010-01-01

Background Restoration of a three-dimensional shape with soft tissue augmentation is a challenge for surgical reconstruction and esthetic improvement of intraoral mucosa and perioral skin tissues. A connective tissue graft or free gingival graft, classically used for such indications, requires a donor site, which may lead to various clinical complications. Methods In this article, a new three-dimensional scaffold made of silk fibroin that could be of great interest for these indications was studied. Mechanical tests were conducted to characterize the physical properties of the materials. The biocompatibility of such scaffolds was positively assessed in vitro using a combination of immunostaining, 5-bromo-2′-deoxyuridine proliferation assays, and histologic staining. Finally, the shaped material was grafted subcutaneously in nude mice for a long-time implantation study. Results Human fibroblasts embedded in this material had a survival rate up to 68.4% and were able to proliferate and synthesize proteins. One month after subcutaneous implantation, the three-dimensional soft tissue augmentation was stable, and histologic analysis revealed revascularization of the area through the biomaterial. A mild inflammatory reaction disappeared after 12 weeks. Conclusion The results indicate that silk-gel material was able to create a lasting three-dimensional soft tissue augmentation and is a promising biomaterial for periodontal and maxillofacial therapies, either as a scaffold for cells or alone as a biomaterial. PMID:19905955

Cell Sheet-Based Tissue Engineering for Organizing Anisotropic Tissue Constructs Produced Using Microfabricated Thermoresponsive Substrates.

PubMed

Takahashi, Hironobu; Okano, Teruo

2015-11-18

In some native tissues, appropriate microstructures, including orientation of the cell/extracellular matrix, provide specific mechanical and biological functions. For example, skeletal muscle is made of oriented myofibers that is responsible for the mechanical function. Native artery and myocardial tissues are organized three-dimensionally by stacking sheet-like tissues of aligned cells. Therefore, to construct any kind of complex tissue, the microstructures of cells such as myotubes, smooth muscle cells, and cardiomyocytes also need to be organized three-dimensionally just as in the native tissues of the body. Cell sheet-based tissue engineering allows the production of scaffold-free engineered tissues through a layer-by-layer construction technique. Recently, using microfabricated thermoresponsive substrates, aligned cells are being harvested as single continuous cell sheets. The cell sheets act as anisotropic tissue units to build three-dimensional tissue constructs with the appropriate anisotropy. This cell sheet-based technology is straightforward and has the potential to engineer a wide variety of complex tissues. In addition, due to the scaffold-free cell-dense environment, the physical and biological cell-cell interactions of these cell sheet constructs exhibit unique cell behaviors. These advantages will provide important clues to enable the production of well-organized tissues that closely mimic the structure and function of native tissues, required for the future of tissue engineering. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mouse fetal whole intestine culture system for ex vivo manipulation of signaling pathways and three-dimensional live imaging of villus development.

PubMed

Walton, Katherine D; Kolterud, Asa

2014-09-04

Most morphogenetic processes in the fetal intestine have been inferred from thin sections of fixed tissues, providing snapshots of changes over developmental stages. Three-dimensional information from thin serial sections can be challenging to interpret because of the difficulty of reconstructing serial sections perfectly and maintaining proper orientation of the tissue over serial sections. Recent findings by Grosse et al., 2011 highlight the importance of three- dimensional information in understanding morphogenesis of the developing villi of the intestine(1). Three-dimensional reconstruction of singly labeled intestinal cells demonstrated that the majority of the intestinal epithelial cells contact both the apical and basal surfaces. Furthermore, three-dimensional reconstruction of the actin cytoskeleton at the apical surface of the epithelium demonstrated that the intestinal lumen is continuous and that secondary lumens are an artifact of sectioning. Those two points, along with the demonstration of interkinetic nuclear migration in the intestinal epithelium, defined the developing intestinal epithelium as a pseudostratified epithelium and not stratified as previously thought(1). The ability to observe the epithelium three-dimensionally was seminal to demonstrating this point and redefining epithelial morphogenesis in the fetal intestine. With the evolution of multi-photon imaging technology and three-dimensional reconstruction software, the ability to visualize intact, developing organs is rapidly improving. Two-photon excitation allows less damaging penetration deeper into tissues with high resolution. Two-photon imaging and 3D reconstruction of the whole fetal mouse intestines in Walton et al., 2012 helped to define the pattern of villus outgrowth(2). Here we describe a whole organ culture system that allows ex vivo development of villi and extensions of that culture system to allow the intestines to be three-dimensionally imaged during their development.

A computer simulation approach to measurement of human control strategy

NASA Technical Reports Server (NTRS)

Green, J.; Davenport, E. L.; Engler, H. F.; Sears, W. E., III

1982-01-01

Human control strategy is measured through use of a psychologically-based computer simulation which reflects a broader theory of control behavior. The simulation is called the human operator performance emulator, or HOPE. HOPE was designed to emulate control learning in a one-dimensional preview tracking task and to measure control strategy in that setting. When given a numerical representation of a track and information about current position in relation to that track, HOPE generates positions for a stick controlling the cursor to be moved along the track. In other words, HOPE generates control stick behavior corresponding to that which might be used by a person learning preview tracking.

[Differential diagnosis of papillary carcinomas of the thyroid, using image analysis and three dimensional reconstruction from serial sections].

PubMed

Holschbach, A; Kriete, A; Schäffer, R

1990-01-01

Papillae with fibrovascular cores are characteristic of papillary carcinoma of the thyroid. Papillae may be found in diffuse hyperplasia, nodular hyperplasia, Hashimoto's disease and follicular adenoma. Tissues from ten benign hyperplasias and ten papillary carcinomas were reconstructed from serial sections with three dimensional reconstruction programs. Significant qualitative and quantitative differences were found between the hyperplasia and the carcinoma. The principal differences between papillae of papillary carcinoma and hyperplasia were more clearly seen in the three dimensional reconstruction, than by means of morphometric methods. Certain criteria, e.g. the volume of papillae, were useful only with regard to the third dimension. Nevertheless, three dimensional reconstruction of biological tissue is a time consuming procedure which is not yet suitable for routine examination.

Extraction and Assembly of Tissue-Derived Gels for Cell Culture and Tissue Engineering

PubMed Central

Uriel, Shiri; Labay, Edwardine; Francis-Sedlak, Megan; Moya, Monica L.; Weichselbaum, Ralph R.; Ervin, Natalia; Cankova, Zdravka

2009-01-01

Interactions with the extracellular matrix (ECM) play an important role in regulating cell function. Cells cultured in, or on, three-dimensional ECM recapitulate similar features to those found in vivo that are not present in traditional two-dimensional culture. In addition, both natural and synthetic materials containing ECM components have shown promise in a number of tissue engineering applications. Current materials available for cell culture and tissue engineering do not adequately reflect the diversity of ECM composition between tissues. In this paper, a method is presented for extracting solutions of proteins and glycoproteins from soft tissues and inducing assembly of these proteins into gels. The extracts contain ECM proteins specific to the tissue source with low levels of intracellular molecules. Gels formed from the tissue-derived extracts have nanostructure similar to ECM in vivo and can be used to culture cells as both a thin substrate coating and a thick gel. This technique could be used to assemble hydrogels with varying composition depending upon the tissue source, hydrogels for three-dimensional culture, as scaffolds for tissue engineering therapies, and to study cell–matrix interactions. PMID:19115821

Biocompatible Near-Infrared Three-Dimensional Tracking System.

PubMed

Decker, Ryan S; Shademan, Azad; Opfermann, Justin D; Leonard, Simon; Kim, Peter C W; Krieger, Axel

2017-03-01

A fundamental challenge in soft-tissue surgery is that target tissue moves and deforms, becomes occluded by blood or other tissue, and is difficult to differentiate from surrounding tissue. We developed small biocompatible near-infrared fluorescent (NIRF) markers with a novel fused plenoptic and NIR camera tracking system, enabling three-dimensional tracking of tools and target tissue while overcoming blood and tissue occlusion in the uncontrolled, rapidly changing surgical environment. In this work, we present the tracking system and marker design and compare tracking accuracies to standard optical tracking methods using robotic experiments. At speeds of 1 mm/s, we observe tracking accuracies of 1.61 mm, degrading only to 1.71 mm when the markers are covered in blood and tissue.

Tissuelike 3D Assemblies of Human Broncho-Epithelial Cells

NASA Technical Reports Server (NTRS)

Goodwin, Thomas J.

2010-01-01

Three-dimensional (3D) tissuelike assemblies (TLAs) of human broncho-epithelial (HBE) cells have been developed for use in in vitro research on infection of humans by respiratory viruses. The 2D monolayer HBE cell cultures heretofore used in such research lack the complex cell structures and interactions characteristic of in vivo tissues and, consequently, do not adequately emulate the infection dynamics of in-vivo microbial adhesion and invasion. In contrast, the 3D HBE TLAs are characterized by more-realistic reproductions of the geometrical and functional complexity, differentiation of cells, cell-to-cell interactions, and cell-to-matrix interactions characteristic of human respiratory epithelia. Hence, the 3D HBE TLAs are expected to make it possible to perform at least some of the research in vitro under more-realistic conditions, without need to infect human subjects. The TLAs are grown on collagen-coated cyclodextran microbeads under controlled conditions in a nutrient liquid in the simulated microgravitational environment of a bioreactor of the rotating- wall-vessel type. Primary human mesenchymal bronchial-tracheal cells are used as a foundation matrix, while adult human bronchial epithelial immortalized cells are used as the overlying component. The beads become coated with cells, and cells on adjacent beads coalesce into 3D masses. The resulting TLAs have been found to share significant characteristics with in vivo human respiratory epithelia including polarization, tight junctions, desmosomes, and microvilli. The differentiation of the cells in these TLAs into tissues functionally similar to in vivo tissues is confirmed by the presence of compounds, including villin, keratins, and specific lung epithelium marker compounds, and by the production of tissue mucin. In a series of initial infection tests, TLA cultures were inoculated with human respiratory syncytial viruses and parainfluenza type 3 viruses. Infection was confirmed by photomicrographs that showed signs of damage by viruses and virus titers (see figure) that indicated large increases in the populations of viruses during the days following inoculation.

Three-dimensional bioprinting in tissue engineering and regenerative medicine.

PubMed

Gao, Guifang; Cui, Xiaofeng

2016-02-01

With the advances of stem cell research, development of intelligent biomaterials and three-dimensional biofabrication strategies, highly mimicked tissue or organs can be engineered. Among all the biofabrication approaches, bioprinting based on inkjet printing technology has the promises to deliver and create biomimicked tissue with high throughput, digital control, and the capacity of single cell manipulation. Therefore, this enabling technology has great potential in regenerative medicine and translational applications. The most current advances in organ and tissue bioprinting based on the thermal inkjet printing technology are described in this review, including vasculature, muscle, cartilage, and bone. In addition, the benign side effect of bioprinting to the printed mammalian cells can be utilized for gene or drug delivery, which can be achieved conveniently during precise cell placement for tissue construction. With layer-by-layer assembly, three-dimensional tissues with complex structures can be printed using converted medical images. Therefore, bioprinting based on thermal inkjet is so far the most optimal solution to engineer vascular system to the thick and complex tissues. Collectively, bioprinting has great potential and broad applications in tissue engineering and regenerative medicine. The future advances of bioprinting include the integration of different printing mechanisms to engineer biphasic or triphasic tissues with optimized scaffolds and further understanding of stem cell biology.

The Use of Finite Element Analyses to Design and Fabricate Three-Dimensional Scaffolds for Skeletal Tissue Engineering

PubMed Central

Hendrikson, Wim. J.; van Blitterswijk, Clemens. A.; Rouwkema, Jeroen; Moroni, Lorenzo

2017-01-01

Computational modeling has been increasingly applied to the field of tissue engineering and regenerative medicine. Where in early days computational models were used to better understand the biomechanical requirements of targeted tissues to be regenerated, recently, more and more models are formulated to combine such biomechanical requirements with cell fate predictions to aid in the design of functional three-dimensional scaffolds. In this review, we highlight how computational modeling has been used to understand the mechanisms behind tissue formation and can be used for more rational and biomimetic scaffold-based tissue regeneration strategies. With a particular focus on musculoskeletal tissues, we discuss recent models attempting to predict cell activity in relation to specific mechanical and physical stimuli that can be applied to them through porous three-dimensional scaffolds. In doing so, we review the most common scaffold fabrication methods, with a critical view on those technologies that offer better properties to be more easily combined with computational modeling. Finally, we discuss how modeling, and in particular finite element analysis, can be used to optimize the design of scaffolds for skeletal tissue regeneration. PMID:28567371

Three-dimensional modelling and three-dimensional printing in pediatric and congenital cardiac surgery.

PubMed

Kiraly, Laszlo

2018-04-01

Three-dimensional (3D) modelling and printing methods greatly support advances in individualized medicine and surgery. In pediatric and congenital cardiac surgery, personalized imaging and 3D modelling presents with a range of advantages, e.g., better understanding of complex anatomy, interactivity and hands-on approach, possibility for preoperative surgical planning and virtual surgery, ability to assess expected results, and improved communication within the multidisciplinary team and with patients. 3D virtual and printed models often add important new anatomical findings and prompt alternative operative scenarios. For the lack of critical mass of evidence, controlled randomized trials, however, most of these general benefits remain anecdotal. For an individual surgical case-scenario, prior knowledge, preparedness and possibility of emulation are indispensable in raising patient-safety. It is advocated that added value of 3D printing in healthcare could be raised by establishment of a multidisciplinary centre of excellence (COE). Policymakers, research scientists, clinicians, as well as health care financers and local entrepreneurs should cooperate and communicate along a legal framework and established scientific guidelines for the clinical benefit of patients, and towards financial sustainability. It is expected that besides the proven utility of 3D printed patient-specific anatomical models, 3D printing will have a major role in pediatric and congenital cardiac surgery by providing individually customized implants and prostheses, especially in combination with evolving techniques of bioprinting.

Three-dimensional modelling and three-dimensional printing in pediatric and congenital cardiac surgery

PubMed Central

2018-01-01

Three-dimensional (3D) modelling and printing methods greatly support advances in individualized medicine and surgery. In pediatric and congenital cardiac surgery, personalized imaging and 3D modelling presents with a range of advantages, e.g., better understanding of complex anatomy, interactivity and hands-on approach, possibility for preoperative surgical planning and virtual surgery, ability to assess expected results, and improved communication within the multidisciplinary team and with patients. 3D virtual and printed models often add important new anatomical findings and prompt alternative operative scenarios. For the lack of critical mass of evidence, controlled randomized trials, however, most of these general benefits remain anecdotal. For an individual surgical case-scenario, prior knowledge, preparedness and possibility of emulation are indispensable in raising patient-safety. It is advocated that added value of 3D printing in healthcare could be raised by establishment of a multidisciplinary centre of excellence (COE). Policymakers, research scientists, clinicians, as well as health care financers and local entrepreneurs should cooperate and communicate along a legal framework and established scientific guidelines for the clinical benefit of patients, and towards financial sustainability. It is expected that besides the proven utility of 3D printed patient-specific anatomical models, 3D printing will have a major role in pediatric and congenital cardiac surgery by providing individually customized implants and prostheses, especially in combination with evolving techniques of bioprinting. PMID:29770294

Apical polarity in three-dimensional culture systems: where to now?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Inman, J.L.; Bissell, Mina

2010-01-21

Delineation of the mechanisms that establish and maintain the polarity of epithelial tissues is essential to understanding morphogenesis, tissue specificity and cancer. Three-dimensional culture assays provide a useful platform for dissecting these processes but, as discussed in a recent study in BMC Biology on the culture of mammary gland epithelial cells, multiple parameters that influence the model must be taken into account.

[Application advances of three-dimensional bioprinting in burn and plastic surgery field].

PubMed

Li, R B; Li, M X; Guo, G H; Zhang, H Y

2017-10-20

Three-dimensional bioprinting is one of the latest and fastest growing technologies in the medical field. It has been implemented to print part of the transplantable tissues and organs, such as skin, ear, and bone. This paper introduces the application status, challenges, and application prospect of three-dimensional bioprinting in burn and plastic surgery field.

A virtual reality atlas of craniofacial anatomy.

PubMed

Smith, Darren M; Oliker, Aaron; Carter, Christina R; Kirov, Miro; McCarthy, Joseph G; Cutting, Court B

2007-11-01

Head and neck anatomy is complex and represents an educational challenge to the student. Conventional two-dimensional illustrations inherently fall short in conveying intricate anatomical relationships that exist in three dimensions. A gratis three-dimensional virtual reality atlas of craniofacial anatomy is presented in an effort to address the paucity of readily accessible and customizable three-dimensional educational material available to the student of head and neck anatomy. Three-dimensional model construction was performed in Alias Maya 4.5 and 6.0. A basic three-dimensional skull model was altered to include surgical landmarks and proportions. Some of the soft tissues were adapted from previous work, whereas others were constructed de novo. Texturing was completed with Adobe Photoshop 7.0 and Maya. The Internet application was designed in Viewpoint Enliven 1.0. A three-dimensional computer model of craniofacial anatomy (bone and soft tissue) was completed. The model is compatible with many software packages and can be accessed by means of the Internet or downloaded to a personal computer. As the three-dimensional meshes are publicly available, they can be extensively manipulated by the user, even at the polygonal level. Three-dimensional computer graphics has yet to be fully exploited for head and neck anatomy education. In this context, the authors present a publicly available computer model of craniofacial anatomy. This model may also find applications beyond clinical medicine. The model can be accessed gratis at the Plastic and Reconstructive Surgery Web site or obtained as a three-dimensional mesh, also gratis, by contacting the authors.

Engineered cell and tissue models of pulmonary fibrosis.

PubMed

Sundarakrishnan, Aswin; Chen, Ying; Black, Lauren D; Aldridge, Bree B; Kaplan, David L

2018-04-01

Pulmonary fibrosis includes several lung disorders characterized by scar formation and Idiopathic Pulmonary Fibrosis (IPF) is a particularly severe form of pulmonary fibrosis of unknown etiology with a mean life expectancy of 3years' post-diagnosis. Treatments for IPF are limited to two FDA approved drugs, pirfenidone and nintedanib. Most lead candidate drugs that are identified in pre-clinical animal studies fail in human clinical trials. Thus, there is a need for advanced humanized in vitro models of the lung to improve candidate treatments prior to moving to human clinical trials. The development of 3D tissue models has created systems capable of emulating human lung structure, function, and cell and matrix interactions. The specific models accomplish these features and preliminary studies conducted using some of these systems have shown potential for in vitro anti-fibrotic drug testing. Further characterization and improvements will enable these tissue models to extend their utility for in vitro drug testing, to help identify signaling pathways and mechanisms for new drug targets, and potentially reduce animal models as standard pre-clinical models of study. In the current review, we contrast different in vitro models based on increasing dimensionality (2D, 2.5D and 3D), with added focus on contemporary 3D pulmonary models of fibrosis. Copyright © 2017. Published by Elsevier B.V.

Extra-dimensional Demons: a method for incorporating missing tissue in deformable image registration.

PubMed

Nithiananthan, Sajendra; Schafer, Sebastian; Mirota, Daniel J; Stayman, J Webster; Zbijewski, Wojciech; Reh, Douglas D; Gallia, Gary L; Siewerdsen, Jeffrey H

2012-09-01

A deformable registration method capable of accounting for missing tissue (e.g., excision) is reported for application in cone-beam CT (CBCT)-guided surgical procedures. Excisions are identified by a segmentation step performed simultaneous to the registration process. Tissue excision is explicitly modeled by increasing the dimensionality of the deformation field to allow motion beyond the dimensionality of the image. The accuracy of the model is tested in phantom, simulations, and cadaver models. A variant of the Demons deformable registration algorithm is modified to include excision segmentation and modeling. Segmentation is performed iteratively during the registration process, with initial implementation using a threshold-based approach to identify voxels corresponding to "tissue" in the moving image and "air" in the fixed image. With each iteration of the Demons process, every voxel is assigned a probability of excision. Excisions are modeled explicitly during registration by increasing the dimensionality of the deformation field so that both deformations and excisions can be accounted for by in- and out-of-volume deformations, respectively. The out-of-volume (i.e., fourth) component of the deformation field at each voxel carries a magnitude proportional to the excision probability computed in the excision segmentation step. The registration accuracy of the proposed "extra-dimensional" Demons (XDD) and conventional Demons methods was tested in the presence of missing tissue in phantom models, simulations investigating the effect of excision size on registration accuracy, and cadaver studies emulating realistic deformations and tissue excisions imparted in CBCT-guided endoscopic skull base surgery. Phantom experiments showed the normalized mutual information (NMI) in regions local to the excision to improve from 1.10 for the conventional Demons approach to 1.16 for XDD, and qualitative examination of the resulting images revealed major differences: the conventional Demons approach imparted unrealistic distortions in areas around tissue excision, whereas XDD provided accurate "ejection" of voxels within the excision site and maintained the registration accuracy throughout the rest of the image. Registration accuracy in areas far from the excision site (e.g., > ∼5 mm) was identical for the two approaches. Quantitation of the effect was consistent in analysis of NMI, normalized cross-correlation (NCC), target registration error (TRE), and accuracy of voxels ejected from the volume (true-positive and false-positive analysis). The registration accuracy for conventional Demons was found to degrade steeply as a function of excision size, whereas XDD was robust in this regard. Cadaver studies involving realistic excision of the clivus, vidian canal, and ethmoid sinuses demonstrated similar results, with unrealistic distortion of anatomy imparted by conventional Demons and accurate ejection and deformation for XDD. Adaptation of the Demons deformable registration process to include segmentation (i.e., identification of excised tissue) and an extra dimension in the deformation field provided a means to accurately accommodate missing tissue between image acquisitions. The extra-dimensional approach yielded accurate "ejection" of voxels local to the excision site while preserving the registration accuracy (typically subvoxel) of the conventional Demons approach throughout the rest of the image. The ability to accommodate missing tissue volumes is important to application of CBCT for surgical guidance (e.g., skull base drillout) and may have application in other areas of CBCT guidance.

Three-dimensional cell to tissue assembly process

NASA Technical Reports Server (NTRS)

Wolf, David A. (Inventor); Schwarz, Ray P. (Inventor); Lewis, Marian L. (Inventor); Cross, John H. (Inventor); Huls, Mary H. (Inventor)

1992-01-01

The present invention relates a 3-dimensional cell to tissue and maintenance process, more particularly to methods of culturing cells in a culture environment, either in space or in a gravity field, with minimum fluid shear stress, freedom for 3-dimensional spatial orientation of the suspended particles and localization of particles with differing or similar sedimentation properties in a similar spatial region.

Magnetic resonance imaging-three-dimensional printing technology fabricates customized scaffolds for brain tissue engineering

PubMed Central

Fu, Feng; Qin, Zhe; Xu, Chao; Chen, Xu-yi; Li, Rui-xin; Wang, Li-na; Peng, Ding-wei; Sun, Hong-tao; Tu, Yue; Chen, Chong; Zhang, Sai; Zhao, Ming-liang; Li, Xiao-hong

2017-01-01

Conventional fabrication methods lack the ability to control both macro- and micro-structures of generated scaffolds. Three-dimensional printing is a solid free-form fabrication method that provides novel ways to create customized scaffolds with high precision and accuracy. In this study, an electrically controlled cortical impactor was used to induce randomized brain tissue defects. The overall shape of scaffolds was designed using rat-specific anatomical data obtained from magnetic resonance imaging, and the internal structure was created by computer-aided design. As the result of limitations arising from insufficient resolution of the manufacturing process, we magnified the size of the cavity model prototype five-fold to successfully fabricate customized collagen-chitosan scaffolds using three-dimensional printing. Results demonstrated that scaffolds have three-dimensional porous structures, high porosity, highly specific surface areas, pore connectivity and good internal characteristics. Neural stem cells co-cultured with scaffolds showed good viability, indicating good biocompatibility and biodegradability. This technique may be a promising new strategy for regenerating complex damaged brain tissues, and helps pave the way toward personalized medicine. PMID:28553343

Development of human nervous tissue upon differentiation of embryonic stem cells in three-dimensional culture.

PubMed

Preynat-Seauve, Olivier; Suter, David M; Tirefort, Diderik; Turchi, Laurent; Virolle, Thierry; Chneiweiss, Herve; Foti, Michelangelo; Lobrinus, Johannes-Alexander; Stoppini, Luc; Feki, Anis; Dubois-Dauphin, Michel; Krause, Karl Heinz

2009-03-01

Researches on neural differentiation using embryonic stem cells (ESC) require analysis of neurogenesis in conditions mimicking physiological cellular interactions as closely as possible. In this study, we report an air-liquid interface-based culture of human ESC. This culture system allows three-dimensional cell expansion and neural differentiation in the absence of added growth factors. Over a 3-month period, a macroscopically visible, compact tissue developed. Histological coloration revealed a dense neural-like neural tissue including immature tubular structures. Electron microscopy, immunochemistry, and electrophysiological recordings demonstrated a dense network of neurons, astrocytes, and oligodendrocytes able to propagate signals. Within this tissue, tubular structures were niches of cells resembling germinal layers of human fetal brain. Indeed, the tissue contained abundant proliferating cells expressing markers of neural progenitors. Finally, the capacity to generate neural tissues on air-liquid interface differed for different ESC lines, confirming variations of their neurogenic potential. In conclusion, this study demonstrates in vitro engineering of a human neural-like tissue with an organization that bears resemblance to early developing brain. As opposed to previously described methods, this differentiation (a) allows three-dimensional organization, (b) yields dense interconnected neural tissue with structurally and functionally distinct areas, and (c) is spontaneously guided by endogenous developmental cues.

Three-dimensional multifunctional optical coherence tomography for skin imaging

NASA Astrophysics Data System (ADS)

Li, En; Makita, Shuichi; Hong, Young-Joo; Kasaragod, Deepa; Sasaoka, Tomoko; Yamanari, Masahiro; Sugiyama, Satoshi; Yasuno, Yoshiaki

2016-02-01

Optical coherence tomography (OCT) visualizes cross-sectional microstructures of biological tissues. Recent developments of multifunctional OCT (MF-OCT) provides multiple optical contrasts which can reveal currently unknown tissue properties. In this contribution we demonstrate multifunctional OCT specially designed for dermatological investigation. And by utilizing it to measure four different body parts of in vivo human skin, three-dimensional scattering OCT, OCT angiography, polarization uniformity tomography, and local birefringence tomography images were obtained by a single scan. They respectively contrast the structure and morphology, vasculature, melanin content and collagen traits of the tissue.

A review of evolution of electrospun tissue engineering scaffold: From two dimensions to three dimensions.

PubMed

Ngadiman, Nor Hasrul Akhmal; Noordin, M Y; Idris, Ani; Kurniawan, Denni

2017-07-01

The potential of electrospinning process to fabricate ultrafine fibers as building blocks for tissue engineering scaffolds is well recognized. The scaffold construct produced by electrospinning process depends on the quality of the fibers. In electrospinning, material selection and parameter setting are among many factors that contribute to the quality of the ultrafine fibers, which eventually determine the performance of the tissue engineering scaffolds. The major challenge of conventional electrospun scaffolds is the nature of electrospinning process which can only produce two-dimensional electrospun mats, hence limiting their applications. Researchers have started to focus on overcoming this limitation by combining electrospinning with other techniques to fabricate three-dimensional scaffold constructs. This article reviews various polymeric materials and their composites/blends that have been successfully electrospun for tissue engineering scaffolds, their mechanical properties, and the various parameters settings that influence the fiber morphology. This review also highlights the secondary processes to electrospinning that have been used to develop three-dimensional tissue engineering scaffolds as well as the steps undertaken to overcome electrospinning limitations.

Printing three-dimensional tissue analogues with decellularized extracellular matrix bioink

PubMed Central

Pati, Falguni; Jang, Jinah; Ha, Dong-Heon; Won Kim, Sung; Rhie, Jong-Won; Shim, Jin-Hyung; Kim, Deok-Ho; Cho, Dong-Woo

2014-01-01

The ability to print and pattern all the components that make up a tissue (cells and matrix materials) in three dimensions to generate structures similar to tissues is an exciting prospect of bioprinting. However, the majority of the matrix materials used so far for bioprinting cannot represent the complexity of natural extracellular matrix (ECM) and thus are unable to reconstitute the intrinsic cellular morphologies and functions. Here, we develop a method for the bioprinting of cell-laden constructs with novel decellularized extracellular matrix (dECM) bioink capable of providing an optimized microenvironment conducive to the growth of three-dimensional structured tissue. We show the versatility and flexibility of the developed bioprinting process using tissue-specific dECM bioinks, including adipose, cartilage and heart tissues, capable of providing crucial cues for cells engraftment, survival and long-term function. We achieve high cell viability and functionality of the printed dECM structures using our bioprinting method. PMID:24887553

Printing three-dimensional tissue analogues with decellularized extracellular matrix bioink

NASA Astrophysics Data System (ADS)

Pati, Falguni; Jang, Jinah; Ha, Dong-Heon; Won Kim, Sung; Rhie, Jong-Won; Shim, Jin-Hyung; Kim, Deok-Ho; Cho, Dong-Woo

2014-06-01

The ability to print and pattern all the components that make up a tissue (cells and matrix materials) in three dimensions to generate structures similar to tissues is an exciting prospect of bioprinting. However, the majority of the matrix materials used so far for bioprinting cannot represent the complexity of natural extracellular matrix (ECM) and thus are unable to reconstitute the intrinsic cellular morphologies and functions. Here, we develop a method for the bioprinting of cell-laden constructs with novel decellularized extracellular matrix (dECM) bioink capable of providing an optimized microenvironment conducive to the growth of three-dimensional structured tissue. We show the versatility and flexibility of the developed bioprinting process using tissue-specific dECM bioinks, including adipose, cartilage and heart tissues, capable of providing crucial cues for cells engraftment, survival and long-term function. We achieve high cell viability and functionality of the printed dECM structures using our bioprinting method.

Nanowired three-dimensional cardiac patches

NASA Astrophysics Data System (ADS)

Dvir, Tal; Timko, Brian P.; Brigham, Mark D.; Naik, Shreesh R.; Karajanagi, Sandeep S.; Levy, Oren; Jin, Hongwei; Parker, Kevin K.; Langer, Robert; Kohane, Daniel S.

2011-11-01

Engineered cardiac patches for treating damaged heart tissues after a heart attack are normally produced by seeding heart cells within three-dimensional porous biomaterial scaffolds. These biomaterials, which are usually made of either biological polymers such as alginate or synthetic polymers such as poly(lactic acid) (PLA), help cells organize into functioning tissues, but poor conductivity of these materials limits the ability of the patch to contract strongly as a unit. Here, we show that incorporating gold nanowires within alginate scaffolds can bridge the electrically resistant pore walls of alginate and improve electrical communication between adjacent cardiac cells. Tissues grown on these composite matrices were thicker and better aligned than those grown on pristine alginate and when electrically stimulated, the cells in these tissues contracted synchronously. Furthermore, higher levels of the proteins involved in muscle contraction and electrical coupling are detected in the composite matrices. It is expected that the integration of conducting nanowires within three-dimensional scaffolds may improve the therapeutic value of current cardiac patches.

Three-Dimensional Printing of Tissue/Organ Analogues Containing Living Cells.

PubMed

Park, Jeong Hun; Jang, Jinah; Lee, Jung-Seob; Cho, Dong-Woo

2017-01-01

The technical advances of three-dimensional (3D) printing in the field of tissue engineering have enabled the creation of 3D living tissue/organ analogues. Diverse 3D tissue/organ printing techniques with computer-aided systems have been developed and used to dispose living cells together with biomaterials and supporting biochemicals as pre-designed 3D tissue/organ models. Furthermore, recent advances in bio-inks, which are printable hydrogels with living cell encapsulation, have greatly enhanced the versatility of 3D tissue/organ printing. Here, we introduce 3D tissue/organ printing techniques and biomaterials that have been developed and widely used thus far. We also review a variety of applications in an attempt to repair or replace the damaged or defective tissue/organ, and develop the in vitro tissue/organ models. The potential challenges are finally discussed from the technical perspective of 3D tissue/organ printing.

Novel synthesis strategies for natural polymer and composite biomaterials as potential scaffolds for tissue engineering

PubMed Central

Ko, Hsu-Feng; Sfeir, Charles; Kumta, Prashant N.

2010-01-01

Recent developments in tissue engineering approaches frequently revolve around the use of three-dimensional scaffolds to function as the template for cellular activities to repair, rebuild and regenerate damaged or lost tissues. While there are several biomaterials to select as three-dimensional scaffolds, it is generally agreed that a biomaterial to be used in tissue engineering needs to possess certain material characteristics such as biocompatibility, suitable surface chemistry, interconnected porosity, desired mechanical properties and biodegradability. The use of naturally derived polymers as three-dimensional scaffolds has been gaining widespread attention owing to their favourable attributes of biocompatibility, low cost and ease of processing. This paper discusses the synthesis of various polysaccharide-based, naturally derived polymers, and the potential of using these biomaterials to serve as tissue engineering three-dimensional scaffolds is also evaluated. In this study, naturally derived polymers, specifically cellulose, chitosan, alginate and agarose, and their composites, are examined. Single-component scaffolds of plain cellulose, plain chitosan and plain alginate as well as composite scaffolds of cellulose–alginate, cellulose–agarose, cellulose–chitosan, chitosan–alginate and chitosan–agarose are synthesized, and their suitability as tissue engineering scaffolds is assessed. It is shown that naturally derived polymers in the form of hydrogels can be synthesized, and the lyophilization technique is used to synthesize various composites comprising these natural polymers. The composite scaffolds appear to be sponge-like after lyophilization. Scanning electron microscopy is used to demonstrate the formation of an interconnected porous network within the polymeric scaffold following lyophilization. It is also established that HeLa cells attach and proliferate well on scaffolds of cellulose, chitosan or alginate. The synthesis protocols reported in this study can therefore be used to manufacture naturally derived polymer-based scaffolds as potential biomaterials for various tissue engineering applications. PMID:20308112

In vitro fabrication of functional three-dimensional tissues with perfusable blood vessels

PubMed Central

Sekine, Hidekazu; Shimizu, Tatsuya; Sakaguchi, Katsuhisa; Dobashi, Izumi; Wada, Masanori; Yamato, Masayuki; Kobayashi, Eiji; Umezu, Mitsuo; Okano, Teruo

2013-01-01

In vitro fabrication of functional vascularized three-dimensional tissues has been a long-standing objective in the field of tissue engineering. Here we report a technique to engineer cardiac tissues with perfusable blood vessels in vitro. Using resected tissue with a connectable artery and vein as a vascular bed, we overlay triple-layer cardiac cell sheets produced from coculture with endothelial cells, and support the tissue construct with media perfused in a bioreactor. We show that endothelial cells connect to capillaries in the vascular bed and form tubular lumens, creating in vitro perfusable blood vessels in the cardiac cell sheets. Thicker engineered tissues can be produced in vitro by overlaying additional triple-layer cell sheets. The vascularized cardiac tissues beat and can be transplanted with blood vessel anastomoses. This technique may create new opportunities for in vitro tissue engineering and has potential therapeutic applications. PMID:23360990

Three-dimensional radiation transfer modeling in a dicotyledon leaf

NASA Astrophysics Data System (ADS)

Govaerts, Yves M.; Jacquemoud, Stéphane; Verstraete, Michel M.; Ustin, Susan L.

1996-11-01

The propagation of light in a typical dicotyledon leaf is investigated with a new Monte Carlo ray-tracing model. The three-dimensional internal cellular structure of the various leaf tissues, including the epidermis, the palisade parenchyma, and the spongy mesophyll, is explicitly described. Cells of different tissues are assigned appropriate morphologies and contain realistic amounts of water and chlorophyll. Each cell constituent is characterized by an index of refraction and an absorption coefficient. The objective of this study is to investigate how the internal three-dimensional structure of the tissues and the optical properties of cell constituents control the reflectance and transmittance of the leaf. Model results compare favorably with laboratory observations. The influence of the roughness of the epidermis on the reflection and absorption of light is investigated, and simulation results confirm that convex cells in the epidermis focus light on the palisade parenchyma and increase the absorption of radiation.

Human endothelial cell growth and phenotypic expression on three dimensional poly(lactide-co-glycolide) sintered microsphere scaffolds for bone tissue engineering.

PubMed

Jabbarzadeh, Ehsan; Jiang, Tao; Deng, Meng; Nair, Lakshmi S; Khan, Yusuf M; Laurencin, Cato T

2007-12-01

Bone tissue engineering offers promising alternatives to repair and restore tissues. Our laboratory has employed poly(lactide-co-glycolide) PLAGA microspheres to develop a three dimensional (3-D) porous bioresorbable scaffold with a biomimetic pore structure. Osseous healing and integration with the surrounding tissue depends in part on new blood vessel formation within the porous structure. Since endothelial cells play a key role in angiogenesis (formation of new blood vessels from pre-existing vasculature), the purpose of this study was to better understand human endothelial cell attachment, viability, growth, and phenotypic expression on sintered PLAGA microsphere scaffold. Scanning electron microscopy (SEM) examination showed cells attaching to the surface of microspheres and bridging the pores between the microspheres. Cell proliferation studies indicated that cell number increased during early stages and reached a plateau between days 10 and 14. Immunofluorescent staining for actin showed that cells were proliferating three dimensionally through the scaffolds while staining for PECAM-1 (platelet endothelial cell adhesion molecule) displayed typical localization at cell-cell contacts. Gene expression analysis showed that endothelial cells grown on PLAGA scaffolds maintained their normal characteristic phenotype. The cell proliferation and phenotypic expression were independent of scaffold pore architecture. These results demonstrate that PLAGA sintered microsphere scaffolds can support the growth and biological functions of human endothelial cells. The insights from this study should aid future studies aimed at enhancing angiogenesis in three dimensional tissue engineered scaffolds.

Application of an object-oriented programming paradigm in three-dimensional computer modeling of mechanically active gastrointestinal tissues.

PubMed

Rashev, P Z; Mintchev, M P; Bowes, K L

2000-09-01

The aim of this study was to develop a novel three-dimensional (3-D) object-oriented modeling approach incorporating knowledge of the anatomy, electrophysiology, and mechanics of externally stimulated excitable gastrointestinal (GI) tissues and emphasizing the "stimulus-response" principle of extracting the modeling parameters. The modeling method used clusters of class hierarchies representing GI tissues from three perspectives: 1) anatomical; 2) electrophysiological; and 3) mechanical. We elaborated on the first four phases of the object-oriented system development life-cycle: 1) analysis; 2) design; 3) implementation; and 4) testing. Generalized cylinders were used for the implementation of 3-D tissue objects modeling the cecum, the descending colon, and the colonic circular smooth muscle tissue. The model was tested using external neural electrical tissue excitation of the descending colon with virtual implanted electrodes and the stimulating current density distributions over the modeled surfaces were calculated. Finally, the tissue deformations invoked by electrical stimulation were estimated and represented by a mesh-surface visualization technique.

Glassy dynamics in three-dimensional embryonic tissues

PubMed Central

Schötz, Eva-Maria; Lanio, Marcos; Talbot, Jared A.; Manning, M. Lisa

2013-01-01

Many biological tissues are viscoelastic, behaving as elastic solids on short timescales and fluids on long timescales. This collective mechanical behaviour enables and helps to guide pattern formation and tissue layering. Here, we investigate the mechanical properties of three-dimensional tissue explants from zebrafish embryos by analysing individual cell tracks and macroscopic mechanical response. We find that the cell dynamics inside the tissue exhibit features of supercooled fluids, including subdiffusive trajectories and signatures of caging behaviour. We develop a minimal, three-parameter mechanical model for these dynamics, which we calibrate using only information about cell tracks. This model generates predictions about the macroscopic bulk response of the tissue (with no fit parameters) that are verified experimentally, providing a strong validation of the model. The best-fit model parameters indicate that although the tissue is fluid-like, it is close to a glass transition, suggesting that small changes to single-cell parameters could generate a significant change in the viscoelastic properties of the tissue. These results provide a robust framework for quantifying and modelling mechanically driven pattern formation in tissues. PMID:24068179

Multiview hyperspectral topography of tissue structural and functional characteristics

NASA Astrophysics Data System (ADS)

Zhang, Shiwu; Liu, Peng; Huang, Jiwei; Xu, Ronald

2012-12-01

Accurate and in vivo characterization of structural, functional, and molecular characteristics of biological tissue will facilitate quantitative diagnosis, therapeutic guidance, and outcome assessment in many clinical applications, such as wound healing, cancer surgery, and organ transplantation. However, many clinical imaging systems have limitations and fail to provide noninvasive, real time, and quantitative assessment of biological tissue in an operation room. To overcome these limitations, we developed and tested a multiview hyperspectral imaging system. The multiview hyperspectral imaging system integrated the multiview and the hyperspectral imaging techniques in a single portable unit. Four plane mirrors are cohered together as a multiview reflective mirror set with a rectangular cross section. The multiview reflective mirror set was placed between a hyperspectral camera and the measured biological tissue. For a single image acquisition task, a hyperspectral data cube with five views was obtained. The five-view hyperspectral image consisted of a main objective image and four reflective images. Three-dimensional topography of the scene was achieved by correlating the matching pixels between the objective image and the reflective images. Three-dimensional mapping of tissue oxygenation was achieved using a hyperspectral oxygenation algorithm. The multiview hyperspectral imaging technique is currently under quantitative validation in a wound model, a tissue-simulating blood phantom, and an in vivo biological tissue model. The preliminary results have demonstrated the technical feasibility of using multiview hyperspectral imaging for three-dimensional topography of tissue functional properties.

Microfluidic Device to Quantify the Behavior of Therapeutic Bacteria in Three-Dimensional Tumor Tissue.

PubMed

Brackett, Emily L; Swofford, Charles A; Forbes, Neil S

2016-01-01

Microfluidic devices enable precise quantification of the interactions between anti-cancer bacteria and tumor tissue. Direct observation of bacterial movement and gene expression in tissue is difficult with either monolayers of cells or tumor-bearing mice. Quantification of these interactions is necessary to understand the inherent mechanisms of bacterial targeting and to develop modified organisms with enhanced therapeutic properties. Here we describe the procedures for designing, printing, and assembling microfluidic tumor-on-a-chip devices. We also describe the procedures for inserting three-dimensional tumor-cell masses, exposure to bacteria, and analyzing the resultant images.

Hand-held optoacoustic probe for three-dimensional imaging of human morphology and function

NASA Astrophysics Data System (ADS)

Deán-Ben, X. Luís.; Razansky, Daniel

2014-03-01

We report on a hand-held imaging probe for real-time optoacoustic visualization of deep tissues in three dimensions. The proposed solution incorporates a two-dimensional array of ultrasonic sensors densely distributed on a spherical surface, whereas illumination is performed coaxially through a cylindrical cavity in the array. Visualization of three-dimensional tomographic data at a frame rate of 10 images per second is enabled by parallel recording of 256 time-resolved signals for each individual laser pulse along with a highly efficient GPUbased real-time reconstruction. A liquid coupling medium (water), enclosed in a transparent membrane, is used to guarantee transmission of the optoacoustically generated waves to the ultrasonic detectors. Excitation at multiple wavelengths further allows imaging spectrally distinctive tissue chromophores such as oxygenated and deoxygenated haemoglobin. The performance is showcased by video-rate tracking of deep tissue vasculature and three-dimensional measurements of blood oxygenenation in a healthy human volunteer. The flexibility provided by the hand-held hardware design, combined with the real-time operation, makes the developed platform highly usable for both small animal research and clinical imaging in multiple indications, including cancer, inflammation, skin and cardiovascular diseases, diagnostics of lymphatic system and breast

Engineering three-dimensional cardiac microtissues for potential drug screening applications.

PubMed

Wang, L; Huang, G; Sha, B; Wang, S; Han, Y L; Wu, J; Li, Y; Du, Y; Lu, T J; Xu, F

2014-01-01

Heart disease is one of the major global health issues. Despite rapid advances in cardiac tissue engineering, limited successful strategies have been achieved to cure cardiovascular diseases. This situation is mainly due to poor understanding of the mechanism of diverse heart diseases and unavailability of effective in vitro heart tissue models for cardiovascular drug screening. With the development of microengineering technologies, three-dimensional (3D) cardiac microtissue (CMT) models, mimicking 3D architectural microenvironment of native heart tissues, have been developed. The engineered 3D CMT models hold greater potential to be used for assessing effective drugs candidates than traditional two-dimensional cardiomyocyte culture models. This review discusses the development of 3D CMT models and highlights their potential applications for high-throughput screening of cardiovascular drug candidates.

Toward a computational theory for motion understanding: The expert animators model

NASA Technical Reports Server (NTRS)

Mohamed, Ahmed S.; Armstrong, William W.

1988-01-01

Artificial intelligence researchers claim to understand some aspect of human intelligence when their model is able to emulate it. In the context of computer graphics, the ability to go from motion representation to convincing animation should accordingly be treated not simply as a trick for computer graphics programmers but as important epistemological and methodological goal. In this paper we investigate a unifying model for animating a group of articulated bodies such as humans and robots in a three-dimensional environment. The proposed model is considered in the framework of knowledge representation and processing, with special reference to motion knowledge. The model is meant to help setting the basis for a computational theory for motion understanding applied to articulated bodies.

A Weather Radar Simulator for the Evaluation of Polarimetric Phased Array Performance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Byrd, Andrew D.; Ivic, Igor R.; Palmer, Robert D.

A radar simulator capable of generating time series data for a polarimetric phased array weather radar has been designed and implemented. The received signals are composed from a high-resolution numerical prediction weather model. Thousands of scattering centers, each with an independent randomly generated Doppler spectrum, populate the field of view of the radar. The moments of the scattering center spectra are derived from the numerical weather model, and the scattering center positions are updated based on the three-dimensional wind field. In order to accurately emulate the effects of the system-induced cross-polar contamination, the array is modeled using a complete setmore » of dual-polarization radiation patterns. The simulator offers reconfigurable element patterns and positions as well as access to independent time series data for each element, resulting in easy implementation of any beamforming method. It also allows for arbitrary waveform designs and is able to model the effects of quantization on waveform performance. Simultaneous, alternating, quasi-simultaneous, and pulse-to-pulse phase coded modes of polarimetric signal transmission have been implemented. This framework allows for realistic emulation of the effects of cross-polar fields on weather observations, as well as the evaluation of possible techniques for the mitigation of those effects.« less

Three-dimensional spectral-spatial EPR imaging of free radicals in the heart: a technique for imaging tissue metabolism and oxygenation.

PubMed Central

Kuppusamy, P; Chzhan, M; Vij, K; Shteynbuk, M; Lefer, D J; Giannella, E; Zweier, J L

1994-01-01

It has been hypothesized that free radical metabolism and oxygenation in living organs and tissues such as the heart may vary over the spatially defined tissue structure. In an effort to study these spatially defined differences, we have developed electron paramagnetic resonance imaging instrumentation enabling the performance of three-dimensional spectral-spatial images of free radicals infused into the heart and large vessels. Using this instrumentation, high-quality three-dimensional spectral-spatial images of isolated perfused rat hearts and rabbit aortas are obtained. In the isolated aorta, it is shown that spatially and spectrally accurate images of the vessel lumen and wall could be obtained in this living vascular tissue. In the isolated rat heart, imaging experiments were performed to determine the kinetics of radical clearance at different spatial locations within the heart during myocardial ischemia. The kinetic data show the existence of regional and transmural differences in myocardial free radical clearance. It is further demonstrated that EPR imaging can be used to noninvasively measure spatially localized oxygen concentrations in the heart. Thus, the technique of spectral-spatial EPR imaging is shown to be a powerful tool in providing spatial information regarding the free radical distribution, metabolism, and tissue oxygenation in living biological organs and tissues. Images PMID:8159757

Biodynamic imaging for phenotypic profiling of three-dimensional tissue culture

PubMed Central

Sun, Hao; Merrill, Daniel; An, Ran; Turek, John; Matei, Daniela; Nolte, David D.

2017-01-01

Abstract. Three-dimensional (3-D) tissue culture represents a more biologically relevant environment for testing new drugs compared to conventional two-dimensional cancer cell culture models. Biodynamic imaging is a high-content 3-D optical imaging technology based on low-coherence interferometry and digital holography that uses dynamic speckle as high-content image contrast to probe deep inside 3-D tissue. Speckle contrast is shown to be a scaling function of the acquisition time relative to the persistence time of intracellular transport and hence provides a measure of cellular activity. Cellular responses of 3-D multicellular spheroids to paclitaxel are compared among three different growth techniques: rotating bioreactor (BR), hanging-drop (HD), and nonadherent (U-bottom, UB) plate spheroids, compared with ex vivo living tissues. HD spheroids have the most homogeneous tissue, whereas BR spheroids display large sample-to-sample variability as well as spatial heterogeneity. The responses of BR-grown tumor spheroids to paclitaxel are more similar to those of ex vivo biopsies than the responses of spheroids grown using HD or plate methods. The rate of mitosis inhibition by application of taxol is measured through tissue dynamics spectroscopic imaging, demonstrating the ability to monitor antimitotic chemotherapy. These results illustrate the potential use of low-coherence digital holography for 3-D pharmaceutical screening applications. PMID:28301634

Biodynamic imaging for phenotypic profiling of three-dimensional tissue culture

NASA Astrophysics Data System (ADS)

Sun, Hao; Merrill, Daniel; An, Ran; Turek, John; Matei, Daniela; Nolte, David D.

2017-01-01

Three-dimensional (3-D) tissue culture represents a more biologically relevant environment for testing new drugs compared to conventional two-dimensional cancer cell culture models. Biodynamic imaging is a high-content 3-D optical imaging technology based on low-coherence interferometry and digital holography that uses dynamic speckle as high-content image contrast to probe deep inside 3-D tissue. Speckle contrast is shown to be a scaling function of the acquisition time relative to the persistence time of intracellular transport and hence provides a measure of cellular activity. Cellular responses of 3-D multicellular spheroids to paclitaxel are compared among three different growth techniques: rotating bioreactor (BR), hanging-drop (HD), and nonadherent (U-bottom, UB) plate spheroids, compared with ex vivo living tissues. HD spheroids have the most homogeneous tissue, whereas BR spheroids display large sample-to-sample variability as well as spatial heterogeneity. The responses of BR-grown tumor spheroids to paclitaxel are more similar to those of ex vivo biopsies than the responses of spheroids grown using HD or plate methods. The rate of mitosis inhibition by application of taxol is measured through tissue dynamics spectroscopic imaging, demonstrating the ability to monitor antimitotic chemotherapy. These results illustrate the potential use of low-coherence digital holography for 3-D pharmaceutical screening applications.

Microswitch and Keyboard-Emulator Technology to Facilitate the Writing Performance of Persons with Extensive Motor Disabilities

ERIC Educational Resources Information Center

Lancioni, Giulio E.; Singh, Nirbhay N.; O'Reilly, Mark F.; Sigafoos, Jeff; Green, Vanessa; Oliva, Doretta; Lang, Russell

2011-01-01

This study assessed the effectiveness of microswitches for simple responses (i.e., partial hand closure, vocalization, and hand stroking) and a keyboard emulator to facilitate the writing performance of three participants with extensive motor disabilities. The study was carried out according to an ABAB design. During the A phases, the participants…

A Review of Three-Dimensional Printing in Tissue Engineering.

PubMed

Sears, Nick A; Seshadri, Dhruv R; Dhavalikar, Prachi S; Cosgriff-Hernandez, Elizabeth

2016-08-01

Recent advances in three-dimensional (3D) printing technologies have led to a rapid expansion of applications from the creation of anatomical training models for complex surgical procedures to the printing of tissue engineering constructs. In addition to achieving the macroscale geometry of organs and tissues, a print layer thickness as small as 20 μm allows for reproduction of the microarchitectures of bone and other tissues. Techniques with even higher precision are currently being investigated to enable reproduction of smaller tissue features such as hepatic lobules. Current research in tissue engineering focuses on the development of compatible methods (printers) and materials (bioinks) that are capable of producing biomimetic scaffolds. In this review, an overview of current 3D printing techniques used in tissue engineering is provided with an emphasis on the printing mechanism and the resultant scaffold characteristics. Current practical challenges and technical limitations are emphasized and future trends of bioprinting are discussed.

Three-dimensional mapping and regulation of action potential propagation in nanoelectronics-innervated tissues.

PubMed

Dai, Xiaochuan; Zhou, Wei; Gao, Teng; Liu, Jia; Lieber, Charles M

2016-09-01

Real-time mapping and manipulation of electrophysiology in three-dimensional (3D) tissues could have important impacts on fundamental scientific and clinical studies, yet realization is hampered by a lack of effective methods. Here we introduce tissue-scaffold-mimicking 3D nanoelectronic arrays consisting of 64 addressable devices with subcellular dimensions and a submillisecond temporal resolution. Real-time extracellular action potential (AP) recordings reveal quantitative maps of AP propagation in 3D cardiac tissues, enable in situ tracing of the evolving topology of 3D conducting pathways in developing cardiac tissues and probe the dynamics of AP conduction characteristics in a transient arrhythmia disease model and subsequent tissue self-adaptation. We further demonstrate simultaneous multisite stimulation and mapping to actively manipulate the frequency and direction of AP propagation. These results establish new methodologies for 3D spatiotemporal tissue recording and control, and demonstrate the potential to impact regenerative medicine, pharmacology and electronic therapeutics.

Three-dimensional mapping and regulation of action potential propagation in nanoelectronics innervated tissues

PubMed Central

Dai, Xiaochuan; Zhou, Wei; Gao, Teng; Liu, Jia; Lieber, Charles M.

2016-01-01

Real-time mapping and manipulation of electrophysiology in three-dimensional (3D) tissues could impact broadly fundamental scientific and clinical studies, yet realization lacks effective methods. Here we introduce tissue-scaffold-mimicking 3D nanoelectronic arrays consisting of 64 addressable devices with subcellular dimensions and sub-millisecond time-resolution. Real-time extracellular action potential (AP) recordings reveal quantitative maps of AP propagation in 3D cardiac tissues, enable in situ tracing of the evolving topology of 3D conducting pathways in developing cardiac tissues, and probe the dynamics of AP conduction characteristics in a transient arrhythmia disease model and subsequent tissue self-adaptation. We further demonstrate simultaneous multi-site stimulation and mapping to manipulate actively the frequency and direction of AP propagation. These results establish new methodologies for 3D spatiotemporal tissue recording and control, and demonstrate the potential to impact regenerative medicine, pharmacology and electronic therapeutics. PMID:27347837

A physical process of the radial acceleration of disc galaxies

NASA Astrophysics Data System (ADS)

Wilhelm, Klaus; Dwivedi, Bhola N.

2018-03-01

An impact model of gravity designed to emulate Newton's law of gravitation is applied to the radial acceleration of disc galaxies. Based on this model (Wilhelm et al. 2013), the rotation velocity curves can be understood without the need to postulate any dark matter contribution. The increased acceleration in the plane of the disc is a consequence of multiple interactions of gravitons (called `quadrupoles' in the original paper) and the subsequent propagation in this plane and not in three-dimensional space. The concept provides a physical process that relates the fit parameter of the acceleration scale defined by McGaugh et al. (2016) to the mean free path length of gravitons in the discs of galaxies. It may also explain the gravitational interaction at low acceleration levels in MOdification of the Newtonian Dynamics (MOND, Milgrom 1983, 1994, 2015, 2016). Three examples are discussed in some detail: the spiral galaxies NGC 7814, NGC 6503 and M 33.

Three-Dimensional Coculture Of Human Small-Intestine Cells

NASA Technical Reports Server (NTRS)

Wolf, David; Spaulding, Glen; Goodwin, Thomas J.; Prewett, Tracy

1994-01-01

Complex three-dimensional masses of normal human epithelial and mesenchymal small-intestine cells cocultured in process involving specially designed bioreactors. Useful as tissued models for studies of growth, regulatory, and differentiation processes in normal intestinal tissues; diseases of small intestine; and interactions between cells of small intestine and viruses causing disease both in small intestine and elsewhere in body. Process used to produce other tissue models, leading to advances in understanding of growth and differentiation in developing organisms, of renewal of tissue, and of treatment of myriad of clinical conditions. Prior articles describing design and use of rotating-wall culture vessels include "Growing And Assembling Cells Into Tissues" (MSC-21559), "High-Aspect-Ratio Rotating Cell-Culture Vessel" (MSC-21662), and "In Vitro, Matrix-Free Formation Of Solid Tumor Spheroids" (MSC-21843).

Bayesian uncertainty analysis for complex systems biology models: emulation, global parameter searches and evaluation of gene functions.

PubMed

Vernon, Ian; Liu, Junli; Goldstein, Michael; Rowe, James; Topping, Jen; Lindsey, Keith

2018-01-02

Many mathematical models have now been employed across every area of systems biology. These models increasingly involve large numbers of unknown parameters, have complex structure which can result in substantial evaluation time relative to the needs of the analysis, and need to be compared to observed data of various forms. The correct analysis of such models usually requires a global parameter search, over a high dimensional parameter space, that incorporates and respects the most important sources of uncertainty. This can be an extremely difficult task, but it is essential for any meaningful inference or prediction to be made about any biological system. It hence represents a fundamental challenge for the whole of systems biology. Bayesian statistical methodology for the uncertainty analysis of complex models is introduced, which is designed to address the high dimensional global parameter search problem. Bayesian emulators that mimic the systems biology model but which are extremely fast to evaluate are embeded within an iterative history match: an efficient method to search high dimensional spaces within a more formal statistical setting, while incorporating major sources of uncertainty. The approach is demonstrated via application to a model of hormonal crosstalk in Arabidopsis root development, which has 32 rate parameters, for which we identify the sets of rate parameter values that lead to acceptable matches between model output and observed trend data. The multiple insights into the model's structure that this analysis provides are discussed. The methodology is applied to a second related model, and the biological consequences of the resulting comparison, including the evaluation of gene functions, are described. Bayesian uncertainty analysis for complex models using both emulators and history matching is shown to be a powerful technique that can greatly aid the study of a large class of systems biology models. It both provides insight into model behaviour and identifies the sets of rate parameters of interest.

Cytokeratin expression of engrafted three-dimensional culture tissues using epithelial cells derived from porcine periodontal ligaments.

PubMed

Yamada, Rie; Kitajima, Kayoko; Arai, Kyoko; Igarashi, Masaru

2014-09-01

This study investigated the differentiation and proliferation of epithelial cells derived from periodontal ligaments after three-dimensional culture using collagen gel with fibroblasts in vitro and in vivo. Epithelial cells and fibroblasts were derived from porcine periodontal ligaments. Epithelial cells were labeled using a fluorescent red membrane marker (PKH-26GL) and were seeded onto collagen gel with fibroblasts, followed by incubation in an air-liquid interface for 7 days. Three-dimensional cultures were grafted onto the backs of nude mice and removed at 1, 7, and 14 days after surgery (in vivo model). Unfixed sections (5 μm) were used to detect the presence of red fluorescent cells. Paraffin sections were analyzed histologically and immunohistochemically. Specimens were compared with three-dimensional culture tissues at 8, 14 and 21 days (in vitro model). Grafted three-dimensional cultures formed a stratified epithelial structure similar to skin in vivo. Epithelial cells were sequenced in basal-layer-like structures at 14 days in vivo. Immunohistochemical findings showed that the expression of cytokeratin was detected in the epithelial layer in in vitro and in vivo models. Ck8 + 18 + 19 was expressed in the upper epithelial layer in the in vitro model at 14 and 21 days, but not in vivo. Involucrin was expressed in the certified layers in vitro at 14 days, but not in vivo. Laminin was detected at the dermo-epidermal junction in vivo at 7 and 14 days, but not in vitro. These results suggest that differentiation of three-dimensional culture tissues differs in vivo and in vitro. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Non-destructive phase contrast hard x-ray imaging to reveal the three-dimensional microstructure of soft and hard tissues

NASA Astrophysics Data System (ADS)

Khimchenko, Anna; Schulz, Georg; Deyhle, Hans; Hieber, Simone E.; Hasan, Samiul; Bikis, Christos; Schulz, Joachim; Costeur, Loïc.; Müller, Bert

2016-04-01

X-ray imaging in the absorption contrast mode is an established method of visualising calcified tissues such as bone and teeth. Physically soft tissues such as brain or muscle are often imaged using magnetic resonance imaging (MRI). However, the spatial resolution of MRI is insufficient for identifying individual biological cells within three-dimensional tissue. X-ray grating interferometry (XGI) has advantages for the investigation of soft tissues or the simultaneous three-dimensional visualisation of soft and hard tissues. Since laboratory microtomography (μCT) systems have better accessibility than tomography set-ups at synchrotron radiation facilities, a great deal of effort has been invested in optimising XGI set-ups for conventional μCT systems. In this conference proceeding, we present how a two-grating interferometer is incorporated into a commercially available nanotom m (GE Sensing and Inspection Technologies GmbH) μCT system to extend its capabilities toward phase contrast. We intend to demonstrate superior contrast in spiders (Hogna radiata (Fam. Lycosidae) and Xysticus erraticus (Fam. Thomisidae)), as well as the simultaneous visualisation of hard and soft tissues. XGI is an imaging modality that provides quantitative data, and visualisation is an important part of biomimetics; consequently, hard X-ray imaging provides a sound basis for bioinspiration, bioreplication and biomimetics and allows for the quantitative comparison of biofabricated products with their natural counterparts.

Three-dimensional contractile muscle tissue consisting of human skeletal myocyte cell line.

PubMed

Shima, Ai; Morimoto, Yuya; Sweeney, H Lee; Takeuchi, Shoji

2018-06-18

This paper describes a method to construct three-dimensional (3D) contractile human skeletal muscle tissues from a cell line. The 3D tissue was fabricated as a fiber-based structure and cultured for two weeks under tension by anchoring its both ends. While myotubes from the immortalized human skeletal myocytes used in this study never contracted in the conventional two-dimensional (2D) monolayer culture, myotubes in the 3D tissue showed spontaneous contraction at a high frequency and also reacted to the electrical stimulation. Immunofluorescence revealed that the myotubes in the 3D tissues had sarcomeres and expressed ryanodine receptor (RyR) and sarco/endoplasmic reticulum Ca 2+ -ATPase (SERCA). In addition, intracellular calcium oscillations in the myotubes in the 3D tissue were observed. These results indicated that the 3D culture enabled the myocyte cell line to reach a more highly matured state compared to 2D culture. Since contraction is the most significant feature of skeletal muscle, we believe that our 3D human muscle tissue with the contractile ability would be a useful tool for both basic biology research and drug discovery as one of the muscle-on-chips. Copyright © 2018. Published by Elsevier Inc.

Evolution of the three-dimensional collagen structure in vascular walls during deformation: an in situ mechanical testing under multiphoton microscopy observation.

PubMed

Nierenberger, Mathieu; Fargier, Guillaume; Ahzi, Saïd; Rémond, Yves

2015-08-01

The collagen fibers' three-dimensional architecture has a strong influence on the mechanical behavior of biological tissues. To accurately model this behavior, it is necessary to get some knowledge about the structure of the collagen network. In the present paper, we focus on the in situ characterization of the collagenous structure, which is present in porcine jugular vein walls. An observation of the vessel wall is first proposed in an unloaded configuration. The vein is then put into a mechanical tensile testing device. As the vein is stretched, three-dimensional images of its collagenous structure are acquired using multiphoton microscopy. Orientation analyses are provided for the multiple images recorded during the mechanical test. From these analyses, the reorientation of the two families of collagen fibers existing in the vein wall is quantified. We noticed that the reorientation of the fibers stops as the tissue stiffness starts decreasing, corresponding to the onset of damage. Besides, no relevant evolutions of the out of plane collagen orientations were observed. Due to the applied loading, our analysis also allowed for linking the stress relaxation within the tissue to its internal collagenous structure. Finally, this analysis constitutes the first mechanical test performed under a multiphoton microscope with a continuous three-dimensional observation of the tissue structure all along the test. It allows for a quantitative evaluation of microstructural parameters combined with a measure of the global mechanical behavior. Such data are useful for the development of structural mechanical models for living tissues.

Emulating Native Periosteum Cell Population and Subsequent Paracrine Factor Production To Promote Tissue Engineered Periosteum-Mediated Allograft Healing

PubMed Central

Hoffman, Michael D.

2015-01-01

Emulating autograft healing within the context of decellularized bone allografts has immediate clinical applications in the treatment of critical-sized bone defects. The periosteum, a thin, osteogenic tissue that surrounds bone, houses a heterogeneous population of stem cells and osteoprogenitors. There is evidence that periosteum-cell derived paracrine factors, specifically vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP2), orchestrate autograft healing through host cell recruitment and subsequent tissue elaboration. In previous work, we demonstrated that the use of poly(ethylene glycol) (PEG) hydrogels as a tissue engineered (T.E.) periosteum to localize mesenchymal stem cells (MSCs) to the surface of decellularized bone enhances allograft healing and integration. Herein, we utilize a mixed population of 50:50 MSCs and osteoprogenitor cells to better mimic native periosteum cell population and paracrine factor production to further promote allograft healing. This mixed cell population was localized to the surface of decellularized allografts within degradable hydrogels and shown to expedite allograft healing. Specifically, bone callus formation and biomechanical graft-host integration are increased as compared to unmodified allografts. These results demonstrate the dual importance of periosteum-mediated paracrine factors orchestrating host cell recruitment as well as new bone formation while developing clinically translatable strategies for allograft healing and integration. PMID:25818449

Three-Dimensional Gene Map of Cancer Cell Types: Structural Entropy Minimisation Principle for Defining Tumour Subtypes

PubMed Central

Li, Angsheng; Yin, Xianchen; Pan, Yicheng

2016-01-01

In this study, we propose a method for constructing cell sample networks from gene expression profiles, and a structural entropy minimisation principle for detecting natural structure of networks and for identifying cancer cell subtypes. Our method establishes a three-dimensional gene map of cancer cell types and subtypes. The identified subtypes are defined by a unique gene expression pattern, and a three-dimensional gene map is established by defining the unique gene expression pattern for each identified subtype for cancers, including acute leukaemia, lymphoma, multi-tissue, lung cancer and healthy tissue. Our three-dimensional gene map demonstrates that a true tumour type may be divided into subtypes, each defined by a unique gene expression pattern. Clinical data analyses demonstrate that most cell samples of an identified subtype share similar survival times, survival indicators and International Prognostic Index (IPI) scores and indicate that distinct subtypes identified by our algorithms exhibit different overall survival times, survival ratios and IPI scores. Our three-dimensional gene map establishes a high-definition, one-to-one map between the biologically and medically meaningful tumour subtypes and the gene expression patterns, and identifies remarkable cells that form singleton submodules. PMID:26842724

Extra-dimensional Demons: A method for incorporating missing tissue in deformable image registration

PubMed Central

Nithiananthan, Sajendra; Schafer, Sebastian; Mirota, Daniel J.; Stayman, J. Webster; Zbijewski, Wojciech; Reh, Douglas D.; Gallia, Gary L.; Siewerdsen, Jeffrey H.

2012-01-01

Purpose: A deformable registration method capable of accounting for missing tissue (e.g., excision) is reported for application in cone-beam CT (CBCT)-guided surgical procedures. Excisions are identified by a segmentation step performed simultaneous to the registration process. Tissue excision is explicitly modeled by increasing the dimensionality of the deformation field to allow motion beyond the dimensionality of the image. The accuracy of the model is tested in phantom, simulations, and cadaver models. Methods: A variant of the Demons deformable registration algorithm is modified to include excision segmentation and modeling. Segmentation is performed iteratively during the registration process, with initial implementation using a threshold-based approach to identify voxels corresponding to “tissue” in the moving image and “air” in the fixed image. With each iteration of the Demons process, every voxel is assigned a probability of excision. Excisions are modeled explicitly during registration by increasing the dimensionality of the deformation field so that both deformations and excisions can be accounted for by in- and out-of-volume deformations, respectively. The out-of-volume (i.e., fourth) component of the deformation field at each voxel carries a magnitude proportional to the excision probability computed in the excision segmentation step. The registration accuracy of the proposed “extra-dimensional” Demons (XDD) and conventional Demons methods was tested in the presence of missing tissue in phantom models, simulations investigating the effect of excision size on registration accuracy, and cadaver studies emulating realistic deformations and tissue excisions imparted in CBCT-guided endoscopic skull base surgery. Results: Phantom experiments showed the normalized mutual information (NMI) in regions local to the excision to improve from 1.10 for the conventional Demons approach to 1.16 for XDD, and qualitative examination of the resulting images revealed major differences: the conventional Demons approach imparted unrealistic distortions in areas around tissue excision, whereas XDD provided accurate “ejection” of voxels within the excision site and maintained the registration accuracy throughout the rest of the image. Registration accuracy in areas far from the excision site (e.g., > ∼5 mm) was identical for the two approaches. Quantitation of the effect was consistent in analysis of NMI, normalized cross-correlation (NCC), target registration error (TRE), and accuracy of voxels ejected from the volume (true-positive and false-positive analysis). The registration accuracy for conventional Demons was found to degrade steeply as a function of excision size, whereas XDD was robust in this regard. Cadaver studies involving realistic excision of the clivus, vidian canal, and ethmoid sinuses demonstrated similar results, with unrealistic distortion of anatomy imparted by conventional Demons and accurate ejection and deformation for XDD. Conclusions: Adaptation of the Demons deformable registration process to include segmentation (i.e., identification of excised tissue) and an extra dimension in the deformation field provided a means to accurately accommodate missing tissue between image acquisitions. The extra-dimensional approach yielded accurate “ejection” of voxels local to the excision site while preserving the registration accuracy (typically subvoxel) of the conventional Demons approach throughout the rest of the image. The ability to accommodate missing tissue volumes is important to application of CBCT for surgical guidance (e.g., skull base drillout) and may have application in other areas of CBCT guidance. PMID:22957637

Usefulness of three-dimensional echocardiography in the assessment of valvular involvement in Loeffler endocarditis.

PubMed

Hernandez, Carlos M; Arisha, Mohammed J; Ahmad, Amier; Oates, Ethan; Nanda, Navin C; Nanda, Anil; Wasan, Anita; Caleti, Beda E; Bernal, Cinthia L P; Gallardo, Sergio M

2017-07-01

Loeffler endocarditis is a complication of hypereosinophilic syndrome resulting from eosinophilic infiltration of heart tissue. We report a case of Loeffler endocarditis in which three-dimensional transthoracic and transesophageal echocardiography provided additional information to what was found by two-dimensional transthoracic echocardiography alone. Our case illustrates the usefulness of combined two- and three-dimensional echocardiography in the assessment of Loeffler endocarditis. In addition, a summary of the features of hypereosinophilic syndrome and Loeffler endocarditis is provided in tabular form. © 2017, Wiley Periodicals, Inc.

Cultured normal mammalian tissue and process

NASA Technical Reports Server (NTRS)

Goodwin, Thomas J. (Inventor); Prewett, Tacey L. (Inventor); Wolf, David A. (Inventor); Spaulding, Glenn F. (Inventor)

1993-01-01

Normal mammalian tissue and the culturing process has been developed for the three groups of organ, structural and blood tissue. The cells are grown in vitro under microgravity culture conditions and form three dimensional cell aggregates with normal cell function. The microgravity culture conditions may be microgravity or simulated microgravity created in a horizontal rotating wall culture vessel.

Imaging challenges in biomaterials and tissue engineering

PubMed Central

Appel, Alyssa A.; Anastasio, Mark A.; Larson, Jeffery C.; Brey, Eric M.

2013-01-01

Biomaterials are employed in the fields of tissue engineering and regenerative medicine (TERM) in order to enhance the regeneration or replacement of tissue function and/or structure. The unique environments resulting from the presence of biomaterials, cells, and tissues result in distinct challenges in regards to monitoring and assessing the results of these interventions. Imaging technologies for three-dimensional (3D) analysis have been identified as a strategic priority in TERM research. Traditionally, histological and immunohistochemical techniques have been used to evaluate engineered tissues. However, these methods do not allow for an accurate volume assessment, are invasive, and do not provide information on functional status. Imaging techniques are needed that enable non-destructive, longitudinal, quantitative, and three-dimensional analysis of TERM strategies. This review focuses on evaluating the application of available imaging modalities for assessment of biomaterials and tissue in TERM applications. Included is a discussion of limitations of these techniques and identification of areas for further development. PMID:23768903

Three-Dimensional Magnetic Levitation Culture System Simulating White Adipose Tissue.

PubMed

Tseng, Hubert; Daquinag, Alexes C; Souza, Glauco R; Kolonin, Mikhail G

2018-01-01

White adipose tissue (WAT) has attracted interest for tissue engineering and cell-based therapies as an abundant source of adipose stem/stromal cells (ASC). However, technical challenges in WAT cell culture have limited its applications in regenerative medicine. Traditional two-dimensional (2D) cell culture models, which are essentially monolayers of cells on glass or plastic substrates, inadequately represent tissue architecture, biochemical concentration gradients, substrate stiffness, and most importantly for WAT research, cell phenotypic heterogeneity. Physiological cell culture platforms for WAT modeling must recapitulate the native diversity of cell types and their coordination within the organ. For this purpose, we developed a three-dimensional (3D) model using magnetic levitation. Here, we describe our protocol that we successfully employed to build adipose tissue organoids (adipospheres) that preserve the heterogeneity of the constituent cell types in vitro. We demonstrate the capacity of assembling adipospheres from multiple cell types, including ASCs, endohtelial cells, and leukocytes that recreate tissue organization. These adipospheres mimicked WAT organogenesis in that they enabled the formation of vessel-like endothelial structures with lumens and differentiation of unilocular adipocytes. Altogether, magnetic levitation is a cell culture platform that recreates tissue structure, function, and heterogeneity in vitro, and serves as a foundation for high-throughput WAT tissue culture and analysis.

Exciton Polaritons in a Two-Dimensional Lieb Lattice with Spin-Orbit Coupling

NASA Astrophysics Data System (ADS)

Whittaker, C. E.; Cancellieri, E.; Walker, P. M.; Gulevich, D. R.; Schomerus, H.; Vaitiekus, D.; Royall, B.; Whittaker, D. M.; Clarke, E.; Iorsh, I. V.; Shelykh, I. A.; Skolnick, M. S.; Krizhanovskii, D. N.

2018-03-01

We study exciton polaritons in a two-dimensional Lieb lattice of micropillars. The energy spectrum of the system features two flat bands formed from S and Px ,y photonic orbitals, into which we trigger bosonic condensation under high power excitation. The symmetry of the orbital wave functions combined with photonic spin-orbit coupling gives rise to emission patterns with pseudospin texture in the flat band condensates. Our Letter shows the potential of polariton lattices for emulating flat band Hamiltonians with spin-orbit coupling, orbital degrees of freedom, and interactions.

Exciton Polaritons in a Two-Dimensional Lieb Lattice with Spin-Orbit Coupling.

PubMed

Whittaker, C E; Cancellieri, E; Walker, P M; Gulevich, D R; Schomerus, H; Vaitiekus, D; Royall, B; Whittaker, D M; Clarke, E; Iorsh, I V; Shelykh, I A; Skolnick, M S; Krizhanovskii, D N

2018-03-02

We study exciton polaritons in a two-dimensional Lieb lattice of micropillars. The energy spectrum of the system features two flat bands formed from S and P_{x,y} photonic orbitals, into which we trigger bosonic condensation under high power excitation. The symmetry of the orbital wave functions combined with photonic spin-orbit coupling gives rise to emission patterns with pseudospin texture in the flat band condensates. Our Letter shows the potential of polariton lattices for emulating flat band Hamiltonians with spin-orbit coupling, orbital degrees of freedom, and interactions.

Three-dimensional spheroid culture targeting versatile tissue bioassays using a PDMS-based hanging drop array.

PubMed

Kuo, Ching-Te; Wang, Jong-Yueh; Lin, Yu-Fen; Wo, Andrew M; Chen, Benjamin P C; Lee, Hsinyu

2017-06-29

Biomaterial-based tissue culture platforms have emerged as useful tools to mimic in vivo physiological microenvironments in experimental cell biology and clinical studies. We describe herein a three-dimensional (3D) tissue culture platform using a polydimethylsiloxane (PDMS)-based hanging drop array (PDMS-HDA) methodology. Multicellular spheroids can be achieved within 24 h and further boosted by incorporating collagen fibrils in PDMS-HDA. In addition, the spheroids generated from different human tumor cells exhibited distinct sensitivities toward drug chemotherapeutic agents and radiation as compared with two-dimensional (2D) cultures that often lack in vivo-like biological insights. We also demonstrated that multicellular spheroids may enable key hallmarks of tissue-based bioassays, including drug screening, tumor dissemination, cell co-culture, and tumor invasion. Taken together, these results offer new opportunities not only to achieve the active control of 3D multicellular spheroids on demand, but also to establish a rapid and cost-effective platform to study anti-cancer therapeutics and tumor microenvironments.

Computational cell quantification in the human brain tissues based on hard x-ray phase-contrast tomograms

NASA Astrophysics Data System (ADS)

Hieber, Simone E.; Bikis, Christos; Khimchenko, Anna; Schulz, Georg; Deyhle, Hans; Thalmann, Peter; Chicherova, Natalia; Rack, Alexander; Zdora, Marie-Christine; Zanette, Irene; Schweighauser, Gabriel; Hench, Jürgen; Müller, Bert

2016-10-01

Cell visualization and counting plays a crucial role in biological and medical research including the study of neurodegenerative diseases. The neuronal cell loss is typically determined to measure the extent of the disease. Its characterization is challenging because the cell density and size already differs by more than three orders of magnitude in a healthy cerebellum. Cell visualization is commonly performed by histology and fluorescence microscopy. These techniques are limited to resolve complex microstructures in the third dimension. Phase- contrast tomography has been proven to provide sufficient contrast in the three-dimensional imaging of soft tissue down to the cell level and, therefore, offers the basis for the three-dimensional segmentation. Within this context, a human cerebellum sample was embedded in paraffin and measured in local phase-contrast mode at the beamline ID19 (ESRF, Grenoble, France) and the Diamond Manchester Imaging Branchline I13-2 (Diamond Light Source, Didcot, UK). After the application of Frangi-based filtering the data showed sufficient contrast to automatically identify the Purkinje cells and to quantify their density to 177 cells per mm3 within the volume of interest. Moreover, brain layers were segmented in a region of interest based on edge detection. Subsequently performed histological analysis validated the presence of the cells, which required a mapping from the two- dimensional histological slices to the three-dimensional tomogram. The methodology can also be applied to further tissue types and shows potential for the computational tissue analysis in health and disease.

Estimating oxygen distribution from vasculature in three-dimensional tumour tissue

PubMed Central

Kannan, Pavitra; Warren, Daniel R.; Markelc, Bostjan; Bates, Russell; Muschel, Ruth; Partridge, Mike

2016-01-01

Regions of tissue which are well oxygenated respond better to radiotherapy than hypoxic regions by up to a factor of three. If these volumes could be accurately estimated, then it might be possible to selectively boost dose to radio-resistant regions, a concept known as dose-painting. While imaging modalities such as 18F-fluoromisonidazole positron emission tomography (PET) allow identification of hypoxic regions, they are intrinsically limited by the physics of such systems to the millimetre domain, whereas tumour oxygenation is known to vary over a micrometre scale. Mathematical modelling of microscopic tumour oxygen distribution therefore has the potential to complement and enhance macroscopic information derived from PET. In this work, we develop a general method of estimating oxygen distribution in three dimensions from a source vessel map. The method is applied analytically to line sources and quasi-linear idealized line source maps, and also applied to full three-dimensional vessel distributions through a kernel method and compared with oxygen distribution in tumour sections. The model outlined is flexible and stable, and can readily be applied to estimating likely microscopic oxygen distribution from any source geometry. We also investigate the problem of reconstructing three-dimensional oxygen maps from histological and confocal two-dimensional sections, concluding that two-dimensional histological sections are generally inadequate representations of the three-dimensional oxygen distribution. PMID:26935806

Estimating oxygen distribution from vasculature in three-dimensional tumour tissue.

PubMed

Grimes, David Robert; Kannan, Pavitra; Warren, Daniel R; Markelc, Bostjan; Bates, Russell; Muschel, Ruth; Partridge, Mike

2016-03-01

Regions of tissue which are well oxygenated respond better to radiotherapy than hypoxic regions by up to a factor of three. If these volumes could be accurately estimated, then it might be possible to selectively boost dose to radio-resistant regions, a concept known as dose-painting. While imaging modalities such as 18F-fluoromisonidazole positron emission tomography (PET) allow identification of hypoxic regions, they are intrinsically limited by the physics of such systems to the millimetre domain, whereas tumour oxygenation is known to vary over a micrometre scale. Mathematical modelling of microscopic tumour oxygen distribution therefore has the potential to complement and enhance macroscopic information derived from PET. In this work, we develop a general method of estimating oxygen distribution in three dimensions from a source vessel map. The method is applied analytically to line sources and quasi-linear idealized line source maps, and also applied to full three-dimensional vessel distributions through a kernel method and compared with oxygen distribution in tumour sections. The model outlined is flexible and stable, and can readily be applied to estimating likely microscopic oxygen distribution from any source geometry. We also investigate the problem of reconstructing three-dimensional oxygen maps from histological and confocal two-dimensional sections, concluding that two-dimensional histological sections are generally inadequate representations of the three-dimensional oxygen distribution. © 2016 The Authors.

Performance Guaranteed Inertia Emulation forDiesel-Wind System Feed Microgrid via ModelReference Control

DOE Office of Scientific and Technical Information (OSTI.GOV)

Melin, Alexander M.; Zhang, Yichen; Djouadi, Seddik

In this paper, a model reference control based inertia emulation strategy is proposed. Desired inertia can be precisely emulated through this control strategy so that guaranteed performance is ensured. A typical frequency response model with parametrical inertia is set to be the reference model. A measurement at a specific location delivers the information of disturbance acting on the diesel-wind system to the referencemodel. The objective is for the speed of the diesel-wind system to track the reference model. Since active power variation is dominantly governed by mechanical dynamics and modes, only mechanical dynamics and states, i.e., a swing-engine-governor system plusmore » a reduced-order wind turbine generator, are involved in the feedback control design. The controller is implemented in a three-phase diesel-wind system feed microgrid. The results show exact synthetic inertia is emulated, leading to guaranteed performance and safety bounds.« less

Cornea and ocular lens visualized with three-dimensional confocal microscopy

NASA Astrophysics Data System (ADS)

Masters, Barry R.

1992-08-01

This paper demonstrates the advantages of three-dimensional reconstruction of the cornea and the ocular crystalline lens by confocal microscopy and volume rendering computer techniques. The advantages of noninvasive observation of ocular structures in living, unstained, unfixed tissue include the following: the tissue is in a natural living state without the artifacts of fixation, mechanical sectioning, and staining; the three-dimensional structure can be observed from any view point and quantitatively analyzed; the dynamics of morphological changes can be studied; and the use of confocal microscopic observation results in a reduction of the number of animals required for ocular morphometric studies. The main advantage is that the dynamic morphology of ocular structures can be investigated in living ocular tissue. A laser scanning confocal microscope was used in the reflected light mode to obtain the two- dimensional images from the cornea and the ocular lens of a freshly enucleated rabbit eye. The light source was an argon ion laser with 488 nm wavelength. The microscope objective was a Leitz 25X, NA 0.6 water immersion lens. The 400 micron thick cornea was optically sectioned into 133, three micron sections. The semi-transparent cornea and the in-situ ocular lens was visualized as high resolution, high contrast two-dimensional images. The under sampling resulted in a three-dimensional visualization rendering in which the corneal thickness (z-axis) is compressed. The structures observed in the cornea include: superficial epithelial cells and their nuclei, basal epithelial cells and their `beaded' cell borders, basal lamina, nerve plexus, nerve fibers, free nerve endings in the basal epithelial cells, nuclei of stromal keratocytes, and endothelial cells. The structures observed in the in-situ ocular lens include: lens capsule, lens epithelial cells, and individual lens fibers.

In Situ Tissue Engineering Using Magnetically Guided Three-Dimensional Cell Patterning

PubMed Central

Grogan, Shawn P.; Pauli, Chantal; Chen, Peter; Du, Jiang; Chung, Christine B.; Kong, Seong Deok; Colwell, Clifford W.; Lotz, Martin K.; Jin, Sungho

2012-01-01

Manipulation of cell patterns in three dimensions in a manner that mimics natural tissue organization and function is critical for cell biological studies and likely essential for successfully regenerating tissues—especially cells with high physiological demands, such as those of the heart, liver, lungs, and articular cartilage.1,2 In the present study, we report on the feasibility of arranging iron oxide-labeled cells in three-dimensional hydrogels using magnetic fields. By manipulating the strength, shape, and orientation of the magnetic field and using crosslinking gradients in hydrogels, multi-directional cell arrangements can be produced in vitro and even directly in situ. We show that these ferromagnetic particles are nontoxic between 0.1 and 10 mg/mL; certain species of particles can permit or even enhance tissue formation, and these particles can be tracked using magnetic resonance imaging. Taken together, this approach can be adapted for studying basic biological processes in vitro, for general tissue engineering approaches, and for producing organized repair tissues directly in situ. PMID:22224660

Cell viability viscoelastic measurement in a rheometer used to stress and engineer tissues at low sonic frequencies.

PubMed

Klemuk, Sarah A; Jaiswal, Sanyukta; Titze, Ingo R

2008-10-01

Effects of vibration on human vocal fold extracellular matrix composition and the resultant tissue viscoelastic properties are difficult to study in vivo. Therefore, an in vitro bioreactor, simulating the in vivo physiological environment, was explored. A stress-controlled commercial rheometer was used to administer shear vibrations to living tissues at stresses and frequencies corresponding to male phonation, while simultaneously measuring tissue viscoelastic properties. Tissue environment was evaluated and adjustments made in order to sustain cell life for short term experimentation up to 6 h. Cell nutrient medium evaporation, osmolality, pH, and cell viability of cells cultured in three-dimensional synthetic scaffolds were quantified under comparably challenging environments to the rheometer bioreactor for 4 or 6 h. The functionality of the rheometer bioreactor was demonstrated by applying three vibration regimes to cell-seeded three-dimensional substrates for 2 h. Resulting strain was quantified throughout the test period. Rheologic data and cell viability are reported for each condition, and future improvements are discussed.

Three-dimensional light-tissue interaction models for bioluminescence tomography

NASA Astrophysics Data System (ADS)

Côté, D.; Allard, M.; Henkelman, R. M.; Vitkin, I. A.

2005-09-01

Many diagnostic and therapeutic approaches in medical physics today take advantage of the unique properties of light and its interaction with tissues. Because light scatters in tissue, our ability to develop these techniques depends critically on our knowledge of the distribution of light in tissue. Solutions to the diffusion equation can provide such information, but often lack the flexibility required for more general problems that involve, for instance, inhomogeneous optical properties, light polarization, arbitrary three-dimensional geometries, or arbitrary scattering. Monte Carlo techniques, which statistically sample the light distribution in tissue, offer a better alternative to analytical models. First, we discuss our implementation of a validated three-dimensional polarization-sensitive Monte Carlo algorithm and demonstrate its generality with respect to the geometry and scattering models it can treat. Second, we apply our model to bioluminescence tomography. After appropriate genetic modifications to cell lines, bioluminescence can be used as an indicator of cell activity, and is often used to study tumour growth and treatment in animal models. However, the amount of light escaping the animal is strongly dependent on the position and size of the tumour. Using forward models and structural data from magnetic resonance imaging, we show how the models can help to determine the location and size of tumour made of bioluminescent cancer cells in the brain of a mouse.

Cell culture in autologous fibrin scaffolds for applications in tissue engineering.

PubMed

de la Puente, Pilar; Ludeña, Dolores

2014-03-10

In tissue engineering techniques, three-dimensional scaffolds are needed to adjust and guide cell growth and to allow tissue regeneration. The scaffold must be biocompatible, biodegradable and must benefit the interactions between cells and biomaterial. Some natural biomaterials such as fibrin provide a structure similar to the native extracellular matrix containing the cells. Fibrin was first used as a sealant based on pools of commercial fibrinogen. However, the high risk of viral transmission of these pools led to the development of techniques of viral inactivation and elimination and the use of autologous fibrins. In recent decades, fibrin has been used as a release system and three-dimensional scaffold for cell culture. Fibrin scaffolds have been widely used for the culture of different types of cells, and have found several applications in tissue engineering. The structure and development of scaffolds is a key point for cell culture because scaffolds of autologous fibrin offer an important alternative due to their low fibrinogen concentrations, which are more suitable for cell growth. With this review our aim is to follow methods of development, analyze the commercial and autologous fibrins available and assess the possible applications of cell culture in tissue engineering in these three-dimensional structures. Copyright © 2013 Elsevier Inc. All rights reserved.

Meta-modelling, visualization and emulation of multi-dimensional data for virtual production intelligence

NASA Astrophysics Data System (ADS)

Schulz, Wolfgang; Hermanns, Torsten; Al Khawli, Toufik

2017-07-01

Decision making for competitive production in high-wage countries is a daily challenge where rational and irrational methods are used. The design of decision making processes is an intriguing, discipline spanning science. However, there are gaps in understanding the impact of the known mathematical and procedural methods on the usage of rational choice theory. Following Benjamin Franklin's rule for decision making formulated in London 1772, he called "Prudential Algebra" with the meaning of prudential reasons, one of the major ingredients of Meta-Modelling can be identified finally leading to one algebraic value labelling the results (criteria settings) of alternative decisions (parameter settings). This work describes the advances in Meta-Modelling techniques applied to multi-dimensional and multi-criterial optimization by identifying the persistence level of the corresponding Morse-Smale Complex. Implementations for laser cutting and laser drilling are presented, including the generation of fast and frugal Meta-Models with controlled error based on mathematical model reduction Reduced Models are derived to avoid any unnecessary complexity. Both, model reduction and analysis of multi-dimensional parameter space are used to enable interactive communication between Discovery Finders and Invention Makers. Emulators and visualizations of a metamodel are introduced as components of Virtual Production Intelligence making applicable the methods of Scientific Design Thinking and getting the developer as well as the operator more skilled.

Three-dimensional co-culture process

NASA Technical Reports Server (NTRS)

Wolf, David A. (Inventor); Goodwin, Thomas J. (Inventor)

1992-01-01

The present invention relates to a 3-dimensional co-culture process, more particularly to methods or co-culturing at least two types of cells in a culture environment, either in space or in unit gravity, with minimum shear stress, freedom for 3-dimensional spatial orientation of the suspended particles and localization of particles with differing or similar sedimentation properties in a similar spatial region to form 3-dimensional tissue-like structures. Several examples of multicellular 3-dimensional experiences are included. The protocol and procedure are also set forth. The process allows simultaneous culture of multiple cell types and supporting substrates in a manner which does not disrupt the 3-dimensional spatial orientation of these components. The co-cultured cells cause a mutual induction effect which mimics the natural hormonal signals and cell interactions found in the intact organism. This causes the tissues to differentiate and form higher 3-dimensional structures such as glands, junctional complexes polypoid geometries, and microvilli which represent the corresponding in-vitro structures to a greater degree than when the cell types are cultured individually or by conventional processes. This process was clearly demonstrated for the case of two epithelial derived colon cancer lines, each co-cultured with normal human fibroblasts and with microcarrier bead substrates. The results clearly demonstrate increased 3-dimensional tissue-like structure and biochemical evidence of an increased differentiation state. With the present invention a variety of cells may be co-cultured to produce tissue which has 3-dimensionality and has some of the characteristics of in-vitro tissue. The process provides enhanced 3-dimensional tissue which create a multicellular organoid differentiation model.

Three-Dimensional Geometry of Collagenous Tissues by Second Harmonic Polarimetry.

PubMed

Reiser, Karen; Stoller, Patrick; Knoesen, André

2017-06-01

Collagen is a biological macromolecule capable of second harmonic generation, allowing label-free detection in tissues; in addition, molecular orientation can be determined from the polarization dependence of the second harmonic signal. Previously we reported that in-plane orientation of collagen fibrils could be determined by modulating the polarization angle of the laser during scanning. We have now extended this method so that out-of-plane orientation angles can be determined at the same time, allowing visualization of the 3-dimensional structure of collagenous tissues. This approach offers advantages compared with other methods for determining out-of-plane orientation. First, the orientation angles are directly calculated from the polarimetry data obtained in a single scan, while other reported methods require data from multiple scans, use of iterative optimization methods, application of fitting algorithms, or extensive post-optical processing. Second, our method does not require highly specialized instrumentation, and thus can be adapted for use in almost any nonlinear optical microscopy setup. It is suitable for both basic and clinical applications. We present three-dimensional images of structurally complex collagenous tissues that illustrate the power of such 3-dimensional analyses to reveal the architecture of biological structures.

Three-Dimensional Geometry of Collagenous Tissues by Second Harmonic Polarimetry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reiser, Karen; Stoller, Patrick; Knoesen, André

Collagen is a biological macromolecule capable of second harmonic generation, allowing label-free detection in tissues; in addition, molecular orientation can be determined from the polarization dependence of the second harmonic signal. Previously we reported that in-plane orientation of collagen fibrils could be determined by modulating the polarization angle of the laser during scanning. We have now extended this method so that out-of-plane orientation angles can be determined at the same time, allowing visualization of the 3-dimensional structure of collagenous tissues. This approach offers advantages compared with other methods for determining out-of-plane orientation. First, the orientation angles are directly calculated frommore » the polarimetry data obtained in a single scan, while other reported methods require data from multiple scans, use of iterative optimization methods, application of fitting algorithms, or extensive post-optical processing. Second, our method does not require highly specialized instrumentation, and thus can be adapted for use in almost any nonlinear optical microscopy setup. It is suitable for both basic and clinical applications. We present three-dimensional images of structurally complex collagenous tissues that illustrate the power of such 3-dimensional analyses to reveal the architecture of biological structures.« less

Three-Dimensional Geometry of Collagenous Tissues by Second Harmonic Polarimetry

DOE PAGES

Reiser, Karen; Stoller, Patrick; Knoesen, André

2017-06-01

Collagen is a biological macromolecule capable of second harmonic generation, allowing label-free detection in tissues; in addition, molecular orientation can be determined from the polarization dependence of the second harmonic signal. Previously we reported that in-plane orientation of collagen fibrils could be determined by modulating the polarization angle of the laser during scanning. We have now extended this method so that out-of-plane orientation angles can be determined at the same time, allowing visualization of the 3-dimensional structure of collagenous tissues. This approach offers advantages compared with other methods for determining out-of-plane orientation. First, the orientation angles are directly calculated frommore » the polarimetry data obtained in a single scan, while other reported methods require data from multiple scans, use of iterative optimization methods, application of fitting algorithms, or extensive post-optical processing. Second, our method does not require highly specialized instrumentation, and thus can be adapted for use in almost any nonlinear optical microscopy setup. It is suitable for both basic and clinical applications. We present three-dimensional images of structurally complex collagenous tissues that illustrate the power of such 3-dimensional analyses to reveal the architecture of biological structures.« less

Layer-by-layer 3-dimensional nanofiber tissue scaffold with controlled gap by electrospinning

NASA Astrophysics Data System (ADS)

Lin, Sai-Jun; Xue, Ya-Ping; Chang, Guoqing; Han, Qiao-Ling; Chen, Li-Fang; Jia, Yan-Bo; Zheng, Yu-Guo

2018-02-01

The development of three-dimensional (3D) nanofiber structures by electrospinning has drawn considerable attention in the field of tissue scaffolds. However, the generation of two dimensional mats using the conventional method limits electrospinning, the electrical charging of polymer liquids, as a means of nanofiber fabrication. In this study, we established a facile method of fabrication of layer-by-layer 3D polycaprolactone (PCL) nanofiber structures by utilizing a booklet collector with controlled morphology. Meanwhile, we explore the application of the manufactured 3D architectures in the field of tissue scaffolds. The approximately 20 μm layer-to-layer distance enhanced the ability of cells to migrate freely into tissues and induce cells in an ordered arrangement.

Three-dimensional prediction of the human eyeball and canthi for craniofacial reconstruction using cone-beam computed tomography.

PubMed

Kim, Sang-Rok; Lee, Kyung-Min; Cho, Jin-Hyoung; Hwang, Hyeon-Shik

2016-04-01

An anatomical relationship between the hard and soft tissues of the face is mandatory for facial reconstruction. The purpose of this study was to investigate the positions of the eyeball and canthi three-dimensionally from the relationships between the facial hard and soft tissues using cone-beam computed tomography (CBCT). CBCT scan data of 100 living subjects were used to obtain the measurements of facial hard and soft tissues. Stepwise multiple regression analyses were carried out using the hard tissue measurements in the orbit, nasal bone, nasal cavity and maxillary canine to predict the most probable positions of the eyeball and canthi within the orbit. Orbital width, orbital height, and orbital depth were strong predictors of the eyeball and canthi position. Intercanine width was also a predictor of the mediolateral position of the eyeball. Statistically significant regression models for the positions of the eyeball and canthi could be derived from the measurements of orbit and maxillary canine. These results suggest that CBCT data can be useful in predicting the positions of the eyeball and canthi three-dimensionally. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Three-dimensional Tissue Culture Based on Magnetic Cell Levitation

PubMed Central

Souza, Glauco R.; Molina, Jennifer R.; Raphael, Robert M.; Ozawa, Michael G.; Stark, Daniel J.; Levin, Carly S.; Bronk, Lawrence F.; Ananta, Jeyarama S.; Mandelin, Jami; Georgescu, Maria-Magdalena; Bankson, James A.; Gelovani, Juri G.

2015-01-01

Cell culture is an essential tool for drug discovery, tissue engineering, and stem cell research. Conventional tissue culture produces two-dimensional (2D) cell growth with gene expression, signaling, and morphology that can differ from those in vivo and thus compromise clinical relevancy1–5. Here we report a three-dimensional (3D) culture of cells based on magnetic levitation in the presence of hydrogels containing gold and magnetic iron oxide (MIO) nanoparticles plus filamentous bacteriophage. This methodology allows for control of cell mass geometry and guided, multicellular clustering of different cell types in co-culture through spatial variance of the magnetic field. Moreover, magnetic levitation of human glioblastoma cells demonstrates similar protein expression profiles to those observed in human tumor xenografts. Taken together, these results suggest levitated 3D culture with magnetized phage-based hydrogels more closely recapitulates in vivo protein expression and allows for long-term multi-cellular studies. PMID:20228788

Integrating three-dimensional printing and nanotechnology for musculoskeletal regeneration

NASA Astrophysics Data System (ADS)

Nowicki, Margaret; Castro, Nathan J.; Rao, Raj; Plesniak, Michael; Zhang, Lijie Grace

2017-09-01

The field of tissue engineering is advancing steadily, partly due to advancements in rapid prototyping technology. Even with increasing focus, successful complex tissue regeneration of vascularized bone, cartilage and the osteochondral interface remains largely illusive. This review examines current three-dimensional printing techniques and their application towards bone, cartilage and osteochondral regeneration. The importance of, and benefit to, nanomaterial integration is also highlighted with recent published examples. Early-stage successes and challenges of recent studies are discussed, with an outlook to future research in the related areas.

Integrating three-dimensional printing and nanotechnology for musculoskeletal regeneration

PubMed Central

Nowicki, Margaret; Castro, Nathan J; Rao, Raj; Plesniak, Michael; Zhang, Lijie Grace

2017-01-01

The field of tissue engineering is advancing steadily, partly due to advancements in rapid prototyping technology. Even with increasing focus, successful complex tissue regeneration of vascularized bone, cartilage and the osteochondral interface remains largely illusive. This review examines current three-dimensional printing techniques and their application towards bone, cartilage and osteochondral regeneration. The importance of, and benefit to, nanomaterial integration is also highlighted with recent published examples. Early-stage successes and challenges of recent studies are discussed, with an outlook to future research in the related areas. PMID:28762957

The Billion Cell Construct: Will Three-Dimensional Printing Get Us There?

PubMed Central

Miller, Jordan S.

2014-01-01

How structure relates to function—across spatial scales, from the single molecule to the whole organism—is a central theme in biology. Bioengineers, however, wrestle with the converse question: will function follow form? That is, we struggle to approximate the architecture of living tissues experimentally, hoping that the structure we create will lead to the function we desire. A new means to explore the relationship between form and function in living tissue has arrived with three-dimensional printing, but the technology is not without limitations. PMID:24937565

Collagen-coated cellulose sponge: three dimensional matrix for tissue culture of Walker tumor 256.

PubMed

Leighton, J; Justh, G; Esper, M; Kronenthal, R L

1967-03-10

Three-dimensional growth of large populations of cells in vitro has been observed in the interstices of a matrix consisting of collagen-coated cellu lose sponge. The growth of Walker tumor 256 in this composite matrix is com pared with that found in a matrix composed of either cellulose sponge alone or collagen sponge alone. The composite matrix is superior to either one. Collagen coated cellulose sponge may provide a simple tool for the study of social interaction of cells in the formation of organized elementary tissue structures.

Surface acquisition through virtual milling

NASA Technical Reports Server (NTRS)

Merriam, Marshal L.

1993-01-01

Surface acquisition deals with the reconstruction of three dimensional objects from a set of data points. The most straightforward techniques require human intervention, a time consuming proposition. It is desirable to develop a fully automated alternative. Such a method is proposed in this paper. It makes use of surface measurements obtained from a 3-D laser digitizer - an instrument which provides the (x,y,z) coordinates of surface data points from various viewpoints. These points are assembled into several partial surfaces using a visibility constraint and a 2-D triangulation technique. Reconstruction of the final object requires merging these partial surfaces. This is accomplished through a procedure that emulates milling, a standard machining operation. From a geometrical standpoint the problem reduces to constructing the intersection of two or more non-convex polyhedra.

Three-dimensional organotypic culture: experimental models of mammalian biology and disease.

PubMed

Shamir, Eliah R; Ewald, Andrew J

2014-10-01

Mammalian organs are challenging to study as they are fairly inaccessible to experimental manipulation and optical observation. Recent advances in three-dimensional (3D) culture techniques, coupled with the ability to independently manipulate genetic and microenvironmental factors, have enabled the real-time study of mammalian tissues. These systems have been used to visualize the cellular basis of epithelial morphogenesis, to test the roles of specific genes in regulating cell behaviours within epithelial tissues and to elucidate the contribution of microenvironmental factors to normal and disease processes. Collectively, these novel models can be used to answer fundamental biological questions and generate replacement human tissues, and they enable testing of novel therapeutic approaches, often using patient-derived cells.

Label-free three-dimensional imaging of cell nucleus using third-harmonic generation microscopy

NASA Astrophysics Data System (ADS)

Lin, Jian; Zheng, Wei; Wang, Zi; Huang, Zhiwei

2014-09-01

We report the implementation of the combined third-harmonic generation (THG) and two-photon excited fluorescence (TPEF) microscopy for label-free three-dimensional (3-D) imaging of cell nucleus morphological changes in liver tissue. THG imaging shows regular spherical shapes of normal hepatocytes nuclei with inner chromatin structures while revealing the condensation of chromatins and nuclear fragmentations in hepatocytes of diseased liver tissue. Colocalized THG and TPEF imaging provides complementary information of cell nuclei and cytoplasm in tissue. This work suggests that 3-D THG microscopy has the potential for quantitative analysis of nuclear morphology in cells at a submicron-resolution without the need for DNA staining.

Bioprinted three dimensional human tissues for toxicology and disease modeling.

PubMed

Nguyen, Deborah G; Pentoney, Stephen L

2017-03-01

The high rate of attrition among clinical-stage therapies, due largely to an inability to predict human toxicity and/or efficacy, underscores the need for in vitro models that better recapitulate in vivo human biology. In much the same way that additive manufacturing has revolutionized the production of solid objects, three-dimensional (3D) bioprinting is enabling the automated production of more architecturally and functionally accurate in vitro tissue culture models. Here, we provide an overview of the most commonly used bioprinting approaches and how they are being used to generate complex in vitro tissues for use in toxicology and disease modeling research. Copyright © 2017 Elsevier Ltd. All rights reserved.

Label-free three-dimensional imaging of cell nucleus using third-harmonic generation microscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Jian; Zheng, Wei; Wang, Zi

2014-09-08

We report the implementation of the combined third-harmonic generation (THG) and two-photon excited fluorescence (TPEF) microscopy for label-free three-dimensional (3-D) imaging of cell nucleus morphological changes in liver tissue. THG imaging shows regular spherical shapes of normal hepatocytes nuclei with inner chromatin structures while revealing the condensation of chromatins and nuclear fragmentations in hepatocytes of diseased liver tissue. Colocalized THG and TPEF imaging provides complementary information of cell nuclei and cytoplasm in tissue. This work suggests that 3-D THG microscopy has the potential for quantitative analysis of nuclear morphology in cells at a submicron-resolution without the need for DNA staining.

Three-Dimensional Bioprinting for Regenerative Dentistry and Craniofacial Tissue Engineering.

PubMed

Obregon, F; Vaquette, C; Ivanovski, S; Hutmacher, D W; Bertassoni, L E

2015-09-01

Craniofacial tissues are organized with complex 3-dimensional (3D) architectures. Mimicking such 3D complexity and the multicellular interactions naturally occurring in craniofacial structures represents one of the greatest challenges in regenerative dentistry. Three-dimensional bioprinting of tissues and biological structures has been proposed as a promising alternative to address some of these key challenges. It enables precise manufacture of various biomaterials with complex 3D architectures, while being compatible with multiple cell sources and being customizable to patient-specific needs. This review describes different 3D bioprinting methods and summarizes how different classes of biomaterials (polymer hydrogels, ceramics, composites, and cell aggregates) may be used for 3D biomanufacturing of scaffolds, as well as craniofacial tissue analogs. While the fabrication of scaffolds upon which cells attach, migrate, and proliferate is already in use, printing of all the components that form a tissue (living cells and matrix materials together) to produce tissue constructs is still in its early stages. In summary, this review seeks to highlight some of the key advantages of 3D bioprinting technology for the regeneration of craniofacial structures. Additionally, it stimulates progress on the development of strategies that will promote the translation of craniofacial tissue engineering from the laboratory bench to the chair side. © International & American Associations for Dental Research 2015.

Human cartilage tissue fabrication using three-dimensional inkjet printing technology.

PubMed

Cui, Xiaofeng; Gao, Guifang; Yonezawa, Tomo; Dai, Guohao

2014-06-10

Bioprinting, which is based on thermal inkjet printing, is one of the most attractive enabling technologies in the field of tissue engineering and regenerative medicine. With digital control cells, scaffolds, and growth factors can be precisely deposited to the desired two-dimensional (2D) and three-dimensional (3D) locations rapidly. Therefore, this technology is an ideal approach to fabricate tissues mimicking their native anatomic structures. In order to engineer cartilage with native zonal organization, extracellular matrix composition (ECM), and mechanical properties, we developed a bioprinting platform using a commercial inkjet printer with simultaneous photopolymerization capable for 3D cartilage tissue engineering. Human chondrocytes suspended in poly(ethylene glycol) diacrylate (PEGDA) were printed for 3D neocartilage construction via layer-by-layer assembly. The printed cells were fixed at their original deposited positions, supported by the surrounding scaffold in simultaneous photopolymerization. The mechanical properties of the printed tissue were similar to the native cartilage. Compared to conventional tissue fabrication, which requires longer UV exposure, the viability of the printed cells with simultaneous photopolymerization was significantly higher. Printed neocartilage demonstrated excellent glycosaminoglycan (GAG) and collagen type II production, which was consistent with gene expression. Therefore, this platform is ideal for accurate cell distribution and arrangement for anatomic tissue engineering.

Multifactorial Optimization of Contrast-Enhanced Nanofocus Computed Tomography for Quantitative Analysis of Neo-Tissue Formation in Tissue Engineering Constructs.

PubMed

Sonnaert, Maarten; Kerckhofs, Greet; Papantoniou, Ioannis; Van Vlierberghe, Sandra; Boterberg, Veerle; Dubruel, Peter; Luyten, Frank P; Schrooten, Jan; Geris, Liesbet

2015-01-01

To progress the fields of tissue engineering (TE) and regenerative medicine, development of quantitative methods for non-invasive three dimensional characterization of engineered constructs (i.e. cells/tissue combined with scaffolds) becomes essential. In this study, we have defined the most optimal staining conditions for contrast-enhanced nanofocus computed tomography for three dimensional visualization and quantitative analysis of in vitro engineered neo-tissue (i.e. extracellular matrix containing cells) in perfusion bioreactor-developed Ti6Al4V constructs. A fractional factorial 'design of experiments' approach was used to elucidate the influence of the staining time and concentration of two contrast agents (Hexabrix and phosphotungstic acid) and the neo-tissue volume on the image contrast and dataset quality. Additionally, the neo-tissue shrinkage that was induced by phosphotungstic acid staining was quantified to determine the operating window within which this contrast agent can be accurately applied. For Hexabrix the staining concentration was the main parameter influencing image contrast and dataset quality. Using phosphotungstic acid the staining concentration had a significant influence on the image contrast while both staining concentration and neo-tissue volume had an influence on the dataset quality. The use of high concentrations of phosphotungstic acid did however introduce significant shrinkage of the neo-tissue indicating that, despite sub-optimal image contrast, low concentrations of this staining agent should be used to enable quantitative analysis. To conclude, design of experiments allowed us to define the most optimal staining conditions for contrast-enhanced nanofocus computed tomography to be used as a routine screening tool of neo-tissue formation in Ti6Al4V constructs, transforming it into a robust three dimensional quality control methodology.

Three-Dimensional Printing and Cell Therapy for Wound Repair.

PubMed

van Kogelenberg, Sylvia; Yue, Zhilian; Dinoro, Jeremy N; Baker, Christopher S; Wallace, Gordon G

2018-05-01

Significance: Skin tissue damage is a major challenge and a burden on healthcare systems, from burns and other trauma to diabetes and vascular disease. Although the biological complexities are relatively well understood, appropriate repair mechanisms are scarce. Three-dimensional bioprinting is a layer-based approach to regenerative medicine, whereby cells and cell-based materials can be dispensed in fine spatial arrangements to mimic native tissue. Recent Advances: Various bioprinting techniques have been employed in wound repair-based skin tissue engineering, from laser-induced forward transfer to extrusion-based methods, and with the investigation of the benefits and shortcomings of each, with emphasis on biological compatibility and cell proliferation, migration, and vitality. Critical issues: Development of appropriate biological inks and the vascularization of newly developed tissues remain a challenge within the field of skin tissue engineering. Future Directions: Progress within bioprinting requires close interactions between material scientists, tissue engineers, and clinicians. Microvascularization, integration of multiple cell types, and skin appendages will be essential for creation of complex skin tissue constructs.

Three-dimensional bio-printing.

PubMed

Gu, Qi; Hao, Jie; Lu, YangJie; Wang, Liu; Wallace, Gordon G; Zhou, Qi

2015-05-01

Three-dimensional (3D) printing technology has been widely used in various manufacturing operations including automotive, defence and space industries. 3D printing has the advantages of personalization, flexibility and high resolution, and is therefore becoming increasingly visible in the high-tech fields. Three-dimensional bio-printing technology also holds promise for future use in medical applications. At present 3D bio-printing is mainly used for simulating and reconstructing some hard tissues or for preparing drug-delivery systems in the medical area. The fabrication of 3D structures with living cells and bioactive moieties spatially distributed throughout will be realisable. Fabrication of complex tissues and organs is still at the exploratory stage. This review summarize the development of 3D bio-printing and its potential in medical applications, as well as discussing the current challenges faced by 3D bio-printing.

Comparison of mechanisms involved in image enhancement of Tissue Harmonic Imaging

NASA Astrophysics Data System (ADS)

Cleveland, Robin O.; Jing, Yuan

2006-05-01

Processes that have been suggested as responsible for the improved imaging in Tissue Harmonic Imaging (THI) include: 1) reduced sensitivity to reverberation, 2) reduced sensitivity to aberration, and 3) reduction in the amplitude of diffraction side lobes. A three-dimensional model of the forward propagation of nonlinear sound beams in media with arbitrary spatial properties (a generalized KZK equation) was developed and solved using a time-domain code. The numerical simulations were validated through experiments with tissue mimicking phantoms. The impact of aberration from tissue-like media was determined through simulations using three-dimensional maps of tissue properties derived from datasets available through the Visible Female Project. The experiments and simulations demonstrated that second harmonic imaging suffers less clutter from reverberation and side-lobes but is not immune to aberration effects. The results indicate that side lobe suppression is the most significant reason for the improvement of second harmonic imaging.

Engineering Three-dimensional Epithelial Tissues Embedded within Extracellular Matrix.

PubMed

Piotrowski-Daspit, Alexandra S; Nelson, Celeste M

2016-07-10

The architecture of branched organs such as the lungs, kidneys, and mammary glands arises through the developmental process of branching morphogenesis, which is regulated by a variety of soluble and physical signals in the microenvironment. Described here is a method created to study the process of branching morphogenesis by forming engineered three-dimensional (3D) epithelial tissues of defined shape and size that are completely embedded within an extracellular matrix (ECM). This method enables the formation of arrays of identical tissues and enables the control of a variety of environmental factors, including tissue geometry, spacing, and ECM composition. This method can also be combined with widely used techniques such as traction force microscopy (TFM) to gain more information about the interactions between cells and their surrounding ECM. The protocol can be used to investigate a variety of cell and tissue processes beyond branching morphogenesis, including cancer invasion.

[Phagocyte migration: an overview].

PubMed

Le Cabec, Véronique; Van Goethem, Emeline; Guiet, Romain; Maridonneau-Parini, Isabelle

2011-12-01

Phagocytes are the first line of host defense thanks to their capacity to infiltrate infected and wounded tissues, where they exert their bactericidal and tissue repair functions. However, tissue infiltration of phagocytes also stimulates the progression of pathologies such as cancer and chronic inflammatory diseases. It is therefore necessary to identify the molecular and cellular mechanisms that control this process to identify new therapeutic targets. Phagocytes leave the blood stream by crossing the vascular wall and infiltrate interstitial tissues, a three-dimensional environment. A state-of-the-art of the different steps of phagocyte tissue recruitment in vivo and of the different in vitro models is developed in this synthesis. We focus on recent data concerning the migration of phagocytes in three-dimensional environments. The use of two different migration modes, amoeboid and mesenchymal, by macrophages and the role of podosomes and proteases in the mesenchymal migration are discussed. © 2011 médecine/sciences – Inserm / SRMS.

Toward a nanoscience emulator with two dimensional atomic gases

NASA Astrophysics Data System (ADS)

Wang, Ping; Ma, Q.; Dutta, S.; Chen, Yong P.

2009-05-01

We report our experimental progress in constructing a cold atom apparatus for emulating phenomena in nanoscience using low dimensional atom gases. Our first experiments will be performed with a 2D ^87Rb Bose-Einstein condensate created in an optical lattice. Our compact vacuum system consists of two AR-coated glass cells --- a low vacuum magneto-optical trap (MOT) chamber and a high vacuum ``science chamber'', connected by a 15cm-long tube for differential pumping. We have used elliptically shaped cooling laser beams and magnet field coils to realize an elongated MOT in the first chamber, and transferred the atoms to a second MOT in the science chamber by a push laser beam. In the science chamber, a 50W, 1550nm single frequency erbium fiber laser is used to produce an optical dipole trap and optical lattice.In addition, controllable disorder can be introduced with laser speckle and inter-atomic interactions can be tuned by atomic density or Feshbach resonance. We plan to explore important phenomena in nanoscience, such as 2D disorder-induced conductor-insulator transition, quantum Hall effect and graphene-like physics in such a tunable 2D atomic gas in optical lattices.

Three-dimensional ultrastructural analyses of anterior pituitary gland expose spatial relationships between endocrine cell secretory granule localization and capillary distribution.

PubMed

Yoshitomi, Munetake; Ohta, Keisuke; Kanazawa, Tomonoshin; Togo, Akinobu; Hirashima, Shingo; Uemura, Kei-Ichiro; Okayama, Satoko; Morioka, Motohiro; Nakamura, Kei-Ichiro

2016-10-31

Endocrine and endothelial cells of the anterior pituitary gland frequently make close appositions or contacts, and the secretory granules of each endocrine cell tend to accumulate at the perivascular regions, which is generally considered to facilitate secretory functions of these cells. However, three-dimensional relationships between the localization pattern of secretory granules and blood vessels are not fully understood. To define and characterize these spatial relationships, we used scanning electron microscopy (SEM) three-dimensional reconstruction method based on focused ion-beam slicing and scanning electron microscopy (FIB/SEM). Full three-dimensional cellular architectures of the anterior pituitary tissue at ultrastructural resolution revealed that about 70% of endocrine cells were in apposition to the endothelial cells, while almost 30% of endocrine cells were entirely isolated from perivascular space in the tissue. Our three-dimensional analyses also visualized the distribution pattern of secretory granules in individual endocrine cells, showing an accumulation of secretory granules in regions in close apposition to the blood vessels in many cases. However, secretory granules in cells isolated from the perivascular region tended to distribute uniformly in the cytoplasm of these cells. These data suggest that the cellular interactions between the endocrine and endothelial cells promote an uneven cytoplasmic distribution of the secretory granules.

Three-dimensional Organotypic Cultures of Vestibular and Auditory Sensory Organs.

PubMed

Gnedeva, Ksenia; Hudspeth, A J; Segil, Neil

2018-06-01

The sensory organs of the inner ear are challenging to study in mammals due to their inaccessibility to experimental manipulation and optical observation. Moreover, although existing culture techniques allow biochemical perturbations, these methods do not provide a means to study the effects of mechanical force and tissue stiffness during development of the inner ear sensory organs. Here we describe a method for three-dimensional organotypic culture of the intact murine utricle and cochlea that overcomes these limitations. The technique for adjustment of a three-dimensional matrix stiffness described here permits manipulation of the elastic force opposing tissue growth. This method can therefore be used to study the role of mechanical forces during inner ear development. Additionally, the cultures permit virus-mediated gene delivery, which can be used for gain- and loss-of-function experiments. This culture method preserves innate hair cells and supporting cells and serves as a potentially superior alternative to the traditional two-dimensional culture of vestibular and auditory sensory organs.

Becoming a high-fidelity - super - imitator: what are the contributions of social and individual learning?

PubMed

Subiaul, Francys; Patterson, Eric M; Schilder, Brian; Renner, Elizabeth; Barr, Rachel

2015-11-01

In contrast to other primates, human children's imitation performance goes from low to high fidelity soon after infancy. Are such changes associated with the development of other forms of learning? We addressed this question by testing 215 children (26-59 months) on two social conditions (imitation, emulation) - involving a demonstration - and two asocial conditions (trial-and-error, recall) - involving individual learning - using two touchscreen tasks. The tasks required responding to either three different pictures in a specific picture order (Cognitive: Airplane→Ball→Cow) or three identical pictures in a specific spatial order (Motor-Spatial: Up→Down→Right). There were age-related improvements across all conditions and imitation, emulation and recall performance were significantly better than trial-and-error learning. Generalized linear models demonstrated that motor-spatial imitation fidelity was associated with age and motor-spatial emulation performance, but cognitive imitation fidelity was only associated with age. While this study provides evidence for multiple imitation mechanisms, the development of one of those mechanisms - motor-spatial imitation - may be bootstrapped by the development of another social learning skill - motor-spatial emulation. Together, these findings provide important clues about the development of imitation, which is arguably a distinctive feature of the human species. © 2014 John Wiley & Sons Ltd.

Three-dimensional Model of Tissue and Heavy Ions Effects

NASA Technical Reports Server (NTRS)

Ponomarev, Artem L.; Sundaresan, Alamelu; Huff, Janice L.; Cucinotta, Francis A.

2007-01-01

A three-dimensional tissue model was incorporated into a new Monte Carlo algorithm that simulates passage of heavy ions in a tissue box . The tissue box was given as a realistic model of tissue based on confocal microscopy images. The action of heavy ions on the cellular matrix for 2- or 3-dimensional cases was simulated. Cells were modeled as a cell culture monolayer in one example, where the data were taken directly from microscopy (2-d cell matrix), and as a multi-layer obtained from confocal microscopy (3-d case). Image segmentation was used to identify cells with precise areas/volumes in an irradiated cell culture monolayer, and slices of tissue with many cell layers. The cells were then inserted into the model box of the simulated physical space pixel by pixel. In the case of modeled tissues (3-d), the tissue box had periodic boundary conditions imposed, which extrapolates the technique to macroscopic volumes of tissue. For the real tissue (3-d), specific spatial patterns for cell apoptosis and necrosis are expected. The cell patterns were modeled based on action cross sections for apoptosis and necrosis estimated from current experimental data. A spatial correlation function indicating a higher spatial concentration of damaged cells from heavy ions relative to the low-LET radiation cell damage pattern is presented. The spatial correlation effects among necrotic cells can help studying microlesions in organs, and probable effects of directionality of heavy ion radiation on epithelium and endothelium.

Multiscale reconstruction of a synthetic biomimetic micro-niche for enhancing and monitoring the differentiation of stem cells.

PubMed

Li, Rui; Li, Jinming; Xu, Jianbin; Hong Wong, Dexter Siu; Chen, Xiaoyu; Yuan, Weihao; Bian, Liming

2018-05-04

Stem cells reside in a three-dimensional (3D) niche microenvironment, which provides specific cues, including cell-matrix interactions and soluble factors, that are essential to the differentiation of stem cells in vivo. Herein we demonstrate a general approach to the synthetic reconstruction of 3D biomimetic niche environment of stem cells by the multiscale combination of macroscopic porous hydrogels and a nanoscale upconversion nanoparticles (UCNP)-based nanocomplex. The porous biopolymeric hydrogels emulate the spongy bone microstructure and provide 3D environment conducive to the differentiation of seeded stem cells. The UCNP-based nanocomplex (Pur-UCNP-peptide-FITC), which is stably encapsulated in the porous hydrogels, emulates the repertoire of inductive factors in bone matrix by maintaining localized long-term delivery of inductive small molecules. The nanocomplex also generates biomarker-specific reporting emissions that correlate with the extent and stage of differentiation of the stem cells in synthetic niche, thereby allowing long-term tracking of stem cell fate in a non-contact, non-destructive, and potentially high-throughput manner in living cultures. To the best of our knowledge, this is first demonstration of synthetic niche reconstruction. The modular nature of this synthetic niche platform allows various parameters to be easily tuned to accommodate a variety of fundamental studies of dynamic cellular events under controlled settings. Copyright © 2018 Elsevier Ltd. All rights reserved.

3-d finite element model development for biomechanics: a software demonstration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hollerbach, K.; Hollister, A.M.; Ashby, E.

1997-03-01

Finite element analysis is becoming an increasingly important part of biomechanics and orthopedic research, as computational resources become more powerful, and data handling algorithms become more sophisticated. Until recently, tools with sufficient power did not exist or were not accessible to adequately model complicated, three-dimensional, nonlinear biomechanical systems. In the past, finite element analyses in biomechanics have often been limited to two-dimensional approaches, linear analyses, or simulations of single tissue types. Today, we have the resources to model fully three-dimensional, nonlinear, multi-tissue, and even multi-joint systems. The authors will present the process of developing these kinds of finite element models,more » using human hand and knee examples, and will demonstrate their software tools.« less

Three-dimensional reconstruction of frozen and thawed plant tissues from microscopic images

USDA-ARS?s Scientific Manuscript database

Histological analysis of frozen and thawed plants has been conducted for many years but the observation of individual sections only provides a 2 dimensional representation of a 3 dimensional phenomenon. Most techniques for viewing internal plant structure in 3 dimensions is either low in resolution...

Playing relativistic billiards beyond graphene

NASA Astrophysics Data System (ADS)

Sadurní, E.; Seligman, T. H.; Mortessagne, F.

2010-05-01

The possibility of using hexagonal structures in general, and graphene in particular, to emulate the Dirac equation is the topic under consideration here. We show that Dirac oscillators with or without rest mass can be emulated by distorting a tight-binding model on a hexagonal structure. In the quest to make a toy model for such relativistic equations, we first show that a hexagonal lattice of attractive potential wells would be a good candidate. Firstly, we consider the corresponding one-dimensional (1D) model giving rise to a 1D Dirac oscillator and then construct explicitly the deformations needed in the 2D case. Finally, we discuss how such a model can be implemented as an electromagnetic billiard using arrays of dielectric resonators between two conducting plates that ensure evanescent modes outside the resonators for transversal electric modes, and we describe a feasible experimental setup.

"Deep-media culture condition" promoted lumen formation of endothelial cells within engineered three-dimensional tissues in vitro.

PubMed

Sekiya, Sachiko; Shimizu, Tatsuya; Yamato, Masayuki; Okano, Teruo

2011-03-01

In the field of tissue engineering, the induction of microvessels into tissues is an important task because of the need to overcome diffusion limitations of oxygen and nutrients within tissues. Powerful methods to create vessels in engineered tissues are needed for creating real living tissues. In this study, we utilized three-dimensional (3D) highly cell dense tissues fabricated by cell sheet technology. The 3D tissue constructs are close to living-cell dense tissue in vivo. Additionally, creating an endothelial cell (EC) network within tissues promoted neovascularization promptly within the tissue after transplantation in vivo. Compared to the conditions in vivo, however, common in vitro cell culture conditions provide a poor environment for creating lumens within 3D tissue constructs. Therefore, for determining adequate conditions for vascularizing engineered tissue in vitro, our 3D tissue constructs were cultured under a "deep-media culture conditions." Compared to the control conditions, the morphology of ECs showed a visibly strained cytoskeleton, and the density of lumen formation within tissues increased under hydrostatic pressure conditions. Moreover, the increasing expression of vascular endothelial cadherin in the lumens suggested that the vessels were stabilized in the stimulated tissues compared with the control. These findings suggested that deep-media culture conditions improved lumen formation in engineered tissues in vitro.

CUBIC pathology: three-dimensional imaging for pathological diagnosis.

PubMed

Nojima, Satoshi; Susaki, Etsuo A; Yoshida, Kyotaro; Takemoto, Hiroyoshi; Tsujimura, Naoto; Iijima, Shohei; Takachi, Ko; Nakahara, Yujiro; Tahara, Shinichiro; Ohshima, Kenji; Kurashige, Masako; Hori, Yumiko; Wada, Naoki; Ikeda, Jun-Ichiro; Kumanogoh, Atsushi; Morii, Eiichi; Ueda, Hiroki R

2017-08-24

The examination of hematoxylin and eosin (H&E)-stained tissues on glass slides by conventional light microscopy is the foundation for histopathological diagnosis. However, this conventional method has some limitations in x-y axes due to its relatively narrow range of observation area and in z-axis due to its two-dimensionality. In this study, we applied a CUBIC pipeline, which is the most powerful tissue-clearing and three-dimensional (3D)-imaging technique, to clinical pathology. CUBIC was applicable to 3D imaging of both normal and abnormal patient-derived, human lung and lymph node tissues. Notably, the combination of deparaffinization and CUBIC enabled 3D imaging of specimens derived from paraffin-embedded tissue blocks, allowing quantitative evaluation of nuclear and structural atypia of an archival malignant lymphoma tissue. Furthermore, to examine whether CUBIC can be applied to practical use in pathological diagnosis, we performed a histopathological screening of a lymph node metastasis based on CUBIC, which successfully improved the sensitivity in detecting minor metastatic carcinoma nodules in lymph nodes. Collectively, our results indicate that CUBIC significantly contributes to retrospective and prospective clinicopathological diagnosis, which might lead to the establishment of a novel field of medical science based on 3D histopathology.

Effects of different rapid maxillary expansion appliances on facial soft tissues using three-dimensional imaging.

PubMed

Altındiş, Sedat; Toy, Ebubekir; Başçiftçi, Faruk Ayhan

2016-07-01

To determine three-dimensional (3D) effects of three different rapid maxillary expansion (RME) appliances on facial soft tissues. Forty-two children (18 boys, 24 girls) who required RME treatment were included in this study. Patients were randomly divided into three equal groups: banded RME, acrylic splint RME, and modified acrylic splint RME. For each patient, 3D images were obtained before treatment (T1) and at the end of the 3-month retention (T2) with the 3dMD system. When three RME appliances were compared in terms of the effects on the facial soft tissues, there were no significant differences among them. The mouth and nasal width showed a significant increase in all groups. Although the effect of the acrylic splint RME appliances on total face height was less than that of the banded RME, there was no significant difference between the appliances. The effect of the modified acrylic splint appliance on the upper lip was significant according to the volumetric measurements (P < .01). There were no significant differences among three RME appliances on the facial soft tissues. The modified acrylic splint RME produced a more protrusive effect on the upper lip.

[Development of computer aided forming techniques in manufacturing scaffolds for bone tissue engineering].

PubMed

Wei, Xuelei; Dong, Fuhui

2011-12-01

To review recent advance in the research and application of computer aided forming techniques for constructing bone tissue engineering scaffolds. The literature concerning computer aided forming techniques for constructing bone tissue engineering scaffolds in recent years was reviewed extensively and summarized. Several studies over last decade have focused on computer aided forming techniques for bone scaffold construction using various scaffold materials, which is based on computer aided design (CAD) and bone scaffold rapid prototyping (RP). CAD include medical CAD, STL, and reverse design. Reverse design can fully simulate normal bone tissue and could be very useful for the CAD. RP techniques include fused deposition modeling, three dimensional printing, selected laser sintering, three dimensional bioplotting, and low-temperature deposition manufacturing. These techniques provide a new way to construct bone tissue engineering scaffolds with complex internal structures. With rapid development of molding and forming techniques, computer aided forming techniques are expected to provide ideal bone tissue engineering scaffolds.

A review of rapid prototyping techniques for tissue engineering purposes.

PubMed

Peltola, Sanna M; Melchels, Ferry P W; Grijpma, Dirk W; Kellomäki, Minna

2008-01-01

Rapid prototyping (RP) is a common name for several techniques, which read in data from computer-aided design (CAD) drawings and manufacture automatically three-dimensional objects layer-by-layer according to the virtual design. The utilization of RP in tissue engineering enables the production of three-dimensional scaffolds with complex geometries and very fine structures. Adding micro- and nanometer details into the scaffolds improves the mechanical properties of the scaffold and ensures better cell adhesion to the scaffold surface. Thus, tissue engineering constructs can be customized according to the data acquired from the medical scans to match the each patient's individual needs. In addition RP enables the control of the scaffold porosity making it possible to fabricate applications with desired structural integrity. Unfortunately, every RP process has its own unique disadvantages in building tissue engineering scaffolds. Hence, the future research should be focused on the development of RP machines designed specifically for fabrication of tissue engineering scaffolds, although RP methods already can serve as a link between tissue and engineering.

Multiplexed and scalable super-resolution imaging of three-dimensional protein localization in size-adjustable tissues.

PubMed

Ku, Taeyun; Swaney, Justin; Park, Jeong-Yoon; Albanese, Alexandre; Murray, Evan; Cho, Jae Hun; Park, Young-Gyun; Mangena, Vamsi; Chen, Jiapei; Chung, Kwanghun

2016-09-01

The biology of multicellular organisms is coordinated across multiple size scales, from the subnanoscale of molecules to the macroscale, tissue-wide interconnectivity of cell populations. Here we introduce a method for super-resolution imaging of the multiscale organization of intact tissues. The method, called magnified analysis of the proteome (MAP), linearly expands entire organs fourfold while preserving their overall architecture and three-dimensional proteome organization. MAP is based on the observation that preventing crosslinking within and between endogenous proteins during hydrogel-tissue hybridization allows for natural expansion upon protein denaturation and dissociation. The expanded tissue preserves its protein content, its fine subcellular details, and its organ-scale intercellular connectivity. We use off-the-shelf antibodies for multiple rounds of immunolabeling and imaging of a tissue's magnified proteome, and our experiments demonstrate a success rate of 82% (100/122 antibodies tested). We show that specimen size can be reversibly modulated to image both inter-regional connections and fine synaptic architectures in the mouse brain.

A Review of the Responses of Two- and Three-Dimensional Engineered Tissues to Electric Fields

PubMed Central

Hronik-Tupaj, Marie

2012-01-01

The application of external biophysical signals is one approach to tissue engineering that is explored less often than more traditional additions of exogenous biochemical and chemical factors to direct cell and tissue outcomes. The study of bioelectromagnetism and the field of electrotherapeutics have evolved over the years, and we review biocompatible electric stimulation devices and their successful application to tissue growth. Specifically, information on capacitively coupled alternating current, inductively coupled alternating current, and direct current devices is described. Cell and tissue responses from the application of these devices, including two- and three-dimensional in vitro studies and in vivo studies, are reviewed with regard to cell proliferation, adhesion, differentiation, morphology, and migration and tissue function. The current understanding of cellular mechanisms related to electric stimulation is detailed. The advantages of electric stimulation are compared with those pf other techniques, and areas in which electric fields are used as an adjuvant therapy for healing and regeneration are discussed. PMID:22046979

Tissue constructs: platforms for basic research and drug discovery.

PubMed

Elson, Elliot L; Genin, Guy M

2016-02-06

The functions, form and mechanical properties of cells are inextricably linked to their extracellular environment. Cells from solid tissues change fundamentally when, isolated from this environment, they are cultured on rigid two-dimensional substrata. These changes limit the significance of mechanical measurements on cells in two-dimensional culture and motivate the development of constructs with cells embedded in three-dimensional matrices that mimic the natural tissue. While measurements of cell mechanics are difficult in natural tissues, they have proven effective in engineered tissue constructs, especially constructs that emphasize specific cell types and their functions, e.g. engineered heart tissues. Tissue constructs developed as models of disease also have been useful as platforms for drug discovery. Underlying the use of tissue constructs as platforms for basic research and drug discovery is integration of multiscale biomaterials measurement and computational modelling to dissect the distinguishable mechanical responses separately of cells and extracellular matrix from measurements on tissue constructs and to quantify the effects of drug treatment on these responses. These methods and their application are the main subjects of this review.

Tissue constructs: platforms for basic research and drug discovery

PubMed Central

Elson, Elliot L.; Genin, Guy M.

2016-01-01

The functions, form and mechanical properties of cells are inextricably linked to their extracellular environment. Cells from solid tissues change fundamentally when, isolated from this environment, they are cultured on rigid two-dimensional substrata. These changes limit the significance of mechanical measurements on cells in two-dimensional culture and motivate the development of constructs with cells embedded in three-dimensional matrices that mimic the natural tissue. While measurements of cell mechanics are difficult in natural tissues, they have proven effective in engineered tissue constructs, especially constructs that emphasize specific cell types and their functions, e.g. engineered heart tissues. Tissue constructs developed as models of disease also have been useful as platforms for drug discovery. Underlying the use of tissue constructs as platforms for basic research and drug discovery is integration of multiscale biomaterials measurement and computational modelling to dissect the distinguishable mechanical responses separately of cells and extracellular matrix from measurements on tissue constructs and to quantify the effects of drug treatment on these responses. These methods and their application are the main subjects of this review. PMID:26855763

Apico-basal forces exerted by apoptotic cells drive epithelium folding.

PubMed

Monier, Bruno; Gettings, Melanie; Gay, Guillaume; Mangeat, Thomas; Schott, Sonia; Guarner, Ana; Suzanne, Magali

2015-02-12

Epithelium folding is a basic morphogenetic event that is essential in transforming simple two-dimensional epithelial sheets into three-dimensional structures in both vertebrates and invertebrates. Folding has been shown to rely on apical constriction. The resulting cell-shape changes depend either on adherens junction basal shift or on a redistribution of myosin II, which could be driven by mechanical signals. Yet the initial cellular mechanisms that trigger and coordinate cell remodelling remain largely unknown. Here we unravel the active role of apoptotic cells in initiating morphogenesis, thus revealing a novel mechanism of epithelium folding. We show that, in a live developing tissue, apoptotic cells exert a transient pulling force upon the apical surface of the epithelium through a highly dynamic apico-basal myosin II cable. The apoptotic cells then induce a non-autonomous increase in tissue tension together with cortical myosin II apical stabilization in the surrounding tissue, eventually resulting in epithelium folding. Together our results, supported by a theoretical biophysical three-dimensional model, identify an apoptotic myosin-II-dependent signal as the initial signal leading to cell reorganization and tissue folding. This work further reveals that, far from being passively eliminated as generally assumed (for example, during digit individualization), apoptotic cells actively influence their surroundings and trigger tissue remodelling through regulation of tissue tension.

Extracting three-dimensional orientation and tractography of myofibers using optical coherence tomography

PubMed Central

Gan, Yu; Fleming, Christine P.

2013-01-01

Abnormal changes in orientation of myofibers are associated with various cardiac diseases such as arrhythmia, irregular contraction, and cardiomyopathy. To extract fiber information, we present a method of quantifying fiber orientation and reconstructing three-dimensional tractography of myofibers using optical coherence tomography (OCT). A gradient based algorithm was developed to quantify fiber orientation in three dimensions and particle filtering technique was employed to track myofibers. Prior to image processing, three-dimensional image data set were acquired from all cardiac chambers and ventricular septum of swine hearts using OCT system without optical clearing. The algorithm was validated through rotation test and comparison with manual measurements. The experimental results demonstrate that we are able to visualize three-dimensional fiber tractography in myocardium tissues. PMID:24156071

Alignment hierarchies: engineering architecture from the nanometre to the micrometre scale.

PubMed

Kureshi, Alvena; Cheema, Umber; Alekseeva, Tijna; Cambrey, Alison; Brown, Robert

2010-12-06

Natural tissues are built of metabolites, soluble proteins and solid extracellular matrix components (largely fibrils) together with cells. These are configured in highly organized hierarchies of structure across length scales from nanometre to millimetre, with alignments that are dominated by anisotropies in their fibrillar matrix. If we are to successfully engineer tissues, these hierarchies need to be mimicked with an understanding of the interaction between them. In particular, the movement of different elements of the tissue (e.g. molecules, cells and bulk fluids) is controlled by matrix structures at distinct scales. We present three novel systems to introduce alignment of collagen fibrils, cells and growth factor gradients within a three-dimensional collagen scaffold using fluid flow, embossing and layering of construct. Importantly, these can be seen as different parts of the same hierarchy of three-dimensional structure, as they are all formed into dense collagen gels. Fluid flow aligns collagen fibrils at the nanoscale, embossed topographical features provide alignment cues at the microscale and introducing layered configuration to three-dimensional collagen scaffolds provides microscale- and mesoscale-aligned pathways for protein factor delivery as well as barriers to confine protein diffusion to specific spatial directions. These seemingly separate methods can be employed to increase complexity of simple extracellular matrix scaffolds, providing insight into new approaches to directly fabricate complex physical and chemical cues at different hierarchical scales, similar to those in natural tissues.

Morphological adaptations in breast cancer cells as a function of prolonged passaging on compliant substrates

PubMed Central

Syed, Sana; Schober, Joseph; Blanco, Alexandra

2017-01-01

Standard tissue culture practices involve propagating cells on tissue culture polystyrene (TCP) dishes, which are flat, 2-dimensional (2D) and orders of magnitude stiffer than most tissues in the body. Such simplified conditions lead to phenotypical cell changes and altered cell behaviors. Hence, much research has been focused on developing novel biomaterials and culture conditions that more closely emulate in vivo cell microenvironments. In particular, biomaterial stiffness has emerged as a key property that greatly affects cell behaviors such as adhesion, morphology, proliferation and motility among others. Here we ask whether cells that have been conditioned to TCP, would still show significant dependence on substrate stiffness if they are first pre-adapted to a more physiologically relevant environment. We used two commonly utilized breast cancer cell lines, namely MDA-MB-231 and MCF-7, and examined the effect of prolonged cell culturing on polyacrylamide substrates of varying compliance. We followed changes in cell adhesion, proliferation, shape factor, spreading area and spreading rate. After pre-adaptation, we noted diminished differences in cell behaviors when comparing between soft (1 kPa) and stiff (103 kPa) gels as well as rigid TCP control. Prolonged culturing of cells on complaint substrates further influenced responses of pre-adapted cells when transferred back to TCP. Our results have implications for the study of stiffness-dependent cell behaviors and indicate that cell pre-adaptation to the substrate needs consideration. PMID:29136040

Emergence of Three-Dimensional Printing Technology and Its Utility in Spine Surgery.

PubMed

Gadia, Akshay; Shah, Kunal; Nene, Abhay

2018-04-01

In the last decade, spine surgery has advanced tremendously. Tissue engineering and three-dimensional (3D) printing/additive manufacturing have provided promising new research avenues in the fields of medicine and orthopedics in recent literature, and their emergent role in spine surgery is encouraging. We reviewed recent articles that highlighted the role of 3D printing in medicine, orthopedics, and spine surgery and summarized the utility of 3D printing. 3D printing has shown promising results in various aspects of spine surgery and can be a useful tool for spine surgeons. The growing research on tissue bioengineering and its application in conjunction with additive manufacturing has revealed great potential for tissue bioengineering in the treatment of spinal ailments.

Emergence of Three-Dimensional Printing Technology and Its Utility in Spine Surgery

PubMed Central

Gadia, Akshay; Nene, Abhay

2018-01-01

In the last decade, spine surgery has advanced tremendously. Tissue engineering and three-dimensional (3D) printing/additive manufacturing have provided promising new research avenues in the fields of medicine and orthopedics in recent literature, and their emergent role in spine surgery is encouraging. We reviewed recent articles that highlighted the role of 3D printing in medicine, orthopedics, and spine surgery and summarized the utility of 3D printing. 3D printing has shown promising results in various aspects of spine surgery and can be a useful tool for spine surgeons. The growing research on tissue bioengineering and its application in conjunction with additive manufacturing has revealed great potential for tissue bioengineering in the treatment of spinal ailments. PMID:29713420

Three-Dimensional Cell Culture Models for Infectious Disease and Drug Development

NASA Technical Reports Server (NTRS)

Nickerson, Cheryl A.; Honer zu Bentrup, Kerstin; Ott, C. Mark

2005-01-01

Three-dimensional (3-D) cell cultures hold enormous potential to advance our understanding of infectious disease and to effectively translate basic cellular research into clinical applications. Using novel NASA bioreactor technology, the rotating wall vessel (RWV), we have engineered physiologically relevant 3-D human tissue culture models for infectious disease studies. The design of the RWV is based on the understanding that organs and tissues function in a 3-D environment, and that this 3-D architecture is critical for the differentiated form and function of tissues in vivo. The RWV provides large numbers of cells which are amenable to a wide variety of experimental manipulations and provides an easy, reproducible, and cost-effective approach to enhance differentiated features of cell culture models.

The third dimension bridges the gap between cell culture and live tissue.

PubMed

Pampaloni, Francesco; Reynaud, Emmanuel G; Stelzer, Ernst H K

2007-10-01

Moving from cell monolayers to three-dimensional (3D) cultures is motivated by the need to work with cellular models that mimic the functions of living tissues. Essential cellular functions that are present in tissues are missed by 'petri dish'-based cell cultures. This limits their potential to predict the cellular responses of real organisms. However, establishing 3D cultures as a mainstream approach requires the development of standard protocols, new cell lines and quantitative analysis methods, which include well-suited three-dimensional imaging techniques. We believe that 3D cultures will have a strong impact on drug screening and will also decrease the use of laboratory animals, for example, in the context of toxicity assays.

Three-dimensional organotypic culture: experimental models of mammalian biology and disease

PubMed Central

Shamir, Eliah R.; Ewald, Andrew J.

2015-01-01

Mammalian organs are challenging to study as they are fairly inaccessible to experimental manipulation and optical observation. Recent advances in three-dimensional (3D) culture techniques, coupled with the ability to independently manipulate genetic and microenvironmental factors, have enabled the real-time study of mammalian tissues. These systems have been used to visualize the cellular basis of epithelial morphogenesis, to test the roles of specific genes in regulating cell behaviours within epithelial tissues and to elucidate the contribution of microenvironmental factors to normal and disease processes. Collectively, these novel models can be used to answer fundamental biological questions and generate replacement human tissues, and they enable testing of novel therapeutic approaches, often using patient-derived cells. PMID:25237826

Three-Dimensional Printing of Nanomaterial Scaffolds for Complex Tissue Regeneration

PubMed Central

O'Brien, Christopher M.; Holmes, Benjamin; Faucett, Scott

2015-01-01

Three-dimensional (3D) printing has recently expanded in popularity, and become the cutting edge of tissue engineering research. A growing emphasis from clinicians on patient-specific care, coupled with an increasing knowledge of cellular and biomaterial interaction, has led researchers to explore new methods that enable the greatest possible control over the arrangement of cells and bioactive nanomaterials in defined scaffold geometries. In this light, the cutting edge technology of 3D printing also enables researchers to more effectively compose multi-material and cell-laden scaffolds with less effort. In this review, we explore the current state of 3D printing with a focus on printing of nanomaterials and their effect on various complex tissue regeneration applications. PMID:25084122

[Nasolabial muscle finite-element study and clinical application].

PubMed

Yin, Ningbei; Wu, Jiajun; Chen, Bo; Wang, Yongqian; Song, Tao; Ma, Hengyuan

2015-05-01

To investigate the nasolabial muscle anatomy and biomechanical characteristics. Micro-computed tomography scan was performed in 8 cases of spontaneous abortion fetus lip nasal specimens to construct a three-dimensional model. The nasolabial muscle structure was analyzed using Mimics software. The three-dimensional configuration model of nasolabial muscle was established based on local anatomy and tissue section, and compared with tissue section. Three dimensional finite element analysis was performed on lip nasal muscle related biomechanics and surface deformation in Application verification was carried out in 263 cases of microform cleft lip surgery. There was close relationship between nasolabial muscle. The nasolabial muscle tension system was constituted, based on which a new cleft lip repair surgery was designed and satisfied results were achieved. There is close relationship among nasolabial muscle in anatomy, histology and biomechanics. To obtain better effect, cleft lip repair should be performed on the basis of recovering muscle tension system.

A k-space method for acoustic propagation using coupled first-order equations in three dimensions.

PubMed

Tillett, Jason C; Daoud, Mohammad I; Lacefield, James C; Waag, Robert C

2009-09-01

A previously described two-dimensional k-space method for large-scale calculation of acoustic wave propagation in tissues is extended to three dimensions. The three-dimensional method contains all of the two-dimensional method features that allow accurate and stable calculation of propagation. These features are spectral calculation of spatial derivatives, temporal correction that produces exact propagation in a homogeneous medium, staggered spatial and temporal grids, and a perfectly matched boundary layer. Spectral evaluation of spatial derivatives is accomplished using a fast Fourier transform in three dimensions. This computational bottleneck requires all-to-all communication; execution time in a parallel implementation is therefore sensitive to node interconnect latency and bandwidth. Accuracy of the three-dimensional method is evaluated through comparisons with exact solutions for media having spherical inhomogeneities. Large-scale calculations in three dimensions were performed by distributing the nearly 50 variables per voxel that are used to implement the method over a cluster of computers. Two computer clusters used to evaluate method accuracy are compared. Comparisons of k-space calculations with exact methods including absorption highlight the need to model accurately the medium dispersion relationships, especially in large-scale media. Accurately modeled media allow the k-space method to calculate acoustic propagation in tissues over hundreds of wavelengths.

Three-dimensional fuse deposition modeling of tissue-simulating phantom for biomedical optical imaging

NASA Astrophysics Data System (ADS)

Dong, Erbao; Zhao, Zuhua; Wang, Minjie; Xie, Yanjun; Li, Shidi; Shao, Pengfei; Cheng, Liuquan; Xu, Ronald X.

2015-12-01

Biomedical optical devices are widely used for clinical detection of various tissue anomalies. However, optical measurements have limited accuracy and traceability, partially owing to the lack of effective calibration methods that simulate the actual tissue conditions. To facilitate standardized calibration and performance evaluation of medical optical devices, we develop a three-dimensional fuse deposition modeling (FDM) technique for freeform fabrication of tissue-simulating phantoms. The FDM system uses transparent gel wax as the base material, titanium dioxide (TiO2) powder as the scattering ingredient, and graphite powder as the absorption ingredient. The ingredients are preheated, mixed, and deposited at the designated ratios layer-by-layer to simulate tissue structural and optical heterogeneities. By printing the sections of human brain model based on magnetic resonance images, we demonstrate the capability for simulating tissue structural heterogeneities. By measuring optical properties of multilayered phantoms and comparing with numerical simulation, we demonstrate the feasibility for simulating tissue optical properties. By creating a rat head phantom with embedded vasculature, we demonstrate the potential for mimicking physiologic processes of a living system.

Three-dimensional macroporous nanoelectronic networks as minimally invasive brain probes

NASA Astrophysics Data System (ADS)

Xie, Chong; Liu, Jia; Fu, Tian-Ming; Dai, Xiaochuan; Zhou, Wei; Lieber, Charles M.

2015-12-01

Direct electrical recording and stimulation of neural activity using micro-fabricated silicon and metal micro-wire probes have contributed extensively to basic neuroscience and therapeutic applications; however, the dimensional and mechanical mismatch of these probes with the brain tissue limits their stability in chronic implants and decreases the neuron-device contact. Here, we demonstrate the realization of a three-dimensional macroporous nanoelectronic brain probe that combines ultra-flexibility and subcellular feature sizes to overcome these limitations. Built-in strains controlling the local geometry of the macroporous devices are designed to optimize the neuron/probe interface and to promote integration with the brain tissue while introducing minimal mechanical perturbation. The ultra-flexible probes were implanted frozen into rodent brains and used to record multiplexed local field potentials and single-unit action potentials from the somatosensory cortex. Significantly, histology analysis revealed filling-in of neural tissue through the macroporous network and attractive neuron-probe interactions, consistent with long-term biocompatibility of the device.

Real-time three-dimensional ultrasound-assisted axillary plexus block defines soft tissue planes.

PubMed

Clendenen, Steven R; Riutort, Kevin; Ladlie, Beth L; Robards, Christopher; Franco, Carlo D; Greengrass, Roy A

2009-04-01

Two-dimensional (2D) ultrasound is commonly used for regional block of the axillary brachial plexus. In this technical case report, we described a real-time three-dimensional (3D) ultrasound-guided axillary block. The difference between 2D and 3D ultrasound is similar to the difference between plain radiograph and computer tomography. Unlike 2D ultrasound that captures a planar image, 3D ultrasound technology acquires a 3D volume of information that enables multiple planes of view by manipulating the image without movement of the ultrasound probe. Observation of the brachial plexus in cross-section demonstrated distinct linear hyperechoic tissue structures (loose connective tissue) that initially inhibited the flow of the local anesthesia. After completion of the injection, we were able to visualize the influence of arterial pulsation on the spread of the local anesthesia. Possible advantages of this novel technology over current 2D methods are wider image volume and the capability to manipulate the planes of the image without moving the probe.

Complex structures from patterned cell sheets

PubMed Central

Misra, M.; Audoly, B.; Shvartsman, S. Y.

2017-01-01

The formation of three-dimensional structures from patterned epithelial sheets plays a key role in tissue morphogenesis. An important class of morphogenetic mechanisms relies on the spatio-temporal control of apical cell contractility, which can result in the localized bending of cell sheets and in-plane cell rearrangements. We have recently proposed a modified vertex model that can be used to systematically explore the connection between the two-dimensional patterns of cell properties and the emerging three-dimensional structures. Here we review the proposed modelling framework and illustrate it through the computational analysis of the vertex model that captures the salient features of the formation of the dorsal appendages during Drosophila oogenesis. This article is part of the themed issue ‘Systems morphodynamics: understanding the development of tissue hardware’. PMID:28348251

Cooling Atomic Gases With Disorder

DOE PAGES

Paiva, Thereza; Khatami, Ehsan; Yang, Shuxiang; ...

2015-12-10

Cold atomic gases have proven capable of emulating a number of fundamental condensed matter phenomena including Bose-Einstein condensation, the Mott transition, Fulde-Ferrell-Larkin-Ovchinnikov pairing, and the quantum Hall effect. Cooling to a low enough temperature to explore magnetism and exotic superconductivity in lattices of fermionic atoms remains a challenge. Here in this paper, we propose a method to produce a low temperature gas by preparing it in a disordered potential and following a constant entropy trajectory to deliver the gas into a nondisordered state which exhibits these incompletely understood phases. We show, using quantum Monte Carlo simulations, that we can approachmore » the Néel temperature of the three-dimensional Hubbard model for experimentally achievable parameters. Recent experimental estimates suggest the randomness required lies in a regime where atom transport and equilibration are still robust.« less

Modifying three-dimensional scaffolds from novel nanocomposite materials using dissolvable porogen particles for use in liver tissue engineering

PubMed Central

Fuller, Barry; Seldon, Clare; Davidson, Brian; Seifalian, Alexander

2013-01-01

Background: Although hepatocytes have a remarkable regenerative power, the rapidity of acute liver failure makes liver transplantation the only definitive treatment. Attempts to incorporate engineered three-dimensional liver tissue in bioartificial liver devices or in implantable tissue constructs, to treat or bridge patients to self-recovery, were met with many challenges, amongst which is to find suitable polymeric matrices. We studied the feasibility of utilising nanocomposite polymers in three-dimensional scaffolds for hepatocytes. Materials and methods: Hepatocytes (HepG2) were seeded on a flat sheet and in three-dimensional scaffolds made of a nanocomposite polymer (Polyhedral Oligomeric Silsesquioxane [POSS]-modified polycaprolactone urea urethane) alone as well as with porogen particles, i.e. glucose, sodium bicarbonate and sodium chloride. The scaffold architecture, cell attachment and morphology were studied with scanning electron microscopy, and we assessed cell viability and functionality. Results: Cell attachment to the scaffolds was demonstrated. The scaffold made with glucose particles as porogen showed a narrower range of pore size with higher porosity and better inter-pore communications and seemed to encourage near normal cell morphology. There was a steady increase of albumin secretion throughout the experiment while the control (monolayer cell culture) showed a steep decrease after day 7. At the end of the experiment, there was no significant difference in viability and functionality between the scaffolds and the control. Conclusion: In this initial study, porogen particles were used to modify the scaffolds produced from the novel polymer. Although there was no significance against the control in functionality and viability, the demonstrable attachment on scanning electron microscopy suggest potential roles for this polymer and in particular for scaffolds made with glucose particles in liver tissue engineering. PMID:22532408

Roles of Diffusion Dynamics in Stem Cell Signaling and Three-Dimensional Tissue Development.

PubMed

McMurtrey, Richard J

2017-09-15

Recent advancements in the ability to construct three-dimensional (3D) tissues and organoids from stem cells and biomaterials have not only opened abundant new research avenues in disease modeling and regenerative medicine but also have ignited investigation into important aspects of molecular diffusion in 3D cellular architectures. This article describes fundamental mechanics of diffusion with equations for modeling these dynamic processes under a variety of scenarios in 3D cellular tissue constructs. The effects of these diffusion processes and resultant concentration gradients are described in the context of the major molecular signaling pathways in stem cells that both mediate and are influenced by gas and nutrient concentrations, including how diffusion phenomena can affect stem cell state, cell differentiation, and metabolic states of the cell. The application of these diffusion models and pathways is of vital importance for future studies of developmental processes, disease modeling, and tissue regeneration.

Investigation of optimal method for inducing harmonic motion in tissue using a linear ultrasound phased array--a simulation study.

PubMed

Heikkilä, Janne; Hynynen, Kullervo

2006-04-01

Many noninvasive ultrasound techniques have been developed to explore mechanical properties of soft tissues. One of these methods, Localized Harmonic Motion Imaging (LHMI), has been proposed to be used for ultrasound surgery monitoring. In LHMI, dynamic ultrasound radiation-force stimulation induces displacements in a target that can be measured using pulse-echo imaging and used to estimate the elastic properties of the target. In this initial, simulation study, the use of a one-dimensional phased array is explored for the induction of the tissue motion. The study compares three different dual-frequency and amplitude-modulated single-frequency methods for the inducing tissue motion. Simulations were computed in a homogeneous soft-tissue volume. The Rayleigh integral was used in the simulations of the ultrasound fields and the tissue displacements were computed using a finite-element method (FEM). The simulations showed that amplitude-modulated sonication using a single frequency produced the largest vibration amplitude of the target tissue. These simulations demonstrate that the properties of the tissue motion are highly dependent on the sonication method and that it is important to consider the full three-dimensional distribution of the ultrasound field for controlling the induction of tissue motion.

Three-Dimensional Right Ventricular Strain Versus Volume Quantification in Heart Transplant Recipients in Relation to Pulmonary Artery Pressure.

PubMed

Sade, Leyla Elif; Kozan, Hatice; Eroglu, Serpil; Pirat, Bahar; Aydinalp, Alp; Sezgin, Atilla; Muderrisoglu, Haldun

2017-02-01

Residual pulmonary hypertension challenges the right ventricular function and worsens the prognosis in heart transplant recipients. The complex geometry of the right ventricle complicates estimation of its function with conventional transthoracic echocardiography. We evaluated right ventricular function in heart transplant recipients with the use of 3-dimensional echocardiography in relation to systolic pulmonary artery pressure. We performed 32 studies in 26 heart transplant patients, with 6 patients having 2 studies at different time points with different pressures and thus included. Right atrial volume, tricuspid annular plane systolic excursion, peak systolic annular velocity, fractional area change, and 2-dimensional speckle tracking longitudinal strain were obtained by 2-dimensional and tissue Doppler imaging. Three-dimensional right ventricular volumes, ejection fraction, and 3-dimensional right ventricular strain were obtained from the 3-dimensional data set by echocardiographers. Systolic pulmonary artery pressure was obtained during right heart catheterization. Overall mean systolic pulmonary artery pressure was 26 ± 7 mm Hg (range, 14-44 mmHg). Three-dimensional end-diastolic (r = 0.75; P < .001) and end-systolic volumes (r = 0.55; P = .001)correlated well with systolic pulmonary artery pressure. Right ventricular ejection fraction and right atrium volume also significantly correlated with systolic pulmonary artery pressure (r = 0.49 and P = .01 for both). However, right ventricular 2- and 3-dimensional strain, tricuspid annular plane systolic excursion, and tricuspid annular velocity did not. The effects of pulmonary hemodynamic burden on right ventricular function are better estimated by a 3-dimensional volume evaluation than with 3-dimensional longitudinal strain and other 2-dimensional and tissue Doppler measurements. These results suggest that the peculiar anatomy of the right ventricle necessitates 3-dimensional volume quantification in heart transplant recipients in relation to residual pulmonary hypertension.

[Advances in the research of application of collagen in three-dimensional bioprinting].

PubMed

Li, H H; Luo, P F; Sheng, J J; Liu, G C; Zhu, S H

2016-10-20

As a new industrial technology with characteristics of high precision and accuracy, the application of three-dimensional bioprinting technology is increasingly wide in the field of medical research. Collagen is one of the most common ingredients in tissue, and it has good biological material properties. There are many reports of using collagen as main composition of " ink" of three-dimensional bioprinting technology. However, the applied collagen is mainly from heterogeneous sources, which may cause some problems in application. Recombinant human source collagen can be obtained from microorganism fermentation by transgenic technology, but more research should be done to confirm its property. This article reviews the advances in the research of collagen and its biological application in three-dimensional bioprinting.

Toward a patient-specific tissue engineered vascular graft

PubMed Central

Best, Cameron; Strouse, Robert; Hor, Kan; Pepper, Victoria; Tipton, Amy; Kelly, John; Shinoka, Toshiharu; Breuer, Christopher

2018-01-01

Integrating three-dimensional printing with the creation of tissue-engineered vascular grafts could provide a readily available, patient-specific, autologous tissue source that could significantly improve outcomes in newborns with congenital heart disease. Here, we present the recent case of a candidate for our tissue-engineered vascular graft clinical trial deemed ineligible due to complex anatomical requirements and consider the application of three-dimensional printing technologies for a patient-specific graft. We 3D-printed a closed-disposable seeding device and validated that it performed equivalently to the traditional open seeding technique using ovine bone marrow–derived mononuclear cells. Next, our candidate’s preoperative imaging was reviewed to propose a patient-specific graft. A seeding apparatus was then designed to accommodate the custom graft and 3D-printed on a commodity fused deposition modeler. This exploratory feasibility study represents an important proof of concept advancing progress toward a rationally designed patient-specific tissue-engineered vascular graft for clinical application. PMID:29568478

Mouse embryonic stem cell culture for generation of three-dimensional retinal and cortical tissues.

PubMed

Eiraku, Mototsugu; Sasai, Yoshiki

2011-12-15

Generation of compound tissues with complex structures is a major challenge in cell biology. In this article, we describe a protocol for mouse embryonic stem cell (ESC) culture for in vitro generation of three-dimensional retinal tissue, comparing it with the culture protocol for cortical tissue generation. Dissociated ESCs are reaggregated in a 96-well plate with reduced cell-plate adhesion and cultured as floating aggregates. Retinal epithelium is efficiently generated when ESC aggregates are cultured in serum-free medium containing extracellular matrix proteins, spontaneously forming hemispherical vesicles and then progressively transforming into a shape reminiscent of the embryonic optic cup in 9-10 d. In long-term culture, the ESC-derived optic cup generates a fully stratified retinal tissue consisting of all major neural retinal components. In contrast, the cortical differentiation culture can be started without exogenous extracellular matrix proteins, and it generates stratified cortical epithelia consisting of four distinct layers in 13 d.

E-cadherin suppression accelerates squamous cell carcinoma progression in three-dimensional, human tissue constructs.

PubMed

Margulis, Alexander; Zhang, Weitian; Alt-Holland, Addy; Crawford, Howard C; Fusenig, Norbert E; Garlick, Jonathan A

2005-03-01

We studied the link between loss of E-cadherin-mediated adhesion and acquisition of malignant properties in three-dimensional, human tissue constructs that mimicked the initial stages of squamous cell cancer progression. Suppression of E-cadherin expression in early-stage, skin-derived tumor cells (HaCaT-II-4) was induced by cytoplasmic sequestration of beta-catenin upon stable expression of a dominant-negative E-cadherin fusion protein (H-2Kd-Ecad). In monolayer cultures, expression of H-2Kd-Ecad resulted in decreased levels of E-cadherin, redistribution of beta-catenin to the cytoplasm, and complete loss of intercellular adhesion when compared with control II-4 cells. This was accompanied by a 7-fold decrease in beta-catenin-mediated transcription and a 12-fold increase in cell migration. In three-dimensional constructs, E-cadherin-deficient tissues showed disruption of architecture, loss of adherens junctional proteins from cell contacts, and focal tumor cell invasion. Invasion was linked to activation of matrix metalloproteinase (MMP)-mediated degradation of basement membrane in H-2Kd-Ecad-expressing tissue constructs that was blocked by MMP inhibition (GM6001). Quantitative reverse transcription-PCR showed a 2.5-fold increase in MMP-2 and an 8-fold increase in MMP-9 in cells expressing the H-2Kd-Ecad fusion protein when compared with controls, and gel zymography showed increased MMP protein levels. Following surface transplantation of three-dimensional tissues, suppression of E-cadherin expression greatly accelerated tumorigenesis in vivo by inducing a switch to high-grade carcinomas that resulted in a 5-fold increase in tumor size after 4 weeks. Suppression of E-cadherin expression and loss of its function fundamentally modified squamous cell carcinoma progression by activating a highly invasive, aggressive tumor phenotype, whereas maintenance of E-cadherin prevented invasion in vitro and limited tumor progression in vivo.

[RESEARCH PROGRESS OF THREE-DIMENSIONAL PRINTING POROUS SCAFFOLDS FOR BONE TISSUE ENGINEERING].

PubMed

Wu, Tianqi; Yang, Chunxi

2016-04-01

To summarize the research progress of several three-dimensional (3-D)-printing scaffold materials in bone tissue engineering. The recent domestic and international articles about 3-D printing scaffold materials were reviewed and summarized. Compared with conventional manufacturing methods, 3-D printing has distinctive advantages, such as enhancing the controllability of the structure and increasing the productivity. In addition to the traditional metal and ceramic scaffolds, 3-D printing scaffolds carrying seeding cells and tissue factors as well as scaffolds filling particular drugs for special need have been paid more and more attention. The development of 3-D printing porous scaffolds have revealed new perspectives in bone repairing. But it is still at the initial stage, more basic and clinical researches are still needed.

Three-Dimensional Model of the Scatterer Distribution in Cirrhotic Liver

NASA Astrophysics Data System (ADS)

Yamaguchi, Tadashi; Nakamura, Keigo; Hachiya, Hiroyuki

2003-05-01

Ultrasonic B-mode images are affected by changes in scatterer distribution. It is hard to estimate the relationship between the ultrasonic image and the tissue structure quantitatively because we cannot observe the continuous stages of liver cirrhosis tissue clinically, particularly the beginning stage. In this paper, we propose a three-dimensional modeling method of scatterer distribution for normal and cirrhotic livers to confirm the influence of the change in the form of scatterer distribution on echo information. The algorithm of the method includes parameters which determine the expansion of nodules and fibers. Using the B-mode images which are obtained from these scatterer distributions, we analyze the relationship between the changes in the form of biological tissue and the changes in the B-mode images during progressive liver cirrhosis.

Fancy plots for SIG

DOE Office of Scientific and Technical Information (OSTI.GOV)

Norris, J.; Daniels, B.

1986-02-01

The fancy plot package is a group of five programs which allow the user to make 2- and 3-dimensional document quality plots from the SIG data base. The fancyplot package was developed using a DEC VT100 terminal fitted with a Digital Engineering Retrographics board and the QMS Laserprinter. If a terminal emulates the VT100/Retrographic terminal the package should work. A Pericom terminal for example, works perfectly. The fancy plot package is available to provide report-ready plots without resorting to cutting and pasting. This package is contained in programs FFP, TFP, TDFD, 3DFFP and 3DTFP in directory ERD131::USER2 DISK:(HUDSON.SIG). These programsmore » may be summarized as follows: FFP - 2-Dimensional Frequency Fancy Plots with magnitude/phase option; TFP - 2-Dimensional Time Fancy Plots; TDFD - 2-Dimensional Time Domain Frequency Domain Plots; and 3DFFP - equally spaced 3-Dimensional Frequency Fancy Plots; 3DTFP - equally spaced 3-Dimensional Time Plots. 8 figs.« less

Numerical simulation of fluid field and in vitro three-dimensional fabrication of tissue-engineered bones in a rotating bioreactor and in vivo implantation for repairing segmental bone defects.

PubMed

Song, Kedong; Wang, Hai; Zhang, Bowen; Lim, Mayasari; Liu, Yingchao; Liu, Tianqing

2013-03-01

In this paper, two-dimensional flow field simulation was conducted to determine shear stresses and velocity profiles for bone tissue engineering in a rotating wall vessel bioreactor (RWVB). In addition, in vitro three-dimensional fabrication of tissue-engineered bones was carried out in optimized bioreactor conditions, and in vivo implantation using fabricated bones was performed for segmental bone defects of Zelanian rabbits. The distribution of dynamic pressure, total pressure, shear stress, and velocity within the culture chamber was calculated for different scaffold locations. According to the simulation results, the dynamic pressure, velocity, and shear stress around the surface of cell-scaffold construction periodically changed at different locations of the RWVB, which could result in periodical stress stimulation for fabricated tissue constructs. However, overall shear stresses were relatively low, and the fluid velocities were uniform in the bioreactor. Our in vitro experiments showed that the number of cells cultured in the RWVB was five times higher than those cultured in a T-flask. The tissue-engineered bones grew very well in the RWVB. This study demonstrates that stress stimulation in an RWVB can be beneficial for cell/bio-derived bone constructs fabricated in an RWVB, with an application for repairing segmental bone defects.

Piecewise linear emulator of the nonlinear Schrödinger equation and the resulting analytic solutions for Bose-Einstein condensates.

PubMed

Theodorakis, Stavros

2003-06-01

We emulate the cubic term Psi(3) in the nonlinear Schrödinger equation by a piecewise linear term, thus reducing the problem to a set of uncoupled linear inhomogeneous differential equations. The resulting analytic expressions constitute an excellent approximation to the exact solutions, as is explicitly shown in the case of the kink, the vortex, and a delta function trap. Such a piecewise linear emulation can be used for any differential equation where the only nonlinearity is a Psi(3) one. In particular, it can be used for the nonlinear Schrödinger equation in the presence of harmonic traps, giving analytic Bose-Einstein condensate solutions that reproduce very accurately the numerically calculated ones in one, two, and three dimensions.

A Comparative Study of Rat Lung Decellularization by Chemical Detergents for Lung Tissue Engineering

PubMed Central

Tebyanian, Hamid; Karami, Ali; Motavallian, Ebrahim; Aslani, Jafar; Samadikuchaksaraei, Ali; Arjmand, Babak; Nourani, Mohammad Reza

2017-01-01

BACKGROUND: Lung disease is the most common cause of death in the world. The last stage of pulmonary diseases is lung transplantation. Limitation and shortage of donor organs cause to appear tissue engineering field. Decellularization is a hope for producing intact ECM in the development of engineered organs. AIM: The goal of the decellularization process is to remove cellular and nuclear material while retaining lung three-dimensional and molecular proteins. Different concentration of detergents was used for finding the best approach in lung decellularization. MATERIAL AND METHODS: In this study, three-time approaches (24, 48 and 96 h) with four detergents (CHAPS, SDS, SDC and Triton X-100) were used for decellularizing rat lungs for maintaining of three-dimensional lung architecture and ECM protein composition which have significant roles in differentiation and migration of stem cells. This comparative study determined that variable decellularization approaches can cause significantly different effects on decellularized lungs. RESULTS: Results showed that destruction was increased with increasing the detergent concentration. Single detergent showed a significant reduction in maintaining of three-dimensional of lung and ECM proteins (Collagen and Elastin). But, the best methods were mixed detergents of SDC and CHAPS in low concentration in 48 and 96 h decellularization. CONCLUSION: Decellularized lung tissue can be used in the laboratory to study various aspects of pulmonary biology and physiology and also, these results can be used in the continued improvement of engineered lung tissue. PMID:29362610

Generation of a Three-Dimensional Kidney Structure from Pluripotent Stem Cells.

PubMed

Yoshimura, Yasuhiro; Taguchi, Atsuhiro; Nishinakamura, Ryuichi

2017-01-01

The kidney is a vital organ that has an important role in the maintenance of homeostasis by fluid volume regulation and waste product excretion. This role cannot be performed without the three-dimensional (3D) structure of the kidney. Therefore, it is important to generate the 3D structure of the kidney when inducing functional kidney tissue or the whole organ from pluripotent stem cells. In this chapter, we describe the detailed methods to induce kidney progenitor cells from pluripotent stem cells, which are based on embryological development. We also provide a method to generate 3D kidney tissue with vascularized glomeruli upon transplantation.

Three-dimensional shape transformations of hydrogel sheets induced by small-scale modulation of internal stresses

NASA Astrophysics Data System (ADS)

Wu, Zi Liang; Moshe, Michael; Greener, Jesse; Therien-Aubin, Heloise; Nie, Zhihong; Sharon, Eran; Kumacheva, Eugenia

2013-03-01

Although Nature has always been a common source of inspiration in the development of artificial materials, only recently has the ability of man-made materials to produce complex three-dimensional (3D) structures from two-dimensional sheets been explored. Here we present a new approach to the self-shaping of soft matter that mimics fibrous plant tissues by exploiting small-scale variations in the internal stresses to form three-dimensional morphologies. We design single-layer hydrogel sheets with chemically distinct, fibre-like regions that exhibit differential shrinkage and elastic moduli under the application of external stimulus. Using a planar-to-helical three-dimensional shape transformation as an example, we explore the relation between the internal architecture of the sheets and their transition to cylindrical and conical helices with specific structural characteristics. The ability to engineer multiple three-dimensional shape transformations determined by small-scale patterns in a hydrogel sheet represents a promising step in the development of programmable soft matter.

X-ray Phase Contrast Allows Three Dimensional, Quantitative Imaging of Hydrogel Implants

PubMed Central

Appel, Alyssa A.; Larson, Jeffery C.; Jiang, Bin; Zhong, Zhong; Anastasio, Mark A.; Brey, Eric M.

2015-01-01

Three dimensional imaging techniques are needed for the evaluation and assessment of biomaterials used for tissue engineering and drug delivery applications. Hydrogels are a particularly popular class of materials for medical applications but are difficult to image in tissue using most available imaging modalities. Imaging techniques based on X-ray Phase Contrast (XPC) have shown promise for tissue engineering applications due to their ability to provide image contrast based on multiple X-ray properties. In this manuscript, we investigate the use of XPC for imaging a model hydrogel and soft tissue structure. Porous fibrin loaded poly(ethylene glycol) hydrogels were synthesized and implanted in a rodent subcutaneous model. Samples were explanted and imaged with an analyzer-based XPC technique and processed and stained for histology for comparison. Both hydrogel and soft tissues structures could be identified in XPC images. Structure in skeletal muscle adjacent could be visualized and invading fibrovascular tissue could be quantified. There were no differences between invading tissue measurements from XPC and the gold-standard histology. These results provide evidence of the significant potential of techniques based on XPC for 3D imaging of hydrogel structure and local tissue response. PMID:26487123

Tissue specificity of the hormonal response in sex accessory tissues is associated with nuclear matrix protein patterns.

PubMed

Getzenberg, R H; Coffey, D S

1990-09-01

The DNA of interphase nuclei have very specific three-dimensional organizations that are different in different cell types, and it is possible that this varying DNA organization is responsible for the tissue specificity of gene expression. The nuclear matrix organizes the three-dimensional structure of the DNA and is believed to be involved in the control of gene expression. This study compares the nuclear structural proteins between two sex accessory tissues in the same animal responding to the same androgen stimulation by the differential expression of major tissue-specific secretory proteins. We demonstrate here that the nuclear matrix is tissue specific in the rat ventral prostate and seminal vesicle, and undergoes characteristic alterations in its protein composition upon androgen withdrawal. Three types of nuclear matrix proteins were observed: 1) nuclear matrix proteins that are different and tissue specific in the rat ventral prostate and seminal vesicle, 2) a set of nuclear matrix proteins that either appear or disappear upon androgen withdrawal, and 3) a set of proteins that are common to both the ventral prostate and seminal vesicle and do not change with the hormonal state of the animal. Since the nuclear matrix is known to bind androgen receptors in a tissue- and steroid-specific manner, we propose that the tissue specificity of the nuclear matrix arranges the DNA in a unique conformation, which may be involved in the specific interaction of transcription factors with DNA sequences, resulting in tissue-specific patterns of secretory protein expression.

Improved Cell Culture Method for Growing Contracting Skeletal Muscle Models

NASA Technical Reports Server (NTRS)

Marquette, Michele L.; Sognier, Marguerite A.

2013-01-01

An improved method for culturing immature muscle cells (myoblasts) into a mature skeletal muscle overcomes some of the notable limitations of prior culture methods. The development of the method is a major advance in tissue engineering in that, for the first time, a cell-based model spontaneously fuses and differentiates into masses of highly aligned, contracting myotubes. This method enables (1) the construction of improved two-dimensional (monolayer) skeletal muscle test beds; (2) development of contracting three-dimensional tissue models; and (3) improved transplantable tissues for biomedical and regenerative medicine applications. With adaptation, this method also offers potential application for production of other tissue types (i.e., bone and cardiac) from corresponding precursor cells.

Evaluation of a three-dimensional human dermal model as a predictor of shampoo ocular irritation.

PubMed

Decker, D; Harper, R

1994-04-01

A three-dimensional human tissue model (Skin(2) ZK1100) was used to evaluate 43 adult and baby shampoos. The ZK1100 model consists of metabolically active proliferating human fibroblasts isolated from the dermis of neonatal foreskins and seeded onto a nylon mesh. The fibroblasts multiply and produce matrix proteins to form a living tissue. MTT reduction (mitochondrial function) was used as the cytotoxicity endpoint. The primary components of the adult shampoos are alkyl sulfate surfactants, while the baby shampoos contain ethoxylated alkyl sulfates and amphoteric surfactants. All shampoos were diluted to five concentrations (100, 300, 700, 1000 and 3000 mug/ml) in aqueous cell culture media and the tissue exposed for 24 hr. An EC(50) value for each test was generated from a dose-response curve. All samples were tested in two or more separate experiments, and the EC(50) values were averaged and plotted versus their respective 24-hr unwashed Draize eye irritation values (r(2) = 0.81). The adult shampoos had Draize values in the moderate irritation category and EC(50) values ranging from 220 to 1051 mug/ml, while the baby shampoos had Draize values in the minimal irritation category and EC(50) values ranging from 820 to 2285 mug/ml. These results indicate that the three-dimensional human tissue model can be useful in predicting the Draize ocular irritation category for shampoos.

Parameter variation effects on temperature elevation in a steady-state, one-dimensional thermal model for millimeter wave exposure of one- and three-layer human tissue.

PubMed

Kanezaki, Akio; Hirata, Akimasa; Watanabe, Soichi; Shirai, Hiroshi

2010-08-21

The present study describes theoretical parametric analysis of the steady-state temperature elevation in one-dimensional three-layer (skin, fat and muscle) and one-layer (skin only) models due to millimeter-wave exposure. The motivation of this fundamental investigation is that some variability of warmth sensation in the human skin has been reported. An analytical solution for a bioheat equation was derived by using the Laplace transform for the one-dimensional human models. Approximate expressions were obtained to investigate the dependence of temperature elevation on different thermal and tissue thickness parameters. It was shown that the temperature elevation on the body surface decreases monotonically with the blood perfusion rate, heat conductivity and heat transfer from the body to air. Also revealed were the conditions where maximum and minimum surface temperature elevations were observed for different thermal and tissue thickness parameters. The surface temperature elevation in the three-layer model is 1.3-2.8 times greater than that in the one-layer model. The main reason for this difference is attributed to the adiabatic nature of the fat layer. By considering the variation range of thermal and tissue thickness parameters which causes the maximum and minimum temperature elevations, the dominant parameter influencing the surface temperature elevation was found to be the heat transfer coefficient between the body surface and air.

An application of synchrotron based x-ray tomography in palaeontology: Investigating small, three-dimensional, exceptionally preserved fossil arthropods

NASA Astrophysics Data System (ADS)

Braiden, A. K.; Orr, P. J.; Tafforeau, P.; Kearns, S. L.

2009-04-01

The fossil record is biased towards biomineralised elements (for example bones, shells and teeth) that usually retain their original three-dimensional shape. Non-biomineralised arthropods, often comprising only exoskeletal tissues such as cuticle, are comparatively rare and are usually preserved in two-dimensions (including examples inside early diagenetic concretions). Rarer still are exceptionally preserved fossils that contain replicated soft tissues; although tissues that are replicated during the initial stages of decay are usually three- dimensional and often preserved in detail, the fossil as a whole is almost invariably two dimensional. Fossil shrimp recovered from Upper Triassic (Rhaetian) unconsolidated clays at Frome, Somerset, England represent a low diversity, three-dimensionally preserved fauna, in which certain labile tissues and organs are routinely preserved in three dimensions in life position. Initial SEM analysis of exposed, internal structures in unprepared specimens confirmed the presence of musculature (replicated in calcium phosphate) and a clay infilled gut. Due to the rarity of the material, and small size of the specimens (maximum length 12mm), non-destructive synchrotron radiation, x-ray microtomography was used to determine the extent, and fidelity, of preservation of the internal anatomy. Medium resolution (voxel size of 5.3μm) and high resolution (voxel size 0.7μm) imaging was carried out on selected specimens. This confirmed high fidelity replication of the following: limited volumes of abdominal, and more rarely, cephalothoracic musculature; the hepatopancreas; gonads and, in rare cases, blood vessels and antennal glands. Notably, these are all preserved in situ enveloped by structureless, fine-grained, authigenic carbonate. This carbonate precipitated inside the cuticle, but only at the periphery of the carcass and after, or during, the initial stages of decay; it infills voids created by the initial shrinkage of abdominal musculature (possibly due to dehydration) but not those created by its subsequent decay. The digestive tract is infilled with ingested clay material. X-ray microtomographic imaging also revealed the presence of pyrite as framboids and polyhedra. The spatial distribution of framboidal pyrite, and tissue replicating calcium phosphate, indicates their precipitation is likely to be related to the original composition of the biological tissues. For example, although the pyrite framboids do not replicate tissues, they are found in association with the hepatopancreas. It is probably not coincidental that iron is especially abundant in this area in vivo. Notably, subtle differences in greyscale tone in the x-ray images are shown to correspond to authigenic phases of different composition. When calibrated against phases for which accurate compositions can be determined using other criteria (e.g. SEM-EDX), it is possible to identify the presence of particular authigenic mineral phases in such fossils.

Dimensionality and noise in energy selective x-ray imaging

PubMed Central

Alvarez, Robert E.

2013-01-01

Purpose: To develop and test a method to quantify the effect of dimensionality on the noise in energy selective x-ray imaging. Methods: The Cramèr-Rao lower bound (CRLB), a universal lower limit of the covariance of any unbiased estimator, is used to quantify the noise. It is shown that increasing dimensionality always increases, or at best leaves the same, the variance. An analytic formula for the increase in variance in an energy selective x-ray system is derived. The formula is used to gain insight into the dependence of the increase in variance on the properties of the additional basis functions, the measurement noise covariance, and the source spectrum. The formula is also used with computer simulations to quantify the dependence of the additional variance on these factors. Simulated images of an object with three materials are used to demonstrate the trade-off of increased information with dimensionality and noise. The images are computed from energy selective data with a maximum likelihood estimator. Results: The increase in variance depends most importantly on the dimension and on the properties of the additional basis functions. With the attenuation coefficients of cortical bone, soft tissue, and adipose tissue as the basis functions, the increase in variance of the bone component from two to three dimensions is 1.4 × 103. With the soft tissue component, it is 2.7 × 104. If the attenuation coefficient of a high atomic number contrast agent is used as the third basis function, there is only a slight increase in the variance from two to three basis functions, 1.03 and 7.4 for the bone and soft tissue components, respectively. The changes in spectrum shape with beam hardening also have a substantial effect. They increase the variance by a factor of approximately 200 for the bone component and 220 for the soft tissue component as the soft tissue object thickness increases from 1 to 30 cm. Decreasing the energy resolution of the detectors increases the variance of the bone component markedly with three dimension processing, approximately a factor of 25 as the resolution decreases from 100 to 3 bins. The increase with two dimension processing for adipose tissue is a factor of two and with the contrast agent as the third material for two or three dimensions is also a factor of two for both components. The simulated images show that a maximum likelihood estimator can be used to process energy selective x-ray data to produce images with noise close to the CRLB. Conclusions: The method presented can be used to compute the effects of the object attenuation coefficients and the x-ray system properties on the relationship of dimensionality and noise in energy selective x-ray imaging systems. PMID:24320442

Development of a 3D cell printed construct considering angiogenesis for liver tissue engineering.

PubMed

Lee, Jin Woo; Choi, Yeong-Jin; Yong, Woon-Jae; Pati, Falguni; Shim, Jin-Hyung; Kang, Kyung Shin; Kang, In-Hye; Park, Jaesung; Cho, Dong-Woo

2016-01-12

Several studies have focused on the regeneration of liver tissue in a two-dimensional (2D) planar environment, whereas actual liver tissue is three-dimensional (3D). Cell printing technology has been successfully utilized for building 3D structures; however, the poor mechanical properties of cell-laden hydrogels are a major concern. Here, we demonstrate the printing of a 3D cell-laden construct and its application to liver tissue engineering using 3D cell printing technology through a multi-head tissue/organ building system. Polycaprolactone (PCL) was used as a framework material because of its excellent mechanical properties. Collagen bioink containing three different types of cells-hepatocytes (HCs), human umbilical vein endothelial cells , and human lung fibroblasts--was infused into the canals of a PCL framework to induce the formation of capillary--like networks and liver cell growth. A co-cultured 3D microenvironment of the three types of cells was successfully established and maintained. The vascular formation and functional abilities of HCs (i.e., albumin secretion and urea synthesis) demonstrated that the heterotypic interaction among HCs and nonparenchymal cells increased the survivability and functionality of HCs within the collagen gel. Therefore, our results demonstrate the prospect of using cell printing technology for the creation of heterotypic cellular interaction within a structure for liver tissue engineering.

Terahertz Imaging of Three-Dimensional Dehydrated Breast Cancer Tumors

NASA Astrophysics Data System (ADS)

Bowman, Tyler; Wu, Yuhao; Gauch, John; Campbell, Lucas K.; El-Shenawee, Magda

2017-06-01

This work presents the application of terahertz imaging to three-dimensional formalin-fixed, paraffin-embedded human breast cancer tumors. The results demonstrate the capability of terahertz for in-depth scanning to produce cross section images without the need to slice the tumor. Samples of tumors excised from women diagnosed with infiltrating ductal carcinoma and lobular carcinoma are investigated using a pulsed terahertz time domain imaging system. A time of flight estimation is used to obtain vertical and horizontal cross section images of tumor tissues embedded in paraffin block. Strong agreement is shown comparing the terahertz images obtained by electronically scanning the tumor in-depth in comparison with histopathology images. The detection of cancer tissue inside the block is found to be accurate to depths over 1 mm. Image processing techniques are applied to provide improved contrast and automation of the obtained terahertz images. In particular, unsharp masking and edge detection methods are found to be most effective for three-dimensional block imaging.

Engineering Three-Dimensional Collagen-IKVAV Matrix to Mimic Neural Microenvironment

PubMed Central

2013-01-01

Engineering the cellular microenvironment has great potential to create a platform technology toward engineering of tissue and organs. This study aims to engineer a neural microenvironment through fabrication of three-dimensional (3D) engineered collagen matrixes mimicking in-vivo-like conditions. Collagen was chemically modified with a pentapeptide epitope consisting of isoleucine-lysine-valine-alanine-valine (IKVAV) to mimic laminin structure supports of the neural extracellular matrix (ECM). Three-dimensional collagen matrixes with and without IKVAV peptide modification were fabricated by freeze-drying technology and chemical cross-linking with glutaraldehyde. Structural information of 3D collagen matrixes indicated interconnected pores structure with an average pore size of 180 μm. Our results indicated that culture of dorsal root ganglion (DRG) cells in 3D collagen matrix was greatly influenced by 3D culture method and significantly enhanced with engineered collagen matrix conjugated with IKVAV peptide. It may be concluded that an appropriate 3D culture of neurons enables DRG to positively improve the cellular fate toward further acceleration in tissue regeneration. PMID:23705903

Three-Dimensional Bioprinting: Toward the Era of Manufacturing Human Organs as Spare Parts for Healthcare and Medicine^.

PubMed

Mir, Tanveer Ahmad; Nakamura, Makoto

2017-06-01

Three-dimensional (3D) printing technology has been used in industrial worlds for decades. Three-dimensional bioprinting has recently received an increasing attention across the globe among researchers, academicians, students, and even the ordinary people. This emerging technique has a great potential to engineer highly organized functional bioconstructs with complex geometries and tailored components for engineering bioartificial tissues/organs for widespread applications, including transplantation, therapeutic investigation, drug development, bioassay, and disease modeling. Although many specialized 3D printers have been developed and applied to print various types of 3D tissue constructs, bioprinting technologies still have several technical challenges, including high resolution distribution of cells, controlled deposition of bioinks, suitable bioink materials, maturation of cells, and effective vascularization and innervation within engineered complex structures. In this brief review, we discuss about bioprinting approach, current limitations, and possibility of future advancements for producing engineered bioconstructs and bioartificial organs with desired functionalities.

Three-dimensional multispectral hand-held optoacoustic imaging with microsecond-level delayed laser pulses

NASA Astrophysics Data System (ADS)

Deán-Ben, X. L.; Bay, Erwin; Razansky, Daniel

2015-03-01

Three-dimensional hand-held optoacoustic imaging comes with important advantages that prompt the clinical translation of this modality, with applications envisioned in cardiovascular and peripheral vascular disease, disorders of the lymphatic system, breast cancer, arthritis or inflammation. Of particular importance is the multispectral acquisition of data by exciting the tissue at several wavelengths, which enables functional imaging applications. However, multispectral imaging of entire three-dimensional regions is significantly challenged by motion artefacts in concurrent acquisitions at different wavelengths. A method based on acquisition of volumetric datasets having a microsecond-level delay between pulses at different wavelengths is described in this work. This method can avoid image artefacts imposed by a scanning velocity greater than 2 m/s, thus, does not only facilitate imaging influenced by respiratory, cardiac or other intrinsic fast movements in living tissues, but can achieve artifact-free imaging in the presence of more significant motion, e.g., abrupt displacements during handheld-mode operation in a clinical environment.

Pinatubo Emulation in Multiple Models (POEMs): co-ordinated experiments in the ISA-MIP model intercomparison activity component of the SPARC Stratospheric Sulphur and it's Role in Climate initiative (SSiRC)

NASA Astrophysics Data System (ADS)

Lee, Lindsay; Mann, Graham; Carslaw, Ken; Toohey, Matthew; Aquila, Valentina

2016-04-01

The World Climate Research Program's SPARC initiative has a new international activity "Stratospheric Sulphur and its Role in Climate" (SSiRC) to better understand changes in stratospheric aerosol and precursor gaseous sulphur species. One component of SSiRC involves an intercomparison "ISA-MIP" of composition-climate models that simulate the stratospheric aerosol layer interactively. Within PoEMS each modelling group will run a "perturbed physics ensemble" (PPE) of interactive stratospheric aerosol (ISA) simulations of the Pinatubo eruption, varying several uncertain parameters associated with the eruption's SO2 emissions and model processes. A powerful new technique to quantify and attribute sources of uncertainty in complex global models is described by Lee et al. (2011, ACP). The analysis uses Gaussian emulation to derive a probability density function (pdf) of predicted quantities, essentially interpolating the PPE results in multi-dimensional parameter space. Once trained on the ensemble, a Monte Carlo simulation with the fast Gaussian emulator enabling a full variance-based sensitivity analysis. The approach has already been used effectively by Carslaw et al., (2013, Nature) to quantify the uncertainty in the cloud albedo effect forcing from a 3D global aerosol-microphysics model allowing to compare the sensitivy of different predicted quantities to uncertainties in natural and anthropogenic emissions types, and structural parameters in the models. Within ISA-MIP, each group will carry out a PPE of runs, with the subsequent analysis with the emulator assessing the uncertainty in the volcanic forcings predicted by each model. In this poster presentation we will give an outline of the "PoEMS" analysis, describing the uncertain parameters to be varied and the relevance to further understanding differences identified in previous international stratospheric aerosol assessments.

Two-photon excitation based photochemistry and neural imaging

NASA Astrophysics Data System (ADS)

Hatch, Kevin Andrew

Two-photon microscopy is a fluorescence imaging technique which provides distinct advantages in three-dimensional cellular and molecular imaging. The benefits of this technology may extend beyond imaging capabilities through exploitation of the quantum processes responsible for fluorescent events. This study utilized a two-photon microscope to investigate a synthetic photoreactive collagen peptidomimetic, which may serve as a potential material for tissue engineering using the techniques of two-photon photolysis and two-photon polymerization. The combination of these techniques could potentially be used to produce a scaffold for the vascularization of engineered three-dimensional tissues in vitro to address the current limitations of tissue engineering. Additionally, two-photon microscopy was used to observe the effects of the application of the neurotransmitter dopamine to the mushroom body neural structures of Drosophila melanogaster to investigate dopamine's connection to cognitive degeneration.

Three-dimensional bioprinting of stem-cell derived tissues for human regenerative medicine.

PubMed

Skeldon, Gregor; Lucendo-Villarin, Baltasar; Shu, Wenmiao

2018-07-05

Stem cell technology in regenerative medicine has the potential to provide an unlimited supply of cells for drug testing, medical transplantation and academic research. In order to engineer a realistic tissue model using stem cells as an alternative to human tissue, it is essential to create artificial stem cell microenvironment or niches. Three-dimensional (3D) bioprinting is a promising tissue engineering field that offers new opportunities to precisely place stem cells within their niches layer-by-layer. This review covers bioprinting technologies, the current development of 'bio-inks' and how bioprinting has already been applied to stem-cell culture, as well as their applications for human regenerative medicine. The key considerations for bioink properties such as stiffness, stability and biodegradation, biocompatibility and printability are highlighted. Bioprinting of both adult and pluriopotent stem cells for various types of artificial tissues from liver to brain has been reviewed. 3D bioprinting of stem-cell derived tissues for human regenerative medicine is an exciting emerging area that represents opportunities for new research, industries and products as well as future challenges in clinical translation.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'. © 2018 The Author(s).

Three-Dimensional Microstructure of Biological Tissues during Freezing and Thawing

NASA Astrophysics Data System (ADS)

Ishiguro, Hiroshi; Horimizu, Takashi; Kataori, Akinobu; Kajigaya, Hiroshi

Three-dimensional behavior of ice crystals and cells during the freezing and thawing of biological tissues was investigated microscopically in real time by using a confocal laser scanning microscope(CLSM) and a fluorescent dye, acridine orange (AO). Fresh tender meat (2nd pectoral muscles) of chicken was stained with the AO in physiological saline to distinguish ice crystals and cells by their different colors, and then frozen and thawed under two different thermal protocols: a) slow-cooling and rapid-warming and b) rapid-cooling and rapid-warming. The CLSM noninvasively produced optical tomograms of the tissues to clarify the pattern of freezing, morphology of ice crystals in the tissues, and the interaction between ice crystals and cells. Also, the tissues were morphologically investigated by pathological means after the freezing and thawing. Typical freezing pattern during the slow-cooling was extracellular-freezing, and those during the rapid-cooling were extracellular-freezing and intracellular freezing with a lot of fine ice crystals in the cells. Cracks caused by the extracellular and intracellular ice crystals remained in the muscle tissues after the thawing. The results obtained by using the CLSM/dye method were consistent with pathologically morphological changes in the tissues through freezing and thawing.

X-ray Phase Contrast Allows Three Dimensional, Quantitative Imaging of Hydrogel Implants

DOE PAGES

Appel, Alyssa A.; Larson, Jeffrey C.; Jiang, Bin; ...

2015-10-20

Three dimensional imaging techniques are needed for the evaluation and assessment of biomaterials used for tissue engineering and drug delivery applications. Hydrogels are a particularly popular class of materials for medical applications but are difficult to image in tissue using most available imaging modalities. Imaging techniques based on X-ray Phase Contrast (XPC) have shown promise for tissue engineering applications due to their ability to provide image contrast based on multiple X-ray properties. In this manuscript we describe results using XPC to image a model hydrogel and soft tissue structure. Porous fibrin loaded poly(ethylene glycol) hydrogels were synthesized and implanted inmore » a rodent subcutaneous model. Samples were explanted and imaged with an analyzer-based XPC technique and processed and stained for histology for comparison. Both hydrogel and soft tissues structures could be identified in XPC images. Structure in skeletal muscle adjacent could be visualized and invading fibrovascular tissue could be quantified. In quantitative results, there were no differences between XPC and the gold-standard histological measurements. These results provide evidence of the significant potential of techniques based on XPC for 3D imaging of hydrogel structure and local tissue response.« less

Quantification of Cardiomyocyte Alignment from Three-Dimensional (3D) Confocal Microscopy of Engineered Tissue.

PubMed

Kowalski, William J; Yuan, Fangping; Nakane, Takeichiro; Masumoto, Hidetoshi; Dwenger, Marc; Ye, Fei; Tinney, Joseph P; Keller, Bradley B

2017-08-01

Biological tissues have complex, three-dimensional (3D) organizations of cells and matrix factors that provide the architecture necessary to meet morphogenic and functional demands. Disordered cell alignment is associated with congenital heart disease, cardiomyopathy, and neurodegenerative diseases and repairing or replacing these tissues using engineered constructs may improve regenerative capacity. However, optimizing cell alignment within engineered tissues requires quantitative 3D data on cell orientations and both efficient and validated processing algorithms. We developed an automated method to measure local 3D orientations based on structure tensor analysis and incorporated an adaptive subregion size to account for multiple scales. Our method calculates the statistical concentration parameter, κ, to quantify alignment, as well as the traditional orientational order parameter. We validated our method using synthetic images and accurately measured principal axis and concentration. We then applied our method to confocal stacks of cleared, whole-mount engineered cardiac tissues generated from human-induced pluripotent stem cells or embryonic chick cardiac cells and quantified cardiomyocyte alignment. We found significant differences in alignment based on cellular composition and tissue geometry. These results from our synthetic images and confocal data demonstrate the efficiency and accuracy of our method to measure alignment in 3D tissues.

Organotypic three-dimensional culture model of mesenchymal and epithelial cells to examine tissue fusion events.

EPA Science Inventory

Tissue fusion during early mammalian development requires coordination of multiple cell types, the extracellular matrix, and complex signaling pathways. Fusion events during processes including heart development, neural tube closure, and palatal fusion are dependent on signaling ...

Kinetic and dynamic Delaunay tetrahedralizations in three dimensions

NASA Astrophysics Data System (ADS)

Schaller, Gernot; Meyer-Hermann, Michael

2004-09-01

We describe algorithms to implement fully dynamic and kinetic three-dimensional unconstrained Delaunay triangulations, where the time evolution of the triangulation is not only governed by moving vertices but also by a changing number of vertices. We use three-dimensional simplex flip algorithms, a stochastic visibility walk algorithm for point location and in addition, we propose a new simple method of deleting vertices from an existing three-dimensional Delaunay triangulation while maintaining the Delaunay property. As an example, we analyse the performance in various cases of practical relevance. The dual Dirichlet tessellation can be used to solve differential equations on an irregular grid, to define partitions in cell tissue simulations, for collision detection etc.

Thicker three-dimensional tissue from a "symbiotic recycling system" combining mammalian cells and algae.

PubMed

Haraguchi, Yuji; Kagawa, Yuki; Sakaguchi, Katsuhisa; Matsuura, Katsuhisa; Shimizu, Tatsuya; Okano, Teruo

2017-01-31

In this paper, we report an in vitro co-culture system that combines mammalian cells and algae, Chlorococcum littorale, to create a three-dimensional (3-D) tissue. While the C2C12 mouse myoblasts and rat cardiac cells consumed oxygen actively, intense oxygen production was accounted for by the algae even in the co-culture system. Although cell metabolism within thicker cardiac cell-layered tissues showed anaerobic respiration, the introduction of innovative co-cultivation partially changed the metabolism to aerobic respiration. Moreover, the amount of glucose consumption and lactate production in the cardiac tissues and the amount of ammonia in the culture media decreased significantly when co-cultivated with algae. In the cardiac tissues devoid of algae, delamination was observed histologically, and the release of creatine kinase (CK) from the tissues showed severe cardiac cell damage. On the other hand, the layered cell tissues with algae were observed to be in a good histological condition, with less than one-fifth decline in CK release. The co-cultivation with algae improved the culture condition of the thicker tissues, resulting in the formation of 160 μm-thick cardiac tissues. Thus, the present study proposes the possibility of creating an in vitro "symbiotic recycling system" composed of mammalian cells and algae.

Thicker three-dimensional tissue from a “symbiotic recycling system” combining mammalian cells and algae

PubMed Central

Haraguchi, Yuji; Kagawa, Yuki; Sakaguchi, Katsuhisa; Matsuura, Katsuhisa; Shimizu, Tatsuya; Okano, Teruo

2017-01-01

In this paper, we report an in vitro co-culture system that combines mammalian cells and algae, Chlorococcum littorale, to create a three-dimensional (3-D) tissue. While the C2C12 mouse myoblasts and rat cardiac cells consumed oxygen actively, intense oxygen production was accounted for by the algae even in the co-culture system. Although cell metabolism within thicker cardiac cell-layered tissues showed anaerobic respiration, the introduction of innovative co-cultivation partially changed the metabolism to aerobic respiration. Moreover, the amount of glucose consumption and lactate production in the cardiac tissues and the amount of ammonia in the culture media decreased significantly when co-cultivated with algae. In the cardiac tissues devoid of algae, delamination was observed histologically, and the release of creatine kinase (CK) from the tissues showed severe cardiac cell damage. On the other hand, the layered cell tissues with algae were observed to be in a good histological condition, with less than one-fifth decline in CK release. The co-cultivation with algae improved the culture condition of the thicker tissues, resulting in the formation of 160 μm-thick cardiac tissues. Thus, the present study proposes the possibility of creating an in vitro “symbiotic recycling system” composed of mammalian cells and algae. PMID:28139713

Three-Dimensionally Engineered Normal Human Lung Tissue-Like Assemblies: Target Tissues for Human Respiratory Viral Infections

NASA Technical Reports Server (NTRS)

Goodwin, Thomas J.; McCarthy, M.; Lin, Y-H.; Deatly, A. M.

2008-01-01

In vitro three-dimensional (3D) human lung epithelio-mesenchymal tissue-like assemblies (3D hLEM TLAs) from this point forward referred to as TLAs were engineered in Rotating Wall Vessel (RWV) technology to mimic the characteristics of in vivo tissues thus providing a tool to study human respiratory viruses and host cell interactions. The TLAs were bioengineered onto collagen-coated cyclodextran microcarriers using primary human mesenchymal bronchial-tracheal cells (HBTC) as the foundation matrix and an adult human bronchial epithelial immortalized cell line (BEAS-2B) as the overlying component. The resulting TLAs share significant characteristics with in vivo human respiratory epithelium including polarization, tight junctions, desmosomes, and microvilli. The presence of tissue-like differentiation markers including villin, keratins, and specific lung epithelium markers, as well as the production of tissue mucin, further confirm these TLAs differentiated into tissues functionally similar to in vivo tissues. Increasing virus titers for human respiratory syncytial virus (wtRSVA2) and the detection of membrane bound glycoproteins over time confirm productive infection with the virus. Therefore, we assert TLAs mimic aspects of the human respiratory epithelium and provide a unique capability to study the interactions of respiratory viruses and their primary target tissue independent of the host s immune system.

Three-Dimensionally Engineered Normal Human Broncho-epithelial Tissue-Like Assemblies: Target Tissues for Human Respiratory Viral Infections

NASA Technical Reports Server (NTRS)

Goodwin, T. J.; McCarthy, M.; Lin, Y-H

2006-01-01

In vitro three-dimensional (3D) human broncho-epithelial (HBE) tissue-like assemblies (3D HBE TLAs) from this point forward referred to as TLAs were engineered in Rotating Wall Vessel (RWV) technology to mimic the characteristics of in vivo tissues thus providing a tool to study human respiratory viruses and host cell interactions. The TLAs were bioengineered onto collagen-coated cyclodextran microcarriers using primary human mesenchymal bronchial-tracheal cells (HBTC) as the foundation matrix and an adult human bronchial epithelial immortalized cell line (BEAS-2B) as the overlying component. The resulting TLAs share significant characteristics with in vivo human respiratory epithelium including polarization, tight junctions, desmosomes, and microvilli. The presence of tissue-like differentiation markers including villin, keratins, and specific lung epithelium markers, as well as the production of tissue mucin, further confirm these TLAs differentiated into tissues functionally similar to in vivo tissues. Increasing virus titers for human respiratory syncytial virus (wtRSVA2) and parainfluenza virus type 3 (wtPIV3 JS) and the detection of membrane bound glycoproteins over time confirm productive infections with both viruses. Therefore, TLAs mimic aspects of the human respiratory epithelium and provide a unique capability to study the interactions of respiratory viruses and their primary target tissue independent of the host's immune system.

Three-dimensional head anthropometric analysis

NASA Astrophysics Data System (ADS)

Enciso, Reyes; Shaw, Alex M.; Neumann, Ulrich; Mah, James

2003-05-01

Currently, two-dimensional photographs are most commonly used to facilitate visualization, assessment and treatment of facial abnormalities in craniofacial care but are subject to errors because of perspective, projection, lack metric and 3-dimensional information. One can find in the literature a variety of methods to generate 3-dimensional facial images such as laser scans, stereo-photogrammetry, infrared imaging and even CT however each of these methods contain inherent limitations and as such no systems are in common clinical use. In this paper we will focus on development of indirect 3-dimensional landmark location and measurement of facial soft-tissue with light-based techniques. In this paper we will statistically evaluate and validate a current three-dimensional image-based face modeling technique using a plaster head model. We will also develop computer graphics tools for indirect anthropometric measurements in a three-dimensional head model (or polygonal mesh) including linear distances currently used in anthropometry. The measurements will be tested against a validated 3-dimensional digitizer (MicroScribe 3DX).

Negating Tissue Contracture Improves Volume Maintenance and Longevity of In Vivo Engineered Tissues.

PubMed

Lytle, Ian F; Kozlow, Jeffrey H; Zhang, Wen X; Buffington, Deborah A; Humes, H David; Brown, David L

2015-10-01

Engineering large, complex tissues in vivo requires robust vascularization to optimize survival, growth, and function. Previously, the authors used a "chamber" model that promotes intense angiogenesis in vivo as a platform for functional three-dimensional muscle and renal engineering. A silicone membrane used to define the structure and to contain the constructs is successful in the short term. However, over time, generated tissues contract and decrease in size in a manner similar to capsular contracture seen around many commonly used surgical implants. The authors hypothesized that modification of the chamber structure or internal surface would promote tissue adherence and maintain construct volume. Three chamber configurations were tested against volume maintenance. Previously studied, smooth silicone surfaces were compared to chambers modified for improved tissue adherence, with multiple transmembrane perforations or lined with a commercially available textured surface. Tissues were allowed to mature long term in a rat model, before analysis. On explantation, average tissue masses were 49, 102, and 122 mg; average volumes were 74, 158 and 176 μl; and average cross-sectional areas were 1.6, 6.7, and 8.7 mm for the smooth, perforated, and textured groups, respectively. Both perforated and textured designs demonstrated significantly greater measures than the smooth-surfaced constructs in all respects. By modifying the design of chambers supporting vascularized, three-dimensional, in vivo tissue engineering constructs, generated tissue mass, volume, and area can be maintained over a long time course. Successful progress in the scale-up of construct size should follow, leading to improved potential for development of increasingly complex engineered tissues.

Three-dimensional plotted hydroxyapatite scaffolds with predefined architecture: comparison of stabilization by alginate cross-linking versus sintering.

PubMed

Kumar, Alok; Akkineni, Ashwini R; Basu, Bikramjit; Gelinsky, Michael

2016-03-01

Scaffolds for bone tissue engineering are essentially characterized by porous three-dimensional structures with interconnected pores to facilitate the exchange of nutrients and removal of waste products from cells, thereby promoting cell proliferation in such engineered scaffolds. Although hydroxyapatite is widely being considered for bone tissue engineering applications due to its occurrence in the natural extracellular matrix of this tissue, limited reports are available on additive manufacturing of hydroxyapatite-based materials. In this perspective, hydroxyapatite-based three-dimensional porous scaffolds with two different binders (maltodextrin and sodium alginate) were fabricated using the extrusion method of three-dimensional plotting and the results were compared in reference to the structural properties of scaffolds processed via chemical stabilization and sintering routes, respectively. With the optimal processing conditions regarding to pH and viscosity of binder-loaded hydroxyapatite pastes, scaffolds with parallelepiped porous architecture having up to 74% porosity were fabricated. Interestingly, sintering of the as-plotted hydroxyapatite-sodium alginate (cross-linked with CaCl2 solution) scaffolds led to the formation of chlorapatite (Ca9.54P5.98O23.8Cl1.60(OH)2.74). Both the sintered scaffolds displayed progressive deformation and delayed fracture under compressive loading, with hydroxyapatite-alginate scaffolds exhibiting a higher compressive strength (9.5 ± 0.5 MPa) than hydroxyapatite-maltodextrin scaffolds (7.0 ± 0.6 MPa). The difference in properties is explained in terms of the phase assemblage and microstructure. © The Author(s) 2015.

The 1986 advances in bioengineering

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lantz, S.A.; King, A.I.

1986-01-01

This book presents the papers given at a conference on biomedicine. Topics considered at the conference included a mathematical method for obtaining three-dimensional information from standard two-dimensional radiographs, the human lumbar spine, scoliosis and instrumentation, vehicle crashworthiness, lung mechanics, physiological fluid mechanics, microgravity, cardiovascular mechanics, and soft tissue.

3D Ta/TaO x /TiO2/Ti synaptic array and linearity tuning of weight update for hardware neural network applications

NASA Astrophysics Data System (ADS)

Wang, I.-Ting; Chang, Chih-Cheng; Chiu, Li-Wen; Chou, Teyuh; Hou, Tuo-Hung

2016-09-01

The implementation of highly anticipated hardware neural networks (HNNs) hinges largely on the successful development of a low-power, high-density, and reliable analog electronic synaptic array. In this study, we demonstrate a two-layer Ta/TaO x /TiO2/Ti cross-point synaptic array that emulates the high-density three-dimensional network architecture of human brains. Excellent uniformity and reproducibility among intralayer and interlayer cells were realized. Moreover, at least 50 analog synaptic weight states could be precisely controlled with minimal drifting during a cycling endurance test of 5000 training pulses at an operating voltage of 3 V. We also propose a new state-independent bipolar-pulse-training scheme to improve the linearity of weight updates. The improved linearity considerably enhances the fault tolerance of HNNs, thus improving the training accuracy.

Magneto-rheological fluid shock absorbers for HMMWV

NASA Astrophysics Data System (ADS)

Gordaninejad, Faramarz; Kelso, Shawn P.

2000-04-01

This paper presents the development and evaluation of a controllable, semi-active magneto-rheological fluid (MRF) shock absorber for a High Mobility Multi-purpose Wheeled Vehicle (HMMWV). The University of Nevada, Reno (UNR) MRF damper is tailored for structures and ground vehicles that undergo a wide range of dynamic loading. It also has the capability for unique rebound and compression characteristics. The new MRF shock absorber emulates the original equipment manufacturer (OEM) shock absorber behavior in passive mode, and provides a wide controllable damping force range. A theoretical study is performed to evaluate the UNR MRF shock absorber. The Bingham plastic theory is employed to model the nonlinear behavior of the MR fluid. A fluid-mechanics-based theoretical model along with a three-dimensional finite element electromagnetic analysis is utilized to predict the MRF damper performance. The theoretical results are compared with experimental data and are demonstrated to be in excellent agreement.

Three types of dermal grafts in rats: the importance of mechanical property and structural design.

PubMed

You, Chuangang; Wang, Xingang; Zheng, Yurong; Han, Chunmao

2013-12-04

To determine how the mechanical property and micro structure affect tissue regeneration and angiogenesis, three types of scaffolds were studied. Acellular dermal matrices (ADM), produced from human skin by removing the epidermis and cells, has been widely used in wound healing because of its high mechanical strength. Collagen scaffolds (CS) incorporated with poly(glycolide-co-L-lactide) (PLGA) mesh forms a well-supported hybrid dermal equivalent poly(glycolide-co-L-lactide) mesh/collagen scaffolds (PMCS). We designed this scaffold to enhance the CS mechanical property. These three different dermal substitutes-ADM, CS and PMCSs are different in the tensile properties and microstructure. Several basic physical characteristics of dermal substitutes were investigated in vitro. To characterize the angiogenesis and tissue regeneration, the materials were embedded subcutaneously in Sprague-Dawley (SD) rats. At weeks 1, 2, 4 and 8 post-surgery, the tissue specimens were harvested for histology, immunohistochemistry and real-time quantitative PCR (RT-qPCR). In vitro studies demonstrated ADM had a higher Young's modulus (6.94 MPa) rather than CS (0.19 MPa) and PMCS (3.33 MPa) groups in the wet state. Compared with ADMs and CSs, PMCSs with three-dimensional porous structures resembling skin and moderate mechanical properties can promote tissue ingrowth more quickly after implantation. In addition, the vascularization of the PMCS group is more obvious than that of the other two groups. The incorporation of a PLGA knitted mesh in CSs can improve the mechanical properties with little influence on the three-dimensional porous microstructure. After implantation, PMCSs can resist the contraction and promote cell infiltration, neotissue formation and blood vessel ingrowth, especially from the mesh side. Although ADM has high mechanical strength, its vascularization is poor because the pore size is too small. In conclusion, the mechanical properties of scaffolds are important for maintaining the three-dimensional microarchitecture of constructs used to induce tissue regeneration and vascularization. The results illustrated that tissue regeneration requires the proper pore size and an appropriate mechanical property like PMCS which could satisfy these conditions to sustain growth.

Three types of dermal grafts in rats: the importance of mechanical property and structural design

PubMed Central

2013-01-01

Background To determine how the mechanical property and micro structure affect tissue regeneration and angiogenesis, three types of scaffolds were studied. Acellular dermal matrices (ADM), produced from human skin by removing the epidermis and cells, has been widely used in wound healing because of its high mechanical strength. Collagen scaffolds (CS) incorporated with poly(glycolide-co-L-lactide) (PLGA) mesh forms a well-supported hybrid dermal equivalent poly(glycolide-co-L-lactide) mesh/collagen scaffolds (PMCS). We designed this scaffold to enhance the CS mechanical property. These three different dermal substitutes—ADM, CS and PMCSs are different in the tensile properties and microstructure. Methods Several basic physical characteristics of dermal substitutes were investigated in vitro. To characterize the angiogenesis and tissue regeneration, the materials were embedded subcutaneously in Sprague–Dawley (SD) rats. At weeks 1, 2, 4 and 8 post-surgery, the tissue specimens were harvested for histology, immunohistochemistry and real-time quantitative PCR (RT-qPCR). Results In vitro studies demonstrated ADM had a higher Young’s modulus (6.94 MPa) rather than CS (0.19 MPa) and PMCS (3.33 MPa) groups in the wet state. Compared with ADMs and CSs, PMCSs with three-dimensional porous structures resembling skin and moderate mechanical properties can promote tissue ingrowth more quickly after implantation. In addition, the vascularization of the PMCS group is more obvious than that of the other two groups. The incorporation of a PLGA knitted mesh in CSs can improve the mechanical properties with little influence on the three-dimensional porous microstructure. After implantation, PMCSs can resist the contraction and promote cell infiltration, neotissue formation and blood vessel ingrowth, especially from the mesh side. Although ADM has high mechanical strength, its vascularization is poor because the pore size is too small. In conclusion, the mechanical properties of scaffolds are important for maintaining the three-dimensional microarchitecture of constructs used to induce tissue regeneration and vascularization. Conclusion The results illustrated that tissue regeneration requires the proper pore size and an appropriate mechanical property like PMCS which could satisfy these conditions to sustain growth. PMID:24304500

Three-dimensional direct cell patterning in collagen hydrogels with near-infrared femtosecond laser

PubMed Central

Hribar, Kolin C.; Meggs, Kyle; Liu, Justin; Zhu, Wei; Qu, Xin; Chen, Shaochen

2015-01-01

We report a methodology for three-dimensional (3D) cell patterning in a hydrogel in situ. Gold nanorods within a cell-encapsulating collagen hydrogel absorb a focused near-infrared femtosecond laser beam, locally denaturing the collagen and forming channels, into which cells migrate, proliferate, and align in 3D. Importantly, pattern resolution is tunable based on writing speed and laser power, and high cell viability (>90%) is achieved using higher writing speeds and lower laser intensities. Overall, this patterning technique presents a flexible direct-write method that is applicable in tissue engineering systems where 3D alignment is critical (such as vascular, neural, cardiac, and muscle tissue). PMID:26603915

[Evaluation of three-dimensional tumor microvascular architecture phenotype heterogeneity in non-small cell carcinoma and its significance].

PubMed

Zhou, Hui; Liu, Jinkang; Chen, Shengxi; Xiong, Zeng; Zhou, Jianhua; Tong, Shiyu; Chen, Hao; Zhou, Moling

2012-06-01

To explore the degree, mechanism and clinical significance of three-dimensional tumor microvascular architecture phenotype heterogeneity (3D-TMAPH) in non-small cell carcinoma (NSCLC). Twenty-one samples of solitary pulmonary nodules were collected integrally. To establish two-dimensional tumor microvascular architecture phenotype (2D-TMAP) and three-dimensional tumor microvascular architecture phenotype (3D-TMAP), five layers of each nodule were selected and embedded in paraffin. Test indices included the expressions of vascular endothelial growth factor (VEGF), proliferating cell nuclear antigen (PCNA), EphB4, ephfinB2 and microvascular density marked by anti-CD34 (CD34-MVD). The degrees of 3D-TMAPH were evaluated by the coefficient of variation and extend of heterogeneity. Spearman rank correlation analysis was used to investigate the relationships between 2D-TMAP, 3D-TMAP and clinicopathological features. 3D-TMAPH showed that 2D-TMAP heterogeneity was expressed in the tissues of NSCLC. The heterogeneities in the malignant nodules were significantly higher than those in the active inflammatory nodules and tubercular nodules. In addition, different degrees of heterogeneity of CD34-MVD and PCNA were found in NSCLC tissues. The coefficients of variation of CD34- MVD and PCNA were positively related to the degree of differentiation (all P<0.05), but not related to the P-TNM stages, histological type or lymphatic metastasis (all P>0.05). The level of heterogeneity of various expression indexes (ephrinB2, EphB4, VEGF) in NSCLC tissues were inconsistent, but there were no significant differences in heterogeneity in NSCLC tissues with different histological types (P>0.05). 3D-TMAPH exists widely in the microenvironment during the genesis and development of NSCLC and has a significant impact on its biological complexity.

Tissue Engineering and Cellular Regeneration at NASA Report to Regenetech SAB

NASA Technical Reports Server (NTRS)

Goodwin, Thomas J.

2004-01-01

A project overview describing three dimensional tissue models is shown. The topics include: 1) cellular regeneration; 2) haemopoietic replacement; 3) novel vaccine development; 4) pharmacology and toxicology interventions; 5) development of synthetic viruses; and 6) molecular genetics and proteomics of recapitulated models.

Design of 3-D adipospheres for quantitative metabolic study

PubMed Central

Akama, Takeshi; Leung, Brendan M.; Labuz, Joseph M.; Takayama, Shuichi; Chun, Tae-Hwa

2017-01-01

Quantitative assessment of adipose mitochondrial activity is critical for better understanding of adipose tissue function in obesity and diabetes. While the two-dimensional (2-D) tissue culture method has been sufficient to discover key molecules that regulate adipocyte differentiation and function, the method is insufficient to determine the role of extracellular matrix (ECM) molecules and their modifiers, such as matrix metalloproteinases (MMPs), in regulating adipocyte function in three-dimensional (3-D) in vivo-like microenvironments. By using a 3-D hanging drop tissue culture system, we are able to produce scalable 3-D adipospheres that are suitable for quantitative mitochondrial study in 3-D microenvironment. PMID:28244051

Bipolar stimulation of a three-dimensional bidomain incorporating rotational anisotropy.

PubMed

Muzikant, A L; Henriquez, C S

1998-04-01

A bidomain model of cardiac tissue was used to examine the effect of transmural fiber rotation during bipolar stimulation in three-dimensional (3-D) myocardium. A 3-D tissue block with unequal anisotropy and two types of fiber rotation (none and moderate) was stimulated along and across fibers via bipolar electrodes on the epicardial surface, and the resulting steady-state interstitial (phi e) and transmembrane (Vm) potentials were computed. Results demonstrate that the presence of rotated fibers does not change the amount of tissue polarized by the point surface stimuli, but does cause changes in the orientation of phi e and Vm in the depth of the tissue, away from the epicardium. Further analysis revealed a relationship between the Laplacian of phi e, regions of virtual electrodes, and fiber orientation that was dependent upon adequacy of spatial sampling and the interstitial anisotropy. These findings help to understand the role of fiber architecture during extracellular stimulation of cardiac muscle.

Scanning ion conductance microscopy for visualizing the three-dimensional surface topography of cells and tissues.

PubMed

Nakajima, Masato; Mizutani, Yusuke; Iwata, Futoshi; Ushiki, Tatsuo

2018-01-01

Scanning ion conductance microscopy (SICM), which belongs to the family of scanning probe microscopy, regulates the tip-sample distance by monitoring the ion current through the use of an electrolyte-filled nanopipette as the probing tip. Thus, SICM enables "contact-free" imaging of cell surface topography in liquid conditions. In this paper, we applied hopping mode SICM for obtaining topographical images of convoluted tissue samples such as trachea and kidney in phosphate buffered saline. Some of the SICM images were compared with the images obtained by scanning electron microscopy (SEM) after drying the same samples. We showed that the imaging quality of hopping mode SICM was excellent enough for investigating the three-dimensional surface structure of the soft tissue samples. Thus, SICM is expected to be used for imaging a wide variety of cells and tissues - either fixed or alive- at high resolution under physiologically relevant liquid conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Three-Dimensional Adipose Tissue Imaging Reveals Regional Variation in Beige Fat Biogenesis and PRDM16-Dependent Sympathetic Neurite Density.

PubMed

Chi, Jingyi; Wu, Zhuhao; Choi, Chan Hee J; Nguyen, Lily; Tegegne, Saba; Ackerman, Sarah E; Crane, Audrey; Marchildon, François; Tessier-Lavigne, Marc; Cohen, Paul

2018-01-09

While the cell-intrinsic pathways governing beige adipocyte development and phenotype have been increasingly delineated, comparatively little is known about how beige adipocytes interact with other cell types in fat. Here, we introduce a whole-tissue clearing method for adipose that permits immunolabeling and three-dimensional profiling of structures including thermogenic adipocytes and sympathetic innervation. We found that tissue architecture and sympathetic innervation differ significantly between subcutaneous and visceral depots. Subcutaneous fat demonstrates prominent regional variation in beige fat biogenesis with localization of UCP1 + beige adipocytes to areas with dense sympathetic neurites. We present evidence that the density of sympathetic projections is dependent on PRDM16 in adipocytes, providing another potential mechanism underlying the metabolic benefits mediated by PRDM16. This powerful imaging tool highlights the interaction of tissue components during beige fat biogenesis and reveals a previously undescribed mode of regulation of the sympathetic nervous system by adipocytes. Copyright © 2017 Elsevier Inc. All rights reserved.

Instrumented cardiac microphysiological devices via multimaterial three-dimensional printing

NASA Astrophysics Data System (ADS)

Lind, Johan U.; Busbee, Travis A.; Valentine, Alexander D.; Pasqualini, Francesco S.; Yuan, Hongyan; Yadid, Moran; Park, Sung-Jin; Kotikian, Arda; Nesmith, Alexander P.; Campbell, Patrick H.; Vlassak, Joost J.; Lewis, Jennifer A.; Parker, Kevin K.

2017-03-01

Biomedical research has relied on animal studies and conventional cell cultures for decades. Recently, microphysiological systems (MPS), also known as organs-on-chips, that recapitulate the structure and function of native tissues in vitro, have emerged as a promising alternative. However, current MPS typically lack integrated sensors and their fabrication requires multi-step lithographic processes. Here, we introduce a facile route for fabricating a new class of instrumented cardiac microphysiological devices via multimaterial three-dimensional (3D) printing. Specifically, we designed six functional inks, based on piezo-resistive, high-conductance, and biocompatible soft materials that enable integration of soft strain gauge sensors within micro-architectures that guide the self-assembly of physio-mimetic laminar cardiac tissues. We validated that these embedded sensors provide non-invasive, electronic readouts of tissue contractile stresses inside cell incubator environments. We further applied these devices to study drug responses, as well as the contractile development of human stem cell-derived laminar cardiac tissues over four weeks.

Measurement of cell death by oxidative stress in three-dimensional spheroids from trophoblast and in fragments of decidua tissue.

PubMed

Theuerkauf, Regine-Susanne; Ahammer, Helmut; Siwetz, Monika; Helige, Christine; Dohr, Gottfried; Walcher, Wolfgang; Palacio, José Ramón; Martinez, Paz; Sedlmayr, Peter

2010-05-01

We report a new morphometric method for measurement of the amount of cell death in three-dimensional multicellular spheroids of the trophoblast-like cell line AC1-M59 and of cultured pieces of decidua tissue (decidua spheroids) in response to a cytotoxic agent. The viability of the spheroids was assessed by adding propidium iodide to the culture medium at the end of the toxic treatment. On fluorescence and brightfield images of serial cryosections the areas of propidium iodide fluorescence and the entire corresponding spheroids were measured by applying digital image processing and ratiometrical quantification. As an example, we evaluated the cytotoxic effect of hydrogen peroxide on both types of spheroids. The relative potency of hydrogen peroxide to induce tissue damage was assessed quantitatively for determination of the minimal concentration that leads to an increase in cytotoxicity. The method presented suggests general applicability for in vitro determination of toxicity against tissues. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Deep and high-resolution three-dimensional tracking of single particles using nonlinear and multiplexed illumination

NASA Astrophysics Data System (ADS)

Perillo, Evan P.; Liu, Yen-Liang; Huynh, Khang; Liu, Cong; Chou, Chao-Kai; Hung, Mien-Chie; Yeh, Hsin-Chih; Dunn, Andrew K.

2015-07-01

Molecular trafficking within cells, tissues and engineered three-dimensional multicellular models is critical to the understanding of the development and treatment of various diseases including cancer. However, current tracking methods are either confined to two dimensions or limited to an interrogation depth of ~15 μm. Here we present a three-dimensional tracking method capable of quantifying rapid molecular transport dynamics in highly scattering environments at depths up to 200 μm. The system has a response time of 1 ms with a temporal resolution down to 50 μs in high signal-to-noise conditions, and a spatial localization precision as good as 35 nm. Built on spatiotemporally multiplexed two-photon excitation, this approach requires only one detector for three-dimensional particle tracking and allows for two-photon, multicolour imaging. Here we demonstrate three-dimensional tracking of epidermal growth factor receptor complexes at a depth of ~100 μm in tumour spheroids.

Multispectral breast imaging using a ten-wavelength, 64 x 64 source/detector channels silicon photodiode-based diffuse optical tomography system.

PubMed

Li, Changqing; Zhao, Hongzhi; Anderson, Bonnie; Jiang, Huabei

2006-03-01

We describe a compact diffuse optical tomography system specifically designed for breast imaging. The system consists of 64 silicon photodiode detectors, 64 excitation points, and 10 diode lasers in the near-infrared region, allowing multispectral, three-dimensional optical imaging of breast tissue. We also detail the system performance and optimization through a calibration procedure. The system is evaluated using tissue-like phantom experiments and an in vivo clinic experiment. Quantitative two-dimensional (2D) and three-dimensional (3D) images of absorption and reduced scattering coefficients are obtained from these experiments. The ten-wavelength spectra of the extracted reduced scattering coefficient enable quantitative morphological images to be reconstructed with this system. From the in vivo clinic experiment, functional images including deoxyhemoglobin, oxyhemoglobin, and water concentration are recovered and tumors are detected with correct size and position compared with the mammography.

A multiphysics 3D model of tissue growth under interstitial perfusion in a tissue-engineering bioreactor.

PubMed

Nava, Michele M; Raimondi, Manuela T; Pietrabissa, Riccardo

2013-11-01

The main challenge in engineered cartilage consists in understanding and controlling the growth process towards a functional tissue. Mathematical and computational modelling can help in the optimal design of the bioreactor configuration and in a quantitative understanding of important culture parameters. In this work, we present a multiphysics computational model for the prediction of cartilage tissue growth in an interstitial perfusion bioreactor. The model consists of two separate sub-models, one two-dimensional (2D) sub-model and one three-dimensional (3D) sub-model, which are coupled between each other. These sub-models account both for the hydrodynamic microenvironment imposed by the bioreactor, using a model based on the Navier-Stokes equation, the mass transport equation and the biomass growth. The biomass, assumed as a phase comprising cells and the synthesised extracellular matrix, has been modelled by using a moving boundary approach. In particular, the boundary at the fluid-biomass interface is moving with a velocity depending from the local oxygen concentration and viscous stress. In this work, we show that all parameters predicted, such as oxygen concentration and wall shear stress, by the 2D sub-model with respect to the ones predicted by the 3D sub-model are systematically overestimated and thus the tissue growth, which directly depends on these parameters. This implies that further predictive models for tissue growth should take into account of the three dimensionality of the problem for any scaffold microarchitecture.

The use of total human bone marrow fraction in a direct three-dimensional expansion approach for bone tissue engineering applications: focus on angiogenesis and osteogenesis.

PubMed

Guerrero, Julien; Oliveira, Hugo; Catros, Sylvain; Siadous, Robin; Derkaoui, Sidi-Mohammed; Bareille, Reine; Letourneur, Didier; Amédée, Joëlle

2015-03-01

Current approaches in bone tissue engineering have shown limited success, mostly owing to insufficient vascularization of the construct. A common approach consists of co-culture of endothelial cells and osteoblastic cells. This strategy uses cells from different sources and differentiation states, thus increasing the complexity upstream of a clinical application. The source of reparative cells is paramount for the success of bone tissue engineering applications. In this context, stem cells obtained from human bone marrow hold much promise. Here, we analyzed the potential of human whole bone marrow cells directly expanded in a three-dimensional (3D) polymer matrix and focused on the further characterization of this heterogeneous population and on their ability to promote angiogenesis and osteogenesis, both in vitro and in vivo, in a subcutaneous model. Cellular aggregates were formed within 24 h and over the 12-day culture period expressed endothelial and bone-specific markers and a specific junctional protein. Ectopic implantation of the tissue-engineered constructs revealed osteoid tissue and vessel formation both at the periphery and within the implant. This work sheds light on the potential clinical use of human whole bone marrow for bone regeneration strategies, focusing on a simplified approach to develop a direct 3D culture without two-dimensional isolation or expansion.

Three dimensional time reversal optical tomography

NASA Astrophysics Data System (ADS)

Wu, Binlin; Cai, W.; Alrubaiee, M.; Xu, M.; Gayen, S. K.

2011-03-01

Time reversal optical tomography (TROT) approach is used to detect and locate absorptive targets embedded in a highly scattering turbid medium to assess its potential in breast cancer detection. TROT experimental arrangement uses multi-source probing and multi-detector signal acquisition and Multiple-Signal-Classification (MUSIC) algorithm for target location retrieval. Light transport from multiple sources through the intervening medium with embedded targets to the detectors is represented by a response matrix constructed using experimental data. A TR matrix is formed by multiplying the response matrix by its transpose. The eigenvectors with leading non-zero eigenvalues of the TR matrix correspond to embedded objects. The approach was used to: (a) obtain the location and spatial resolution of an absorptive target as a function of its axial position between the source and detector planes; and (b) study variation in spatial resolution of two targets at the same axial position but different lateral positions. The target(s) were glass sphere(s) of diameter ~9 mm filled with ink (absorber) embedded in a 60 mm-thick slab of Intralipid-20% suspension in water with an absorption coefficient μa ~ 0.003 mm-1 and a transport mean free path lt ~ 1 mm at 790 nm, which emulate the average values of those parameters for human breast tissue. The spatial resolution and accuracy of target location depended on axial position, and target contrast relative to the background. Both the targets could be resolved and located even when they were only 4-mm apart. The TROT approach is fast, accurate, and has the potential to be useful in breast cancer detection and localization.

Physics of tissue harmonic imaging by ultrasound

NASA Astrophysics Data System (ADS)

Jing, Yuan

Tissue Harmonic Imaging (THI) is an imaging modality that is currently deployed on diagnostic ultrasound scanners. In THI the amplitude of the ultrasonic pulse that is used to probe the tissue is large enough that the pulse undergoes nonlinear distortion as it propagates into the tissue. One result of the distortion is that as the pulse propagates energy is shifted from the fundamental frequency of the source pulse into its higher harmonics. These harmonics will scatter off objects in the tissue and images formed from the scattered higher harmonics are considered to have superior quality to the images formed from the fundamental frequency. Processes that have been suggested as possibly responsible for the improved imaging in THI include: (1) reduced sensitivity to reverberation, (2) reduced sensitivity to aberration, and (3) reduction in side lobes. By using a combination of controlled experiments and numerical simulations, these three reasons have been investigated. A single element transducer and a clinical ultrasound scanner with a phased array transducer were used to image a commercial tissue-mimicking phantom with calibrated targets. The higher image quality achieved with THI was quantified in terms of spatial resolution and "clutter" signals. A three-dimensional model of the forward propagation of nonlinear sound beams in media with arbitrary spatial properties (a generalized KZK equation) was developed. A time-domain code for solving the KZK equation was validated with measurements of the acoustic field generated by the single element transducer and the phased array transducer. The code was used to investigate the impact of aberration using tissue-like media with three-dimensional variations in all acoustic properties. The three-dimensional maps of tissue properties were derived from the datasets available through the Visible Female project. The experiments and simulations demonstrated that second harmonic imaging (1) suffers less clutter associated with reverberation; (2) is not immune to aberration effects and (3) suffers less clutter due to reduced side-lobe levels. The results indicate that side lobe suppression is the most significant reason for the improvement of second harmonic imaging.

A combined three-dimensional in vitro–in silico approach to modelling bubble dynamics in decompression sickness

PubMed Central

Stride, E.; Cheema, U.

2017-01-01

The growth of bubbles within the body is widely believed to be the cause of decompression sickness (DCS). Dive computer algorithms that aim to prevent DCS by mathematically modelling bubble dynamics and tissue gas kinetics are challenging to validate. This is due to lack of understanding regarding the mechanism(s) leading from bubble formation to DCS. In this work, a biomimetic in vitro tissue phantom and a three-dimensional computational model, comprising a hyperelastic strain-energy density function to model tissue elasticity, were combined to investigate key areas of bubble dynamics. A sensitivity analysis indicated that the diffusion coefficient was the most influential material parameter. Comparison of computational and experimental data revealed the bubble surface's diffusion coefficient to be 30 times smaller than that in the bulk tissue and dependent on the bubble's surface area. The initial size, size distribution and proximity of bubbles within the tissue phantom were also shown to influence their subsequent dynamics highlighting the importance of modelling bubble nucleation and bubble–bubble interactions in order to develop more accurate dive algorithms. PMID:29263127

3D tissue-like assemblies: A novel approach to investigate virus-cell interactions.

PubMed

Goodwin, Thomas J; McCarthy, Maureen; Cohrs, Randall J; Kaufer, Benedikt B

2015-11-15

Virus-host cell interactions are most commonly analyzed in cells maintained in vitro as two-dimensional tissue cultures. However, these in vitro conditions vary quite drastically from the tissues that are commonly infected in vivo. Over the years, a number of systems have been developed that allow the establishment of three-dimensional (3D) tissue structures that have properties similar to their in vivo 3D counterparts. These 3D systems have numerous applications including drug testing, maintenance of large tissue explants, monitoring migration of human lymphocytes in tissues, analysis of human organ tissue development and investigation of virus-host interactions including viral latency. Here, we describe the establishment of tissue-like assemblies for human lung and neuronal tissue that we infected with a variety of viruses including the respiratory pathogens human parainfluenza virus type 3 (PIV3), respiratory syncytial virus (RSV) and SARS corona virus (SARS-CoV) as well as the human neurotropic herpesvirus, varicella-zoster virus (VZV). Copyright © 2015 Elsevier Inc. All rights reserved.

3D Tissue-Like Assemblies: A Novel Approach to Investigate Virus-Cell Interactions

PubMed Central

Goodwin, Thomas J.; McCarthy, Maureen; Cohrs, Randall J.; Kaufer, Benedikt B.

2017-01-01

Virus-host cell interactions are most commonly analyzed in cells maintained in vitro as two-dimensional tissue cultures. However, these in vitro conditions vary quite drastically from the tissues that are commonly infected in vivo. Over the years, a number of systems have been developed that allow the establishment of three-dimensional (3D) tissue structures that have properties similar to their in vivo 3D counterparts. These 3D systems have numerous applications including drug testing, maintenance of large tissue explants, monitoring migration of human lymphocytes in tissues, analysis of human organ tissue development and investigation of virus-host interactions including viral latency. Here, we describe the establishment of tissue-like assemblies for human lung and neuronal tissue that we infected with a variety of viruses including the respiratory pathogens human parainfluenza virus type 3 (PIV3), respiratory syncytial virus (RSV) and SARS corona virus (SARS-CoV) as well as the human neurotropic herpesvirus, varicella-zoster virus (VZV) PMID:25986169

Tissue matrix arrays for high throughput screening and systems analysis of cell function

PubMed Central

Beachley, Vince Z.; Wolf, Matthew T.; Sadtler, Kaitlyn; Manda, Srikanth S.; Jacobs, Heather; Blatchley, Michael; Bader, Joel S.; Pandey, Akhilesh; Pardoll, Drew; Elisseeff, Jennifer H.

2015-01-01

Cell and protein arrays have demonstrated remarkable utility in the high-throughput evaluation of biological responses; however, they lack the complexity of native tissue and organs. Here, we describe tissue extracellular matrix (ECM) arrays for screening biological outputs and systems analysis. We spotted processed tissue ECM particles as two-dimensional arrays or incorporated them with cells to generate three-dimensional cell-matrix microtissue arrays. We then investigated the response of human stem, cancer, and immune cells to tissue ECM arrays originating from 11 different tissues, and validated the 2D and 3D arrays as representative of the in vivo microenvironment through quantitative analysis of tissue-specific cellular responses, including matrix production, adhesion and proliferation, and morphological changes following culture. The biological outputs correlated with tissue proteomics, and network analysis identified several proteins linked to cell function. Our methodology enables broad screening of ECMs to connect tissue-specific composition with biological activity, providing a new resource for biomaterials research and translation. PMID:26480475

Ultrasound Technologies for the Spatial Patterning of Cells and Extracellular Matrix Proteins and the Vascularization of Engineered Tissue

NASA Astrophysics Data System (ADS)

Garvin, Kelley A.

Technological advancements in the field of tissue engineering could save the lives of thousands of organ transplant patients who die each year while waiting for donor organs. Currently, two of the primary challenges preventing tissue engineers from developing functional replacement tissues and organs are the need to recreate complex cell and extracellular microenvironments and to vascularize the tissue to maintain cell viability and function. Ultrasound is a form of mechanical energy that can noninvasively and nondestructively interact with tissues at the cell and protein level. In this thesis, novel ultrasound-based technologies were developed for the spatial patterning of cells and extracellular matrix proteins and the vascularization of three-dimensional engineered tissue constructs. Acoustic radiation forces associated with ultrasound standing wave fields were utilized to noninvasively control the spatial organization of cells and cell-bound extracellular matrix proteins within collagen-based engineered tissue. Additionally, ultrasound induced thermal mechanisms were exploited to site-specifically pattern various extracellular matrix collagen microstructures within a single engineered tissue construct. Finally, ultrasound standing wave field technology was used to promote the rapid and extensive vascularization of three-dimensional tissue constructs. As such, the ultrasound technologies developed in these studies have the potential to provide the field of tissue engineering with novel strategies to spatially pattern cells and extracellular matrix components and to vascularize engineered tissue, and thus, could advance the fabrication of functional replacement tissues and organs in the field of tissue engineering.

Analyzing Remodeling of Cardiac Tissue: A Comprehensive Approach Based on Confocal Microscopy and 3D Reconstructions

PubMed Central

Sachse, F. B.

2015-01-01

Microstructural characterization of cardiac tissue and its remodeling in disease is a crucial step in many basic research projects. We present a comprehensive approach for three-dimensional characterization of cardiac tissue at the submicrometer scale. We developed a compression-free mounting method as well as labeling and imaging protocols that facilitate acquisition of three-dimensional image stacks with scanning confocal microscopy. We evaluated the approach with normal and infarcted ventricular tissue. We used the acquired image stacks for segmentation, quantitative analysis and visualization of important tissue components. In contrast to conventional mounting, compression-free mounting preserved cell shapes, capillary lumens and extracellular laminas. Furthermore, the new approach and imaging protocols resulted in high signal-to-noise ratios at depths up to 60 μm. This allowed extensive analyses revealing major differences in volume fractions and distribution of cardiomyocytes, blood vessels, fibroblasts, myofibroblasts and extracellular space in control versus infarct border zone. Our results show that the developed approach yields comprehensive data on microstructure of cardiac tissue and its remodeling in disease. In contrast to other approaches, it allows quantitative assessment of all major tissue components. Furthermore, we suggest that the approach will provide important data for physiological models of cardiac tissue at the submicrometer scale. PMID:26399990

Digital hardware implementation of a stochastic two-dimensional neuron model.

PubMed

Grassia, F; Kohno, T; Levi, T

2016-11-01

This study explores the feasibility of stochastic neuron simulation in digital systems (FPGA), which realizes an implementation of a two-dimensional neuron model. The stochasticity is added by a source of current noise in the silicon neuron using an Ornstein-Uhlenbeck process. This approach uses digital computation to emulate individual neuron behavior using fixed point arithmetic operation. The neuron model's computations are performed in arithmetic pipelines. It was designed in VHDL language and simulated prior to mapping in the FPGA. The experimental results confirmed the validity of the developed stochastic FPGA implementation, which makes the implementation of the silicon neuron more biologically plausible for future hybrid experiments. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cryo-chemical decellularization of the whole liver for mesenchymal stem cells-based functional hepatic tissue engineering.

PubMed

Jiang, Wei-Cheng; Cheng, Yu-Hao; Yen, Meng-Hua; Chang, Yin; Yang, Vincent W; Lee, Oscar K

2014-04-01

Liver transplantation is the ultimate treatment for severe hepatic failure to date. However, the limited supply of donor organs has severely hampered this treatment. So far, great potentials of using mesenchymal stem cells (MSCs) to replenish the hepatic cell population have been shown; nevertheless, there still is a lack of an optimal three-dimensional scaffold for generation of well-transplantable hepatic tissues. In this study, we utilized a cryo-chemical decellularization method which combines physical and chemical approach to generate acellular liver scaffolds (ALS) from the whole liver. The produced ALS provides a biomimetic three-dimensional environment to support hepatic differentiation of MSCs, evidenced by expression of hepatic-associated genes and marker protein, glycogen storage, albumin secretion, and urea production. It is also found that hepatic differentiation of MSCs within the ALS is much more efficient than two-dimensional culture in vitro. Importantly, the hepatic-like tissues (HLT) generated by repopulating ALS with MSCs are able to act as functional grafts and rescue lethal hepatic failure after transplantation in vivo. In summary, the cryo-chemical method used in this study is suitable for decellularization of liver and create acellular scaffolds that can support hepatic differentiation of MSCs and be used to fabricate functional tissue-engineered liver constructs. Copyright © 2014 Elsevier Ltd. All rights reserved.

Removal of pinned scroll waves in cardiac tissues by electric fields in a generic model of three-dimensional excitable media.

PubMed

Pan, De-Bei; Gao, Xiang; Feng, Xia; Pan, Jun-Ting; Zhang, Hong

2016-02-24

Spirals or scroll waves pinned to heterogeneities in cardiac tissues may cause lethal arrhythmias. To unpin these life-threatening spiral waves, methods of wave emission from heterogeneities (WEH) induced by low-voltage pulsed DC electric fields (PDCEFs) and circularly polarized electric fields (CPEFs) have been used in two-dimensional (2D) cardiac tissues. Nevertheless, the unpinning of scroll waves in three-dimensional (3D) cardiac systems is much more difficult than that of spiral waves in 2D cardiac systems, and there are few reports on the removal of pinned scroll waves in 3D cardiac tissues by electric fields. In this article, we investigate in detail the removal of pinned scroll waves in a generic model of 3D excitable media using PDCEF, AC electric field (ACEF) and CPEF, respectively. We find that spherical waves can be induced from the heterogeneities by these electric fields in initially quiescent excitable media. However, only CPEF can induce spherical waves with frequencies higher than that of the pinned scroll wave. Such higher-frequency spherical waves induced by CPEF can be used to drive the pinned scroll wave out of the cardiac systems. We hope this remarkable ability of CPEF can provide a better alternative to terminate arrhythmias caused by pinned scroll waves.

Noninvasive metabolic imaging of engineered 3D human adipose tissue in a perfusion bioreactor.

PubMed

Ward, Andrew; Quinn, Kyle P; Bellas, Evangelia; Georgakoudi, Irene; Kaplan, David L

2013-01-01

The efficacy and economy of most in vitro human models used in research is limited by the lack of a physiologically-relevant three-dimensional perfused environment and the inability to noninvasively quantify the structural and biochemical characteristics of the tissue. The goal of this project was to develop a perfusion bioreactor system compatible with two-photon imaging to noninvasively assess tissue engineered human adipose tissue structure and function in vitro. Three-dimensional (3D) vascularized human adipose tissues were engineered in vitro, before being introduced to a perfusion environment and tracked over time by automated quantification of endogenous markers of metabolism using two-photon excited fluorescence (TPEF). Depth-resolved image stacks were analyzed for redox ratio metabolic profiling and compared to prior analyses performed on 3D engineered adipose tissue in static culture. Traditional assessments with H&E staining were used to qualitatively measure extracellular matrix generation and cell density with respect to location within the tissue. The distribution of cells within the tissue and average cellular redox ratios were different between static and perfusion cultures, while the trends of decreased redox ratio and increased cellular proliferation with time in both static and perfusion cultures were similar. These results establish a basis for noninvasive optical tracking of tissue structure and function in vitro, which can be applied to future studies to assess tissue development or drug toxicity screening and disease progression.

Automated fiber tracking and tissue characterization of the anterior cruciate ligament with optical coherence tomography

NASA Astrophysics Data System (ADS)

Balasubramanian, Priya S.; Guo, Jiaqi; Yao, Xinwen; Qu, Dovina; Lu, Helen H.; Hendon, Christine P.

2017-02-01

The directionality of collagen fibers across the anterior cruciate ligament (ACL) as well as the insertion of this key ligament into bone are important for understanding the mechanical integrity and functionality of this complex tissue. Quantitative analysis of three-dimensional fiber directionality is of particular interest due to the physiological, mechanical, and biological heterogeneity inherent across the ACL-to-bone junction, the behavior of the ligament under mechanical stress, and the usefulness of this information in designing tissue engineered grafts. We have developed an algorithm to characterize Optical Coherence Tomography (OCT) image volumes of the ACL. We present an automated algorithm for measuring ligamentous fiber angles, and extracting attenuation and backscattering coefficients of ligament, interface, and bone regions within mature and immature bovine ACL insertion samples. Future directions include translating this algorithm for real time processing to allow three-dimensional volumetric analysis within dynamically moving samples.

Three-dimensional Organization of Layered Apical Cytoskeletal Networks Associated with Mouse Airway Tissue Development

NASA Astrophysics Data System (ADS)

Tateishi, Kazuhiro; Nishida, Tomoki; Inoue, Kanako; Tsukita, Sachiko

2017-03-01

The cytoskeleton is an essential cellular component that enables various sophisticated functions of epithelial cells by forming specialized subcellular compartments. However, the functional and structural roles of cytoskeletons in subcellular compartmentalization are still not fully understood. Here we identified a novel network structure consisting of actin filaments, intermediate filaments, and microtubules directly beneath the apical membrane in mouse airway multiciliated cells and in cultured epithelial cells. Three-dimensional imaging by ultra-high voltage electron microscopy and immunofluorescence revealed that the morphological features of each network depended on the cell type and were spatiotemporally integrated in association with tissue development. Detailed analyses using Odf2 mutant mice, which lack ciliary basal feet and apical microtubules, suggested a novel contribution of the intermediate filaments to coordinated ciliary beating. These findings provide a new perspective for viewing epithelial cell differentiation and tissue morphogenesis through the structure and function of apical cytoskeletal networks.

Multi-depth fractionated aesthetic ultrasound surgery

NASA Astrophysics Data System (ADS)

Slayton, Michael H.; Lyke, Stephanie; Barthe, Peter G.

2017-03-01

Objective: Aesthetic ultrasound surgery provides the ability to treat at precise, clinically relevant depths with varied lesion size. This represents a major advantage compared to cosmetic laser and RF based energy sources. We present results of pre-clinical and clinical research aimed at establishing the feasibility of three-dimensional fractional deposition of focused ultrasound energy in the first 3mm of skin. Conformal thermal lesions were created in ex-vivo porcine muscle and live human skin in a variety of depths and geometries. Gross pathology demonstrating a three-dimensional pattern of non-intersecting lesions was micro- photographed and characterized in porcine tissue, and followed up to thirty days post treatment in human tissue. Methods: Image/treat transducers from 7.5 to 10 MHz, focal depths of 1 to 3 mm, and energies of 160 to 300 mJ were used to lay down a three-dimensional pattern of non-intersecting thermal lesions in freshly excised porcine muscle tissue. Human skin was treated in vivo at 120 to 360 mJ per lesion. Results were photographed immediately post-treatment and followed up to 30 days. Results: Porcine tissue lesion geometry was measured. Average lesion dimensions approximated by a sphere ranged from 360 micron (±19%) to 520 micron (±23%) varying with the energy settings. Measured depth and distance between the thermal lesions were within ±13% of the focal depth and lesion spacing. In human skin all lesions for all energy settings were completely resolved during the follow-up period. At lower energy settings of 120 mJ and 160 mJ lesions were completely resolved by day 2. Mild erythema and localized swelling were the only transient side effects and resolved within 48 hours or less. Conclusions: In conclusion, skin may be successfully treated in a three-dimensional fractionated manner with predictable and precise deposition of thermal damage. In vivo results demonstrate tolerability and fast resolution with minimal side effects.

Three-Dimensional Printing Articular Cartilage: Recapitulating the Complexity of Native Tissue.

PubMed

Guo, Ting; Lembong, Josephine; Zhang, Lijie Grace; Fisher, John P

2017-06-01

In the past few decades, the field of tissue engineering combined with rapid prototyping (RP) techniques has been successful in creating biological substitutes that mimic tissues. Its applications in regenerative medicine have drawn efforts in research from various scientific fields, diagnostics, and clinical translation to therapies. While some areas of therapeutics are well developed, such as skin replacement, many others such as cartilage repair can still greatly benefit from tissue engineering and RP due to the low success and/or inefficiency of current existing, often surgical treatments. Through fabrication of complex scaffolds and development of advanced materials, RP provides a new avenue for cartilage repair. Computer-aided design and three-dimensional (3D) printing allow the fabrication of modeled cartilage scaffolds for repair and regeneration of damaged cartilage tissues. Specifically, the various processes of 3D printing will be discussed in details, both cellular and acellular techniques, covering the different materials, geometries, and operational printing conditions for the development of tissue-engineered articular cartilage. Finally, we conclude with some insights on future applications and challenges related to this technology, especially using 3D printing techniques to recapitulate the complexity of native structure for advanced cartilage regeneration.

Three-dimensional vs. two-dimensional shear-wave elastography of the testes - preliminary study on a healthy collective.

PubMed

Marcon, J; Trottmann, M; Rübenthaler, J; D'Anastasi, M; Stief, C G; Reiser, M F; Clevert, D A

2016-01-01

Shear wave elastography (SWE) and its derivative Supersonic Shear Imaging (SSI) are newer techniques for the determination of tissue elasticity by measuring the velocity of generated shear waves (SWV), which correlates positively with tissue stiffness.The techniques are integrated into many modern ultrasound systems and have been examined in the evaluation of viscoelastic properties of different organ systems. Two-dimensional shear wave elastography (2D SWE) of the testes has been found to be a useful tool in recent studies which included the determination of standard values in healthy volunteers. Three-dimensional shear wave elastography (3D SWE) is the latest development in elastography and is made possible by generation of a multiplanar three-dimensional map via volumetric acquisition with a special ultrasound transducer. This technique allows the assessment of tissue elasticity in a three-dimensional, fully accessible organ map.The aim of this preliminary study was to both evaluate the feasibility of 3D SWE and to compare 2D and 3D SWE standard values in the testes of healthy subjects. We examined the testes of healthy male volunteers (n = 32) with a mean age of 51.06±17.75 years (range 25-77 years) by B-mode ultrasound, 2D and 3D SWE techniques in September of 2016. Volunteers with a history of testicular pathologies were excluded. For all imaging procedures the SL15-4 linear transducer (bandwidth 4-15 MHz) as well as the SLV16-4 volumetric probe (bandwidth 4-16 MHz) of the Aixplorer® ultrasound device (SuperSonic Imagine, Aix-en-Provence, France) were used. Seven regions of interest (ROI, Q-Box®) within the testes were evaluated for SWV using both procedures. SWV values were described in m/s. Results were statistically evaluated using univariateanalysis. Mean SWV values were 1.05 m/s for the 2D SWE and 1.12 m/s for the 3D SWE.Comparisons of local areas delivered no statistically significant differences (p = 0.11 to p = 0.66), except for the region in the central portion in the superior part of the coronal plane (p = 0.03). Testicular volume was significanty higher by a mean of 1.72 ml when measured with 3D SWE (p = 0.001). 3D SWE proved to be a feasible diagnostic tool in the assessment of testicular tissue, providing the examiner with a fully accessible three-dimensional map in a multiplanar or multislice view. With this technique a more precise testicular imaging - especially if combined with the display of tissue stiffness in SWE - is available and therefore could improve the diagnostic work-up of scrotal masses or the routine investigation of infertile men. Further studies for a better understanding in the context of various testicular pathologies will be required.

Forces in inhomogeneous open active-particle systems.

PubMed

Razin, Nitzan; Voituriez, Raphael; Elgeti, Jens; Gov, Nir S

2017-11-01

We study the force that noninteracting pointlike active particles apply to a symmetric inert object in the presence of a gradient of activity and particle sources and sinks. We consider two simple patterns of sources and sinks that are common in biological systems. We analytically solve a one-dimensional model designed to emulate higher-dimensional systems, and study a two-dimensional model by numerical simulations. We specify when the particle flux due to the creation and annihilation of particles can act to smooth the density profile that is induced by a gradient in the velocity of the active particles, and find the net resultant force due to both the gradient in activity and the particle flux. These results are compared qualitatively to observations of nuclear motion inside the oocyte, that is driven by a gradient in activity of actin-coated vesicles.

[Exploratory study on the micro-remodeling of dermal tissue].

PubMed

Jiang, Yu-zhi; Ding, Gui-fu; Lu, Shu-liang

2009-10-01

To explore the effect of three-dimensional structure of dermal matrix on biological behavior of fibroblasts (Fb) in the microcosmic perspective. The three-dimensional structure of dermal tissue was analyzed by plane geometric and trigonometric function. Microdots structure array with cell adhesion effect was designed by computer-assisted design software according to the adhesive and non-adhesive components of dermal tissue. Four sizes (8 microm x 3 microm, space 6 microm; 16 microm x 3 microm, space 6 microm; 16 microm x 5 microm, space 8 microm; 20 microm x 3 microm, space 2 microm) of micropier grid used for cell culture (MPGCC) with cell-adhesive microdots, built up with micro-pattern printing and molecule self-assembly method were used to culture dermal Fb. Fb cultured with cell culture matrix without micropier grid was set up as control. The expression of skeleton protein (alpha-SMA) of Fb, cell viability and cell secretion were detected with immunohistochemistry, fluorescent immunohistochemistry, MTT test and the hydroxyproline content assay. The three-dimensional structure of dermal tissue could be simulated by MPGCC as shown in arithmetic analysis. Compared with those of control group [(12 +/- 3)% and (0.53 +/- 0.03) microg/mg, (0.35 +/- 0.04)], the expression of alpha-SMA [(49 +/- 3)%, (61 +/- 3)%, (47 +/- 4)%, (51 +/- 3)%] and the content of hydroxyproline [(0.95 +/- 0.04), (0.87 +/- 0.03), (0.81 +/- 0.03), (0.77 +/- 0.03) microg/mg] were increased significantly (P < 0.05), the cell viability of Fb (0.12 +/- 0.03, 0.13 +/- 0.04, 0.14 +/- 0.03, 0.19 +/- 0.03) cultured in MPGCC was decreased significantly (P < 0.05). When the parameters of micropier grid were changed, the expression of alpha-SMA, the cell viability and the content of hydroxyproline of Fb cultured in four sizes of MPGCC were also significantly changed as compared with one another (P < 0.05). MPGCC may be the basic functional unit of dermal template, or unit of dermal template to call. Different three-dimensional circumstances for dermal tissue can result in different template effect and wound healing condition.

Adipogenesis of human adipose-derived stem cells within three-dimensional hollow fiber-based bioreactors.

PubMed

Gerlach, Jörg C; Lin, Yen-Chih; Brayfield, Candace A; Minteer, Danielle M; Li, Han; Rubin, J Peter; Marra, Kacey G

2012-01-01

To further differentiate adipose-derived stem cells (ASCs) into mature adipocytes and create three-dimensional (3D) adipose tissue in vitro, we applied multicompartment hollow fiber-based bioreactor technology with decentral mass exchange for more physiological substrate gradients and integral oxygenation. We hypothesize that a dynamic 3D perfusion in such a bioreactor will result in longer-term culture of human adipocytes in vitro, thus providing metabolically active tissue serving as a diagnostic model for screening drugs to treat diabetes. ASCs were isolated from discarded human abdominal subcutaneous adipose tissue and then inoculated into dynamic 3D culture bioreactors to undergo adipogenic differentiation. Insulin-stimulated glucose uptake from the medium was assessed with and without TNF-alpha. 3D adipose tissue was generated in the 3D-bioreactors. Immunohistochemical staining indicated that 3D-bioreactor culture displayed multiple mature adipocyte markers with more unilocular morphologies as compared with two-dimensional (2D) cultures. Results of real-time polymerase chain reaction showed 3D-bioreactor treatment had more efficient differentiation in fatty acid-binding protein 4 expression. Repeated insulin stimulation resulted in increased glucose uptake, with a return to baseline between testing. Importantly, TNF-alpha inhibited glucose uptake, an indication of the metabolic activity of the tissue. 3D bioreactors allow more mature adipocyte differentiation of ASCs compared with traditional 2D culture and generate adipose tissue in vitro for up to 2 months. Reproducible metabolic activity of the adipose tissue in the bioreactor was demonstrated, which is potentially useful for drug discovery. We present here, to the best of our knowledge for the first time, the development of a coherent 3D high density fat-like tissue consisting of unilocular structure from primary adipose stem cells in vitro.

Adipogenesis of Human Adipose-Derived Stem Cells Within Three-Dimensional Hollow Fiber-Based Bioreactors

PubMed Central

Gerlach, Jörg C.; Lin, Yen-Chih; Brayfield, Candace A.; Minteer, Danielle M.; Li, Han; Rubin, J. Peter

2012-01-01

To further differentiate adipose-derived stem cells (ASCs) into mature adipocytes and create three-dimensional (3D) adipose tissue in vitro, we applied multicompartment hollow fiber-based bioreactor technology with decentral mass exchange for more physiological substrate gradients and integral oxygenation. We hypothesize that a dynamic 3D perfusion in such a bioreactor will result in longer-term culture of human adipocytes in vitro, thus providing metabolically active tissue serving as a diagnostic model for screening drugs to treat diabetes. ASCs were isolated from discarded human abdominal subcutaneous adipose tissue and then inoculated into dynamic 3D culture bioreactors to undergo adipogenic differentiation. Insulin-stimulated glucose uptake from the medium was assessed with and without TNF-alpha. 3D adipose tissue was generated in the 3D-bioreactors. Immunohistochemical staining indicated that 3D-bioreactor culture displayed multiple mature adipocyte markers with more unilocular morphologies as compared with two-dimensional (2D) cultures. Results of real-time polymerase chain reaction showed 3D-bioreactor treatment had more efficient differentiation in fatty acid-binding protein 4 expression. Repeated insulin stimulation resulted in increased glucose uptake, with a return to baseline between testing. Importantly, TNF-alpha inhibited glucose uptake, an indication of the metabolic activity of the tissue. 3D bioreactors allow more mature adipocyte differentiation of ASCs compared with traditional 2D culture and generate adipose tissue in vitro for up to 2 months. Reproducible metabolic activity of the adipose tissue in the bioreactor was demonstrated, which is potentially useful for drug discovery. We present here, to the best of our knowledge for the first time, the development of a coherent 3D high density fat-like tissue consisting of unilocular structure from primary adipose stem cells in vitro. PMID:21902468

A three-dimensional flexible microprobe array for neural recording assembled through electrostatic actuation.

PubMed

Chen, Chang-Hsiao; Chuang, Shih-Chang; Su, Huan-Chieh; Hsu, Wei-Lun; Yew, Tri-Rung; Chang, Yen-Chung; Yeh, Shih-Rung; Yao, Da-Jeng

2011-05-07

We designed, fabricated and tested a novel three-dimensional flexible microprobe to record neural signals of a lateral giant nerve fiber of the escape circuit of an American crayfish. An electrostatic actuation folded planar probes into three-dimensional neural probes with arbitrary orientations for neuroscientific applications. A batch assembly based on electrostatic forces simplified the fabrication and was non-toxic. A novel fabrication for these three-dimensional flexible probes used SU-8 and Parylene technology. The mechanical strength of the neural probe was great enough to penetrate into a bio-gel. A flexible probe both decreased the micromotion and alleviated tissue encapsulation of the implant caused by chronic inflammation of tissue when an animal breathes or moves. The cortex consisted of six horizontal layers, and the neurons of the cortex were arranged in vertical structures; the three-dimensional microelectrode arrays were suitable to investigate the cooperative activity for neurons in horizontal separate layers and in vertical cortical columns. With this flexible probe we recorded neural signals of a lateral giant cell from an American crayfish. The response amplitude of action potentials was about 343 µV during 1 ms period; the average recorded data had a ratio of signal to noise as great as 30.22 ± 3.58 dB. The improved performance of this electrode made feasible the separation of neural signals according to their distinct shapes. The cytotoxicity indicated a satisfactory biocompatibility and non-toxicity of the flexible device fabricated in this work. © The Royal Society of Chemistry 2011

Electrical stimulation systems for cardiac tissue engineering

PubMed Central

Tandon, Nina; Cannizzaro, Christopher; Chao, Pen-Hsiu Grace; Maidhof, Robert; Marsano, Anna; Au, Hoi Ting Heidi; Radisic, Milica; Vunjak-Novakovic, Gordana

2009-01-01

We describe a protocol for tissue engineering of synchronously contractile cardiac constructs by culturing cardiac cells with the application of pulsatile electrical fields designed to mimic those present in the native heart. Tissue culture is conducted in a customized chamber built to allow for cultivation of (i) engineered three-dimensional (3D) cardiac tissue constructs, (ii) cell monolayers on flat substrates or (iii) cells on patterned substrates. This also allows for analysis of the individual and interactive effects of pulsatile electrical field stimulation and substrate topography on cell differentiation and assembly. The protocol is designed to allow for delivery of predictable electrical field stimuli to cells, monitoring environmental parameters, and assessment of cell and tissue responses. The duration of the protocol is 5 d for two-dimensional cultures and 10 d for 3D cultures. PMID:19180087

Modeling Physiological Events in 2D vs. 3D Cell Culture

PubMed Central

Duval, Kayla; Grover, Hannah; Han, Li-Hsin; Mou, Yongchao; Pegoraro, Adrian F.; Fredberg, Jeffery

2017-01-01

Cell culture has become an indispensable tool to help uncover fundamental biophysical and biomolecular mechanisms by which cells assemble into tissues and organs, how these tissues function, and how that function becomes disrupted in disease. Cell culture is now widely used in biomedical research, tissue engineering, regenerative medicine, and industrial practices. Although flat, two-dimensional (2D) cell culture has predominated, recent research has shifted toward culture using three-dimensional (3D) structures, and more realistic biochemical and biomechanical microenvironments. Nevertheless, in 3D cell culture, many challenges remain, including the tissue-tissue interface, the mechanical microenvironment, and the spatiotemporal distributions of oxygen, nutrients, and metabolic wastes. Here, we review 2D and 3D cell culture methods, discuss advantages and limitations of these techniques in modeling physiologically and pathologically relevant processes, and suggest directions for future research. PMID:28615311

Electrical stimulation: a novel tool for tissue engineering.

PubMed

Balint, Richard; Cassidy, Nigel J; Cartmell, Sarah H

2013-02-01

New advances in tissue engineering are being made through the application of different types of electrical stimuli to influence cell proliferation and differentiation. Developments made in the last decade have allowed us to improve the structure and functionality of tissue-engineered products through the use of growth factors, hormones, drugs, physical stimuli, bioreactor use, and two-dimensional (2-D) and three-dimensional (3-D) artificial extracellular matrices (with various material properties and topography). Another potential type of stimulus is electricity, which is important in the physiology and development of the majority of all human tissues. Despite its great potential, its role in tissue regeneration and its ability to influence cell migration, orientation, proliferation, and differentiation has rarely been considered in tissue engineering. This review highlights the importance of endogenous electrical stimulation, gathering the current knowledge on its natural occurrence and role in vivo, discussing the novel methods of delivering this stimulus and examining its cellular and tissue level effects, while evaluating how the technique could benefit the tissue engineering discipline in the future.

Effect of Chemistry on Osteogenesis and Angiogenesis Towards Bone Tissue Engineering Using 3D Printed Scaffolds.

PubMed

Bose, Susmita; Tarafder, Solaiman; Bandyopadhyay, Amit

2017-01-01

The functionality or survival of tissue engineering constructs depends on the adequate vascularization through oxygen transport and metabolic waste removal at the core. This study reports the presence of magnesium and silicon in direct three dimensional printed (3DP) tricalcium phosphate (TCP) scaffolds promotes in vivo osteogenesis and angiogenesis when tested in rat distal femoral defect model. Scaffolds with three different interconnected macro pore sizes were fabricated using direct three dimensional printing. In vitro ion release in phosphate buffer for 30 days showed sustained Mg 2+  and Si 4+  release from these scaffolds. Histolomorphology and histomorphometric analysis from the histology tissue sections revealed a significantly higher bone formation, between 14 and 20% for 4-16 weeks, and blood vessel formation, between 3 and 6% for 4-12 weeks, due to the presence of magnesium and silicon in TCP scaffolds compared to bare TCP scaffolds. The presence of magnesium in these 3DP TCP scaffolds also caused delayed TRAP activity. These results show that magnesium and silicon incorporated 3DP TCP scaffolds with multiscale porosity have huge potential for bone tissue repair and regeneration.

Induction of carcinoembryonic antigen expression in a three-dimensional culture system

NASA Technical Reports Server (NTRS)

Jessup, J. M.; Brown, D.; Fitzgerald, W.; Ford, R. D.; Nachman, A.; Goodwin, T. J.; Spaulding, G.

1994-01-01

MIP-101 is a poorly differentiated human colon carcinoma cell line established from ascites that produces minimal amounts of carcinoembryonic antigen (CEA), a 180 kDa glycoprotein tumor marker, and nonspecific cross-reacting antigen (NCA), a related protein that has 50 and 90 kDa isoforms, in vitro in monolayer culture. MIP-101 produces CEA when implanted into the peritoneum of nude mice but not when implanted into subcutaneous tissue. We tested whether MIP-101 cells may be induced to express CEA when cultured on microcarrier beads in three-dimensional cultures, either in static cultures as non-adherent aggregates or under dynamic conditions in a NASA-designed low shear stress bioreactor. MIP- 101 cells proliferated well under all three conditions and increased CEA and NCA production 3 - 4 fold when grown in three-dimensional cultures compared to MIP-101 cells growing logarithmically in monolayers. These results suggest that three-dimensional growth in vitro simulates tumor function in vivo and that three-dimensional growth by itself may enhance production of molecules that are associated with the metastatic process.

Evaluation of breast tissue with confocal strip-mosaicking microscopy: a test approach emulating pathology-like examination

PubMed Central

Abeytunge, Sanjee; Larson, Bjorg; Peterson, Gary; Morrow, Monica; Rajadhyaksha, Milind

2017-01-01

Abstract. Confocal microscopy is an emerging technology for rapid imaging of freshly excised tissue without the need for frozen- or fixed-section processing. Initial studies have described imaging of breast tissue using fluorescence confocal microscopy with small regions of interest, typically 750×750  μm2. We present exploration with a microscope, termed confocal strip-mosaicking microscope (CSM microscope), which images an area of 2×2  cm2 of tissue with cellular-level resolution in 10 min of excision. Using the CSM microscope, we imaged 34 fresh, human, large breast tissue specimens from 18 patients, blindly analyzed by a board-certified pathologist and subsequently correlated with the corresponding standard fixed histopathology. Invasive tumors and benign tissue were clearly identified in CSM strip-mosaic images. Thirty specimens were concordant for image-to-histopathology correlation while four were discordant. PMID:28327961

Recent development on computer aided tissue engineering--a review.

PubMed

Sun, Wei; Lal, Pallavi

2002-02-01

The utilization of computer-aided technologies in tissue engineering has evolved in the development of a new field of computer-aided tissue engineering (CATE). This article reviews recent development and application of enabling computer technology, imaging technology, computer-aided design and computer-aided manufacturing (CAD and CAM), and rapid prototyping (RP) technology in tissue engineering, particularly, in computer-aided tissue anatomical modeling, three-dimensional (3-D) anatomy visualization and 3-D reconstruction, CAD-based anatomical modeling, computer-aided tissue classification, computer-aided tissue implantation and prototype modeling assisted surgical planning and reconstruction.

Three-Dimensional Imaging of the Intracellular Fate of Plasmid DNA and Transgene Expression: ZsGreen1 and Tissue Clearing Method CUBIC Are an Optimal Combination for Multicolor Deep Imaging in Murine Tissues.

PubMed

Fumoto, Shintaro; Nishimura, Koyo; Nishida, Koyo; Kawakami, Shigeru

2016-01-01

Evaluation methods for determining the distribution of transgene expression in the body and the in vivo fate of viral and non-viral vectors are necessary for successful development of in vivo gene delivery systems. Here, we evaluated the spatial distribution of transgene expression using tissue clearing methods. After hydrodynamic injection of plasmid DNA into mice, whole tissues were subjected to tissue clearing. Tissue clearing followed by confocal laser scanning microscopy enabled evaluation of the three-dimensional distribution of transgene expression without preparation of tissue sections. Among the tested clearing methods (ClearT2, SeeDB, and CUBIC), CUBIC was the most suitable method for determining the spatial distribution of transgene expression in not only the liver but also other tissues such as the kidney and lung. In terms of the type of fluorescent protein, the observable depth for green fluorescent protein ZsGreen1 was slightly greater than that for red fluorescent protein tdTomato. We observed a depth of ~1.5 mm for the liver and 500 μm for other tissues without preparation of tissue sections. Furthermore, we succeeded in multicolor deep imaging of the intracellular fate of plasmid DNA in the murine liver. Thus, tissue clearing would be a powerful approach for determining the spatial distribution of plasmid DNA and transgene expression in various murine tissues.

Dimensionality and noise in energy selective x-ray imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alvarez, Robert E.

Purpose: To develop and test a method to quantify the effect of dimensionality on the noise in energy selective x-ray imaging.Methods: The Cramèr-Rao lower bound (CRLB), a universal lower limit of the covariance of any unbiased estimator, is used to quantify the noise. It is shown that increasing dimensionality always increases, or at best leaves the same, the variance. An analytic formula for the increase in variance in an energy selective x-ray system is derived. The formula is used to gain insight into the dependence of the increase in variance on the properties of the additional basis functions, the measurementmore » noise covariance, and the source spectrum. The formula is also used with computer simulations to quantify the dependence of the additional variance on these factors. Simulated images of an object with three materials are used to demonstrate the trade-off of increased information with dimensionality and noise. The images are computed from energy selective data with a maximum likelihood estimator.Results: The increase in variance depends most importantly on the dimension and on the properties of the additional basis functions. With the attenuation coefficients of cortical bone, soft tissue, and adipose tissue as the basis functions, the increase in variance of the bone component from two to three dimensions is 1.4 × 10{sup 3}. With the soft tissue component, it is 2.7 × 10{sup 4}. If the attenuation coefficient of a high atomic number contrast agent is used as the third basis function, there is only a slight increase in the variance from two to three basis functions, 1.03 and 7.4 for the bone and soft tissue components, respectively. The changes in spectrum shape with beam hardening also have a substantial effect. They increase the variance by a factor of approximately 200 for the bone component and 220 for the soft tissue component as the soft tissue object thickness increases from 1 to 30 cm. Decreasing the energy resolution of the detectors increases the variance of the bone component markedly with three dimension processing, approximately a factor of 25 as the resolution decreases from 100 to 3 bins. The increase with two dimension processing for adipose tissue is a factor of two and with the contrast agent as the third material for two or three dimensions is also a factor of two for both components. The simulated images show that a maximum likelihood estimator can be used to process energy selective x-ray data to produce images with noise close to the CRLB.Conclusions: The method presented can be used to compute the effects of the object attenuation coefficients and the x-ray system properties on the relationship of dimensionality and noise in energy selective x-ray imaging systems.« less

Surgical Force-Measuring Probe

NASA Technical Reports Server (NTRS)

Tcheng, Ping; Roberts, Paul W.; Scott, Charles E.

1993-01-01

Aerodynamic balance adapted to medical use. Electromechanical probe measures forces and moments applied to human tissue during surgery. Measurements used to document optimum forces and moments for surgical research and training. In neurosurgical research, measurements correlated with monitored responses of nerves. In training, students learn procedures by emulating forces used by experienced surgeons. Lightweight, pen-shaped probe easily held by surgeon. Cable feeds output signals to processing circuitry.

Phase contrast MR angiography techniques.

PubMed

Dumoulin, C L

1995-08-01

Phase contrast MR methods encode information from macroscopic motion into the phase of the MR signal. Phase contrast methods can be applied with small and large fields-of-view, can give quantitative measures of velocity, and provide excellent suppression of signals from stationary tissue. Unlike time-of-flight methods, phase contrast methods directly measure flow and thus are not hindered by the artifactual appearance of tissue having short T1. Phase contrast angiograms can be two-dimensional (thin slice or projectile), three-dimensional, and/or time resolved and have applications throughout the body.

A three-dimensional thermal and electromagnetic model of whole limb heating with a MAPA.

PubMed

Charny, C K; Levin, R L

1991-10-01

Previous studies by the authors have shown that if properly implemented, the Pennes assumptions can be applied to quantify bioheat transfer during extremity heating. Given its relative numerical simplicity and its ability to predict temperatures in thermoregulated tissue, the Pennes model of bioheat transfer was utilized in a three-dimensional thermal model of limb heating. While the arterial blood temperature was assumed to be radially uniform within a cross section of the limb, axial gradients in the arterial and venous blood temperatures were computed with this three-dimensional model. A realistically shaped, three-dimensional finite element model of a tumor-bearing human lower leg was constructed and was "attached" mathematically to the whole body thermal model of man described in previous studies by the authors. The central as well as local thermoregulatory feedback control mechanisms which determine blood perfusion to the various tissues and rate of evaporation by sweating were input into the limb model. In addition, the temperature of the arterial blood which feeds into the most proximal section of the lower leg was computed by the whole body thermal model. The variations in the shape of the tissues which comprise the limb were obtained from computerized tomography scans. Axial variations in the energy deposition patterns along the length of the limb exposed to a miniannular phased array (MAPA) applicator were also input into this model of limb heating. Results indicate that proper positioning of the limb relative to the MAPA is a significant factor in determining the effectiveness of the treatment. A patient-specific hyperthermia protocol can be designed using this coupled electromagnetic and thermal model.

Growing Three-Dimensional Corneal Tissue in a Bioreactor

NASA Technical Reports Server (NTRS)

Spaulding, Glen F.; Goodwin, Thomas J.; Aten, Laurie; Prewett, Tacey; Fitzgerald, Wendy S.; OConnor, Kim; Caldwell, Delmar; Francis, Karen M.

2003-01-01

Spheroids of corneal tissue about 5 mm in diameter have been grown in a bioreactor from an in vitro culture of primary rabbit corneal cells to illustrate the production of optic cells from aggregates and tissue. In comparison with corneal tissues previously grown in vitro by other techniques, this tissue approximates intact corneal tissue more closely in both size and structure. This novel three-dimensional tissue can be used to model cell structures and functions in normal and abnormal corneas. Efforts continue to refine the present in vitro method into one for producing human corneal tissue to overcome the chronic shortage of donors for corneal transplants: The method would be used to prepare corneal tissues, either from in vitro cultures of a patient s own cells or from a well-defined culture from another human donor known to be healthy. As explained in several articles in prior issues of NASA Tech Briefs, generally cylindrical horizontal rotating bioreactors have been developed to provide nutrient-solution environments conducive to the 30 NASA Tech Briefs, October 2003 growth of delicate animal cells, with gentle, low-shear flow conditions that keep the cells in suspension without damaging them. The horizontal rotating bioreactor used in this method, denoted by the acronym "HARV," was described in "High-Aspect-Ratio Rotating Cell-Culture Vessel" (MSC-21662), NASA Tech Briefs, Vol. 16, No. 5 (May, 1992), page 150.

In vitro chemotaxis and tissue remodeling assays quantitatively characterize foreign body reaction.

PubMed

Jannasch, Maren; Weigel, Tobias; Engelhardt, Lisa; Wiezoreck, Judith; Gaetzner, Sabine; Walles, Heike; Schmitz, Tobias; Hansmann, Jan

2017-01-01

Surgical implantation of a biomaterial triggers foreign-body-induced fibrous encapsulation. Two major mechanisms of this complex physiological process are (I) chemotaxis of fibroblasts from surrounding tissue to the implant region, followed by (II) tissue remodeling. As an alternative to animal studies, we here propose a process-aligned in vitro test platform to investigate the material dependency of fibroblast chemotaxis and tissue remodeling mediated by material-resident macrophages. Embedded in a biomimetic three-dimensional collagen hydrogel, chemotaxis of fibroblasts in the direction of macrophage-material-conditioned cell culture supernatant was analyzed by live cell imaging. A combination of statistical analysis with a complementary parameterized random walk model allowed quantitative and qualitative characterization of the cellular walk process. We thereby identified an increasing macrophage-mediated chemotactic potential ranking of biomaterials from glass over polytetrafluorethylene to titanium. To address long-term effects of bio-material-resident macrophages on fibroblasts in a three-dimensional microenvironment, we further studied tissue remodeling by applying macrophage-material-conditioned medium on fibrous in vitro tissue models. A high correlation of the in vitro tissue model to state of the art in vivo study data was found. Titanium exhibited a significantly lower tissue remodeling capacity compared to polytetrafluorethylene. With this approach, we identified a material dependency of both chemotaxis and tissue remodeling processes, strengthening knowledge on their specific contribution to the foreign body reaction.

Composite ultrasound imaging apparatus and method

DOEpatents

Morimoto, Alan K.; Bow, Jr., Wallace J.; Strong, David Scott; Dickey, Fred M.

1998-01-01

An imaging apparatus and method for use in presenting composite two dimensional and three dimensional images from individual ultrasonic frames. A cross-sectional reconstruction is applied by using digital ultrasound frames, transducer orientation and a known center. Motion compensation, rank value filtering, noise suppression and tissue classification are utilized to optimize the composite image.

Composite ultrasound imaging apparatus and method

DOEpatents

Morimoto, A.K.; Bow, W.J. Jr.; Strong, D.S.; Dickey, F.M.

1998-09-15

An imaging apparatus and method for use in presenting composite two dimensional and three dimensional images from individual ultrasonic frames. A cross-sectional reconstruction is applied by using digital ultrasound frames, transducer orientation and a known center. Motion compensation, rank value filtering, noise suppression and tissue classification are utilized to optimize the composite image. 37 figs.

Scaffolding for Three-Dimensional Embryonic Vasculogenesis

NASA Astrophysics Data System (ADS)

Kraehenbuehl, Thomas P.; Aday, Sezin; Ferreira, Lino S.

Biomaterial scaffolds have great potential to support efficient vascular differentiation of embryonic stem cells. Vascular cell fate-specific biochemical and biophysical cues have been identified and incorporated into three-dimensional (3D) biomaterials to efficiently direct embryonic vasculogenesis. The resulting vascular-like tissue can be used for regenerative medicine applications, further elucidation of biophysical and biochemical cues governing vasculogenesis, and drug discovery. In this chapter, we give an overview on the following: (1) developmental cues for directed differentiation of human embryonic stem cells (hESCs) into vascular cells, (2) 3D vascular differentiation in embryoid bodies (EBs), (3) preparation of 3D scaffolds for the vascular differentiation of hESCs, and (4) the most significant studies combining scaffolding and hESCs for development of vascular-like tissue.

High-fidelity meshes from tissue samples for diffusion MRI simulations.

PubMed

Panagiotaki, Eleftheria; Hall, Matt G; Zhang, Hui; Siow, Bernard; Lythgoe, Mark F; Alexander, Daniel C

2010-01-01

This paper presents a method for constructing detailed geometric models of tissue microstructure for synthesizing realistic diffusion MRI data. We construct three-dimensional mesh models from confocal microscopy image stacks using the marching cubes algorithm. Random-walk simulations within the resulting meshes provide synthetic diffusion MRI measurements. Experiments optimise simulation parameters and complexity of the meshes to achieve accuracy and reproducibility while minimizing computation time. Finally we assess the quality of the synthesized data from the mesh models by comparison with scanner data as well as synthetic data from simple geometric models and simplified meshes that vary only in two dimensions. The results support the extra complexity of the three-dimensional mesh compared to simpler models although sensitivity to the mesh resolution is quite robust.

Three-Dimensional Computer-Assisted Two-Layer Elastic Models of the Face.

PubMed

Ueda, Koichi; Shigemura, Yuka; Otsuki, Yuki; Fuse, Asuka; Mitsuno, Daisuke

2017-11-01

To make three-dimensional computer-assisted elastic models for the face, we decided on five requirements: (1) an elastic texture like skin and subcutaneous tissue; (2) the ability to take pen marking for incisions; (3) the ability to be cut with a surgical knife; (4) the ability to keep stitches in place for a long time; and (5) a layered structure. After testing many elastic solvents, we have made realistic three-dimensional computer-assisted two-layer elastic models of the face and cleft lip from the computed tomographic and magnetic resonance imaging stereolithographic data. The surface layer is made of polyurethane and the inner layer is silicone. Using this elastic model, we taught residents and young doctors how to make several typical local flaps and to perform cheiloplasty. They could experience realistic simulated surgery and understand three-dimensional movement of the flaps.

Dual-energy imaging of bone marrow edema on a dedicated multi-source cone-beam CT system for the extremities

NASA Astrophysics Data System (ADS)

Zbijewski, W.; Sisniega, A.; Stayman, J. W.; Thawait, G.; Packard, N.; Yorkston, J.; Demehri, S.; Fritz, J.; Siewerdsen, J. H.

2015-03-01

Purpose: Arthritis and bone trauma are often accompanied by bone marrow edema (BME). BME is challenging to detect in CT due to the overlaying trabecular structure but can be visualized using dual-energy (DE) techniques to discriminate water and fat. We investigate the feasibility of DE imaging of BME on a dedicated flat-panel detector (FPD) extremities cone-beam CT (CBCT) with a unique x-ray tube with three longitudinally mounted sources. Methods: Simulations involved a digital BME knee phantom imaged with a 60 kVp low-energy beam (LE) and 105 kVp high-energy beam (HE) (+0.25 mm Ag filter). Experiments were also performed on a test-bench with a Varian 4030CB FPD using the same beam energies as the simulation study. A three-source configuration was implemented with x-ray sources distributed along the longitudinal axis and DE CBCT acquisition in which the superior and inferior sources operate at HE (and collect half of the projection angles each) and the central source operates at LE. Three-source DE CBCT was compared to a double-scan, single-source orbit. Experiments were performed with a wrist phantom containing a 50 mg/ml densitometry insert submerged in alcohol (simulating fat) with drilled trabeculae down to ~1 mm to emulate the trabecular matrix. Reconstruction-based three-material decomposition of fat, soft tissue, and bone was performed. Results: For a low-dose scan (36 mAs in the HE and LE data), DE CBCT achieved combined accuracy of ~0.80 for a pattern of BME spherical lesions ranging 2.5 - 10 mm diameter in the knee phantom. The accuracy increased to ~0.90 for a 360 mAs scan. Excellent DE discrimination of the base materials was achieved in the experiments. Approximately 80% of the alcohol (fat) voxels in the trabecular phantom was properly identified both for single and 3-source acquisitions, indicating the ability to detect edemous tissue (water-equivalent plastic in the body of the densitometry insert) from the fat inside the trabecular matrix (emulating normal trabecular bone with significant fraction of yellow marrow). Conclusion: Detection of BME and quantification of water and fat content were achieved in extremities DE CBCT with a longitudinal configuration of sources providing DE imaging in a single gantry rotation. The findings support the development of DE imaging capability for CBCT of the extremities in areas conventionally in the domain of MRI.

Dual-Energy Imaging of Bone Marrow Edema on a Dedicated Multi-Source Cone-Beam CT System for the Extremities

PubMed Central

Zbijewski, W.; Sisniega, A.; Stayman, J. W.; Thawait, G.; Packard, N.; Yorkston, J.; Demehri, S.; Fritz, J.; Siewerdsen, J. H.

2015-01-01

Purpose Arthritis and bone trauma are often accompanied by bone marrow edema (BME). BME is challenging to detect in CT due to the overlaying trabecular structure but can be visualized using dual-energy (DE) techniques to discriminate water and fat. We investigate the feasibility of DE imaging of BME on a dedicated flat-panel detector (FPD) extremities cone-beam CT (CBCT) with a unique x-ray tube with three longitudinally mounted sources. Methods Simulations involved a digital BME knee phantom imaged with a 60 kVp low-energy beam (LE) and 105 kVp high-energy beam (HE) (+0.25 mm Ag filter). Experiments were also performed on a test-bench with a Varian 4030CB FPD using the same beam energies as the simulation study. A three-source configuration was implemented with x-ray sources distributed along the longitudinal axis and DE CBCT acquisition in which the superior and inferior sources operate at HE (and collect half of the projection angles each) and the central source operates at LE. Three-source DE CBCT was compared to a double-scan, single-source orbit. Experiments were performed with a wrist phantom containing a 50 mg/ml densitometry insert submerged in alcohol (simulating fat) with drilled trabeculae down to ~1 mm to emulate the trabecular matrix. Reconstruction-based three-material decomposition of fat, soft tissue, and bone was performed. Results For a low-dose scan (36 mAs in the HE and LE data), DE CBCT achieved combined accuracy of ~0.80 for a pattern of BME spherical lesions ranging 2.5 – 10 mm diameter in the knee phantom. The accuracy increased to ~0.90 for a 360 mAs scan. Excellent DE discrimination of the base materials was achieved in the experiments. Approximately 80% of the alcohol (fat) voxels in the trabecular phantom was properly identified both for single and 3-source acquisitions, indicating the ability to detect edemous tissue (water-equivalent plastic in the body of the densitometry insert) from the fat inside the trabecular matrix (emulating normal trabecular bone with significant fraction of yellow marrow). Conclusion Detection of BME and quantification of water and fat content were achieved in extremities DE CBCT with a longitudinal configuration of sources providing DE imaging in a single gantry rotation. The findings support the development of DE imaging capability for CBCT of the extremities in areas conventionally in the domain of MRI. PMID:26045631

Dual-Energy Imaging of Bone Marrow Edema on a Dedicated Multi-Source Cone-Beam CT System for the Extremities.

PubMed

Zbijewski, W; Sisniega, A; Stayman, J W; Thawait, G; Packard, N; Yorkston, J; Demehri, S; Fritz, J; Siewerdsen, J H

2015-02-21

Arthritis and bone trauma are often accompanied by bone marrow edema (BME). BME is challenging to detect in CT due to the overlaying trabecular structure but can be visualized using dual-energy (DE) techniques to discriminate water and fat. We investigate the feasibility of DE imaging of BME on a dedicated flat-panel detector (FPD) extremities cone-beam CT (CBCT) with a unique x-ray tube with three longitudinally mounted sources. Simulations involved a digital BME knee phantom imaged with a 60 kVp low-energy beam (LE) and 105 kVp high-energy beam (HE) (+0.25 mm Ag filter). Experiments were also performed on a test-bench with a Varian 4030CB FPD using the same beam energies as the simulation study. A three-source configuration was implemented with x-ray sources distributed along the longitudinal axis and DE CBCT acquisition in which the superior and inferior sources operate at HE (and collect half of the projection angles each) and the central source operates at LE. Three-source DE CBCT was compared to a double-scan, single-source orbit. Experiments were performed with a wrist phantom containing a 50 mg/ml densitometry insert submerged in alcohol (simulating fat) with drilled trabeculae down to ~1 mm to emulate the trabecular matrix. Reconstruction-based three-material decomposition of fat, soft tissue, and bone was performed. For a low-dose scan (36 mAs in the HE and LE data), DE CBCT achieved combined accuracy of ~0.80 for a pattern of BME spherical lesions ranging 2.5 - 10 mm diameter in the knee phantom. The accuracy increased to ~0.90 for a 360 mAs scan. Excellent DE discrimination of the base materials was achieved in the experiments. Approximately 80% of the alcohol (fat) voxels in the trabecular phantom was properly identified both for single and 3-source acquisitions, indicating the ability to detect edemous tissue (water-equivalent plastic in the body of the densitometry insert) from the fat inside the trabecular matrix (emulating normal trabecular bone with significant fraction of yellow marrow). Detection of BME and quantification of water and fat content were achieved in extremities DE CBCT with a longitudinal configuration of sources providing DE imaging in a single gantry rotation. The findings support the development of DE imaging capability for CBCT of the extremities in areas conventionally in the domain of MRI.

Challenges in Bio-fabrication of Organoid Cultures.

PubMed

Peng, Weijie; Datta, Pallab; Wu, Yang; Dey, Madhuri; Ayan, Bugra; Dababneh, Amer; Ozbolat, Ibrahim T

2018-06-01

Three-dimensional (3D) organoids have shown advantages in cell culture over traditional two-dimensional (2D) culture, and have great potential in various applications of tissue engineering. However, there are limitations in current organoid fabrication technologies, such as uncontrolled size, poor reproductively, and inadequate complexity of organoids. In this chapter, we present the existing techniques and discuss the major challenges for 3D organoid biofabrication. Future perspectives on organoid bioprinting are also discussed, where bioprinting technologies are expected to make a major contribution in organoid fabrication, such as realizing mass production and constructing complex heterotypic tissues, and thus further advance the translational application of organoids in tissue engineering and regenerative medicine as well drug testing and pharmaceutics.

Clinical evaluation of intensity-modulated radiotherapy for head and neck cancers

PubMed Central

Bhide, S A; Newbold, K L; Harrington, K J; Nutting, C M

2012-01-01

Radiotherapy and surgery are the principal curative modalities in treatment of head and neck cancer. Conventional two-dimensional and three-dimensional conformal radiotherapy result in significant side effects and altered quality of life. Intensity-modulated radiotherapy (IMRT) can spare the normal tissues, while delivering a curative dose to the tumour-bearing tissues. This article reviews the current role of IMRT in head and neck cancer from the point of view of normal tissue sparing, and also reviews the current published literature by individual head and neck cancer subsites. In addition, we briefly discuss the role of image guidance in head and neck IMRT, and future directions in this area. PMID:22556403

Computed tomography-guided tissue engineering of upper airway cartilage.

PubMed

Brown, Bryan N; Siebenlist, Nicholas J; Cheetham, Jonathan; Ducharme, Norm G; Rawlinson, Jeremy J; Bonassar, Lawrence J

2014-06-01

Normal laryngeal function has a large impact on quality of life, and dysfunction can be life threatening. In general, airway obstructions arise from a reduction in neuromuscular function or a decrease in mechanical stiffness of the structures of the upper airway. These reductions decrease the ability of the airway to resist inspiratory or expiratory pressures, causing laryngeal collapse. We propose to restore airway patency through methods that replace damaged tissue and improve the stiffness of airway structures. A number of recent studies have utilized image-guided approaches to create cell-seeded constructs that reproduce the shape and size of the tissue of interest with high geometric fidelity. The objective of the present study was to establish a tissue engineering approach to the creation of viable constructs that approximate the shape and size of equine airway structures, in particular the epiglottis. Computed tomography images were used to create three-dimensional computer models of the cartilaginous structures of the larynx. Anatomically shaped injection molds were created from the three-dimensional models and were seeded with bovine auricular chondrocytes that were suspended within alginate before static culture. Constructs were then cultured for approximately 4 weeks post-seeding and evaluated for biochemical content, biomechanical properties, and histologic architecture. Results showed that the three-dimensional molded constructs had the approximate size and shape of the equine epiglottis and that it is possible to seed such constructs while maintaining 75%+ cell viability. Extracellular matrix content was observed to increase with time in culture and was accompanied by an increase in the mechanical stiffness of the construct. If successful, such an approach may represent a significant improvement on the currently available treatments for damaged airway cartilage and may provide clinical options for replacement of damaged tissue during treatment of obstructive airway disease.

Engineered human broncho-epithelial tissue-like assemblies

NASA Technical Reports Server (NTRS)

Goodwin, Thomas J. (Inventor)

2012-01-01

Three-dimensional human broncho-epithelial tissue-like assemblies (TLAs) are produced in a rotating wall vessel (RWV) with microcarriers by coculturing mesenchymal bronchial-tracheal cells (BTC) and bronchial epithelium cells (BEC). These TLAs display structural characteristics and express markers of in vivo respiratory epithelia. TLAs are useful for screening compounds active in lung tissues such as antiviral compounds, cystic fibrosis treatments, allergens, and cytotoxic compounds.

Laser scanning cytometry as a tool for biomarker validation

NASA Astrophysics Data System (ADS)

Mittag, Anja; Füldner, Christiane; Lehmann, Jörg; Tarnok, Attila

2013-03-01

Biomarkers are essential for diagnosis, prognosis, and therapy. As diverse is the range of diseases the broad is the range of biomarkers and the material used for analysis. Whereas body fluids can be relatively easily obtained and analyzed, the investigation of tissue is in most cases more complicated. The same applies for the screening and the evaluation of new biomarkers and the estimation of the binding of biomarkers found in animal models which need to be transferred into applications in humans. The latter in particular is difficult if it recognizes proteins or cells in tissue. A better way to find suitable cellular biomarkers for immunoscintigraphy or PET analyses may be therefore the in situ analysis of the cells in the respective tissue. In this study we present a method for biomarker validation using Laser Scanning Cytometry which allows the emulation of future in vivo analysis. The biomarker validation is exemplarily shown for rheumatoid arthritis (RA) on synovial membrane. Cryosections were scanned and analyzed by phantom contouring. Adequate statistical methods allowed the identification of suitable markers and combinations. The fluorescence analysis of the phantoms allowed the discrimination between synovial membrane of RA patients and non-RA control sections by using median fluorescence intensity and the "affected area". As intensity and area are relevant parameters of in vivo imaging (e.g. PET scan) too, the presented method allows emulation of a probable outcome of in vivo imaging, i.e. the binding of the target protein and hence, the validation of the potential of the respective biomarker.

Three-dimensional virtual planning in orthognathic surgery enhances the accuracy of soft tissue prediction.

PubMed

Van Hemelen, Geert; Van Genechten, Maarten; Renier, Lieven; Desmedt, Maria; Verbruggen, Elric; Nadjmi, Nasser

2015-07-01

Throughout the history of computing, shortening the gap between the physical and digital world behind the screen has always been strived for. Recent advances in three-dimensional (3D) virtual surgery programs have reduced this gap significantly. Although 3D assisted surgery is now widely available for orthognathic surgery, one might still argue whether a 3D virtual planning approach is a better alternative to a conventional two-dimensional (2D) planning technique. The purpose of this study was to compare the accuracy of a traditional 2D technique and a 3D computer-aided prediction method. A double blind randomised prospective study was performed to compare the prediction accuracy of a traditional 2D planning technique versus a 3D computer-aided planning approach. The accuracy of the hard and soft tissue profile predictions using both planning methods was investigated. There was a statistically significant difference between 2D and 3D soft tissue planning (p < 0.05). The statistically significant difference found between 2D and 3D planning and the actual soft tissue outcome was not confirmed by a statistically significant difference between methods. The 3D planning approach provides more accurate soft tissue planning. However, the 2D orthognathic planning is comparable to 3D planning when it comes to hard tissue planning. This study provides relevant results for choosing between 3D and 2D planning in clinical practice. Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Non-Gimbaled Antenna Pointing

NASA Technical Reports Server (NTRS)

Vigil, Jeannine S.

1997-01-01

The small satellite community has been interested in accessing fixed ground stations for means of space-to-ground transmissions, although a problem arises from the limited global coverage. There is a growing interest for using the Space Network (SN) or Tracking and Data Relay Satellites (TDRS) as the primary support for communications because of the coverage it provides. This thesis will address the potential for satellite access of the Space Network with a non-gimbaled antenna configuration and low-power, coded transmission. The non-gimbaled antenna and the TDRS satellites, TDRS-East, TDRS-West, and TDRS-Zone of Exclusion, were configured in an orbital analysis software package called Satellite Tool Kit to emulate the three-dimensional position of the satellites. The access potential, which is the average number of contacts per day and the average time per contact, were obtained through simulations run over a 30-day period to gain all the possible orientations. The orbital altitude was varied from 600 km through 1200 km with the results being a function of orbital inclination angles varying from 20 deg through 100 deg and pointing half-angles of I0 deg through 40 deg. To compare the validity of the simulations, Jet Propulsion Laboratory granted the use of the TOPEX satellite. The TOPEX satellite was configured to emulate a spin-stabilized antenna with its communications antenna stowed in the zenith-pointing direction. This mimicked the antenna pointing spin-stabilized satellite in the simulations. To make valid comparisons, the TOPEX orbital parameters were entered into Satellite Tool Kit and simulated over five test times provided by Jet Propulsion Laboratory.

Three-Dimensional, Transgenic Cell Models to Quantify Space Genotoxic Effects

NASA Technical Reports Server (NTRS)

Gonda, S. R.; Sognier, M. A.; Wu, H.; Pingerelli, P. L.; Glickman, B. W.; Dawson, David L. (Technical Monitor)

1999-01-01

The space environment contains radiation and chemical agents known to be mutagenic and carcinogenic to humans. Additionally, microgravity is a complicating factor that may modify or synergize induced genotoxic effects. Most in vitro models fail to use human cells (making risk extrapolation to humans more difficult), overlook the dynamic effect of tissue intercellular interactions on genotoxic damage, and lack the sensitivity required to measure low-dose effects. Currently a need exists for a model test system that simulates cellular interactions present in tissue, and can be used to quantify genotoxic damage induced by low levels of radiation and chemicals, and extrapolate assessed risk to humans. A state-of-the-art, three-dimensional, multicellular tissue equivalent cell culture model will be presented. It consists of mammalian cells genetically engineered to contain multiple copies of defined target genes for genotoxic assessment,. NASA-designed bioreactors were used to coculture mammalian cells into spheroids, The cells used were human mammary epithelial cells (H184135) and Stratagene's (Austin, Texas) Big Blue(TM) Rat 2 lambda fibroblasts. The fibroblasts were genetically engineered to contain -a high-density target gene for mutagenesis (60 copies of lacl/LacZ per cell). Tissue equivalent spheroids were routinely produced by inoculation of 2 to 7 X 10(exp 5) fibroblasts with Cytodex 3 beads (150 micrometers in diameter). at a 20:1 cell:bead ratio, into 50-ml HARV bioreactors (Synthecon, Inc.). Fibroblasts were cultured for 5 days, an equivalent number of epithelial cells added, and the fibroblast/epithelial cell coculture continued for 21 days. Three-dimensional spheroids with diameters ranging from 400 to 600 micrometers were obtained. Histological and immunohistochemical Characterization revealed i) both cell types present in the spheroids, with fibroblasts located primarily in the center, surrounded by epithelial cells; ii) synthesis of extracellular matrix; and iii,, mitotic cells located throughout the spheroids. Spheroidal integrity and cell viability were retained for the 30-day test period after removal of spheroids from the bioreactor. Potential utility of this three-dimensional, transgenic model for genotoxicity was initially assessed by exposure of spheroids to 0-2 Gy neon at dose rates of 0.3 to 1.5 Gy/min (National Institute of Radiological Sciences, Chiba, Japan). Quantification of mutation at the lacl gene revealed a linear dose response for mutation induction. Limited sequencing analysis of mutant clones revealed higher frequencies of deletions and multiple base sequence changes with increasing dose. These results suggest that our three-dimensional, transgenic model is applicable to a wide variety of studies involving the quantification, identification, and characterization of genotoxicity incurred in space and on Earth. This model uniquely allows investigation of the interaction of relevant factors, namely cell-to-cell interactions and the mechanistic interaction of microgravity with radiation insults and DNA repair. Using this three-dimensional model will allow us to obtain dual genotoxic information (i.e., mutation rate plus chromosome aberration data) from the same system so that one endpoint can be used to reference the other, thereby increasing the fidelity of the data set. Moreover, the tissue-equivalent nature of the three-dimensional model provides high confidence for relevance of risk assessment, i.e., the establishment of quality factors directly applicable to the microgravity environment.

Low vacuum scanning electron microscopy for paraffin sections utilizing the differential stainability of cells and tissues with platinum blue.

PubMed

Inaga, Sumire; Hirashima, Sayuri; Tanaka, Keiichi; Katsumoto, Tetsuo; Kameie, Toshio; Nakane, Hironobu; Naguro, Tomonori

2009-07-01

The present study introduces a novel method for the direct observation of histological paraffin sections by low vacuum scanning electron microscopy (LVSEM) with platinum blue (Pt-blue) treatment. Pt-blue was applied not only as a backscattered electron (BSE) signal enhancer but also as a histologically specific stain. In this method, paraffin sections of the rat tongue prepared for conventional light microscopy (LM) were stained on glass slides with a Pt-blue staining solution (pH 9) and observed in a LVSEM using BSE detector. Under LVSEM, overviews of whole sections as well as three-dimensional detailed observations of individual cells and tissues could be easily made at magnifications from x40 to x10,000. Each kind of cell and tissue observed in the section could be clearly distinguished due to the different yields of BSE signals, which depended on the surface structures and different affinities to Pt-blue. Thus, we roughly classified cellular and tissue components into three groups according to the staining intensity of Pt-blue observed by LM and LVSEM: 1) a strongly stained (deep blue by LM and brightest by LVSEM) group which included epithelial tissue, endothelium and mast cells; 2) a moderately stained (light blue and bright) group which included muscular tissue and nervous tissue; 3) an unstained or weakly stained (colorless and dark) group which included elastic fibers and collagen fibers. We expect that this method will prove useful for the three-dimensional direct observation of histological paraffin sections of various tissues by LVSEM with higher resolutions than LM.

Remodeling of the Connective Tissue Microarchitecture of the Lamina Cribrosa in Early Experimental Glaucoma

PubMed Central

Roberts, Michael D.; Grau, Vicente; Grimm, Jonathan; Reynaud, Juan; Bellezza, Anthony J.; Burgoyne, Claude F.; Downs, J. Crawford

2009-01-01

Purpose To characterize the trabeculated connective tissue microarchitecture of the lamina cribrosa (LC) in terms of total connective tissue volume (CTV), connective tissue volume fraction (CTVF), predominant beam orientation, and material anisotropy in monkeys with early experimental glaucoma (EG). Methods The optic nerve heads from three monkeys with unilateral EG and four bilaterally normal monkeys were three dimensionally reconstructed from tissues perfusion fixed at an intraocular pressure of 10 mm Hg. A three-dimensional segmentation algorithm was used to extract a binary, voxel-based representation of the porous LC connective tissue microstructure that was regionalized into 45 subvolumes, and the following quantities were calculated: total CTV within the LC, mean and regional CTVF, regional predominant beam orientation, and mean and regional material anisotropy. Results Regional variation within the laminar microstructure was considerable within the normal eyes of all monkeys. The laminar connective tissue was generally most dense in the central and superior regions for the paired normal eyes, and laminar beams were radially oriented at the periphery for all eyes considered. CTV increased substantially in EG eyes compared with contralateral normal eyes (82%, 44%, 45% increases; P < 0.05), but average CTVF changed little (−7%, 1%, and −2% in the EG eyes). There were more laminar beams through the thickness of the LC in the EG eyes than in the normal controls (46%, 18%, 17% increases). Conclusions The substantial increase in laminar CTV with little change in CTVF suggests that significant alterations in connective and nonconnective tissue components in the laminar region occur in the early stages of glaucomatous damage. PMID:18806292

Accuracy of three-dimensional soft tissue prediction for Le Fort I osteotomy using Dolphin 3D software: a pilot study.

PubMed

Resnick, C M; Dang, R R; Glick, S J; Padwa, B L

2017-03-01

Three-dimensional (3D) soft tissue prediction is replacing two-dimensional analysis in planning for orthognathic surgery. The accuracy of different computational models to predict soft tissue changes in 3D, however, is unclear. A retrospective pilot study was implemented to assess the accuracy of Dolphin 3D software in making these predictions. Seven patients who had a single-segment Le Fort I osteotomy and had preoperative (T 0 ) and >6-month postoperative (T 1 ) cone beam computed tomography (CBCT) scans and 3D photographs were included. The actual skeletal change was determined by subtracting the T 0 from the T 1 CBCT. 3D photographs were overlaid onto the T 0 CBCT and virtual skeletal movements equivalent to the achieved repositioning were applied using Dolphin 3D planner. A 3D soft tissue prediction (T P ) was generated and differences between the T P and T 1 images (error) were measured at 14 points and at the nasolabial angle. A mean linear prediction error of 2.91±2.16mm was found. The mean error at the nasolabial angle was 8.1±5.6°. In conclusion, the ability to accurately predict 3D soft tissue changes after Le Fort I osteotomy using Dolphin 3D software is limited. Copyright © 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Incompressible Deformation Estimation Algorithm (IDEA) from Tagged MR Images

PubMed Central

Liu, Xiaofeng; Abd-Elmoniem, Khaled Z.; Stone, Maureen; Murano, Emi Z.; Zhuo, Jiachen; Gullapalli, Rao P.; Prince, Jerry L.

2013-01-01

Measuring the three-dimensional motion of muscular tissues, e.g., the heart or the tongue, using magnetic resonance (MR) tagging is typically carried out by interpolating the two-dimensional motion information measured on orthogonal stacks of images. The incompressibility of muscle tissue is an important constraint on the reconstructed motion field and can significantly help to counter the sparsity and incompleteness of the available motion information. Previous methods utilizing this fact produced incompressible motions with limited accuracy. In this paper, we present an incompressible deformation estimation algorithm (IDEA) that reconstructs a dense representation of the three-dimensional displacement field from tagged MR images and the estimated motion field is incompressible to high precision. At each imaged time frame, the tagged images are first processed to determine components of the displacement vector at each pixel relative to the reference time. IDEA then applies a smoothing, divergence-free, vector spline to interpolate velocity fields at intermediate discrete times such that the collection of velocity fields integrate over time to match the observed displacement components. Through this process, IDEA yields a dense estimate of a three-dimensional displacement field that matches our observations and also corresponds to an incompressible motion. The method was validated with both numerical simulation and in vivo human experiments on the heart and the tongue. PMID:21937342

Applications of 3D printing in the management of severe spinal conditions.

PubMed

Provaggi, Elena; Leong, Julian J H; Kalaskar, Deepak M

2017-06-01

The latest and fastest-growing innovation in the medical field has been the advent of three-dimensional printing technologies, which have recently seen applications in the production of low-cost, patient-specific medical implants. While a wide range of three-dimensional printing systems has been explored in manufacturing anatomical models and devices for the medical setting, their applications are cutting-edge in the field of spinal surgery. This review aims to provide a comprehensive overview and classification of the current applications of three-dimensional printing technologies in spine care. Although three-dimensional printing technology has been widely used for the construction of patient-specific anatomical models of the spine and intraoperative guide templates to provide personalized surgical planning and increase pedicle screw placement accuracy, only few studies have been focused on the manufacturing of spinal implants. Therefore, three-dimensional printed custom-designed intervertebral fusion devices, artificial vertebral bodies and disc substitutes for total disc replacement, along with tissue engineering strategies focused on scaffold constructs for bone and cartilage regeneration, represent a set of promising applications towards the trend of individualized patient care.

Biophysics and dynamics of natural and engineered stem cell microenvironments.

PubMed

Keung, Albert J; Healy, Kevin E; Kumar, Sanjay; Schaffer, David V

2010-01-01

Stem cells are defined by their ability to self-renew and to differentiate into one or more mature lineages, and they reside within natural niches in many types of adult and embryonic tissues that present them with complex signals to regulate these two hallmark properties. The diverse nature of these in vivo microenvironments raises important questions about the microenvironmental cues regulating stem cell plasticity, and the stem cell field has built a strong foundation of knowledge on the biochemical identities and regulatory effects of the soluble, cellular, and extracellular matrix factors surrounding stem cells through the isolation and culture of stem cells in vitro within microenvironments that, in effect, emulate the properties of the natural niche. Recent work, however, has expanded the field's perspective to include biophysical and dynamic characteristics of the microenvironment. These include biomechanical characteristics such as elastic modulus, shear force, and cyclic strain; architectural properties such as geometry, topography, and dimensionality; and dynamic structures and ligand profiles. We will review how these microenvironmental characteristics have been shown to regulate stem cell fate and discuss future research directions that may help expand our current understanding of stem cell biology and aid its application to regenerative medicine.

Polyphosphazene/Nano-Hydroxyapatite Composite Microsphere Scaffolds for Bone Tissue Engineering

PubMed Central

Nukavarapu, Syam P.; Kumbar, Sangamesh G.; Brown, Justin L.; Krogman, Nicholas R.; Weikel, Arlin L.; Hindenlang, Mark D.; Nair, Lakshmi S.; Allcock, Harry R; Laurencin, Cato T.

2009-01-01

The non-toxic, neutral degradation products of amino acid ester polyphosphazenes make them ideal candidates for in vivo orthopaedic applications. The quest for new osteocompatible materials for load bearing tissue engineering applications has led us to investigate mechanically competent amino acid ester substituted polyphosphazenes. In this study, we have synthesized three biodegradable polyphosphazenes substituted with side groups namely leucine, valine and phenylalanine ethyl esters. Of these polymers, the phenylalanine ethyl ester substituted polyphosphazene showed the highest glass transition temperature (41.6 °C) and hence was chosen as a candidate material for forming composite microspheres with 100 nm sized hydroxyapatite (nHAp). The fabricated composite microspheres were sintered into a three-dimensional (3-D) porous scaffold by adopting a dynamic solvent sintering approach. The composite microsphere scaffolds showed compressive moduli of 46–81 MPa with mean pore diameters in the range of 86–145 µm. The three-dimensional polyphosphazene-nHAp composite microsphere scaffolds showed good osteoblast cell adhesion, proliferation and alkaline phosphatase expression, and are potential suitors for bone tissue engineering applications. PMID:18517248

Three-dimensional culture in a microgravity bioreactor improves the engraftment efficiency of hepatic tissue constructs in mice.

PubMed

Zhang, Shichang; Zhang, Bo; Chen, Xia; Chen, Li; Wang, Zhengguo; Wang, Yingjie

2014-12-01

Tissue-engineered liver using primary hepatocytes has been considered a valuable new therapeutic modality as an alternative to whole organ liver transplantation for different liver diseases. The development of clinically feasible liver tissue engineering approaches, however, has been hampered by the poor engraftment efficiency of hepatocytes. We developed a three-dimensional (3D) culture system using a microgravity bioreactor (MB), biodegradable scaffolds and growth-factor-reduced Matrigel to construct a tissue-engineered liver for transplantation into the peritoneal cavity of non-obese diabetic severe combined immunodeficient mice. The number of viable cells in the hepatic tissue constructs was stably maintained in the 3D MB culture system. Hematoxylin-eosin staining and zonula occludens-1 expression revealed that neonatal mouse liver cells were reorganized to form tissue-like structures during MB culture. Significantly upregulated hepatic functions (albumin secretion, urea production and cytochrome P450 activity) were observed in the MB culture group. Post-transplantation analysis indicated that the engraftment efficiency of the hepatic tissue constructs prepared in MB cultures was higher than that of those prepared in the static cultures. Higher level of hepatic function in the implants was confirmed by the expression of albumin. These findings suggest that 3D MB culture systems may offer an improved method for creating tissue-engineered liver because of the higher engraftment efficiency and the reduction of the initial cell function loss.

Modeling the Epithelial Morphogenesis of Germ Band Retraction in Three Dimensions

NASA Astrophysics Data System (ADS)

McCleery, W. Tyler; Veldhuis, Jim; Brodland, G. Wayne; Crews, Sarah M.; Hutson, M. Shane

2015-03-01

Embryogenesis of higher-order organisms is driven by an intricate coordination of cellular mechanics. Mechanical analysis of certain developmental events, e.g., dorsal closure in the fruit fly D. melanogaster, has been sufficiently described using two-dimensional models. Here, we present a three-dimensional modeling technique to investigate germ band retraction (GBR) - a whole-embryo, irreducibly 3D morphogenetic event. At the start of GBR, the epithelial tissue known as the germ band is initially wrapped around the posterior end of an ellipsoidal fly embryo. This tissue then retracts as an adjacent epithelial tissue, the amnioserosa, simultaneously contracts. We hypothesize that proper GBR requires maintenance of cell-cell connectivity in the amnioserosa, as well as both cell and tissue topology on the embryo's ellipsoidal surface. The exact interfacial tensions are less important. We test the dynamic interactions between these two tissues on a 3D ellipsoidal last. To speed simulation run times and focus on the relevant tissues, epithelial cells are defined as polygons constrained to lie on the surface of the ellipsoidal last. These cells have adjustable parameters such as edge tensions and cell pressures. Tissue movements are simulated by balancing these dynamic cell-level forces with viscous resistance and allowing cells to exchange neighbors. This modeling approach helps elucidate the multicellular stress fields in normal and aberrant development, providing deeper insight into the mechanical interdependence of developing tissues.

Mechanotransduction mechanisms in growing spherically structured tissues

NASA Astrophysics Data System (ADS)

Littlejohns, Euan; Dunlop, Carina M.

2018-04-01

There is increasing experimental interest in mechanotransduction in multi-cellular tissues as opposed to single cells. This is driven by a growing awareness of the importance of physiologically relevant three-dimensional culture and of cell–cell and cell–gel interactions in directing growth and development. The paradigm biophysical technique for investigating tissue level mechanobiology in this context is to grow model tissues in artificial gels with well-defined mechanical properties. These studies often indicate that the stiffness of the encapsulating gel can significantly alter cellular behaviours. We demonstrate here potential mechanisms linking tissue growth with stiffness-mediated mechanotransduction. We show how tissue growth in gel systems generates points at which there is a significant qualitative change in the cellular stress and strain experienced. We show analytically how these potential switching points depend on the mechanical properties of the constraining gel and predict when they will occur. Significantly, we identify distinct mechanisms that act separately in each of the stress and strain fields at different times. These observations suggest growth as a potential physical mechanism coupling gel stiffness with cellular mechanotransduction in three-dimensional tissues. We additionally show that non-proliferating areas, in the case that the constraining gel is soft compared with the tissue, will expand and contract passively as a result of growth. Central compartment size is thus seen to not be a reliable indicator on its own for growth initiation or active behaviour.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Williams, Brian J.; Marcy, Peter W.

We will investigate the use of derivative information in complex computer model emulation when the correlation function is of the compactly supported Bohman class. To this end, a Gaussian process model similar to that used by Kaufman et al. (2011) is extended to a situation where first partial derivatives in each dimension are calculated at each input site (i.e. using gradients). A simulation study in the ten-dimensional case is conducted to assess the utility of the Bohman correlation function against strictly positive correlation functions when a high degree of sparsity is induced.

Resonance Raman imaging for detecting and monitoring molecular pathological changes in human brain tumors related to Warburg effect

NASA Astrophysics Data System (ADS)

Zhou, Yan; Liu, Cheng-hui; Zhu, Ke; Zhang, Chunyuan; Yang, Yang; Yu, Xinguang; Hu, Hailong; Cheng, Gangge; Wu, Binlin; Shi, Lingyan; Alfano, Robert R.

2018-02-01

The goal of the research is to determine the prognostic molecular pathological changes in components and composition, for human brain glioma gradings in comparison with normal tissues in three-dimensional Raman imaging profiles by visible Resonance Raman (VRR) imaging. VRR images from twenty-five specimens including three healthy tissues, one normal control, and twenty-one glioma tissues of grades II, II-III and III-IV with histology examination were measured and investigated using WITec300R confocal micro Raman imaging system with laser excitation of 532nm. Two-dimensional RR spectral mappings performed in 20μm x 20μm generated 400 images which integrated the intensity of the specific biochemical bonds as the third dimension. The three-dimension (3D) map demonstrated the spatial distributions of three selected sets of RR spectra of molecular biomarkers, and revealed significant differences in the spectra between normal and glioma tissues of different grades due to the composition changes in key molimageecules. These RR molecular spectral fingerprints have displayed: a clear enhancement of RR vibrational modes at 1129-1131cm-1 and 2934cm-1 which are supposed to be arising from lipoproteins; evident decreased RR vibrational modes at 1442cm-1 and 2854cm-1 which are from saturated fatty acids bonds in all-grades of glioma brain tissues compared with normal tissues; and the enhanced RR spectral modes of 1129 cm-1 and 2938cm-1 which suggest contribution from lactate. These findings may provide a novel proof for anaerobic glycolysis metabolic process in brain glioma cancer tissues that has been explained by Warburg effects.

Temporal focusing microscopy combined with three-dimensional structured illumination

NASA Astrophysics Data System (ADS)

Isobe, Keisuke; Toda, Keisuke; Song, Qiyuan; Kannari, Fumihiko; Kawano, Hiroyuki; Miyawaki, Atsushi; Midorikawa, Katsumi

2017-05-01

Temporal focusing microscopy provides the optical sectioning capability in wide-field two-photon fluorescence imaging. Here, we demonstrate temporal focusing microscopy combined with three-dimensional structured illumination, which enables us to enhance the three-dimensional spatial resolution and reject the background fluorescence. Experimentally, the periodic pattern of the illumination was produced not only in the lateral direction but also in the axial direction by the interference between three temporal focusing pulses, which were easily generated using a digital micromirror device. The lateral resolution and optical sectioning capability were successfully enhanced by factors of 1.6 and 3.6, respectively, compared with those of temporal focusing microscopy. In the two-photon fluorescence imaging of a tissue-like phantom, the out-of-focus background fluorescence and the scattered background fluorescence could also be rejected.

Collagen density gradient on three-dimensional printed poly(ε-caprolactone) scaffolds for interface tissue engineering.

PubMed

D'Amora, Ugo; D'Este, Matteo; Eglin, David; Safari, Fatemeh; Sprecher, Christoph M; Gloria, Antonio; De Santis, Roberto; Alini, Mauro; Ambrosio, Luigi

2018-02-01

The ability to engineer scaffolds that resemble the transition between tissues would be beneficial to improve repair of complex organs, but has yet to be achieved. In order to mimic tissue organization, such constructs should present continuous gradients of geometry, stiffness and biochemical composition. Although the introduction of rapid prototyping or additive manufacturing techniques allows deposition of heterogeneous layers and shape control, the creation of surface chemical gradients has not been explored on three-dimensional (3D) scaffolds obtained through fused deposition modelling technique. Thus, the goal of this study was to introduce a gradient functionalization method in which a poly(ε-caprolactone) surface was first aminolysed and subsequently covered with collagen via carbodiimide reaction. The 2D constructs were characterized for their amine and collagen contents, wettability, surface topography and biofunctionality. Finally, chemical gradients were created in 3D printed scaffolds with controlled geometry and porosity. The combination of additive manufacturing and surface modification is a viable tool for the fabrication of 3D constructs with controlled structural and chemical gradients. These constructs can be employed for mimicking continuous tissue gradients for interface tissue engineering. Copyright © 2017 John Wiley & Sons, Ltd.

Detection and three-dimensional visualization of lesion models using sonoelastography

NASA Astrophysics Data System (ADS)

Taylor, Lawrence S.; Gaborski, Thomas R.; Strang, John G.; Rubens, Deborah; Parker, Kevin J.

2002-04-01

Sonoelastography is a vibration Doppler technique for imaging the relative elasticity of tissues. Detectability of hard lesions of various sizes has previously been demonstrated in tissue phantoms by our group. Because real tissue differs from phantom material, the injection of formaldehyde in fresh liver tissue is being used as an in-vitro lesion model. Pieces of fresh calf liver were embedded in an agar gel then injected with a bolus of 37% formaldehyde to create a stiff lesion. Two and three-dimensional sonoelastography and b-mode images were acquired. The lesions were visible in each sonoelastography image as a region of reduced vibration. After imaging, lesions were dissected and measured for size and volume. One 0.4 cc bolus injection of formaldehyde created a lesion with a volume of 10.3 cc in the sonoelastography image compared to 9.3 cc using fluid displacement of the dissected lesion. A 0.33 cc injection of formaldehyde lesion created a volume of 5 cc in the sonoelastography image compared to 4.4 cc using fluid displacement. Sonoelastography imaging techniques for imaging hard lesions in phantoms can be successfully extended to imaging formaldehyde induced lesions in real tissue.

3D printing for clinical application in otorhinolaryngology.

PubMed

Zhong, Nongping; Zhao, Xia

2017-12-01

Three-dimensional (3D) printing is a promising technology that can use a patient's image data to create complex and personalized constructs precisely. It has made great progress over the past few decades and has been widely used in medicine including medical modeling, surgical planning, medical education and training, prosthesis and implants. Three-dimensional (3D) bioprinting is a powerful tool that has the potential to fabricate bioengineered constructs of the desired shape layer-by-layer using computer-aided deposition of living cells and biomaterials. Advances in 3D printed implants and future tissue-engineered constructs will bring great progress to the field of otolaryngology. By integrating 3D printing into tissue engineering and materials, it may be possible for otolaryngologists to implant 3D printed functional grafts into patients for reconstruction of a variety of tissue defects in the foreseeable future. In this review, we will introduce the current state of 3D printing technology and highlight the applications of 3D printed prosthesis and implants, 3D printing technology combined with tissue engineering and future directions of bioprinting in the field of otolaryngology.

Microgravity

NASA Image and Video Library

2001-06-01

Cells cultured on Earth (left) typically settle quickly on the bottom of culture vessels due to gravity. In microgravity (right), cells remain suspended and aggregate to form three-dimensional tissue. The NASA Bioreactor provides a low turbulence culture environment which promotes the formation of large, three-dimensional cell clusters. The Bioreactor is rotated to provide gentle mixing of fresh and spent nutrient without inducing shear forces that would damage the cells. Due to their high level of cellular organization and specialization, samples constructed in the bioreactor more closely resemble the original tumor or tissue found in the body. The work is sponsored by NASA's Office of Biological and Physical Research. The bioreactor is managed by the Biotechnology Cell Science Program at NASA's Johnson Space Center (JSC). NASA-sponsored bioreactor research has been instrumental in helping scientists to better understand normal and cancerous tissue development. In cooperation with the medical community, the bioreactor design is being used to prepare better models of human colon, prostate, breast and ovarian tumors. Cartilage, bone marrow, heart muscle, skeletal muscle, pancreatic islet cells, liver and kidney are just a few of the normal tissues being cultured in rotating bioreactors by investigators.

Muscle-driven finite element simulation of human foot movements.

PubMed

Spyrou, L A; Aravas, N

2012-01-01

This paper describes a finite element scheme for realistic muscle-driven simulation of human foot movements. The scheme is used to simulate human ankle plantar flexion. A three-dimensional anatomically detailed finite element model of human foot and lower leg is developed and the idea of generating natural foot movement based entirely on the contraction of the plantar flexor muscles is used. The bones, ligaments, articular cartilage, muscles, tendons, as well as the rest soft tissues of human foot and lower leg are included in the model. A realistic three-dimensional continuum constitutive model that describes the biomechanical behaviour of muscles and tendons is used. Both the active and passive properties of muscle tissue are accounted for. The materials for bones and ligaments are considered as homogeneous, isotropic and linearly elastic, whereas the articular cartilage and the rest soft tissues (mainly fat) are defined as hyperelastic materials. The model is used to estimate muscle tissue deformations as well as stresses and strains that develop in the lower leg muscles during plantar flexion of the ankle. Stresses and strains that develop in Achilles tendon during such a movement are also investigated.

Current Technologies Based on the Knowledge of the Stem Cells Microenvironments.

PubMed

Mawad, Damia; Figtree, Gemma; Gentile, Carmine

2017-01-01

The stem cell microenvironment or niche plays a critical role in the regulation of survival, differentiation and behavior of stem cells and their progenies. Recapitulating each aspect of the stem cell niche is therefore essential for their optimal use in in vitro studies and in vivo as future therapeutics in humans. Engineering of optimal conditions for three-dimensional stem cell culture includes multiple transient and dynamic physiological stimuli, such as blood flow and tissue stiffness. Bioprinting and microfluidics technologies, including organs-on-a-chip, are among the most recent approaches utilized to replicate the three-dimensional stem cell niche for human tissue fabrication that allow the integration of multiple levels of tissue complexity, including blood flow. This chapter focuses on the physico-chemical and genetic cues utilized to engineer the stem cell niche and provides an overview on how both bioprinting and microfluidics technologies are improving our knowledge in this field for both disease modeling and tissue regeneration, including drug discovery and toxicity high-throughput assays and stem cell-based therapies in humans.

Development of 3D in Vitro Technology for Medical Applications

PubMed Central

Ou, Keng-Liang; Hosseinkhani, Hossein

2014-01-01

In the past few years, biomaterials technologies together with significant efforts on developing biology have revolutionized the process of engineered materials. Three dimensional (3D) in vitro technology aims to develop set of tools that are simple, inexpensive, portable and robust that could be commercialized and used in various fields of biomedical sciences such as drug discovery, diagnostic tools, and therapeutic approaches in regenerative medicine. The proliferation of cells in the 3D scaffold needs an oxygen and nutrition supply. 3D scaffold materials should provide such an environment for cells living in close proximity. 3D scaffolds that are able to regenerate or restore tissue and/or organs have begun to revolutionize medicine and biomedical science. Scaffolds have been used to support and promote the regeneration of tissues. Different processing techniques have been developed to design and fabricate three dimensional scaffolds for tissue engineering implants. Throughout the chapters we discuss in this review, we inform the reader about the potential applications of different 3D in vitro systems that can be applied for fabricating a wider range of novel biomaterials for use in tissue engineering. PMID:25299693

Three-dimensional bioprinting is not only about cell-laden structures.

PubMed

Zhang, Hong-Bo; Xing, Tian-Long; Yin, Rui-Xue; Shi, Yong; Yang, Shi-Mo; Zhang, Wen-Jun

2016-08-01

In this review, we focused on a few obstacles that hinder three-dimensional (3D) bioprinting process in tissue engineering. One of the obstacles is the bioinks used to deliver cells. Hydrogels are the most widely used bioink materials; however, they aremechanically weak in nature and cannot meet the requirements for supporting structures, especially when the tissues, such as cartilage, require extracellular matrix to be mechanically strong. Secondly and more importantly, tissue regeneration is not only about building all the components in a way that mimics the structures of living tissues, but also about how to make the constructs function normally in the long term. One of the key issues is sufficient nutrient and oxygen supply to the engineered living constructs. The other is to coordinate the interplays between cells, bioactive agents and extracellular matrix in a natural way. This article reviews the approaches to improve the mechanical strength of hydrogels and their suitability for 3D bioprinting; moreover, the key issues of multiple cell lines coprinting with multiple growth factors, vascularization within engineered living constructs etc. were also reviewed.

Bioreactor principles

NASA Technical Reports Server (NTRS)

2001-01-01

Cells cultured on Earth (left) typically settle quickly on the bottom of culture vessels due to gravity. In microgravity (right), cells remain suspended and aggregate to form three-dimensional tissue. The NASA Bioreactor provides a low turbulence culture environment which promotes the formation of large, three-dimensional cell clusters. The Bioreactor is rotated to provide gentle mixing of fresh and spent nutrient without inducing shear forces that would damage the cells. Due to their high level of cellular organization and specialization, samples constructed in the bioreactor more closely resemble the original tumor or tissue found in the body. The work is sponsored by NASA's Office of Biological and Physical Research. The bioreactor is managed by the Biotechnology Cell Science Program at NASA's Johnson Space Center (JSC). NASA-sponsored bioreactor research has been instrumental in helping scientists to better understand normal and cancerous tissue development. In cooperation with the medical community, the bioreactor design is being used to prepare better models of human colon, prostate, breast and ovarian tumors. Cartilage, bone marrow, heart muscle, skeletal muscle, pancreatic islet cells, liver and kidney are just a few of the normal tissues being cultured in rotating bioreactors by investigators.

Lateral resolution testing of a novel developed confocal microscopic imaging system

NASA Astrophysics Data System (ADS)

Zhang, Xin; Zhang, Yunhai; Chang, Jian; Huang, Wei; Xue, Xiaojun; Xiao, Yun

2015-10-01

Laser scanning confocal microscope has been widely used in biology, medicine and material science owing to its advantages of high resolution and tomographic imaging. Based on a set of confirmatory experiments and system design, a novel confocal microscopic imaging system is developed. The system is composed of a conventional fluorescence microscope and a confocal scanning unit. In the scanning unit a laser beam coupling module provides four different wavelengths 405nm 488nm 561nm and 638nm which can excite a variety of dyes. The system works in spot-to-spot scanning mode with a two-dimensional galvanometer. A 50 microns pinhole is used to guarantee that stray light is blocked and only the fluorescence signal from the focal point can be received . The three-channel spectral splitter is used to perform fluorescence imaging at three different working wavelengths simultaneously. The rat kidney tissue slice is imaged using the developed confocal microscopic imaging system. Nucleues labeled by DAPI and kidney spherule curved pipe labeled by Alexa Fluor 488 can be imaged clearly and respectively, realizing the distinction between the different components of mouse kidney tissue. The three-dimensional tomographic imaging of mouse kidney tissue is reconstructed by several two-dimensional images obtained in different depths. At last the resolution of the confocal microscopic imaging system is tested quantitatively. The experimental result shows that the system can achieve lateral resolution priority to 230nm.

Three-dimensional culture of a mixed mullerian tumor of the ovary: expression of in vivo characteristics

NASA Technical Reports Server (NTRS)

Goodwin, T. J.; Prewett, T. L.; Spaulding, G. F.; Becker, J. L.

1997-01-01

The Rotating-Wall Vessel (RWV) is a novel in vitro cell culture system used to successfully culture a cell line derived from a heterologous mixed mullerian tumor cell of the ovary. Although the original tumor was comprised of both epithelial and mesodermal components, long-term culture in conventional flasks established a cell line from this tumor with homogeneous epitheliallike growth characteristics (1). Cells from Passage 36 were seeded into a Rotating-Wall Vessel containing Cytodex-3 microcarrier beads. Scanning electron micrographs of tumor cells cultured for 32 d in the RWV showed the presence of heterogeneous cell populations organized into three-dimensional tissuelike architecture. Immunocytochemical analysis confirmed the cellular heterogeneity, as demonstrated by expression of both epithelial and mesenchymal antigens. Reverse transcription polymerase chain reaction amplification demonstrated the presence of mRNA for cellular oncogenes HER-2/neu, H-ras, K-ras, and tumor suppressor p53. Thus, there are two advantages to propagation of tissue in the RWV culture system:(a) tissue diversification representing populations present in the original tumor, and (b) the three-dimensional freedom to organize tissues morphologically akin to those observed in vivo. These data indicate that the RWV culture system is suitable for generating large quantities of ovarian tumor cells in vitro that are amenable to immunocytochemical, oncogenic, morphologic characteristics demonstrated in vivo.

Translating textiles to tissue engineering: Creation and evaluation of microporous, biocompatible, degradable scaffolds using industry relevant manufacturing approaches and human adipose derived stem cells.

PubMed

Haslauer, Carla M; Avery, Matthew R; Pourdeyhimi, Behnam; Loboa, Elizabeth G

2015-07-01

Polymeric scaffolds have emerged as a means of generating three-dimensional tissues, such as for the treatment of bone injuries and nonunions. In this study, a fibrous scaffold was designed using the biocompatible, degradable polymer poly-lactic acid in combination with a water dispersible sacrificial polymer, EastONE. Fibers were generated via industry relevant, facile scale-up melt-spinning techniques with an islands-in-the-sea geometry. Following removal of EastONE, a highly porous fiber remained possessing 12 longitudinal channels and pores throughout all internal and external fiber walls. Weight loss and surface area characterization confirmed the generation of highly porous fibers as observed via focused ion beam/scanning electron microscopy. Porous fibers were then knit into a three-dimensional scaffold and seeded with human adipose-derived stem cells (hASC). Confocal microscopy images confirmed hASC attachment to the fiber walls and proliferation throughout the knit structure. Quantification of cell-mediated calcium accretion following culture in osteogenic differentiation medium confirmed hASC differentiation throughout the porous constructs. These results suggest incorporation of a sacrificial polymer within islands-in-the-sea fibers generates a highly porous scaffold capable of supporting stem cell viability and differentiation with the potential to generate large three-dimensional constructs for bone regeneration and/or other tissue engineering applications. © 2014 Wiley Periodicals, Inc.

Characterization of three-dimensional anisotropic heart valve tissue mechanical properties using inverse finite element analysis.

PubMed

Abbasi, Mostafa; Barakat, Mohammed S; Vahidkhah, Koohyar; Azadani, Ali N

2016-09-01

Computational modeling has an important role in design and assessment of medical devices. In computational simulations, considering accurate constitutive models is of the utmost importance to capture mechanical response of soft tissue and biomedical materials under physiological loading conditions. Lack of comprehensive three-dimensional constitutive models for soft tissue limits the effectiveness of computational modeling in research and development of medical devices. The aim of this study was to use inverse finite element (FE) analysis to determine three-dimensional mechanical properties of bovine pericardial leaflets of a surgical bioprosthesis under dynamic loading condition. Using inverse parameter estimation, 3D anisotropic Fung model parameters were estimated for the leaflets. The FE simulations were validated using experimental in-vitro measurements, and the impact of different constitutive material models was investigated on leaflet stress distribution. The results of this study showed that the anisotropic Fung model accurately simulated the leaflet deformation and coaptation during valve opening and closing. During systole, the peak stress reached to 3.17MPa at the leaflet boundary while during diastole high stress regions were primarily observed in the commissures with the peak stress of 1.17MPa. In addition, the Rayleigh damping coefficient that was introduced to FE simulations to simulate viscous damping effects of surrounding fluid was determined. Copyright © 2016 Elsevier Ltd. All rights reserved.

A finite element evaluation of mechanical function for 3 distal extension partial dental prosthesis designs with a 3-dimensional nonlinear method for modeling soft tissue.

PubMed

Nakamura, Yoshinori; Kanbara, Ryo; Ochiai, Kent T; Tanaka, Yoshinobu

2014-10-01

The mechanical evaluation of the function of partial removable dental prostheses with 3-dimensional finite element modeling requires the accurate assessment and incorporation of soft tissue behavior. The differential behaviors of the residual ridge mucosa and periodontal ligament tissues have been shown to exhibit nonlinear displacement. The mathematic incorporation of known values simulating nonlinear soft tissue behavior has not been investigated previously via 3-dimensional finite element modeling evaluation to demonstrate the effect of prosthesis design on the supporting tissues. The purpose of this comparative study was to evaluate the functional differences of 3 different partial removable dental prosthesis designs with 3-dimensional finite element analysis modeling and a simulated patient model incorporating known viscoelastic, nonlinear soft tissue properties. Three different designs of distal extension removable partial dental prostheses were analyzed. The stress distributions to the supporting abutments and soft tissue displacements of the designs tested were calculated and mechanically compared. Among the 3 dental designs evaluated, the RPI prosthesis demonstrated the lowest stress concentrations on the tissue supporting the tooth abutment and also provided wide mucosa-borne areas of support, thereby demonstrating a mechanical advantage and efficacy over the other designs evaluated. The data and results obtained from this study confirmed that the functional behavior of partial dental prostheses with supporting abutments and soft tissues are consistent with the conventional theories of design and clinical experience. The validity and usefulness of this testing method for future applications and testing protocols are shown. Copyright © 2014 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Three-Dimensional Arrangement of Human Bone Marrow Microvessels Revealed by Immunohistology in Undecalcified Sections

PubMed Central

Wilhelmi, Verena; Seiler, Anja; Lampp, Katrin; Neff, Andreas; Guthe, Michael; Lobachev, Oleg

2016-01-01

The arrangement of microvessels in human bone marrow is so far unknown. We combined monoclonal antibodies against CD34 and against CD141 to visualise all microvessel endothelia in 21 serial sections of about 1 cm2 size derived from a human iliac crest. The specimen was not decalcified and embedded in Technovit® 9100. In different regions of interest, the microvasculature was reconstructed in three dimensions using automatic methods. The three-dimensional models were subject to a rigid semiautomatic and manual quality control. In iliac crest bone marrow, the adipose tissue harbours irregularly distributed haematopoietic areas. These are fed by networks of large sinuses, which are loosely connected to networks of small capillaries prevailing in areas of pure adipose tissue. Our findings are compatible with the hypothesis that capillaries and sinuses in human iliac crest bone marrow are partially arranged in parallel. PMID:27997569

Influence of Objective Three-Dimensional Measures and Movement Images on Surgeon Treatment Planning for Lip Revision Surgery

PubMed Central

Trotman, Carroll-Ann; Phillips, Ceib; Faraway, Julian J.; Hartman, Terry; van Aalst, John A.

2013-01-01

Objective To determine whether a systematic evaluation of facial soft tissues of patients with cleft lip and palate, using facial video images and objective three-dimensional measurements of movement, change surgeons’ treatment plans for lip revision surgery. Design Prospective longitudinal study. Setting The University of North Carolina School of Dentistry. Patients, Participants A group of patients with repaired cleft lip and palate (n = 21), a noncleft control group (n = 37), and surgeons experienced in cleft care. Interventions Lip revision. Main Outcome Measures (1) facial photographic images; (2) facial video images during animations; (3) objective three-dimensional measurements of upper lip movement based on z scores; and (4) objective dynamic and visual three-dimensional measurement of facial soft tissue movement. Results With the use of the video images plus objective three-dimensional measures, changes were made to the problem list of the surgical treatment plan for 86% of the patients (95% confidence interval, 0.64 to 0.97) and the surgical goals for 71% of the patients (95% confidence interval, 0.48 to 0.89). The surgeon group varied in the percentage of patients for whom the problem list was modified, ranging from 24% (95% confidence interval, 8% to 47%) to 48% (95% confidence interval, 26% to 70%) of patients, and the percentage for whom the surgical goals were modified, ranging from 14% (94% confidence interval, 3% to 36%) to 48% (95% confidence interval, 26% to 70%) of patients. Conclusions For all surgeons, the additional assessment components of the systematic valuation resulted in a change in clinical decision making for some patients. PMID:23855676

Removal of pinned scroll waves in cardiac tissues by electric fields in a generic model of three-dimensional excitable media

PubMed Central

Pan, De-Bei; Gao, Xiang; Feng, Xia; Pan, Jun-Ting; Zhang, Hong

2016-01-01

Spirals or scroll waves pinned to heterogeneities in cardiac tissues may cause lethal arrhythmias. To unpin these life-threatening spiral waves, methods of wave emission from heterogeneities (WEH) induced by low-voltage pulsed DC electric fields (PDCEFs) and circularly polarized electric fields (CPEFs) have been used in two-dimensional (2D) cardiac tissues. Nevertheless, the unpinning of scroll waves in three-dimensional (3D) cardiac systems is much more difficult than that of spiral waves in 2D cardiac systems, and there are few reports on the removal of pinned scroll waves in 3D cardiac tissues by electric fields. In this article, we investigate in detail the removal of pinned scroll waves in a generic model of 3D excitable media using PDCEF, AC electric field (ACEF) and CPEF, respectively. We find that spherical waves can be induced from the heterogeneities by these electric fields in initially quiescent excitable media. However, only CPEF can induce spherical waves with frequencies higher than that of the pinned scroll wave. Such higher-frequency spherical waves induced by CPEF can be used to drive the pinned scroll wave out of the cardiac systems. We hope this remarkable ability of CPEF can provide a better alternative to terminate arrhythmias caused by pinned scroll waves. PMID:26905367

High Content Imaging (HCI) on Miniaturized Three-Dimensional (3D) Cell Cultures

PubMed Central

Joshi, Pranav; Lee, Moo-Yeal

2015-01-01

High content imaging (HCI) is a multiplexed cell staining assay developed for better understanding of complex biological functions and mechanisms of drug action, and it has become an important tool for toxicity and efficacy screening of drug candidates. Conventional HCI assays have been carried out on two-dimensional (2D) cell monolayer cultures, which in turn limit predictability of drug toxicity/efficacy in vivo; thus, there has been an urgent need to perform HCI assays on three-dimensional (3D) cell cultures. Although 3D cell cultures better mimic in vivo microenvironments of human tissues and provide an in-depth understanding of the morphological and functional features of tissues, they are also limited by having relatively low throughput and thus are not amenable to high-throughput screening (HTS). One attempt of making 3D cell culture amenable for HTS is to utilize miniaturized cell culture platforms. This review aims to highlight miniaturized 3D cell culture platforms compatible with current HCI technology. PMID:26694477

Three-Dimensional Rotating Wall Vessel-Derived Cell Culture Models for Studying Virus-Host Interactions

PubMed Central

Gardner, Jameson K.; Herbst-Kralovetz, Melissa M.

2016-01-01

The key to better understanding complex virus-host interactions is the utilization of robust three-dimensional (3D) human cell cultures that effectively recapitulate native tissue architecture and model the microenvironment. A lack of physiologically-relevant animal models for many viruses has limited the elucidation of factors that influence viral pathogenesis and of complex host immune mechanisms. Conventional monolayer cell cultures may support viral infection, but are unable to form the tissue structures and complex microenvironments that mimic host physiology and, therefore, limiting their translational utility. The rotating wall vessel (RWV) bioreactor was designed by the National Aeronautics and Space Administration (NASA) to model microgravity and was later found to more accurately reproduce features of human tissue in vivo. Cells grown in RWV bioreactors develop in a low fluid-shear environment, which enables cells to form complex 3D tissue-like aggregates. A wide variety of human tissues (from neuronal to vaginal tissue) have been grown in RWV bioreactors and have been shown to support productive viral infection and physiological meaningful host responses. The in vivo-like characteristics and cellular features of the human 3D RWV-derived aggregates make them ideal model systems to effectively recapitulate pathophysiology and host responses necessary to conduct rigorous basic science, preclinical and translational studies. PMID:27834891

Mapping of Mechanical Strains and Stresses around Quiescent Engineered Three-Dimensional Epithelial Tissues

PubMed Central

Gjorevski, Nikolce; Nelson, Celeste M.

2012-01-01

Understanding how physical signals guide biological processes requires qualitative and quantitative knowledge of the mechanical forces generated and sensed by cells in a physiologically realistic three-dimensional (3D) context. Here, we used computational modeling and engineered epithelial tissues of precise geometry to define the experimental parameters that are required to measure directly the mechanical stress profile of 3D tissues embedded within native type I collagen. We found that to calculate the stresses accurately in these settings, we had to account for mechanical heterogeneities within the matrix, which we visualized and quantified using confocal reflectance and atomic force microscopy. Using this technique, we were able to obtain traction forces at the epithelium-matrix interface, and to resolve and quantify patterns of mechanical stress throughout the surrounding matrix. We discovered that whereas single cells generate tension by contracting and pulling on the matrix, the contraction of multicellular tissues can also push against the matrix, causing emergent compression. Furthermore, tissue geometry defines the spatial distribution of mechanical stress across the epithelium, which communicates mechanically over distances spanning hundreds of micrometers. Spatially resolved mechanical maps can provide insight into the types and magnitudes of physical parameters that are sensed and interpreted by multicellular tissues during normal and pathological processes. PMID:22828342

Macroporous Hydrogel Scaffolds for Three-Dimensional Cell Culture and Tissue Engineering.

PubMed

Fan, Changjiang; Wang, Dong-An

2017-10-01

Hydrogels have been promising candidate scaffolds for cell delivery and tissue engineering due to their tissue-like physical properties and capability for homogeneous cell loading. However, the encapsulated cells are generally entrapped and constrained in the submicron- or nanosized gel networks, seriously limiting cell growth and tissue formation. Meanwhile, the spatially confined settlement inhibits attachment and spreading of anchorage-dependent cells, leading to their apoptosis. In recent years, macroporous hydrogels have attracted increasing attention in use as cell delivery vehicles and tissue engineering scaffolds. The introduction of macropores within gel scaffolds not only improves their permeability for better nutrient transport but also creates space/interface for cell adhesion, proliferation, and extracellular matrix deposition. Herein, we will first review the development of macroporous gel scaffolds and outline the impact of macropores on cell behaviors. In the first part, the advantages and challenges of hydrogels as three-dimensional (3D) cell culture scaffolds will be described. In the second part, the fabrication of various macroporous hydrogels will be presented. Third, the enhancement of cell activities within macroporous gel scaffolds will be discussed. Finally, several crucial factors that are envisaged to propel the improvement of macroporous gel scaffolds are proposed for 3D cell culture and tissue engineering.

Growing Three-Dimensional Cartilage-Cell Cultures

NASA Technical Reports Server (NTRS)

Spaulding, Glenn F.; Prewett, Tacey L.; Goodwin, Thomas J.

1995-01-01

Process for growing three-dimensional cultures of mammalian cartilage from normal mammalian cells devised. Effected using horizontal rotating bioreactor described in companion article, "Simplified Bioreactor for Growing Mammalian Cells" (MSC-22060). Bioreactor provides quiescent environment with generous supplies of nutrient and oxygen. Initiated with noncartilage cells. Artificially grown tissue resembles that in mammalian cartilage. Potential use in developing therapies for damage to cartilage by joint and back injuries and by such inflammatory diseases as arthritis and temporal-mandibular joint disease. Also used to test nonsteroid anti-inflammation medicines.

Pre-operative CT angiography and three-dimensional image post processing for deep inferior epigastric perforator flap breast reconstructive surgery.

PubMed

Lam, D L; Mitsumori, L M; Neligan, P C; Warren, B H; Shuman, W P; Dubinsky, T J

2012-12-01

Autologous breast reconstructive surgery with deep inferior epigastric artery (DIEA) perforator flaps has become the mainstay for breast reconstructive surgery. CT angiography and three-dimensional image post processing can depict the number, size, course and location of the DIEA perforating arteries for the pre-operative selection of the best artery to use for the tissue flap. Knowledge of the location and selection of the optimal perforating artery shortens operative times and decreases patient morbidity.

Diffuse optical correlation tomography of cerebral blood flow during cortical spreading depression in rat brain

NASA Astrophysics Data System (ADS)

Zhou, Chao; Yu, Guoqiang; Furuya, Daisuke; Greenberg, Joel; Yodh, Arjun; Durduran, Turgut

2006-02-01

Diffuse optical correlation methods were adapted for three-dimensional (3D) tomography of cerebral blood flow (CBF) in small animal models. The image reconstruction was optimized using a noise model for diffuse correlation tomography which enabled better data selection and regularization. The tomographic approach was demonstrated with simulated data and during in-vivo cortical spreading depression (CSD) in rat brain. Three-dimensional images of CBF were obtained through intact skull in tissues(~4mm) deep below the cortex.

Exceptional soft tissues preservation in a mummified frog-eating Eocene salamander.

PubMed

Tissier, Jérémy; Rage, Jean-Claude; Laurin, Michel

2017-01-01

Fossils are almost always represented by hard tissues but we present here the exceptional case of a three-dimensionally preserved specimen that was 'mummified' (likely between 40 and 34 million years ago) in a terrestrial karstic environment. This fossil is the incomplete body of a salamander, Phosphotriton sigei , whose skeleton and external morphology are well preserved, as revealed by phase-contrast synchrotron X-ray microtomography. In addition, internal structures composed of soft tissues preserved in three dimensions are now identified: a lung, the spinal cord, a lumbosacral plexus, the digestive tract, muscles and urogenital organs that may be cloacal glands. These are among the oldest known cases of three-dimensional preservation of these organs in vertebrates and shed light on the ecology of this salamander. Indeed, the digestive tract contains remains of a frog, which represents the only known case of an extinct salamander that fed on a frog, an extremely rare type of predation in extant salamanders. These new data improve our scarce knowledge on soft tissue anatomy of early urodeles and should prove useful for future biologists and palaeontologists working on urodele evolutionary biology. We also suggest that the presence of bat guano and carcasses represented a close source of phosphorus, favouring preservation of soft tissues. Bone microanatomy indicates that P. sigei was likely amphibious or terrestrial, and was probably not neotenic.

Basis for the Induction of Tissue-Level Phase-2 Reentry as a Repolarization Disorder in the Brugada Syndrome

PubMed Central

Bueno-Orovio, Alfonso; Cherry, Elizabeth M.; Evans, Steven J.; Fenton, Flavio H.

2015-01-01

Aims. Human action potentials in the Brugada syndrome have been characterized by delayed or even complete loss of dome formation, especially in the right ventricular epicardial layers. Such a repolarization pattern is believed to trigger phase-2 reentry (P2R); however, little is known about the conditions necessary for its initiation. This study aims to determine the specific mechanisms that facilitate P2R induction in Brugada-affected cardiac tissue in humans. Methods. Ionic models for Brugada syndrome in human epicardial cells were developed and used to study the induction of P2R in cables, sheets, and a three-dimensional model of the right ventricular free wall. Results. In one-dimensional cables, P2R can be induced by adjoining lost-dome and delayed-dome regions, as mediated by tissue excitability and transmembrane voltage profiles, and reduced coupling facilitates its induction. In two and three dimensions, sustained reentry can arise when three regions (delayed-dome, lost-dome, and normal epicardium) are present. Conclusions. Not only does P2R induction by Brugada syndrome require regions of action potential with delayed-dome and lost-dome, but in order to generate a sustained reentry from a triggered waveback multiple factors are necessary, including heterogeneity in action potential distribution, tissue coupling, direction of stimulation, the shape of the late plateau, the duration of lost-dome action potentials, and recovery of tissue excitability, which is predominantly modulated by tissue coupling. PMID:26583094

Three-Dimensional Transgenic Cell Models to Quantify Space Genotoxic Effects

NASA Technical Reports Server (NTRS)

Gonda, S.; Wu, H.; Pingerelli, P.; Glickman, B.

2000-01-01

In this paper we describe a three-dimensional, multicellular tissue-equivalent model, produced in NASA-designed, rotating wall bioreactors using mammalian cells engineered for genomic containment of mUltiple copies of defined target genes for genotoxic assessment. The Rat 2(lambda) fibroblasts (Stratagene, Inc.) were genetically engineered to contain high-density target genes for mutagenesis. Stable three-dimensional, multicellular spheroids were formed when human mammary epithelial cells and Rat 2(lambda) fibroblasts were cocultured on Cytodex 3 Beads in a rotating wall bioreactor. The utility of this spheroidal model for genotoxic assessment was indicated by a linear dose response curve and by results of gene sequence analysis of mutant clones from 400micron diameter spheroids following low-dose, high-energy, neon radiation exposure

Algorithms for Spectral Decomposition with Applications to Optical Plume Anomaly Detection

NASA Technical Reports Server (NTRS)

Srivastava, Askok N.; Matthews, Bryan; Das, Santanu

2008-01-01

The analysis of spectral signals for features that represent physical phenomenon is ubiquitous in the science and engineering communities. There are two main approaches that can be taken to extract relevant features from these high-dimensional data streams. The first set of approaches relies on extracting features using a physics-based paradigm where the underlying physical mechanism that generates the spectra is used to infer the most important features in the data stream. We focus on a complementary methodology that uses a data-driven technique that is informed by the underlying physics but also has the ability to adapt to unmodeled system attributes and dynamics. We discuss the following four algorithms: Spectral Decomposition Algorithm (SDA), Non-Negative Matrix Factorization (NMF), Independent Component Analysis (ICA) and Principal Components Analysis (PCA) and compare their performance on a spectral emulator which we use to generate artificial data with known statistical properties. This spectral emulator mimics the real-world phenomena arising from the plume of the space shuttle main engine and can be used to validate the results that arise from various spectral decomposition algorithms and is very useful for situations where real-world systems have very low probabilities of fault or failure. Our results indicate that methods like SDA and NMF provide a straightforward way of incorporating prior physical knowledge while NMF with a tuning mechanism can give superior performance on some tests. We demonstrate these algorithms to detect potential system-health issues on data from a spectral emulator with tunable health parameters.

Unsupervised nonlinear dimensionality reduction machine learning methods applied to multiparametric MRI in cerebral ischemia: preliminary results

NASA Astrophysics Data System (ADS)

Parekh, Vishwa S.; Jacobs, Jeremy R.; Jacobs, Michael A.

2014-03-01

The evaluation and treatment of acute cerebral ischemia requires a technique that can determine the total area of tissue at risk for infarction using diagnostic magnetic resonance imaging (MRI) sequences. Typical MRI data sets consist of T1- and T2-weighted imaging (T1WI, T2WI) along with advanced MRI parameters of diffusion-weighted imaging (DWI) and perfusion weighted imaging (PWI) methods. Each of these parameters has distinct radiological-pathological meaning. For example, DWI interrogates the movement of water in the tissue and PWI gives an estimate of the blood flow, both are critical measures during the evolution of stroke. In order to integrate these data and give an estimate of the tissue at risk or damaged; we have developed advanced machine learning methods based on unsupervised non-linear dimensionality reduction (NLDR) techniques. NLDR methods are a class of algorithms that uses mathematically defined manifolds for statistical sampling of multidimensional classes to generate a discrimination rule of guaranteed statistical accuracy and they can generate a two- or three-dimensional map, which represents the prominent structures of the data and provides an embedded image of meaningful low-dimensional structures hidden in their high-dimensional observations. In this manuscript, we develop NLDR methods on high dimensional MRI data sets of preclinical animals and clinical patients with stroke. On analyzing the performance of these methods, we observed that there was a high of similarity between multiparametric embedded images from NLDR methods and the ADC map and perfusion map. It was also observed that embedded scattergram of abnormal (infarcted or at risk) tissue can be visualized and provides a mechanism for automatic methods to delineate potential stroke volumes and early tissue at risk.

Validation of a computer modelled forensic facial reconstruction technique using CT data from live subjects: a pilot study.

PubMed

Short, Laura J; Khambay, Balvinder; Ayoub, Ashraf; Erolin, Caroline; Rynn, Chris; Wilkinson, Caroline

2014-04-01

Human forensic facial soft tissue reconstructions are used when post-mortem deterioration makes identification difficult by usual means. The aim is to trigger recognition of the in vivo countenance of the individual by a friend or family member. A further use is in the field of archaeology. There are a number of different methods that can be applied to complete the facial reconstruction, ranging from two dimensional drawings, three dimensional clay models and now, with the advances of three dimensional technology, three dimensional computerised modelling. Studies carried out to assess the accuracy of facial reconstructions have produced variable results over the years. Advances in three dimensional imaging techniques in the field of oral and maxillofacial surgery, particularly cone beam computed tomography (CBCT), now provides an opportunity to utilise the data of live subjects and assess the accuracy of the three dimensional computerised facial reconstruction technique. The aim of this study was to assess the accuracy of a computer modelled facial reconstruction technique using CBCT data from live subjects. This retrospective pilot study was carried out at the Glasgow Dental Hospital Orthodontic Department and the Centre of Anatomy and Human Identification, Dundee University School of Life Sciences. Ten patients (5 male and 5 female; mean age 23 years) with mild skeletal discrepancies with pre-surgical cone beam CT data (CBCT) were included in this study. The actual and forensic reconstruction soft tissues were analysed using 3D software to look at differences between landmarks, linear and angular measurements and surface meshes. There were no statistical differences for 18 out of the 23 linear and 7 out of 8 angular measurements between the reconstruction and the target (p<0.05). The use of Procrustes superimposition has highlighted potential problems with soft tissue depth and anatomical landmarks' position. Surface mesh analysis showed that this virtual sculpture technique can be objectively assessed using the distance between the meshes. This study found that the percentage of faces with less than ±2.5mm error ranged from 56% to 90%. This may be improved if Procrustes superimposition could be applied to all the mesh points rather than specific landmarks. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

SU-E-T-279: Realization of Three-Dimensional Conformal Dose Planning in Prostate Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Z; Jiang, S; Yang, Z

2014-06-01

Purpose: Successful clinical treatment in prostate brachytherapy is largely dependent on the effectiveness of pre-surgery dose planning. Conventional dose planning method could hardly arrive at a satisfy result. In this abstract, a three-dimensional conformal localized dose planning method is put forward to ensure the accuracy and effectiveness of pre-implantation dose planning. Methods: Using Monte Carlo method, the pre-calculated 3-D dose map for single source is obtained. As for multiple seeds dose distribution, the maps are combined linearly to acquire the 3-D distribution. The 3-D dose distribution is exhibited in the form of isodose surface together with reconstructed 3-D organs groupmore » real-timely. Then it is possible to observe the dose exposure to target volume and normal tissues intuitively, thus achieving maximum dose irradiation to treatment target and minimum healthy tissues damage. In addition, the exfoliation display of different isodose surfaces can be realized applying multi-values contour extraction algorithm based on voxels. The needles could be displayed in the system by tracking the position of the implanted seeds in real time to conduct block research in optimizing insertion trajectory. Results: This study extends dose planning from two-dimensional to three-dimensional, realizing the three-dimensional conformal irradiation, which could eliminate the limitations of 2-D images and two-dimensional dose planning. A software platform is developed using VC++ and Visualization Toolkit (VTK) to perform dose planning. The 3-D model reconstruction time is within three seconds (on a Intel Core i5 PC). Block research could be conducted to avoid inaccurate insertion into sensitive organs or internal obstructions. Experiments on eight prostate cancer cases prove that this study could make the dose planning results more reasonable. Conclusion: The three-dimensional conformal dose planning method could improve the rationality of dose planning by safely reducing the large target margin and avoiding dose dead zones for prostate cancer treatment. 1) National Natural Science Foundation of People's Republic of China (No. 51175373); 2) New Century Educational Talents Plan of Chinese Education Ministry (NCET-10-0625); 3) Scientific and Technological Major Project, Tianjin (No. 12ZCDZSY10600)« less

Microfluidic 3D cell culture: potential application for tissue-based bioassays

PubMed Central

Li, XiuJun (James); Valadez, Alejandra V.; Zuo, Peng; Nie, Zhihong

2014-01-01

Current fundamental investigations of human biology and the development of therapeutic drugs, commonly rely on two-dimensional (2D) monolayer cell culture systems. However, 2D cell culture systems do not accurately recapitulate the structure, function, physiology of living tissues, as well as highly complex and dynamic three-dimensional (3D) environments in vivo. The microfluidic technology can provide micro-scale complex structures and well-controlled parameters to mimic the in vivo environment of cells. The combination of microfluidic technology with 3D cell culture offers great potential for in vivo-like tissue-based applications, such as the emerging organ-on-a-chip system. This article will review recent advances in microfluidic technology for 3D cell culture and their biological applications. PMID:22793034

Bioprinting Cartilage Tissue from Mesenchymal Stem Cells and PEG Hydrogel.

PubMed

Gao, Guifang; Hubbell, Karen; Schilling, Arndt F; Dai, Guohao; Cui, Xiaofeng

2017-01-01

Bioprinting based on thermal inkjet printing is one of the most attractive enabling technologies for tissue engineering and regeneration. During the printing process, cells, scaffolds , and growth factors are rapidly deposited to the desired two-dimensional (2D) and three-dimensional (3D) locations. Ideally, the bioprinted tissues are able to mimic the native anatomic structures in order to restore the biological functions. In this study, a bioprinting platform for 3D cartilage tissue engineering was developed using a commercially available thermal inkjet printer with simultaneous photopolymerization . The engineered cartilage demonstrated native zonal organization, ideal extracellular matrix (ECM ) composition, and proper mechanical properties. Compared to the conventional tissue fabrication approach, which requires extended UV exposure, the viability of the printed cells with simultaneous photopolymerization was significantly higher. Printed neocartilage demonstrated excellent glycosaminoglycan (GAG) and collagen type II production, which was consistent with gene expression profile. Therefore, this platform is ideal for anatomic tissue engineering with accurate cell distribution and arrangement.

[Progress in application of 3D bioprinting in cartilage regeneration and reconstruction for tissue engineering].

PubMed

Liao, Junlin; Wang, Shaohua; Chen, Jia; Xie, Hongju; Zhou, Jianda

2017-02-28

Three-dimensional (3D) bioprinting provides an advanced technology for tissue engineering and regenerative medicine because of its ability to produce the models or organs with higher precision and more suitable for human body. It has been successfully used to produce a variety of cartilage scaffold materials. In addition, 3D bioprinter can directly to print tissue and organs with live chondrocytes. In conclusion, 3D bioprinting may have broad prospect for cartilage regeneration and reconstruction in tissue engineering.

Three-dimensional simultaneous optical coherence tomography and confocal fluorescence microscopy for investigation of lung tissue.

PubMed

Gaertner, Maria; Cimalla, Peter; Meissner, Sven; Kuebler, Wolfgang M; Koch, Edmund

2012-07-01

Although several strategies exist for a minimal-invasive treatment of patients with lung failure, the mortality rate of acute respiratory distress syndrome still reaches 30% at minimum. This striking number indicates the necessity of understanding lung dynamics on an alveolar level. To investigate the dynamical behavior on a microscale, we used three-dimensional geometrical and functional imaging to observe tissue parameters including alveolar size and length of embedded elastic fibers during ventilation. We established a combined optical coherence tomography (OCT) and confocal fluorescence microscopy system that is able to monitor the distension of alveolar tissue and elastin fibers simultaneously within three dimensions. The OCT system can laterally resolve a 4.9 μm line pair feature and has an approximately 11 μm full-width-half-maximum axial resolution in air. confocal fluorescence microscopy visualizes molecular properties of the tissue with a resolution of 0.75 μm (laterally), and 5.9 μm (axially) via fluorescence detection of the dye sulforhodamine B specifically binding to elastin. For system evaluation, we used a mouse model in situ to perform lung distension by application of different constant pressure values within the physiological regime. Our method enables the investigation of alveolar dynamics by helping to reveal basic processes emerging during artificial ventilation and breathing.

What is the future of 'organ transplantation' in the head and neck?

PubMed

Lott, David G

2014-10-01

To update readers on the current state and future of head and neck tissue transplantation. Many exciting advances have recently occurred in the field of head and neck transplantation and regenerative medicine. Larynx, face, and trachea transplants have all been successfully performed. Significant advancements in tissue engineering have occurred, including the ability to generate three-dimensional tissue structures. Transplantation of regenerated tissues has been successfully incorporated into airway reconstruction. These exciting advancements set the foundation to expand reconstructive options for dysfunctional tissues and to improve a patient's quality of life.

Assessment of geometry in 2D immune systems using high accuracy laser-based bioprinting techniques (Conference Presentation)

NASA Astrophysics Data System (ADS)

Lauzurica, Sara; Márquez, Andrés.; Molpeceres, Carlos; Notario, Laura; Gómez-Fontela, Miguel; Lauzurica, Pilar

2017-02-01

The immune system is a very complex system that comprises a network of genetic and signaling pathways subtending a network of interacting cells. The location of the cells in a network, along with the gene products they interact with, rules the behavior of the immune system. Therefore, there is a great interest in understanding properly the role of a cell in such networks to increase our knowledge of the immune system response. In order to acquire a better understanding of these processes, cell printing with high spatial resolution emerges as one of the promising approaches to organize cells in two and three-dimensional patterns to enable the study the geometry influence in these interactions. In particular, laser assisted bio-printing techniques using sub-nanosecond laser sources have better characteristics for application in this field, mainly due to its higher spatial resolution, cell viability percentage and process automation. This work presents laser assisted bio-printing of antigen-presenting cells (APCs) in two-dimensional geometries, placing cellular components on a matrix previously generated on demand, permitting to test the molecular interactions between APCs and lymphocytes; as well as the generation of two-dimensional structures designed ad hoc in order to study the mechanisms of mobilization of immune system cells. The use of laser assisted bio-printing, along with APCs and lymphocytes emulate the structure of different niches of the immune system so that we can analyse functional requirement of these interaction.

A three-dimensional bioprinting system for use with a hydrogel-based biomaterial and printing parameter characterization.

PubMed

Song, Seung-Joon; Choi, Jaesoon; Park, Yong-Doo; Lee, Jung-Joo; Hong, So Young; Sun, Kyung

2010-11-01

Bioprinting is an emerging technology for constructing tissue or bioartificial organs with complex three-dimensional (3D) structures. It provides high-precision spatial shape forming ability on a larger scale than conventional tissue engineering methods, and simultaneous multiple components composition ability. Bioprinting utilizes a computer-controlled 3D printer mechanism for 3D biological structure construction. To implement minimal pattern width in a hydrogel-based bioprinting system, a study on printing characteristics was performed by varying printer control parameters. The experimental results showed that printing pattern width depends on associated printer control parameters such as printing flow rate, nozzle diameter, and nozzle velocity. The system under development showed acceptable feasibility of potential use for accurate printing pattern implementation in tissue engineering applications and is another example of novel techniques for regenerative medicine based on computer-aided biofabrication system. © 2010, Copyright the Authors. Artificial Organs © 2010, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Scroll wave dynamics in a three-dimensional cardiac tissue model: roles of restitution, thickness, and fiber rotation.

PubMed Central

Qu, Z; Kil, J; Xie, F; Garfinkel, A; Weiss, J N

2000-01-01

Scroll wave (vortex) breakup is hypothesized to underlie ventricular fibrillation, the leading cause of sudden cardiac death. We simulated scroll wave behaviors in a three-dimensional cardiac tissue model, using phase I of the Luo-Rudy (LR1) action potential model. The effects of action potential duration (APD) restitution, tissue thickness, filament twist, and fiber rotation were studied. We found that APD restitution is the major determinant of scroll wave behavior and that instabilities arising from APD restitution are the main determinants of scroll wave breakup in this cardiac model. We did not see a "thickness-induced instability" in the LR1 model, but a minimum thickness is required for scroll breakup in the presence of fiber rotation. The major effect of fiber rotation is to maintain twist in a scroll wave, promoting filament bending and thus scroll breakup. In addition, fiber rotation induces curvature in the scroll wave, which weakens conduction and further facilitates wave break. PMID:10827961

Fabrication and Evaluation of Electrospun, 3D-Bioplotted, and Combination of Electrospun/3D-Bioplotted Scaffolds for Tissue Engineering Applications

PubMed Central

Mellor, Liliana F.; Huebner, Pedro; Cai, Shaobo; Taylor, Michael A.; Spang, Jeffrey

2017-01-01

Electrospun scaffolds provide a dense framework of nanofibers with pore sizes and fiber diameters that closely resemble the architecture of native extracellular matrix. However, it generates limited three-dimensional structures of relevant physiological thicknesses. 3D printing allows digitally controlled fabrication of three-dimensional single/multimaterial constructs with precisely ordered fiber and pore architecture in a single build. However, this approach generally lacks the ability to achieve submicron resolution features to mimic native tissue. The goal of this study was to fabricate and evaluate 3D printed, electrospun, and combination of 3D printed/electrospun scaffolds to mimic the native architecture of heterogeneous tissue. We assessed their ability to support viability and proliferation of human adipose derived stem cells (hASC). Cells had increased proliferation and high viability over 21 days on all scaffolds. We further tested implantation of stacked-electrospun scaffold versus combined electrospun/3D scaffold on a cadaveric pig knee model and found that stacked-electrospun scaffold easily delaminated during implantation while the combined scaffold was easier to implant. Our approach combining these two commonly used scaffold fabrication technologies allows for the creation of a scaffold with more close resemblance to heterogeneous tissue architecture, holding great potential for tissue engineering and regenerative medicine applications of osteochondral tissue and other heterogeneous tissues. PMID:28536700

Combination of biochemical and mechanical cues for tendon tissue engineering.

PubMed

Testa, Stefano; Costantini, Marco; Fornetti, Ersilia; Bernardini, Sergio; Trombetta, Marcella; Seliktar, Dror; Cannata, Stefano; Rainer, Alberto; Gargioli, Cesare

2017-11-01

Tendinopathies negatively affect the life quality of millions of people in occupational and athletic settings, as well as the general population. Tendon healing is a slow process, often with insufficient results to restore complete endurance and functionality of the tissue. Tissue engineering, using tendon progenitors, artificial matrices and bioreactors for mechanical stimulation, could be an important approach for treating rips, fraying and tissue rupture. In our work, C3H10T1/2 murine fibroblast cell line was exposed to a combination of stimuli: a biochemical stimulus provided by Transforming Growth Factor Beta (TGF-β) and Ascorbic Acid (AA); a three-dimensional environment represented by PEGylated-Fibrinogen (PEG-Fibrinogen) biomimetic matrix; and a mechanical induction exploiting a custom bioreactor applying uniaxial stretching. In vitro analyses by immunofluorescence and mechanical testing revealed that the proposed combined approach favours the organization of a three-dimensional tissue-like structure promoting a remarkable arrangement of the cells and the neo-extracellular matrix, reflecting into enhanced mechanical strength. The proposed method represents a novel approach for tendon tissue engineering, demonstrating how the combined effect of biochemical and mechanical stimuli ameliorates biological and mechanical properties of the artificial tissue compared to those obtained with single inducement. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Production of three-dimensional tissue-engineered cartilage through mutual fusion of chondrocyte pellets.

PubMed

Hoshi, K; Fujihara, Y; Mori, Y; Asawa, Y; Kanazawa, S; Nishizawa, S; Misawa, M; Numano, T; Inoue, H; Sakamoto, T; Watanabe, M; Komura, M; Takato, T

2016-09-01

In this study, the mutual fusion of chondrocyte pellets was promoted in order to produce large-sized tissue-engineered cartilage with a three-dimensional (3D) shape. Five pellets of human auricular chondrocytes were first prepared, which were then incubated in an agarose mold. After 3 weeks of culture in matrix production-promoting medium under 5.78g/cm(2) compression, the tissue-engineered cartilage showed a sufficient mechanical strength. To confirm the usefulness of these methods, a transplantation experiment was performed using beagles. Tissue-engineered cartilage prepared with 50 pellets of beagle chondrocytes was transplanted subcutaneously into the cell-donor dog for 2 months. The tissue-engineered cartilage of the beagles maintained a rod-like shape, even after harvest. Histology showed fair cartilage regeneration. Furthermore, 20 pellets were made and placed on a beta-tricalcium phosphate prism, and this was then incubated within the agarose mold for 3 weeks. The construct was transplanted into a bone/cartilage defect in the cell-donor beagle. After 2 months, bone and cartilage regeneration was identified on micro-computed tomography and magnetic resonance imaging. This approach involving the fusion of small pellets into a large structure enabled the production of 3D tissue-engineered cartilage that was close to physiological cartilage tissue in property, without conventional polyper scaffolds. Copyright © 2016. Published by Elsevier Ltd.

Four-Dimensional Imaging of T Cells in Kidney Transplant Rejection.

PubMed

Hughes, Andrew D; Lakkis, Fadi G; Oberbarnscheidt, Martin H

2018-06-01

Kidney transplantation is the treatment of choice for ESRD but is complicated by the response of the recipient's immune system to nonself histocompatibility antigens on the graft, resulting in rejection. Multiphoton intravital microscopy, referred to as four-dimensional imaging because it records dynamic events in three-dimensional tissue volumes, has emerged as a powerful tool to study immunologic processes in living animals. Here, we will review advances in understanding the complex mechanisms of T cell-mediated rejection made possible by four-dimensional imaging of mouse renal allografts. We will summarize recent data showing that activated (effector) T cell migration to the graft is driven by cognate antigen presented by dendritic cells that surround and penetrate peritubular capillaries, and that T cell-dendritic cell interactions persist in the graft over time, maintaining the immune response in the tissue. Copyright © 2018 by the American Society of Nephrology.

Connecting the Brain to Itself through an Emulation

PubMed Central

Serruya, Mijail D.

2017-01-01

Pilot clinical trials of human patients implanted with devices that can chronically record and stimulate ensembles of hundreds to thousands of individual neurons offer the possibility of expanding the substrate of cognition. Parallel trains of firing rate activity can be delivered in real-time to an array of intermediate external modules that in turn can trigger parallel trains of stimulation back into the brain. These modules may be built in software, VLSI firmware, or biological tissue as in vitro culture preparations or in vivo ectopic construct organoids. Arrays of modules can be constructed as early stage whole brain emulators, following canonical intra- and inter-regional circuits. By using machine learning algorithms and classic tasks known to activate quasi-orthogonal functional connectivity patterns, bedside testing can rapidly identify ensemble tuning properties and in turn cycle through a sequence of external module architectures to explore which can causatively alter perception and behavior. Whole brain emulation both (1) serves to augment human neural function, compensating for disease and injury as an auxiliary parallel system, and (2) has its independent operation bootstrapped by a human-in-the-loop to identify optimal micro- and macro-architectures, update synaptic weights, and entrain behaviors. In this manner, closed-loop brain-computer interface pilot clinical trials can advance strong artificial intelligence development and forge new therapies to restore independence in children and adults with neurological conditions. PMID:28713235

Monte Carlo Simulation of Spacecraft Particle Detectors to Assess the True Human Risk

NASA Technical Reports Server (NTRS)

O'Neill, Patrick M.

2002-01-01

Particle detectors (DOSTEL, CPDS, and TEPC) measure the energy deposition spectrum inside earth orbiting - manned spacecraft (shuttle, space station). These instruments attempt to emulate the deposition of energy in human tissue to evaluate the health risk. However, the measurements are often difficult to relate to tissue equivalent because nuclear fragmentation (internuclear cascade/evaporation), energy-loss straggling, heavy ions, spacecraft shielding and detector geometry/orientation, and coincidence thresholds significantly affect the measured spectrum. 'A le have developed a high fidelity Monte Carlo model addressing each of these effects that significantly improves interpretation of these instruments and the resulting assessment of radiation risk to humans.

Three-dimensional spheroid cell culture of umbilical cord tissue-derived mesenchymal stromal cells leads to enhanced paracrine induction of wound healing.

PubMed

Santos, Jorge M; Camões, Sérgio P; Filipe, Elysse; Cipriano, Madalena; Barcia, Rita N; Filipe, Mariana; Teixeira, Mariana; Simões, Sandra; Gaspar, Manuela; Mosqueira, Diogo; Nascimento, Diana S; Pinto-do-Ó, Perpétua; Cruz, Pedro; Cruz, Helder; Castro, Matilde; Miranda, Joana P

2015-05-09

The secretion of trophic factors by mesenchymal stromal cells has gained increased interest given the benefits it may bring to the treatment of a variety of traumatic injuries such as skin wounds. Herein, we report on a three-dimensional culture-based method to improve the paracrine activity of a specific population of umbilical cord tissue-derived mesenchymal stromal cells (UCX®) towards the application of conditioned medium for the treatment of cutaneous wounds. A UCX® three-dimensional culture model was developed and characterized with respect to spheroid formation, cell phenotype and cell viability. The secretion by UCX® spheroids of extracellular matrix proteins and trophic factors involved in the wound-healing process was analysed. The skin regenerative potential of UCX® three-dimensional culture-derived conditioned medium (CM3D) was also assessed in vitro and in vivo against UCX® two-dimensional culture-derived conditioned medium (CM2D) using scratch and tubulogenesis assays and a rat wound splinting model, respectively. UCX® spheroids kept in our three-dimensional system remained viable and multipotent and secreted considerable amounts of vascular endothelial growth factor A, which was undetected in two-dimensional cultures, and higher amounts of matrix metalloproteinase-2, matrix metalloproteinase-9, hepatocyte growth factor, transforming growth factor β1, granulocyte-colony stimulating factor, fibroblast growth factor 2 and interleukin-6, when compared to CM2D. Furthermore, CM3D significantly enhanced elastin production and migration of keratinocytes and fibroblasts in vitro. In turn, tubulogenesis assays revealed increased capillary maturation in the presence of CM3D, as seen by a significant increase in capillary thickness and length when compared to CM2D, and increased branching points and capillary number when compared to basal medium. Finally, CM3D-treated wounds presented signs of faster and better resolution when compared to untreated and CM2D-treated wounds in vivo. Although CM2D proved to be beneficial, CM3D-treated wounds revealed a completely regenerated tissue by day 14 after excisions, with a more mature vascular system already showing glands and hair follicles. This work unravels an important alternative to the use of cells in the final formulation of advanced therapy medicinal products by providing a proof of concept that a reproducible system for the production of UCX®-conditioned medium can be used to prime a secretome for eventual clinical applications.

Three dimensional multi-cellular muscle-like tissue engineering in perfusion-based bioreactors.

PubMed

Cerino, Giulia; Gaudiello, Emanuele; Grussenmeyer, Thomas; Melly, Ludovic; Massai, Diana; Banfi, Andrea; Martin, Ivan; Eckstein, Friedrich; Grapow, Martin; Marsano, Anna

2016-01-01

Conventional tissue engineering strategies often rely on the use of a single progenitor cell source to engineer in vitro biological models; however, multi-cellular environments can better resemble the complexity of native tissues. Previous described co-culture models used skeletal myoblasts, as parenchymal cell source, and mesenchymal or endothelial cells, as stromal component. Here, we propose instead the use of adipose tissue-derived stromal vascular fraction cells, which include both mesenchymal and endothelial cells, to better resemble the native stroma. Percentage of serum supplementation is one of the crucial parameters to steer skeletal myoblasts toward either proliferation (20%) or differentiation (5%) in two-dimensional culture conditions. On the contrary, three-dimensional (3D) skeletal myoblast culture often simply adopts the serum content used in monolayer, without taking into account the new cell environment. When considering 3D cultures of mm-thick engineered tissues, homogeneous and sufficient oxygen supply is paramount to avoid formation of necrotic cores. Perfusion-based bioreactor culture can significantly improve the oxygen access to the cells, enhancing the viability and the contractility of the engineered tissues. In this study, we first investigated the influence of different serum supplementations on the skeletal myoblast ability to proliferate and differentiate during 3D perfusion-based culture. We tested percentages of serum promoting monolayer skeletal myoblast-proliferation (20%) and differentiation (5%) and suitable for stromal cell culture (10%) with a view to identify the most suitable condition for the subsequent co-culture. The 10% serum medium composition resulted in the highest number of mature myotubes and construct functionality. Co-culture with stromal vascular fraction cells at 10% serum also supported the skeletal myoblast differentiation and maturation, hence providing a functional engineered 3D muscle model that resembles the native multi-cellular environment. © 2015 Wiley Periodicals, Inc.

A Simplified Method for Tissue Engineering Skeletal Muscle Organoids in Vitro

NASA Technical Reports Server (NTRS)

Shansky, Janet; DelTatto, Michael; Chromiak, Joseph; Vandenburgh, Herman

1996-01-01

Tissue-engineered three dimensional skeletal muscle organ-like structures have been formed in vitro from primary myoblasts by several different techniques. This report describes a simplified method for generating large numbers of muscle organoids from either primary embryonic avian or neonatal rodent myoblasts, which avoids the requirements for stretching and other mechanical stimulation.

Growing And Assembling Cells Into Tissues

NASA Technical Reports Server (NTRS)

Wolf, David A.; Schwarz, Ray P.; Lewis, Marian L.; Cross, John H.; Huls, M. Helen

1990-01-01

Laboratory process for growth and assembly of mammalian cells into tissue-like masses demonstrated with hamster and rat cells. New process better able to provide culture environment with reduced fluid shear stress, freedom for three-dimensional spatial orientation of particles suspended in culture medium, and localization of particles of different or similar sedimentation properties in similar spatial region.

Extracting cardiac shapes and motion of the chick embryo heart outflow tract from four-dimensional optical coherence tomography images

NASA Astrophysics Data System (ADS)

Yin, Xin; Liu, Aiping; Thornburg, Kent L.; Wang, Ruikang K.; Rugonyi, Sandra

2012-09-01

Recent advances in optical coherence tomography (OCT), and the development of image reconstruction algorithms, enabled four-dimensional (4-D) (three-dimensional imaging over time) imaging of the embryonic heart. To further analyze and quantify the dynamics of cardiac beating, segmentation procedures that can extract the shape of the heart and its motion are needed. Most previous studies analyzed cardiac image sequences using manually extracted shapes and measurements. However, this is time consuming and subject to inter-operator variability. Automated or semi-automated analyses of 4-D cardiac OCT images, although very desirable, are also extremely challenging. This work proposes a robust algorithm to semi automatically detect and track cardiac tissue layers from 4-D OCT images of early (tubular) embryonic hearts. Our algorithm uses a two-dimensional (2-D) deformable double-line model (DLM) to detect target cardiac tissues. The detection algorithm uses a maximum-likelihood estimator and was successfully applied to 4-D in vivo OCT images of the heart outflow tract of day three chicken embryos. The extracted shapes captured the dynamics of the chick embryonic heart outflow tract wall, enabling further analysis of cardiac motion.

Comparing the Microsoft Kinect to a traditional mouse for adjusting the viewed tissue densities of three-dimensional anatomical structures

NASA Astrophysics Data System (ADS)

Juhnke, Bethany; Berron, Monica; Philip, Adriana; Williams, Jordan; Holub, Joseph; Winer, Eliot

2013-03-01

Advancements in medical image visualization in recent years have enabled three-dimensional (3D) medical images to be volume-rendered from magnetic resonance imaging (MRI) and computed tomography (CT) scans. Medical data is crucial for patient diagnosis and medical education, and analyzing these three-dimensional models rather than two-dimensional (2D) slices would enable more efficient analysis by surgeons and physicians, especially non-radiologists. An interaction device that is intuitive, robust, and easily learned is necessary to integrate 3D modeling software into the medical community. The keyboard and mouse configuration does not readily manipulate 3D models because these traditional interface devices function within two degrees of freedom, not the six degrees of freedom presented in three dimensions. Using a familiar, commercial-off-the-shelf (COTS) device for interaction would minimize training time and enable maximum usability with 3D medical images. Multiple techniques are available to manipulate 3D medical images and provide doctors more innovative ways of visualizing patient data. One such example is windowing. Windowing is used to adjust the viewed tissue density of digital medical data. A software platform available at the Virtual Reality Applications Center (VRAC), named Isis, was used to visualize and interact with the 3D representations of medical data. In this paper, we present the methodology and results of a user study that examined the usability of windowing 3D medical imaging using a Kinect™ device compared to a traditional mouse.

Is Brain Emulation Dangerous?

NASA Astrophysics Data System (ADS)

Eckersley, Peter; Sandberg, Anders

2013-12-01

Brain emulation is a hypothetical but extremely transformative technology which has a non-zero chance of appearing during the next century. This paper investigates whether such a technology would also have any predictable characteristics that give it a chance of being catastrophically dangerous, and whether there are any policy levers which might be used to make it safer. We conclude that the riskiness of brain emulation probably depends on the order of the preceding research trajectory. Broadly speaking, it appears safer for brain emulation to happen sooner, because slower CPUs would make the technology`s impact more gradual. It may also be safer if brains are scanned before they are fully understood from a neuroscience perspective, thereby increasing the initial population of emulations, although this prediction is weaker and more scenario-dependent. The risks posed by brain emulation also seem strongly connected to questions about the balance of power between attackers and defenders in computer security contests. If economic property rights in CPU cycles1 are essentially enforceable, emulation appears to be comparatively safe; if CPU cycles are ultimately easy to steal, the appearance of brain emulation is more likely to be a destabilizing development for human geopolitics. Furthermore, if the computers used to run emulations can be kept secure, then it appears that making brain emulation technologies ―open‖ would make them safer. If, however, computer insecurity is deep and unavoidable, openness may actually be more dangerous. We point to some arguments that suggest the former may be true, tentatively implying that it would be good policy to work towards brain emulation using open scientific methodology and free/open source software codebases

Quantifying the correlation between spatially defined oxygen gradients and cell fate in an engineered three-dimensional culture model.

PubMed

Ardakani, Amir G; Cheema, Umber; Brown, Robert A; Shipley, Rebecca J

2014-09-06

A challenge in three-dimensional tissue culture remains the lack of quantitative information linking nutrient delivery and cellular distribution. Both in vivo and in vitro, oxygen is delivered by diffusion from its source (blood vessel or the construct margins). The oxygen level at a defined distance from its source depends critically on the balance of diffusion and cellular metabolism. Cells may respond to this oxygen environment through proliferation, death and chemotaxis, resulting in spatially resolved gradients in cellular density. This study extracts novel spatially resolved and simultaneous data on tissue oxygenation, cellular proliferation, viability and chemotaxis in three-dimensional spiralled, cellular collagen constructs. Oxygen concentration gradients drove preferential cellular proliferation rates and viability in the higher oxygen zones and induced chemotaxis along the spiral of the collagen construct; an oxygen gradient of 1.03 mmHg mm(-1) in the spiral direction induced a mean migratory speed of 1015 μm day(-1). Although this movement was modest, it was effective in balancing the system to a stable cell density distribution, and provided insights into the natural cell mechanism for adapting cell number and activity to a prevailing oxygen regime.

Three-dimensional slice cultures from murine fetal gut for investigations of the enteric nervous system.

PubMed

Metzger, Marco; Bareiss, Petra M; Nikolov, Ivan; Skutella, Thomas; Just, Lothar

2007-01-01

Three-dimensional intestinal cultures offer new possibilities for the examination of growth potential, analysis of time specific gene expression, and spatial cellular arrangement of enteric nervous system in an organotypical environment. We present an easy to produce in vitro model of the enteric nervous system for analysis and manipulation of cellular differentiation processes. Slice cultures of murine fetal colon were cultured on membrane inserts for up to 2 weeks without loss of autonomous contractility. After slice preparation, cultured tissue reorganized within the first days in vitro. Afterward, the culture possessed more than 35 cell layers, including high prismatic epithelial cells, smooth muscle cells, glial cells, and neurons analyzed by immunohistochemistry. The contraction frequency of intestinal slice culture could be modulated by the neurotransmitter serotonin and the sodium channel blocker tetrodotoxin. Coculture experiments with cultured neurospheres isolated from enhanced green fluorescent protein (eGFP) transgenic mice demonstrated that differentiating eGFP-positive neurons were integrated into the intestinal tissue culture. This slice culture model of enteric nervous system proved to be useful for studying cell-cell interactions, cellular signaling, and cell differentiation processes in a three-dimensional cell arrangement.

The relationship between facial 3-D morphometry and the perception of attractiveness in children.

PubMed

Ferrario, V F; Sforza, C; Poggio, C E; Colombo, A; Tartaglia, G

1997-01-01

The aim of this investigation was to determine whether attractive children differ in their three-dimensional facial characteristics from nonattractive children of the same age, race, and sex. The facial characteristics of 36 boys and 44 girls aged 8 to 9 years were investigated. Frontal and profile photographs were analyzed independently by 21 judges, and, for each view, four groups were obtained: attractive boys, nonattractive boys, attractive girls, and nonattractive girls. For each child, the three-dimensional coordinates of 16 standardized soft tissue facial landmarks were automatically collected using an infrared system and used to calculate several three-dimensional angles, linear distances, and linear distance ratios. Mean values were computed in the eight groups, and attractive and nonattractive children were compared within sex and view. Most children received a different esthetic evaluation in the separate frontal and profile assessments; concordance in both attractive and nonattractive groups was only 50%. Moreover, three-dimensional facial morphometry was not able to separate attractive and nonattractive children.

Augmenting computer networks

NASA Technical Reports Server (NTRS)

Bokhari, S. H.; Raza, A. D.

1984-01-01

Three methods of augmenting computer networks by adding at most one link per processor are discussed: (1) A tree of N nodes may be augmented such that the resulting graph has diameter no greater than 4log sub 2((N+2)/3)-2. Thi O(N(3)) algorithm can be applied to any spanning tree of a connected graph to reduce the diameter of that graph to O(log N); (2) Given a binary tree T and a chain C of N nodes each, C may be augmented to produce C so that T is a subgraph of C. This algorithm is O(N) and may be used to produce augmented chains or rings that have diameter no greater than 2log sub 2((N+2)/3) and are planar; (3) Any rectangular two-dimensional 4 (8) nearest neighbor array of size N = 2(k) may be augmented so that it can emulate a single step shuffle-exchange network of size N/2 in 3(t) time steps.

High-speed free-space optical continuous-variable quantum key distribution enabled by three-dimensional multiplexing.

PubMed

Qu, Zhen; Djordjevic, Ivan B

2017-04-03

A high-speed four-state continuous-variable quantum key distribution (CV-QKD) system, enabled by wavelength-division multiplexing, polarization multiplexing, and orbital angular momentum (OAM) multiplexing, is studied in the presence of atmospheric turbulence. The atmospheric turbulence channel is emulated by two spatial light modulators (SLMs) on which two randomly generated azimuthal phase patterns yielding Andrews' spectrum are recorded. The phase noise is mitigated by the phase noise cancellation (PNC) stage, and channel transmittance can be monitored directly by the D.C. level in our PNC stage. After the system calibration, a total SKR of >1.68 Gbit/s can be reached in the ideal system, featured with lossless channel and free of excess noise. In our experiment, based on commercial photodetectors, the minimum transmittances of 0.21 and 0.29 are required for OAM states of 2 (or -2) and 6 (or -6), respectively, to guarantee the secure transmission, while a total SKR of 120 Mbit/s can be obtained in case of mean transmittances.

The Reconstruction of Three-Dimensional Morphological and Electrical Paraneters from Two-Dimensional Sections of Neurones

NASA Astrophysics Data System (ADS)

Brawn, A. D.; Wheal, H. V.

1986-07-01

A system is described which can be used to create a three-dimensional model of a neurone from the central nervous system. This model can then be used to obtain quantitative data on the physical and electrical pro, perties of the neurone. Living neurones are either raised in culture, or taken from in vitro preparations of brain tissue and optically sectioned. These two-dimensional sections are digitised, and input to a 68008-based microcomputer. The system reconstructs the three-dimensional structure of the neurone, both geanetrically and electrically. The user can a) View the structure fran any point at any angle b) "Move through" the structure along any given vector c) Nave through" the structure following a neurone process d) Fire the neurone at any point, and "watch" the action potentials propagate e) Vary the parameters of the electrical model of a process element. The system is targeted to a research programme on epilepsy, which makes frequent use of both geometric and electrical neurone modelling. Current techniques which may involve crude histology and two-dimensional drawings have considerable short camings.

Guidance, Navigation and Control Digital Emulation Technology Laboratory. Volume 1. Part 2. Task 1: Digital Emulation Technology Laboratory

DTIC Science & Technology

1991-09-27

AD-A241 692 II I] II I11 ANNUAL REPORT VOLUME 1 PART 2 TASK 1: DIGITAL EMULATION TECHNOLOGY LABORATOIRY REPORT NO. AR-0142-91-001 September 27, 1991... DIGITAL EMULATION TECHNOLOGY LABORATORY Contract No. DASG60-89-C-0142 Sponsored By The United States Army ? trategic Defense Command COMPUTER...ANNUAL REPORT VOLUME 1 PART 2 TASK 1: DIGITAL EMULATION TECHNOLOGY LABORATORY September 27, 1991 Authors Thomas R. Collins and Stephen R. Wachtel

Highly cytocompatible and flexible three-dimensional graphene/polydimethylsiloxane composite for culture and electrochemical detection of L929 fibroblast cells.

PubMed

Waiwijit, Uraiwan; Maturos, Thitima; Pakapongpan, Saithip; Phokharatkul, Ditsayut; Wisitsoraat, Anurat; Tuantranont, Adisorn

2016-08-01

Recently, three-dimensional graphene interconnected network has attracted great interest as a scaffold structure for tissue engineering due to its high biocompatibility, high electrical conductivity, high specific surface area and high porosity. However, free-standing three-dimensional graphene exhibits poor flexibility and stability due to ease of disintegration during processing. In this work, three-dimensional graphene is composited with polydimethylsiloxane to improve the structural flexibility and stability by a new simple two-step process comprising dip coating of polydimethylsiloxane on chemical vapor deposited graphene/Ni foam and wet etching of nickel foam. Structural characterizations confirmed an interconnected three-dimensional multi-layer graphene structure with thin polydimethylsiloxane scaffold. The composite was employed as a substrate for culture of L929 fibroblast cells and its cytocompatibility was evaluated by cell viability (Alamar blue assay), reactive oxygen species production and vinculin immunofluorescence imaging. The result revealed that cell viability on three-dimensional graphene/polydimethylsiloxane composite increased with increasing culture time and was slightly different from a polystyrene substrate (control). Moreover, cells cultured on three-dimensional graphene/polydimethylsiloxane composite generated less ROS than the control at culture times of 3-6 h. The results of immunofluorescence staining demonstrated that fibroblast cells expressed adhesion protein (vinculin) and adhered well on three-dimensional graphene/polydimethylsiloxane surface. Good cell adhesion could be attributed to suitable surface properties of three-dimensional graphene/polydimethylsiloxane with moderate contact angle and small negative zeta potential in culture solution. The results of electrochemical study by cyclic voltammetry showed that an oxidation current signal with no apparent peak was induced by fibroblast cells and the oxidation current at an oxidation potential of +0.9 V increased linearly with increasing cell number. Therefore, the three-dimensional graphene/polydimethylsiloxane composite exhibits high cytocompatibility and can potentially be used as a conductive substrate for cell-based electrochemical sensing. © The Author(s) 2016.

Quantification of three-dimensional cell-mediated collagen remodeling using graph theory.

PubMed

Bilgin, Cemal Cagatay; Lund, Amanda W; Can, Ali; Plopper, George E; Yener, Bülent

2010-09-30

Cell cooperation is a critical event during tissue development. We present the first precise metrics to quantify the interaction between mesenchymal stem cells (MSCs) and extra cellular matrix (ECM). In particular, we describe cooperative collagen alignment process with respect to the spatio-temporal organization and function of mesenchymal stem cells in three dimensions. We defined two precise metrics: Collagen Alignment Index and Cell Dissatisfaction Level, for quantitatively tracking type I collagen and fibrillogenesis remodeling by mesenchymal stem cells over time. Computation of these metrics was based on graph theory and vector calculus. The cells and their three dimensional type I collagen microenvironment were modeled by three dimensional cell-graphs and collagen fiber organization was calculated from gradient vectors. With the enhancement of mesenchymal stem cell differentiation, acceleration through different phases was quantitatively demonstrated. The phases were clustered in a statistically significant manner based on collagen organization, with late phases of remodeling by untreated cells clustering strongly with early phases of remodeling by differentiating cells. The experiments were repeated three times to conclude that the metrics could successfully identify critical phases of collagen remodeling that were dependent upon cooperativity within the cell population. Definition of early metrics that are able to predict long-term functionality by linking engineered tissue structure to function is an important step toward optimizing biomaterials for the purposes of regenerative medicine.

Emulator-assisted data assimilation in complex models

NASA Astrophysics Data System (ADS)

Margvelashvili, Nugzar Yu; Herzfeld, Mike; Rizwi, Farhan; Mongin, Mathieu; Baird, Mark E.; Jones, Emlyn; Schaffelke, Britta; King, Edward; Schroeder, Thomas

2016-09-01

Emulators are surrogates of complex models that run orders of magnitude faster than the original model. The utility of emulators for the data assimilation into ocean models is still not well understood. High complexity of ocean models translates into high uncertainty of the corresponding emulators which may undermine the quality of the assimilation schemes based on such emulators. Numerical experiments with a chaotic Lorenz-95 model are conducted to illustrate this point and suggest a strategy to alleviate this problem through the localization of the emulation and data assimilation procedures. Insights gained through these experiments are used to design and implement data assimilation scenario for a 3D fine-resolution sediment transport model of the Great Barrier Reef (GBR), Australia.

Vestibulo-Ocular Reflex Responses to a Multichannel Vestibular Prosthesis Incorporating a 3D Coordinate Transformation for Correction of Misalignment

PubMed Central

Fridman, Gene Y.; Davidovics, Natan S.; Dai, Chenkai; Migliaccio, Americo A.

2010-01-01

There is no effective treatment available for individuals unable to compensate for bilateral profound loss of vestibular sensation, which causes chronic disequilibrium and blurs vision by disrupting vestibulo-ocular reflexes that normally stabilize the eyes during head movement. Previous work suggests that a multichannel vestibular prosthesis can emulate normal semicircular canals by electrically stimulating vestibular nerve branches to encode head movements detected by mutually orthogonal gyroscopes affixed to the skull. Until now, that approach has been limited by current spread resulting in distortion of the vestibular nerve activation pattern and consequent inability to accurately encode head movements throughout the full 3-dimensional (3D) range normally transduced by the labyrinths. We report that the electrically evoked 3D angular vestibulo-ocular reflex exhibits vector superposition and linearity to a sufficient degree that a multichannel vestibular prosthesis incorporating a precompensatory 3D coordinate transformation to correct misalignment can accurately emulate semicircular canals for head rotations throughout the range of 3D axes normally transduced by a healthy labyrinth. PMID:20177732

In vivo Degradation of Three-Dimensional Silk Fibroin Scaffolds

PubMed Central

Wang, Yongzhong; Rudym, Darya D.; Walsh, Ashley; Abrahamsen, Lauren; Kim, Hyeon-Joo; Kim, Hyun Suk; Kirker-Head, Carl; Kaplan, David L.

2011-01-01

Three-dimensional porous scaffolds prepared from regenerated silk fibroin using either an all aqueous process or a process involving an organic solvent, hexafluoroisopropanol (HFIP) have shown promise in cell culture and tissue engineering applications. However, their biocompatibility and in vivo degradation has not been fully established. The present study was conducted to systematically investigate how processing method (aqueous vs. organic solvent) and processing variables (silk fibroin concentration and pore size) affect the short-term (up to 2 months) and long-term (up to 1 year) in vivo behavior of the protein scaffolds in both nude and Lewis rats. The samples were analyzed by histology for scaffold morphological changes and tissue ingrowth, and by real-time RT-PCR and immunohistochemistry for immune responses. Throughout the period of implantation, all scaffolds were well-tolerated by the host animals and immune responses to the implants were mild. Most scaffolds prepared from the all aqueous process degraded to completion between two and six months, while those prepared from organic solvent (hexafluoroisopropanol (HFIP)) process persisted beyond one year. Due to widespread cellular invasion throughout the scaffold, the degradation of aqueous-derived scaffolds appears to be more homogeneous than that of HFIP-derived scaffolds. In general and especially for the HFIP-derived scaffolds, a higher original silk fibroin concentration (e.g. 17%) and smaller pore size (e.g. 100–200 µm) resulted in lower levels of tissue ingrowth and slower degradation. These results demonstrate that the in vivo behavior of the three-dimensional silk fibroin scaffolds is related to the morphological and structural features that resulted from different scaffold preparation processes. The insights gained in this study can serve as a guide for processing scenarios to match desired morphological and structural features and degradation time with tissue-specific applications. PMID:18502501

Validation techniques for fault emulation of SRAM-based FPGAs

DOE PAGES

Quinn, Heather; Wirthlin, Michael

2015-08-07

A variety of fault emulation systems have been created to study the effect of single-event effects (SEEs) in static random access memory (SRAM) based field-programmable gate arrays (FPGAs). These systems are useful for augmenting radiation-hardness assurance (RHA) methodologies for verifying the effectiveness for mitigation techniques; understanding error signatures and failure modes in FPGAs; and failure rate estimation. For radiation effects researchers, it is important that these systems properly emulate how SEEs manifest in FPGAs. If the fault emulation systems does not mimic the radiation environment, the system will generate erroneous data and incorrect predictions of behavior of the FPGA inmore » a radiation environment. Validation determines whether the emulated faults are reasonable analogs to the radiation-induced faults. In this study we present methods for validating fault emulation systems and provide several examples of validated FPGA fault emulation systems.« less

Objective breast tissue image classification using Quantitative Transmission ultrasound tomography

NASA Astrophysics Data System (ADS)

Malik, Bilal; Klock, John; Wiskin, James; Lenox, Mark

2016-12-01

Quantitative Transmission Ultrasound (QT) is a powerful and emerging imaging paradigm which has the potential to perform true three-dimensional image reconstruction of biological tissue. Breast imaging is an important application of QT and allows non-invasive, non-ionizing imaging of whole breasts in vivo. Here, we report the first demonstration of breast tissue image classification in QT imaging. We systematically assess the ability of the QT images’ features to differentiate between normal breast tissue types. The three QT features were used in Support Vector Machines (SVM) classifiers, and classification of breast tissue as either skin, fat, glands, ducts or connective tissue was demonstrated with an overall accuracy of greater than 90%. Finally, the classifier was validated on whole breast image volumes to provide a color-coded breast tissue volume. This study serves as a first step towards a computer-aided detection/diagnosis platform for QT.

Identification of muscle necrosis in the mdx mouse model of Duchenne muscular dystrophy using three-dimensional optical coherence tomography

NASA Astrophysics Data System (ADS)

Klyen, Blake R.; Shavlakadze, Thea; Radley-Crabb, Hannah G.; Grounds, Miranda D.; Sampson, David D.

2011-07-01

Three-dimensional optical coherence tomography (3D-OCT) was used to image the structure and pathology of skeletal muscle tissue from the treadmill-exercised mdx mouse model of human Duchenne muscular dystrophy. Optical coherence tomography (OCT) images of excised muscle samples were compared with co-registered hematoxylin and eosin-stained and Evans blue dye fluorescence histology. We show, for the first time, structural 3D-OCT images of skeletal muscle dystropathology well correlated with co-located histology. OCT could identify morphological features of interest and necrotic lesions within the muscle tissue samples based on intrinsic optical contrast. These findings demonstrate the utility of 3D-OCT for the evaluation of small-animal skeletal muscle morphology and pathology, particularly for studies of mouse models of muscular dystrophy.

Analysis of the Material Properties of Early Chondrogenic Differentiated Adipose-Derived Stromal Cells (ASC) Using an in vitro Three-dimensional Micromass Culture System

PubMed Central

Xu, Yue; Balooch, Guive; Chiou, Michael; Bekerman, Elena; Ritchie, Robert O.; Longaker, Michael T.

2009-01-01

Cartilage is an avascular tissue with only a limited potential to heal and chondrocytes in vitro have poor proliferative capacity. Recently, adipose-derived stromal cells (ASC) have demonstrated a great potential for application to tissue engineering due to their ability to differentiate into cartilage, bone, and fat. In this study, we have utilized a high density three-dimensional (3D) micromass model system of early chondrogenesis with ASC. The material properties of these micromasses showed a significant increase in dynamic and static elastic modulus during the early chondrogenic differentiation process. These data suggest that the 3D micromass culture system represents an in vitro model of early chondrogenesis with dynamic cell signaling interactions associated with the mechanical properties of chondrocyte differentiation. PMID:17543281

Analysis of the material properties of early chondrogenic differentiated adipose-derived stromal cells (ASC) using an in vitro three-dimensional micromass culture system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, Yue; Balooch, Guive; Chiou, Michael

2007-07-27

Cartilage is an avascular tissue with only a limited potential to heal and chondrocytes in vitro have poor proliferative capacity. Recently, adipose-derived stromal cells (ASC) have demonstrated a great potential for application to tissue engineering due to their ability to differentiate into cartilage, bone, and fat. In this study, we have utilized a high density three-dimensional (3D) micromass model system of early chondrogenesis with ASC. The material properties of these micromasses showed a significant increase in dynamic and static elastic modulus during the early chondrogenic differentiation process. These data suggest that the 3D micromass culture system represents an in vitromore » model of early chondrogenesis with dynamic cell signaling interactions associated with the mechanical properties of chondrocyte differentiation.« less

A Quantitative Three-Dimensional Image Analysis Tool for Maximal Acquisition of Spatial Heterogeneity Data.

PubMed

Allenby, Mark C; Misener, Ruth; Panoskaltsis, Nicki; Mantalaris, Athanasios

2017-02-01

Three-dimensional (3D) imaging techniques provide spatial insight into environmental and cellular interactions and are implemented in various fields, including tissue engineering, but have been restricted by limited quantification tools that misrepresent or underutilize the cellular phenomena captured. This study develops image postprocessing algorithms pairing complex Euclidean metrics with Monte Carlo simulations to quantitatively assess cell and microenvironment spatial distributions while utilizing, for the first time, the entire 3D image captured. Although current methods only analyze a central fraction of presented confocal microscopy images, the proposed algorithms can utilize 210% more cells to calculate 3D spatial distributions that can span a 23-fold longer distance. These algorithms seek to leverage the high sample cost of 3D tissue imaging techniques by extracting maximal quantitative data throughout the captured image.

Three-dimensional transgenic cell model to quantify genotoxic effects of space environment

NASA Astrophysics Data System (ADS)

Gonda, S. R.; Wu, H.; Pingerelli, P. L.; Glickman, B. W.

In this paper we describe a three-dimensional, multicellular tissue-equivalent model, produced in NASA-designed, rotating wall bioreactors using mammalian cells engineered for genomic containment of multiple copies of defined target genes for genotoxic assessment. Rat 2λ fibroblasts, genetically engineered to contain high-density target genes for mutagenesis (Stratagene, Inc., Austin, TX), were cocultured with human epithelial cells on Cytodex beads in the High Aspect Ratio Bioreactor (Synthecon, Inc, Houston, TX). Multi-bead aggregates were formed by day 5 following the complete covering of the beads by fibroblasts. Cellular retraction occurred 8-14 days after coculture initiation culminating in spheroids retaining few or no beads. Analysis of the resulting tissue assemblies revealed: multicellular spheroids, fibroblasts synthesized collagen, and cell viability was retained for the 30-day test period after removal from the bioreactor. Quantification of mutation at the LacI gene in Rat 2λ fibroblasts in spheroids exposed to 0-2 Gy neon using the Big Blue color assay (Stratagene, Inc.), revealed a linear dose-response for mutation induction. Limited sequencing analysis of mutant clones from 0.25 or 1 Gy exposures revealed a higher frequency of deletions and multiple base sequencing changes with increasing dose. These results suggest that the three-dimensional, multicellular tissue assembly model produced in NASA bioreactors are applicable to a wide variety of studies involving the quantification and identification of genotocity including measurement of the inherent damage incurred in Space.

Microswitch and keyboard-emulator technology to facilitate the writing performance of persons with extensive motor disabilities.

PubMed

Lancioni, Giulio E; Singh, Nirbhay N; O'Reilly, Mark F; Sigafoos, Jeff; Green, Vanessa; Oliva, Doretta; Lang, Russell

2011-01-01

This study assessed the effectiveness of microswitches for simple responses (i.e., partial hand closure, vocalization, and hand stroking) and a keyboard emulator to facilitate the writing performance of three participants with extensive motor disabilities. The study was carried out according to an ABAB design. During the A phases, the participants (one child and two adults) were to write using the responses and technology available to them prior to this study. During the B phases, they used the new responses and technology. Data showed that two of the three participants had a faster writing performance during the B phases while the third participant had a slower writing performance. All three participants indicated a clear preference for the use of the new responses and technology, which were considered relatively easy and comfortable to manage and did not seem to cause any specific signs of tiredness. Implications of the findings are discussed. Copyright © 2010 Elsevier Ltd. All rights reserved.

Skin tissue generation by laser cell printing.

PubMed

Koch, Lothar; Deiwick, Andrea; Schlie, Sabrina; Michael, Stefanie; Gruene, Martin; Coger, Vincent; Zychlinski, Daniela; Schambach, Axel; Reimers, Kerstin; Vogt, Peter M; Chichkov, Boris

2012-07-01

For the aim of ex vivo engineering of functional tissue substitutes, Laser-assisted BioPrinting (LaBP) is under investigation for the arrangement of living cells in predefined patterns. So far three-dimensional (3D) arrangements of single or two-dimensional (2D) patterning of different cell types have been presented. It has been shown that cells are not harmed by the printing procedure. We now demonstrate for the first time the 3D arrangement of vital cells by LaBP as multicellular grafts analogous to native archetype and the formation of tissue by these cells. For this purpose, fibroblasts and keratinocytes embedded in collagen were printed in 3D as a simple example for skin tissue. To study cell functions and tissue formation process in 3D, different characteristics, such as cell localisation and proliferation were investigated. We further analysed the formation of adhering and gap junctions, which are fundamental for tissue morphogenesis and cohesion. In this study, it was demonstrated that LaBP is an outstanding tool for the generation of multicellular 3D constructs mimicking tissue functions. These findings are promising for the realisation of 3D in vitro models and tissue substitutes for many applications in tissue engineering. Copyright © 2012 Wiley Periodicals, Inc.

Modeling the Morphogenesis of Epidermal Tissues on the Surface of a 3D Last

NASA Astrophysics Data System (ADS)

McCleery, W. Tyler; Crews, Sarah M.; Mashburn, David N.; Veldhuis, Jim; Brodland, G. Wayne; Hutson, M. Shane

2014-03-01

Embryogenesis in the fruit fly Drosophila melanogaster is coordinated by the interaction of cells in adjacent tissues. For some events of embryogenesis, e.g., dorsal closure, two-dimensional models have been sufficient to elucidate the relevant cell and tissue mechanics. Here, we describe a new three-dimensional cell-level finite element model for investigating germ band retraction - a morphogenetic event where one epidermal tissue, the germ band, initially wraps around the posterior end of the ellipsoidal embryo. This tissue then retracts with a mechanical assist from contraction of cells in a second epidermal tissue, the amnioserosa. To speed simulation run times and focus on the relevant tissues, we only model epidermal tissue interactions. Epidermal cells are defined as polygons constrained to lie on the surface of the ellipsoidal last, but have adjustable parameters such as edge tensions and cell pressures. Tissue movements are simulated by balancing these dynamic cell-level forces with viscous resistance and allowing cells to exchange neighbors. Our choice of modeling parameters is informed by in vivo measurements of cell-level forces using laser microsurgery. We use this model to investigate the multicellular stress fields in normal and aberrant development.

A kinetic modeling of chondrocyte culture for manufacture of tissue-engineered cartilage.

PubMed

Kino-Oka, Masahiro; Maeda, Yoshikatsu; Yamamoto, Takeyuki; Sugawara, Katsura; Taya, Masahito

2005-03-01

For repairing articular cartilage defects, innovative techniques based on tissue engineering have been developed and are now entering into the practical stage of clinical application by means of grafting in vitro cultured products. A variety of natural and artificial materials available for scaffolds, which permit chondrocyte cells to aggregate, have been designed for their ability to promote cell growth and differentiation. From the viewpoint of the manufacturing process for tissue-engineered cartilage, the diverse nature of raw materials (seeding cells) and end products (cultured cartilage) oblige us to design a tailor-made process with less reproducibility, which is an obstacle to establishing a production doctrine based on bioengineering knowledge concerning growth kinetics and modeling as well as designs of bioreactors and culture operations for certification of high product quality. In this article, we review the recent advances in the manufacturing of tissue-engineered cartilage. After outlining the manufacturing processes for tissue-engineered cartilage in the first section, the second and third sections, respectively, describe the three-dimensional culture of chondrocytes with Aterocollagen gel and kinetic model consideration as a tool for evaluating this culture process. In the final section, culture strategy is discussed in terms of the combined processes of monolayer growth (ex vivo chondrocyte cell expansion) and three-dimensional growth (construction of cultured cartilage in the gel).

Measurement of vibration-induced volumetric strain in the human lung.

PubMed

Hirsch, Sebastian; Posnansky, Oleg; Papazoglou, Sebastian; Elgeti, Thomas; Braun, Jürgen; Sack, Ingolf

2013-03-01

Noninvasive image-based measurement of intrinsic tissue pressure is of great interest in the diagnosis and characterization of diseases. Therefore, we propose to exploit the capability of phase-contrast MRI to measure three-dimensional vector fields of tissue motion for deriving volumetric strain induced by external vibration. Volumetric strain as given by the divergence of mechanical displacement fields is related to tissue compressibility and is thus sensitive to the state of tissue pressure. This principle is demonstrated by the measurement of three-dimensional vector fields of 50-Hz oscillations in a compressible agarose phantom and in the lungs of nine healthy volunteers. In the phantom, the magnitude of the oscillating divergence increased by about 400% with 4.8 bar excess air pressure, corresponding to an effective-medium compression modulus of 230 MPa. In lungs, the averaged divergence magnitude increased in all volunteers (N = 9) between 7 and 78% from expiration to inspiration. Measuring volumetric strain by MRI provides a compression-sensitive parameter of tissue mechanics, which varies with the respiratory state in the lungs. In future clinical applications for diagnosis and characterization of lung emphysema, fibrosis, or cancer, divergence-sensitive MRI may serve as a noninvasive marker sensitive to disease-related alterations of regional elastic recoil pressure in the lungs. Copyright © 2012 Wiley Periodicals, Inc.

A microfabricated platform to form three-dimensional toroidal multicellular aggregate.

PubMed

Masuda, Taisuke; Takei, Natsuki; Nakano, Takuma; Anada, Takahisa; Suzuki, Osamu; Arai, Fumihito

2012-12-01

Techniques that allow cells to self-assemble into three-dimensional (3D) spheroid microtissues provide powerful in vitro models that are becoming increasingly popular in fields such as stem cell research, tissue engineering, and cancer biology. Appropriate simulation of the 3D environment in which tissues normally develop and function is crucial for the engineering of in vitro models that can be used for the formation of complex tissues. We have developed a unique multicellular aggregate formation platform that utilizes a maskless gray-scale photolithography. The cellular aggregate formed using this platform has a toroidal-like geometry and includes a micro lumen that facilitates the supply of oxygen and growth factors and the expulsion of waste products. As a result, this platform was capable of rapidly producing hundreds of multicellular aggregates at a time, and of regulating the diameter of aggregates with complex design. These toroidal multicellular aggregates can grow as long-term culture. In addition, the micro lumen can be used as a continuous channel and for the insertion of a vascular system or a nerve system into the assembled tissue. These platform characteristics highlight its potential to be used in a wide variety of applications, e.g. as a bioactuator, as a micro-machine component or in drug screening and tissue engineering.

Modeling of bioheat equation for skin and a preliminary study on a noninvasive diagnostic method for skin burn wounds.

PubMed

Lee, Shong-Leih; Lu, Yung-Hsiang

2014-08-01

Heat transfer in a unit three-dimensional skin tissue with an embedded vascular system of actual histology structure is computed in the present work. The tissue temperature and the blood temperatures in artery and vein vessels are solved with a multi-grid system. The mean temperature of the tissue over the cross-section of the unit skin area is evaluated. The resulting one-dimensional function is regarded as the temperature of healthy tissue (or injured skin but the blood perfusion is still normally working) for large area of skin in view of the symmetric and periodic structure of the paired artery-vein vessels in nature. A three-dimensional bioheat equation then is formulated by the superposition of the skin burn wound effect and the healthy skin temperature with and without thermal radiation exposure. When this bioheat equation is employed to simulate ADT process on burn wounds, the decaying factor of the skin surface temperature is found to be a sharply decreasing function of time in the self-cooling stage after a thermal radiation heating. Nevertheless, the boundary of non-healing (needing surgery) and healing regions in a large burn wound can be estimated by tracking the peak of the gradient of decaying factor within 30 s after the thermal radiation is turned off. Experimental studies on the full ADT procedure are needed to justify the assumptions in the present computation. Copyright © 2013 Elsevier Ltd and ISBI. All rights reserved.

Live-cell imaging of migrating cells expressing fluorescently-tagged proteins in a three-dimensional matrix.

PubMed

Shih, Wenting; Yamada, Soichiro

2011-12-22

Traditionally, cell migration has been studied on two-dimensional, stiff plastic surfaces. However, during important biological processes such as wound healing, tissue regeneration, and cancer metastasis, cells must navigate through complex, three-dimensional extracellular tissue. To better understand the mechanisms behind these biological processes, it is important to examine the roles of the proteins responsible for driving cell migration. Here, we outline a protocol to study the mechanisms of cell migration using the epithelial cell line (MDCK), and a three-dimensional, fibrous, self-polymerizing matrix as a model system. This optically clear extracellular matrix is easily amenable to live-cell imaging studies and better mimics the physiological, soft tissue environment. This report demonstrates a technique for directly visualizing protein localization and dynamics, and deformation of the surrounding three-dimensional matrix. Examination of protein localization and dynamics during cellular processes provides key insight into protein functions. Genetically encoded fluorescent tags provide a unique method for observing protein localization and dynamics. Using this technique, we can analyze the subcellular accumulation of key, force-generating cytoskeletal components in real-time as the cell maneuvers through the matrix. In addition, using multiple fluorescent tags with different wavelengths, we can examine the localization of multiple proteins simultaneously, thus allowing us to test, for example, whether different proteins have similar or divergent roles. Furthermore, the dynamics of fluorescently tagged proteins can be quantified using Fluorescent Recovery After Photobleaching (FRAP) analysis. This measurement assays the protein mobility and how stably bound the proteins are to the cytoskeletal network. By combining live-cell imaging with the treatment of protein function inhibitors, we can examine in real-time the changes in the distribution of proteins and morphology of migrating cells. Furthermore, we also combine live-cell imaging with the use of fluorescent tracer particles embedded within the matrix to visualize the matrix deformation during cell migration. Thus, we can visualize how a migrating cell distributes force-generating proteins, and where the traction forces are exerted to the surrounding matrix. Through these techniques, we can gain valuable insight into the roles of specific proteins and their contributions to the mechanisms of cell migration.

Composite Scaffolds Containing Silk Fibroin, Gelatin, and Hydroxyapatite for Bone Tissue Regeneration and 3D Cell Culturing

PubMed Central

Moisenovich, M. M.; Arkhipova, A. Yu.; Orlova, A. A.; Drutskaya, M. S; Volkova, S. V.; Zacharov, S. E.; Agapov, I. I.; Kirpichnikov, M. P.

2014-01-01

Three-dimensional (3D) silk fibroin scaffolds were modified with one of the major bone tissue derivatives (nano-hydroxyapatite) and/or a collagen derivative (gelatin). Adhesion and proliferation of mouse embryonic fibroblasts (MEF) within the scaffold were increased after modification with either nano-hydroxyapatite or gelatin. However, a significant increase in MEF adhesion and proliferation was observed when both additives were introduced into the scaffold. Such modified composite scaffolds provide a new and better platform to study wound healing, bone and other tissue regeneration, as well as artificial organ bioengineering. This system can further be applied to establish experimental models to study cell-substrate interactions, cell migration and other complex processes, which may be difficult to address using the conventional two-dimensional culture systems. PMID:24772332

A transverse oscillation approach for estimation of three-dimensional velocity vectors, part I: concept and simulation study.

PubMed

Pihl, Michael Johannes; Jensen, Jørgen Arendt

2014-10-01

A method for 3-D velocity vector estimation using transverse oscillations is presented. The method employs a 2-D transducer and decouples the velocity estimation into three orthogonal components, which are estimated simultaneously and from the same data. The validity of the method is investigated by conducting simulations emulating a 32 × 32 matrix transducer. The results are evaluated using two performance metrics related to precision and accuracy. The study includes several parameters including 49 flow directions, the SNR, steering angle, and apodization types. The 49 flow directions cover the positive octant of the unit sphere. In terms of accuracy, the median bias is -2%. The precision of v(x) and v(y) depends on the flow angle ß and ranges from 5% to 31% relative to the peak velocity magnitude of 1 m/s. For comparison, the range is 0.4 to 2% for v(z). The parameter study also reveals, that the velocity estimation breaks down with an SNR between -6 and -3 dB. In terms of computational load, the estimation of the three velocity components requires 0.75 billion floating point operations per second (0.75 Gflops) for a realistic setup. This is well within the capability of modern scanners.

Serial block face scanning electron microscopy--the future of cell ultrastructure imaging.

PubMed

Hughes, Louise; Hawes, Chris; Monteith, Sandy; Vaughan, Sue

2014-03-01

One of the major drawbacks in transmission electron microscopy has been the production of three-dimensional views of cells and tissues. Currently, there is no one suitable 3D microscopy technique that answers all questions and serial block face scanning electron microscopy (SEM) fills the gap between 3D imaging using high-end fluorescence microscopy and the high resolution offered by electron tomography. In this review, we discuss the potential of the serial block face SEM technique for studying the three-dimensional organisation of animal, plant and microbial cells.

Design and demonstration of a pumpless 14 compartment microphysiological system.

PubMed

Miller, Paula G; Shuler, Michael L

2016-10-01

We describe a human "Body-on-a-chip" device (or microphysiological system) that could be used to emulate drug distribution, metabolism, and action in the body. It is based upon a physiologically based pharmacokinetic-pharmacodynamic (PBPK-PD) model, where multiple chambers representing different organs are connected with fluidic channels to mimic multi-organ interactions within the body. Here we describe a pumpless 14 chamber (13 organs) microfluidic cell culture device that provides a separation between barrier and nonbarrier types of cell cultures. Our barrier chamber layer (skin, GI tract, and lung) allows for direct access and/or exposures to chemical or biological reagents forcing these reagents to pass through a barrier of cells established on a microfabricated membrane before exposing the nonbarrier tissue chambers (fat, kidney, heart, adrenal glands, liver, spleen, pancreas, bone marrow, brain, muscle) or entering the microfluidic circulation within the device. Our nonbarrier tissue chambers were created as three-dimensional configurations by resuspending cells in hydrogel (PGMatrix). We used cell lines to represent five of these organs (barrier lines-A549 [lung] and Caco2 [GI]) (nonbarrier lines-HepG2 C3A [liver], Meg01 [bone marrow], and HK2 [kidney]). The dimensions of our straight duct-like channels to each organ chamber were designed to provide the appropriate flow of a culture medium. The organ volumes and organ flow rates that have been reported for an average human male were used to estimate the desired fluid retention times in each organ chamber. The flow through the channels was induced by gravity on a custom programmed rocker platform which enabled pumpless operation and minimized bubble entrapment. The purpose of this paper is to describe the design and operation of a 14 chamber multi-organ system representing 13 tissues/organs with both barrier and nonbarrier tissue chambers and to study the interactive responses among the various cell lines. We demonstrate that five different cell lines survived with high viability (above 85%) for 7 days. We compared the individual observed flow rates to the compartments to the desired or estimated flow rates. This work demonstrates the feasibility of constructing, operating and maintaining a simple, gravity-driven, multi-organ microphysiological system with the capability of measuring cellular functions such as CYP1A1 and CYP3A4 activities, albumin release, urea, maintenance of tight junctions, and presence of surfactant for a sustained period. Biotechnol. Bioeng. 2016;113: 2213-2227. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Bioprinting technologies for disease modeling.

PubMed

Memic, Adnan; Navaei, Ali; Mirani, Bahram; Cordova, Julio Alvin Vacacela; Aldhahri, Musab; Dolatshahi-Pirouz, Alireza; Akbari, Mohsen; Nikkhah, Mehdi

2017-09-01

There is a great need for the development of biomimetic human tissue models that allow elucidation of the pathophysiological conditions involved in disease initiation and progression. Conventional two-dimensional (2D) in vitro assays and animal models have been unable to fully recapitulate the critical characteristics of human physiology. Alternatively, three-dimensional (3D) tissue models are often developed in a low-throughput manner and lack crucial native-like architecture. The recent emergence of bioprinting technologies has enabled creating 3D tissue models that address the critical challenges of conventional in vitro assays through the development of custom bioinks and patient derived cells coupled with well-defined arrangements of biomaterials. Here, we provide an overview on the technological aspects of 3D bioprinting technique and discuss how the development of bioprinted tissue models have propelled our understanding of diseases' characteristics (i.e. initiation and progression). The future perspectives on the use of bioprinted 3D tissue models for drug discovery application are also highlighted.

From cineradiography to biorobots: an approach for designing robots to emulate and study animal locomotion.

PubMed

Karakasiliotis, K; Thandiackal, R; Melo, K; Horvat, T; Mahabadi, N K; Tsitkov, S; Cabelguen, J M; Ijspeert, A J

2016-06-01

Robots are increasingly used as scientific tools to investigate animal locomotion. However, designing a robot that properly emulates the kinematic and dynamic properties of an animal is difficult because of the complexity of musculoskeletal systems and the limitations of current robotics technology. Here, we propose a design process that combines high-speed cineradiography, optimization, dynamic scaling, three-dimensional printing, high-end servomotors and a tailored dry-suit to construct Pleurobot: a salamander-like robot that closely mimics its biological counterpart, Pleurodeles waltl Our previous robots helped us test and confirm hypotheses on the interaction between the locomotor neuronal networks of the limbs and the spine to generate basic swimming and walking gaits. With Pleurobot, we demonstrate a design process that will enable studies of richer motor skills in salamanders. In particular, we are interested in how these richer motor skills can be obtained by extending our spinal cord models with the addition of more descending pathways and more detailed limb central pattern generator networks. Pleurobot is a dynamically scaled amphibious salamander robot with a large number of actuated degrees of freedom (DOFs: 27 in total). Because of our design process, the robot can capture most of the animal's DOFs and range of motion, especially at the limbs. We demonstrate the robot's abilities by imposing raw kinematic data, extracted from X-ray videos, to the robot's joints for basic locomotor behaviours in water and on land. The robot closely matches the behaviour of the animal in terms of relative forward speeds and lateral displacements. Ground reaction forces during walking also resemble those of the animal. Based on our results, we anticipate that future studies on richer motor skills in salamanders will highly benefit from Pleurobot's design. © 2016 The Author(s).

From cineradiography to biorobots: an approach for designing robots to emulate and study animal locomotion

PubMed Central

Karakasiliotis, K.; Thandiackal, R.; Melo, K.; Horvat, T.; Mahabadi, N. K.; Tsitkov, S.; Cabelguen, J. M.; Ijspeert, A. J.

2016-01-01

Robots are increasingly used as scientific tools to investigate animal locomotion. However, designing a robot that properly emulates the kinematic and dynamic properties of an animal is difficult because of the complexity of musculoskeletal systems and the limitations of current robotics technology. Here, we propose a design process that combines high-speed cineradiography, optimization, dynamic scaling, three-dimensional printing, high-end servomotors and a tailored dry-suit to construct Pleurobot: a salamander-like robot that closely mimics its biological counterpart, Pleurodeles waltl. Our previous robots helped us test and confirm hypotheses on the interaction between the locomotor neuronal networks of the limbs and the spine to generate basic swimming and walking gaits. With Pleurobot, we demonstrate a design process that will enable studies of richer motor skills in salamanders. In particular, we are interested in how these richer motor skills can be obtained by extending our spinal cord models with the addition of more descending pathways and more detailed limb central pattern generator networks. Pleurobot is a dynamically scaled amphibious salamander robot with a large number of actuated degrees of freedom (DOFs: 27 in total). Because of our design process, the robot can capture most of the animal's DOFs and range of motion, especially at the limbs. We demonstrate the robot's abilities by imposing raw kinematic data, extracted from X-ray videos, to the robot's joints for basic locomotor behaviours in water and on land. The robot closely matches the behaviour of the animal in terms of relative forward speeds and lateral displacements. Ground reaction forces during walking also resemble those of the animal. Based on our results, we anticipate that future studies on richer motor skills in salamanders will highly benefit from Pleurobot's design. PMID:27358276

Nondestructive cryomicro-CT imaging enables structural and molecular analysis of human lung tissue.

PubMed

Vasilescu, Dragoş M; Phillion, André B; Tanabe, Naoya; Kinose, Daisuke; Paige, David F; Kantrowitz, Jacob J; Liu, Gang; Liu, Hanqiao; Fishbane, Nick; Verleden, Stijn E; Vanaudenaerde, Bart M; Lenburg, Marc; Stevenson, Christopher S; Spira, Avrum; Cooper, Joel D; Hackett, Tillie-Louise; Hogg, James C

2017-01-01

Micro-computed tomography (CT) enables three-dimensional (3D) imaging of complex soft tissue structures, but current protocols used to achieve this goal preclude cellular and molecular phenotyping of the tissue. Here we describe a radiolucent cryostage that permits micro-CT imaging of unfixed frozen human lung samples at an isotropic voxel size of (11 µm) 3 under conditions where the sample is maintained frozen at -30°C during imaging. The cryostage was tested for thermal stability to maintain samples frozen up to 8 h. This report describes the methods used to choose the materials required for cryostage construction and demonstrates that whole genome mRNA integrity and expression are not compromised by exposure to micro-CT radiation and that the tissue can be used for immunohistochemistry. The new cryostage provides a novel method enabling integration of 3D tissue structure with cellular and molecular analysis to facilitate the identification of molecular determinants of disease. The described micro-CT cryostage provides a novel way to study the three-dimensional lung structure preserved without the effects of fixatives while enabling subsequent studies of the cellular matrix composition and gene expression. This approach will, for the first time, enable researchers to study structural changes of lung tissues that occur with disease and correlate them with changes in gene or protein signatures. Copyright © 2017 the American Physiological Society.

Digital dissection - using contrast-enhanced computed tomography scanning to elucidate hard- and soft-tissue anatomy in the Common Buzzard Buteo buteo.

PubMed

Lautenschlager, Stephan; Bright, Jen A; Rayfield, Emily J

2014-04-01

Gross dissection has a long history as a tool for the study of human or animal soft- and hard-tissue anatomy. However, apart from being a time-consuming and invasive method, dissection is often unsuitable for very small specimens and often cannot capture spatial relationships of the individual soft-tissue structures. The handful of comprehensive studies on avian anatomy using traditional dissection techniques focus nearly exclusively on domestic birds, whereas raptorial birds, and in particular their cranial soft tissues, are essentially absent from the literature. Here, we digitally dissect, identify, and document the soft-tissue anatomy of the Common Buzzard (Buteo buteo) in detail, using the new approach of contrast-enhanced computed tomography using Lugol's iodine. The architecture of different muscle systems (adductor, depressor, ocular, hyoid, neck musculature), neurovascular, and other soft-tissue structures is three-dimensionally visualised and described in unprecedented detail. The three-dimensional model is further presented as an interactive PDF to facilitate the dissemination and accessibility of anatomical data. Due to the digital nature of the data derived from the computed tomography scanning and segmentation processes, these methods hold the potential for further computational analyses beyond descriptive and illustrative proposes. © 2013 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.

Three-dimensional high-resolution second-harmonic generation imaging of endogenous structural proteins in biological tissues.

PubMed Central

Campagnola, Paul J; Millard, Andrew C; Terasaki, Mark; Hoppe, Pamela E; Malone, Christian J; Mohler, William A

2002-01-01

We find that several key endogenous protein structures give rise to intense second-harmonic generation (SHG)-nonabsorptive frequency doubling of an excitation laser line. Second-harmonic imaging microscopy (SHIM) on a laser-scanning system proves, therefore, to be a powerful and unique tool for high-resolution, high-contrast, three-dimensional studies of live cell and tissue architecture. Unlike fluorescence, SHG suffers no inherent photobleaching or toxicity and does not require exogenous labels. Unlike polarization microscopy, SHIM provides intrinsic confocality and deep sectioning in complex tissues. In this study, we demonstrate the clarity of SHIM optical sectioning within unfixed, unstained thick specimens. SHIM and two-photon excited fluorescence (TPEF) were combined in a dual-mode nonlinear microscopy to elucidate the molecular sources of SHG in live cells and tissues. SHG arose not only from coiled-coil complexes within connective tissues and muscle thick filaments, but also from microtubule arrays within interphase and mitotic cells. Both polarization dependence and a local symmetry cancellation effect of SHG allowed the signal from species generating the second harmonic to be decoded, by ratiometric correlation with TPEF, to yield information on local structure below optical resolution. The physical origin of SHG within these tissues is addressed and is attributed to the laser interaction with dipolar protein structures that is enhanced by the intrinsic chirality of the protein helices. PMID:11751336

Rotating three-dimensional dynamic culture of adult human bone marrow-derived cells for tissue engineering of hyaline cartilage.

PubMed

Sakai, Shinsuke; Mishima, Hajime; Ishii, Tomoo; Akaogi, Hiroshi; Yoshioka, Tomokazu; Ohyabu, Yoshimi; Chang, Fei; Ochiai, Naoyuki; Uemura, Toshimasa

2009-04-01

The method of constructing cartilage tissue from bone marrow-derived cells in vitro is considered a valuable technique for hyaline cartilage regenerative medicine. Using a rotating wall vessel (RWV) bioreactor developed in a NASA space experiment, we attempted to efficiently construct hyaline cartilage tissue from human bone marrow-derived cells without using a scaffold. Bone marrow aspirates were obtained from the iliac crest of nine patients during orthopedic operation. After their proliferation in monolayer culture, the adherent cells were cultured in the RWV bioreactor with chondrogenic medium for 2 weeks. Cells from the same source were cultured in pellet culture as controls. Histological and immunohistological evaluations (collagen type I and II) and quantification of glycosaminoglycan were performed on formed tissues and compared. The engineered constructs obtained using the RWV bioreactor showed strong features of hyaline cartilage in terms of their morphology as determined by histological and immunohistological evaluations. The glycosaminoglycan contents per microg DNA of the tissues were 10.01 +/- 3.49 microg/microg DNA in the case of the RWV bioreactor and 6.27 +/- 3.41 microg/microg DNA in the case of the pellet culture, and their difference was significant. The RWV bioreactor could provide an excellent environment for three-dimensional cartilage tissue architecture that can promote the chondrogenic differentiation of adult human bone marrow-derived cells.

Performance of a reduced-order FSI model for flow-induced vocal fold vibration

NASA Astrophysics Data System (ADS)

Chang, Siyuan; Luo, Haoxiang; Luo's lab Team

2016-11-01

Vocal fold vibration during speech production involves a three-dimensional unsteady glottal jet flow and three-dimensional nonlinear tissue mechanics. A full 3D fluid-structure interaction (FSI) model is computationally expensive even though it provides most accurate information about the system. On the other hand, an efficient reduced-order FSI model is useful for fast simulation and analysis of the vocal fold dynamics, which is often needed in procedures such as optimization and parameter estimation. In this work, we study the performance of a reduced-order model as compared with the corresponding full 3D model in terms of its accuracy in predicting the vibration frequency and deformation mode. In the reduced-order model, we use a 1D flow model coupled with a 3D tissue model. Two different hyperelastic tissue behaviors are assumed. In addition, the vocal fold thickness and subglottal pressure are varied for systematic comparison. The result shows that the reduced-order model provides consistent predictions as the full 3D model across different tissue material assumptions and subglottal pressures. However, the vocal fold thickness has most effect on the model accuracy, especially when the vocal fold is thin. Supported by the NSF.

Open-source three-dimensional printing of biodegradable polymer scaffolds for tissue engineering.

PubMed

Trachtenberg, Jordan E; Mountziaris, Paschalia M; Miller, Jordan S; Wettergreen, Matthew; Kasper, Fred K; Mikos, Antonios G

2014-12-01

The fabrication of scaffolds for tissue engineering requires elements of customization depending on the application and is often limited due to the flexibility of the processing technique. This investigation seeks to address this obstacle by utilizing an open-source three-dimensional printing (3DP) system that allows vast customizability and facilitates reproduction of experiments. The effects of processing parameters on printed poly(ε-caprolactone) scaffolds with uniform and gradient pore architectures have been characterized with respect to fiber and pore morphology and mechanical properties. The results demonstrate the ability to tailor the fiber diameter, pore size, and porosity through modification of pressure, printing speed, and programmed fiber spacing. A model was also used to predict the compressive mechanical properties of uniform and gradient scaffolds, and it was found that modulus and yield strength declined with increasing porosity. The use of open-source 3DP technologies for printing tissue-engineering scaffolds provides a flexible system that can be readily modified at a low cost and is supported by community documentation. In this manner, the 3DP system is more accessible to the scientific community, which further facilitates the translation of these technologies toward successful tissue-engineering strategies.

Three-dimensional Biomimetic Technology: Novel Biorubber Creates Defined Micro- and Macro-scale Architectures in Collagen Hydrogels

PubMed Central

Rodriguez-Rivera, Veronica; Weidner, John W.; Yost, Michael J.

2016-01-01

Tissue scaffolds play a crucial role in the tissue regeneration process. The ideal scaffold must fulfill several requirements such as having proper composition, targeted modulus, and well-defined architectural features. Biomaterials that recapitulate the intrinsic architecture of in vivo tissue are vital for studying diseases as well as to facilitate the regeneration of lost and malformed soft tissue. A novel biofabrication technique was developed which combines state of the art imaging, three-dimensional (3D) printing, and selective enzymatic activity to create a new generation of biomaterials for research and clinical application. The developed material, Bovine Serum Albumin rubber, is reaction injected into a mold that upholds specific geometrical features. This sacrificial material allows the adequate transfer of architectural features to a natural scaffold material. The prototype consists of a 3D collagen scaffold with 4 and 3 mm channels that represent a branched architecture. This paper emphasizes the use of this biofabrication technique for the generation of natural constructs. This protocol utilizes a computer-aided software (CAD) to manufacture a solid mold which will be reaction injected with BSA rubber followed by the enzymatic digestion of the rubber, leaving its architectural features within the scaffold material. PMID:26967145

Three-dimensional Biomimetic Technology: Novel Biorubber Creates Defined Micro- and Macro-scale Architectures in Collagen Hydrogels.

PubMed

Rodriguez-Rivera, Veronica; Weidner, John W; Yost, Michael J

2016-02-12

Tissue scaffolds play a crucial role in the tissue regeneration process. The ideal scaffold must fulfill several requirements such as having proper composition, targeted modulus, and well-defined architectural features. Biomaterials that recapitulate the intrinsic architecture of in vivo tissue are vital for studying diseases as well as to facilitate the regeneration of lost and malformed soft tissue. A novel biofabrication technique was developed which combines state of the art imaging, three-dimensional (3D) printing, and selective enzymatic activity to create a new generation of biomaterials for research and clinical application. The developed material, Bovine Serum Albumin rubber, is reaction injected into a mold that upholds specific geometrical features. This sacrificial material allows the adequate transfer of architectural features to a natural scaffold material. The prototype consists of a 3D collagen scaffold with 4 and 3 mm channels that represent a branched architecture. This paper emphasizes the use of this biofabrication technique for the generation of natural constructs. This protocol utilizes a computer-aided software (CAD) to manufacture a solid mold which will be reaction injected with BSA rubber followed by the enzymatic digestion of the rubber, leaving its architectural features within the scaffold material.

Parry-Romberg reconstruction: optimal timing for hard and soft tissue procedures.

PubMed

Slack, Ginger C; Tabit, Christina J; Allam, Karam A; Kawamoto, Henry K; Bradley, James P

2012-11-01

For the treatment of Parry-Romberg syndrome or progressive hemifacial atrophy, we studied 3 controversial issues: (1) optimal timing, (2) need for skeletal reconstruction, and (3) need for soft tissue (medial canthus/lacrimal duct) reconstruction. Patients with Parry-Romberg syndrome (>5 y follow-up) were divided into 2 groups: (1) younger than 14 years and (2) 14 years or older (n = 43). Sex, age, severity of deformity, number of procedures, operative times, and augmentation fat volumes were recorded. Physician and patient satisfaction surveys (5-point scale) were obtained, preoperative and postoperative three-dimensional computed tomographic scans were reviewed, and a digital three-dimensional photogrammetry system was used to determine volume retention. Our results indicate that the younger patient group required more procedures compared with the older patient group (4.3 versus 2.8); however, the younger group had higher patient/family satisfaction scores (3.8 versus 3.0). Skeletal and soft tissue reconstruction resulted in improved symmetry score (60% preoperatively to 93% final) and satisfaction scores (3.4 preoperatively to 3.8 final). Patients with Parry-Romberg syndrome required multiple corrective surgeries but showed improvements even when beginning before puberty. Soft and hard tissue reconstruction was beneficial.

Three-Dimensional Printing of Hollow-Struts-Packed Bioceramic Scaffolds for Bone Regeneration.

PubMed

Luo, Yongxiang; Zhai, Dong; Huan, Zhiguang; Zhu, Haibo; Xia, Lunguo; Chang, Jiang; Wu, Chengtie

2015-11-04

Three-dimensional printing technologies have shown distinct advantages to create porous scaffolds with designed macropores for application in bone tissue engineering. However, until now, 3D-printed bioceramic scaffolds only possessing a single type of macropore have been reported. Generally, those scaffolds with a single type of macropore have relatively low porosity and pore surfaces, limited delivery of oxygen and nutrition to surviving cells, and new bone tissue formation in the center of the scaffolds. Therefore, in this work, we present a useful and facile method for preparing hollow-struts-packed (HSP) bioceramic scaffolds with designed macropores and multioriented hollow channels via a modified coaxial 3D printing strategy. The prepared HSP scaffolds combined high porosity and surface area with impressive mechanical strength. The unique hollow-struts structures of bioceramic scaffolds significantly improved cell attachment and proliferation and further promoted formation of new bone tissue in the center of the scaffolds, indicating that HSP ceramic scaffolds can be used for regeneration of large bone defects. In addition, the strategy can be used to prepare other HSP ceramic scaffolds, indicating a universal application for tissue engineering, mechanical engineering, catalysis, and environmental materials.

The Development of a Virtual 3D Model of the Renal Corpuscle from Serial Histological Sections for E-Learning Environments

ERIC Educational Resources Information Center

Roth, Jeremy A.; Wilson, Timothy D.; Sandig, Martin

2015-01-01

Histology is a core subject in the anatomical sciences where learners are challenged to interpret two-dimensional (2D) information (gained from histological sections) to extrapolate and understand the three-dimensional (3D) morphology of cells, tissues, and organs. In gross anatomical education 3D models and learning tools have been associated…

Receptive fields and the theory of discriminant operators

NASA Astrophysics Data System (ADS)

Gupta, Madan M.; Hungenahally, Suresh K.

1991-02-01

Biological basis for machine vision is a notion which is being used extensively for the development of machine vision systems for various applications. In this paper we have made an attempt to emulate the receptive fields that exist in the biological visual channels. In particular we have exploited the notion of receptive fields for developing the mathematical functions named as discriminantfunctions for the extraction of transition information from signals and multi-dimensional signals and images. These functions are found to be useful for the development of artificial receptive fields for neuro-vision systems. 1.

One-dimensional anyons under three-body interactions.

NASA Astrophysics Data System (ADS)

Silva-Valencia, Jereson; Arcila-Forero, Julian; Franco, Roberto

Anyons are a third class of particles with nontrivial exchange statistics, particles carrying fractional statistics that interpolate between bosons and fermions. In the last years, it has been made some proposals to emulate an anyon gas by confining bosonic atoms in optical lattices [ Nat. Commun. 2, 361 (2011)]. In this work, we studied the ground state of anyons interacting through local three-body terms in one-dimension, motivated by recent experimental and theoretical studies about multi-body interactions in cold atoms setups. We used the density-matrix renormalization group method to find the phase diagram and the von Neumann block entropy to determinate the critical point position. The main quantum phases found are the superfluid and the Mott insulator ones. For the statistical angle θ = π /4, the phase diagram shows that the Mott lobes are surrounded by superfluid regions, the Mott lobes increase with the density and the first Mott lobe has two anyons per site. We found that a Mott lobe with one anyon per site, it is possible for larger statistical angles, a fact that it is impossible with bosons. DIBE- Universidad Nacional de Colombia and Departamento Administrativo de Ciencia, Tecnología e Innovación (COLCIENCAS) (Grant No. FP44842-057-2015).

Emulation-Based Virtual Laboratories: A Low-Cost Alternative to Physical Experiments in Control Engineering Education

ERIC Educational Resources Information Center

Goodwin, G. C.; Medioli, A. M.; Sher, W.; Vlacic, L. B.; Welsh, J. S.

2011-01-01

This paper argues the case for emulation-based virtual laboratories in control engineering education. It demonstrates that such emulation experiments can give students an industrially relevant educational experience at relatively low cost. The paper also describes a particular emulation-based system that has been developed with the aim of giving…

Scalable and reusable emulator for evaluating the performance of SS7 networks

NASA Astrophysics Data System (ADS)

Lazar, Aurel A.; Tseng, Kent H.; Lim, Koon Seng; Choe, Winston

1994-04-01

A scalable and reusable emulator was designed and implemented for studying the behavior of SS7 networks. The emulator design was largely based on public domain software. It was developed on top of an environment supported by PVM, the Parallel Virtual Machine, and managed by OSIMIS-the OSI Management Information Service platform. The emulator runs on top of a commercially available ATM LAN interconnecting engineering workstations. As a case study for evaluating the emulator, the behavior of the Singapore National SS7 Network under fault and unbalanced loading conditions was investigated.

A Prolog Emulator

NASA Technical Reports Server (NTRS)

Tick, Evan

1987-01-01

This note describes an efficient software emulator for the Warren Abstract Machine (WAM) Prolog architecture. The version of the WAM implemented is called Lcode. The Lcode emulator, written in C, executes the 'naive reverse' benchmark at 3900 LIPS. The emulator is one of a set of tools used to measure the memory-referencing characteristics and performance of Prolog programs. These tools include a compiler, assembler, and memory simulators. An overview of the Lcode architecture is given here, followed by a description and listing of the emulator code implementing each Lcode instruction. This note will be of special interest to those studying the WAM and its performance characteristics. In general, this note will be of interest to those creating efficient software emulators for abstract machine architectures.

Electrospun Fibrous Scaffolds for Tissue Engineering: Viewpoints on Architecture and Fabrication.

PubMed

Jun, Indong; Han, Hyung-Seop; Edwards, James R; Jeon, Hojeong

2018-03-06

Electrospinning has been used for the fabrication of extracellular matrix (ECM)-mimicking fibrous scaffolds for several decades. Electrospun fibrous scaffolds provide nanoscale/microscale fibrous structures with interconnecting pores, resembling natural ECM in tissues, and showing a high potential to facilitate the formation of artificial functional tissues. In this review, we summarize the fundamental principles of electrospinning processes for generating complex fibrous scaffold geometries that are similar in structural complexity to the ECM of living tissues. Moreover, several approaches for the formation of three-dimensional fibrous scaffolds arranged in hierarchical structures for tissue engineering are also presented.

Engineering Human Neural Tissue by 3D Bioprinting.

PubMed

Gu, Qi; Tomaskovic-Crook, Eva; Wallace, Gordon G; Crook, Jeremy M

2018-01-01

Bioprinting provides an opportunity to produce three-dimensional (3D) tissues for biomedical research and translational drug discovery, toxicology, and tissue replacement. Here we describe a method for fabricating human neural tissue by 3D printing human neural stem cells with a bioink, and subsequent gelation of the bioink for cell encapsulation, support, and differentiation to functional neurons and supporting neuroglia. The bioink uniquely comprises the polysaccharides alginate, water-soluble carboxymethyl-chitosan, and agarose. Importantly, the method could be adapted to fabricate neural and nonneural tissues from other cell types, with the potential to be applied for both research and clinical product development.

3D culture models of tissues under tension.

PubMed

Eyckmans, Jeroen; Chen, Christopher S

2017-01-01

Cells dynamically assemble and organize into complex tissues during development, and the resulting three-dimensional (3D) arrangement of cells and their surrounding extracellular matrix in turn feeds back to regulate cell and tissue function. Recent advances in engineered cultures of cells to model 3D tissues or organoids have begun to capture this dynamic reciprocity between form and function. Here, we describe the underlying principles that have advanced the field, focusing in particular on recent progress in using mechanical constraints to recapitulate the structure and function of musculoskeletal tissues. © 2017. Published by The Company of Biologists Ltd.

Expansion of the peri-implant attached gingiva with a three-dimensional collagen matrix in head and neck cancer patients-results from a prospective clinical and histological study.

PubMed

Lorenz, Jonas; Blume, Maximilian; Barbeck, Mike; Teiler, Anna; Kirkpatrick, C James; Sader, Robert A; Ghanaati, Shahram

2017-05-01

Attached peri-implant gingiva has proven to have an influence on the long-term stability of dental implants. In patients with head and neck cancer, a functional peri-implant gingiva is even more of critical importance. The aim of the presented prospective study was to investigate a three-dimensional xenogeneic collagen matrix for augmentation around dental implants in patients with former head and neck cancer. Eight patients presenting with insufficient peri-implant gingiva underwent vestibuloplasty on 51 implants using a xenogeneic collagen matrix. The clinical performance and the shrinking tendency of the matrix were analyzed in a cohort study. Furthermore, eight biopsies from the augmented regions were examined histologically to determine the biomaterial-related tissue reaction. Initially after vestibuloplasty, a mean width of attached gingiva of 4.4 ± 0.94 mm could be achieved. At clinical follow up investigation 6 months after vestibuloplasty, a mean width of 3.9 ± 0.65 mm attached peri-implant gingiva with a mean shrinking tendency of 14 % could be detected. Histological analysis of the biopsies revealed a well integrated collagen22 matrix covered with epithelium. Within the compact layer, mononuclear cells were observed only, while the spongious layer was infiltrated with a cell-rich connective tissue. Within its limits, the presented study revealed that the investigated collagen matrix is suitable to enlarge the peri-implant attached gingiva in head and neck cancer patients without adverse reactions or a multinucleated giant cell-triggered tissue reaction. The application of the investigated three-dimensional collagen matrix in vestibuloplasty achieved a sufficient amount of peri-implant attached gingiva in head and neck cancer patients. The favorable tissue reaction and the low shrinking tendency make the collagen matrix a promising alternative to autologous tissue grafts.

Denture-associated biofilm infection in three-dimensional oral mucosal tissue models.

PubMed

Morse, Daniel J; Wilson, Melanie J; Wei, Xiaoqing; Lewis, Michael A O; Bradshaw, David J; Murdoch, Craig; Williams, David W

2018-03-01

In vitro analyses of virulence, pathogenicity and associated host cell responses are important components in the study of biofilm infections. The Candida-related infection, denture-associated oral candidosis, affects up to 60 % of denture wearers and manifests as inflammation of palatal tissues contacting the denture-fitting surface. Commercially available three-dimensional tissue models can be used to study infection, but their use is limited for many academic research institutions, primarily because of the substantial purchase costs. The aim of this study was to develop and evaluate the use of in vitro tissue models to assess infections by biofilms on acrylic surfaces through tissue damage and Candida albicans virulence gene expression. In vitro models were compared against commercially available tissue equivalents (keratinocyte-only, SkinEthic; full-thickness, MatTek Corporation). An in vitro keratinocyte-only tissue was produced using a cancer-derived cell line, TR146, and a full-thickness model incorporating primary fibroblasts and immortalised normal oral keratinocytes was also generated. The in vitro full-thickness tissues incorporated keratinocytes and fibroblasts, and have potential for future further development and analysis. Following polymicrobial infection with biofilms on acrylic surfaces, both in-house developed models were shown to provide equivalent results to the SkinEthic and MatTek models in terms of tissue damage: a significant (P<0.05) increase in LDH activity for mixed species biofilms compared to uninfected control, and no significant difference (P>0.05) in the expression of most C. albicans virulence genes when comparing tissue models of the same type. Our results confirm the feasibility and suitability of using these alternative in vitro tissue models for such analyses.

Mid-infrared spectroscopy in skin cancer cell type identification

NASA Astrophysics Data System (ADS)

Kastl, Lena; Kemper, Björn; Lloyd, Gavin R.; Nallala, Jayakrupakar; Stone, Nick; Naranjo, Valery; Penaranda, Francisco; Schnekenburger, Jürgen

2017-07-01

Mid infrared spectroscopy samples were developed for the analysis of skin tumor cell types and three dimensional tissue phantoms towards the application of midIR spectroscopy for fast and reliable skin cancer diagnostics.

Real-time three-dimensional optical coherence tomography image-guided core-needle biopsy system.

PubMed

Kuo, Wei-Cheng; Kim, Jongsik; Shemonski, Nathan D; Chaney, Eric J; Spillman, Darold R; Boppart, Stephen A

2012-06-01

Advances in optical imaging modalities, such as optical coherence tomography (OCT), enable us to observe tissue microstructure at high resolution and in real time. Currently, core-needle biopsies are guided by external imaging modalities such as ultrasound imaging and x-ray computed tomography (CT) for breast and lung masses, respectively. These image-guided procedures are frequently limited by spatial resolution when using ultrasound imaging, or by temporal resolution (rapid real-time feedback capabilities) when using x-ray CT. One feasible approach is to perform OCT within small gauge needles to optically image tissue microstructure. However, to date, no system or core-needle device has been developed that incorporates both three-dimensional OCT imaging and tissue biopsy within the same needle for true OCT-guided core-needle biopsy. We have developed and demonstrate an integrated core-needle biopsy system that utilizes catheter-based 3-D OCT for real-time image-guidance for target tissue localization, imaging of tissue immediately prior to physical biopsy, and subsequent OCT imaging of the biopsied specimen for immediate assessment at the point-of-care. OCT images of biopsied ex vivo tumor specimens acquired during core-needle placement are correlated with corresponding histology, and computational visualization of arbitrary planes within the 3-D OCT volumes enables feedback on specimen tissue type and biopsy quality. These results demonstrate the potential for using real-time 3-D OCT for needle biopsy guidance by imaging within the needle and tissue during biopsy procedures.

Effect of the architecture of the left ventricle on the speed of the excitation wave in muscle fibers

NASA Astrophysics Data System (ADS)

Nezlobinsky, T. V.; Pravdin, S. F.; Katsnelson, L. B.; Solovyova, O. E.

2016-07-01

It is known that preferential paths for the propagation of an electrical excitation wave in the human ventricular myocardium are associated with muscle fibers in tissue. The speed of the excitation wave along a fiber is several times higher than that across the direction of the fiber. To estimate the effect of the architecture and anisotropy of the myocardium of the left ventricle on the process of its electrical activation, we have studied the relation between the speed of the electrical excitation wave in a one-dimensional isolated myocardial fiber consisting of sequentially coupled cardiomyocytes and in an identical fiber located in the wall of a threedimensional anatomical model of the left ventricle. It has been shown that the speed of a wavefront along the fiber in the three-dimensional myocardial tissue is much higher than that in the one-dimensional fiber. The acceleration of the signal is due to the rotation of directions of fibers in the wall and to the position of the excitation wavefront with respect to the direction of this fiber. The observed phenomenon is caused by the approach of the excitable tissue with rotational anisotropy in its properties to a pseudoisotropic tissue.

Heuristic problems in defining the three-dimensional arrangement of the ventricular myocytes.

PubMed

Anderson, Robert H; Ho, Siew Yen; Sanchez-Quintana, Damian; Redmann, Klaus; Lunkenheimer, Paul P

2006-06-01

There is lack of consensus concerning the three-dimensional arrangement of the myocytes within the ventricular muscle masses. Bioengineers are seeking to model the structure of the heart. Although the success of such models depends on the accuracy of the anatomic evidence, most of them have been based on concepts that are far from anatomical reality, which ignore many significant previous accounts of anatomy presented over the past 400 years. During the 19th century, Pettigrew emphasized that the heart was built on the basis of a modified blood vessel rather than in the form of skeletal muscles. This fact was reemphasized by Lev and Simkins as well as Grant in the 20th century, but the caveats listed by these authors have been ignored by proponents of two current concepts, which state either that the myocardium is arranged in the form of a "unique myocardial band," or that the walls of the ventricles are sequestrated in uniform fashion by laminar sheets of fibrous tissue extending from epicardium to endocardium. These two concepts are themselves incompatible and are further at variance with the majority of anatomic studies, which have emphasized the regional heterogeneity to be found in the three-dimensional packing of the myocytes within a supporting matrix of fibrous tissue. We reemphasize the significance of this three-dimensional muscular mesh, showing how the presence of intruding aggregates of myocytes extending in oblique transmural fashion also contends against the notion that all myocytes are orientated with their long axes parallel to the epicardial and enodcardial surfaces.

Three-dimensional venous visualization with phase-lag computed tomography angiography for reconstructive microsurgery.

PubMed

Sakakibara, Shunsuke; Onishi, Hiroyuki; Hashikawa, Kazunobu; Akashi, Masaya; Sakakibara, Akiko; Nomura, Tadashi; Terashi, Hiroto

2015-05-01

Most free flap reconstruction complications involve vascular compromise. Evaluation of vascular anatomy provides considerable information that can potentially minimize these complications. Previous reports have shown that contrast-enhanced computed tomography is effective for understanding three-dimensional arterial anatomy. However, most vascular complications result from venous thromboses, making imaging of venous anatomy highly desirable. The phase-lag computed tomography angiography (pl-CTA) technique involves 64-channel (virtually, 128-channel) multidetector CT and is used to acquire arterial images using conventional CTA. Venous images are three-dimensionally reconstructed using a subtraction technique involving combined venous phase and arterial phase images, using a computer workstation. This technique was used to examine 48 patients (12 lower leg reconstructions, 34 head and neck reconstructions, and 2 upper extremity reconstructions) without complications. The pl-CTA technique can be used for three-dimensional visualization of peripheral veins measuring approximately 1 mm in diameter. The pl-CTA information was especially helpful for secondary free flap reconstructions in the head and neck region after malignant tumor recurrence. In such cases, radical dissection of the neck was performed as part of the first operation, and many vessels, including veins, were resected and used in the first free-tissue transfer. The pl-CTA images also allowed visualization of varicose changes in the lower leg region and helped us avoid selecting those vessels for anastomosis. Thus, the pl-CTA-derived venous anatomy information was useful for exact evaluations during the planning of free-tissue transfers. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

A three-dimensional model to assess the effect of ankle joint axis misalignments in ankle-foot orthoses.

PubMed

Fatone, Stefania; Johnson, William Brett; Tucker, Kerice

2016-04-01

Misalignment of an articulated ankle-foot orthosis joint axis with the anatomic joint axis may lead to discomfort, alterations in gait, and tissue damage. Theoretical, two-dimensional models describe the consequences of misalignments, but cannot capture the three-dimensional behavior of ankle-foot orthosis use. The purpose of this project was to develop a model to describe the effects of ankle-foot orthosis ankle joint misalignment in three dimensions. Computational simulation. Three-dimensional scans of a leg and ankle-foot orthosis were incorporated into a link segment model where the ankle-foot orthosis joint axis could be misaligned with the anatomic ankle joint axis. The leg/ankle-foot orthosis interface was modeled as a network of nodes connected by springs to estimate interface pressure. Motion between the leg and ankle-foot orthosis was calculated as the ankle joint moved through a gait cycle. While the three-dimensional model corroborated predictions of the previously published two-dimensional model that misalignments in the anterior -posterior direction would result in greater relative motion compared to misalignments in the proximal -distal direction, it provided greater insight showing that misalignments have asymmetrical effects. The three-dimensional model has been incorporated into a freely available computer program to assist others in understanding the consequences of joint misalignments. Models and simulations can be used to gain insight into functioning of systems of interest. We have developed a three-dimensional model to assess the effect of ankle joint axis misalignments in ankle-foot orthoses. The model has been incorporated into a freely available computer program to assist understanding of trainees and others interested in orthotics. © The International Society for Prosthetics and Orthotics 2014.

Cone-Beam Computed Tomography Evaluation of Horizontal and Vertical Dimensional Changes in Buccal Peri-Implant Alveolar Bone and Soft Tissue: A 1-Year Prospective Clinical Study.

PubMed

Kaminaka, Akihiro; Nakano, Tamaki; Ono, Shinji; Kato, Tokinori; Yatani, Hirofumi

2015-10-01

This study evaluated changes in the horizontal and vertical dimensions of the buccal alveolar bone and soft tissue over a 1-year period following implant prosthesis. Thirty-three participants with no history of guided bone regeneration or soft tissue augmentation underwent dental implant placement with different types of connections. The dimensions of the buccal alveolar bone and soft tissue were evaluated immediately and at 1 year after prosthesis from reconstructions of cross-sectional cone-beam computed tomography images. The vertical and horizontal loss of buccal bone and soft tissue around implants with conical connections were lower than around those with external or internal connections. Statistically significant negative correlations were observed between initial horizontal bone thickness and changes in vertical bone and soft tissue height (p < .05), and between initial horizontal soft tissue thickness and the change in vertical soft tissue height (p < .05). Implants with a conical connection preserve peri-implant alveolar bone and soft tissue more effectively than other connection types. Furthermore, the initial buccal alveolar bone and soft tissue thickness around the implant platform may influence their vertical dimensional changes at 1 year after implant prosthesis. © 2014 Wiley Periodicals, Inc.

Coordinated three-dimensional motion of the head and torso by dynamic neural networks.

PubMed

Kim, J; Hemami, H

1998-01-01

The problem of trajectory tracking control of a three dimensional (3D) model of the human upper torso and head is considered. The torso and the head are modeled as two rigid bodies connected at one point, and the Newton-Euler method is used to derive the nonlinear differential equations that govern the motion of the system. The two-link system is driven by six pairs of muscle like actuators that possess physiologically inspired alpha like and gamma like inputs, and spindle like and Golgi tendon organ like outputs. These outputs are utilized as reflex feedback for stability and stiffness control, in a long loop feedback for the purpose of estimating the state of the system (somesthesis), and as part of the input to the controller. Ideal delays of different duration are included in the feedforward and feedback paths of the system to emulate such delays encountered in physiological systems. Dynamical neural networks are trained to learn effective control of the desired maneuvers of the system. The feasibility of the controller is demonstrated by computer simulation of the successful execution of the desired maneuvers. This work demonstrates the capabilities of neural circuits in controlling highly nonlinear systems with multidelays in their feedforward and feedback paths. The ultimate long range goal of this research is toward understanding the working of the central nervous system in controlling movement. It is an interdisciplinary effort relying on mechanics, biomechanics, neuroscience, system theory, physiology and anatomy, and its short range relevance to rehabilitation must be noted.

Magnetic resonance imaging reveals functional anatomy and biomechanics of a living dragon tree

PubMed Central

Hesse, Linnea; Masselter, Tom; Leupold, Jochen; Spengler, Nils; Speck, Thomas; Korvink, Jan Gerrit

2016-01-01

Magnetic resonance imaging (MRI) was used to gain in vivo insight into load-induced displacements of inner plant tissues making a non-invasive and non-destructive stress and strain analysis possible. The central aim of this study was the identification of a possible load-adapted orientation of the vascular bundles and their fibre caps as the mechanically relevant tissue in branch-stem-attachments of Dracaena marginata. The complex three-dimensional deformations that occur during mechanical loading can be analysed on the basis of quasi-three-dimensional data representations of the outer surface, the inner tissue arrangement (meristem and vascular system), and the course of single vascular bundles within the branch-stem-attachment region. In addition, deformations of vascular bundles could be quantified manually and by using digital image correlation software. This combination of qualitative and quantitative stress and strain analysis leads to an improved understanding of the functional morphology and biomechanics of D. marginata, a plant that is used as a model organism for optimizing branched technical fibre-reinforced lightweight trusses in order to increase their load bearing capacity. PMID:27604526

Three-dimensional brain MRI for DBS patients within ultra-low radiofrequency power limits.

PubMed

Sarkar, Subhendra N; Papavassiliou, Efstathios; Hackney, David B; Alsop, David C; Shih, Ludy C; Madhuranthakam, Ananth J; Busse, Reed F; La Ruche, Susan; Bhadelia, Rafeeque A

2014-04-01

For patients with deep brain stimulators (DBS), local absorbed radiofrequency (RF) power is unknown and is much higher than what the system estimates. We developed a comprehensive, high-quality brain magnetic resonance imaging (MRI) protocol for DBS patients utilizing three-dimensional (3D) magnetic resonance sequences at very low RF power. Six patients with DBS were imaged (10 sessions) using a transmit/receive head coil at 1.5 Tesla with modified 3D sequences within ultra-low specific absorption rate (SAR) limits (0.1 W/kg) using T2 , fast fluid-attenuated inversion recovery (FLAIR) and T1 -weighted image contrast. Tissue signal and tissue contrast from the low-SAR images were subjectively and objectively compared with routine clinical images of six age-matched controls. Low-SAR images of DBS patients demonstrated tissue contrast comparable to high-SAR images and were of diagnostic quality except for slightly reduced signal. Although preliminary, we demonstrated diagnostic quality brain MRI with optimized, volumetric sequences in DBS patients within very conservative RF safety guidelines offering a greater safety margin. © 2014 International Parkinson and Movement Disorder Society.

Preparation and characterization of poly (hydroxy butyrate)/chitosan blend scaffolds for tissue engineering applications

PubMed Central

Karbasi, Saeed; Khorasani, Saied Nouri; Ebrahimi, Somayeh; Khalili, Shahla; Fekrat, Farnoosh; Sadeghi, Davoud

2016-01-01

Background: Poly (hydroxy butyrate) (PHB) is a biodegradable and biocompatible polymer with good mechanical properties. This polymer could be a promising material for scaffolds if some features improve. Materials and Methods: In the present work, new PHB/chitosan blend scaffolds were prepared as a three-dimensional substrate in cartilage tissue engineering. Chitosan in different weight percent was added to PHB and solved in trifluoroacetic acid. Statistical Taguchi method was employed in the design of experiments. Results: The Fourier-transform infrared spectroscopy test revealed that the crystallization of PHB in these blends is suppressed with increasing the amount of chitosan. Scanning electron microscopy images showed a thin and rough top layer with a nodular structure, supported with a porous sub-layer in the surface of the scaffolds. In vitro degradation rate of the scaffolds was higher than pure PHB scaffolds. Maximum degradation rate has been seen for the scaffold with 90% wt. NaCl and 40% wt. chitosan. Conclusions: The obtained results suggest that these newly developed PHB/chitosan blend scaffolds may serve as a three-dimensional substrate in cartilage tissue engineering. PMID:28028517

Preparation and characterization of poly (hydroxy butyrate)/chitosan blend scaffolds for tissue engineering applications.

PubMed

Karbasi, Saeed; Khorasani, Saied Nouri; Ebrahimi, Somayeh; Khalili, Shahla; Fekrat, Farnoosh; Sadeghi, Davoud

2016-01-01

Poly (hydroxy butyrate) (PHB) is a biodegradable and biocompatible polymer with good mechanical properties. This polymer could be a promising material for scaffolds if some features improve. In the present work, new PHB/chitosan blend scaffolds were prepared as a three-dimensional substrate in cartilage tissue engineering. Chitosan in different weight percent was added to PHB and solved in trifluoroacetic acid. Statistical Taguchi method was employed in the design of experiments. The Fourier-transform infrared spectroscopy test revealed that the crystallization of PHB in these blends is suppressed with increasing the amount of chitosan. Scanning electron microscopy images showed a thin and rough top layer with a nodular structure, supported with a porous sub-layer in the surface of the scaffolds. In vitro degradation rate of the scaffolds was higher than pure PHB scaffolds. Maximum degradation rate has been seen for the scaffold with 90% wt. NaCl and 40% wt. chitosan. The obtained results suggest that these newly developed PHB/chitosan blend scaffolds may serve as a three-dimensional substrate in cartilage tissue engineering.

Three-Dimensional Human iPSC-Derived Artificial Skeletal Muscles Model Muscular Dystrophies and Enable Multilineage Tissue Engineering.

PubMed

Maffioletti, Sara Martina; Sarcar, Shilpita; Henderson, Alexander B H; Mannhardt, Ingra; Pinton, Luca; Moyle, Louise Anne; Steele-Stallard, Heather; Cappellari, Ornella; Wells, Kim E; Ferrari, Giulia; Mitchell, Jamie S; Tyzack, Giulia E; Kotiadis, Vassilios N; Khedr, Moustafa; Ragazzi, Martina; Wang, Weixin; Duchen, Michael R; Patani, Rickie; Zammit, Peter S; Wells, Dominic J; Eschenhagen, Thomas; Tedesco, Francesco Saverio

2018-04-17

Generating human skeletal muscle models is instrumental for investigating muscle pathology and therapy. Here, we report the generation of three-dimensional (3D) artificial skeletal muscle tissue from human pluripotent stem cells, including induced pluripotent stem cells (iPSCs) from patients with Duchenne, limb-girdle, and congenital muscular dystrophies. 3D skeletal myogenic differentiation of pluripotent cells was induced within hydrogels under tension to provide myofiber alignment. Artificial muscles recapitulated characteristics of human skeletal muscle tissue and could be implanted into immunodeficient mice. Pathological cellular hallmarks of incurable forms of severe muscular dystrophy could be modeled with high fidelity using this 3D platform. Finally, we show generation of fully human iPSC-derived, complex, multilineage muscle models containing key isogenic cellular constituents of skeletal muscle, including vascular endothelial cells, pericytes, and motor neurons. These results lay the foundation for a human skeletal muscle organoid-like platform for disease modeling, regenerative medicine, and therapy development. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Catlas: An magnetic resonance imaging-based three-dimensional cortical atlas and tissue probability maps for the domestic cat (Felis catus).

PubMed

Stolzberg, Daniel; Wong, Carmen; Butler, Blake E; Lomber, Stephen G

2017-10-15

Brain atlases play an important role in effectively communicating results from neuroimaging studies in a standardized coordinate system. Furthermore, brain atlases extend analysis of functional magnetic resonance imaging (MRI) data by delineating regions of interest over which to evaluate the extent of functional activation as well as measures of inter-regional connectivity. Here, we introduce a three-dimensional atlas of the cat cerebral cortex based on established cytoarchitectonic and electrophysiological findings. In total, 71 cerebral areas were mapped onto the gray matter (GM) of an averaged T1-weighted structural MRI acquired at 7 T from eight adult domestic cats. In addition, a nonlinear registration procedure was used to generate a common template brain as well as GM, white matter, and cerebral spinal fluid tissue probability maps to facilitate tissue segmentation as part of the standard preprocessing pipeline for MRI data analysis. The atlas and associated files can also be used for planning stereotaxic surgery and for didactic purposes. © 2017 Wiley Periodicals, Inc.

Morphological imaging and quantification of axial xylem tissue in Fraxinus excelsior L. through X-ray micro-computed tomography.

PubMed

Koddenberg, Tim; Militz, Holger

2018-05-05

The popularity of X-ray based imaging methods has continued to increase in research domains. In wood research, X-ray micro-computed tomography (XμCT) is useful for structural studies examining the three-dimensional and complex xylem tissue of trees qualitatively and quantitatively. In this study, XμCT made it possible to visualize and quantify the spatial xylem organization of the angiosperm species Fraxinus excelsior L. on the microscopic level. Through image analysis, it was possible to determine morphological characteristics of the cellular axial tissue (vessel elements, fibers, and axial parenchyma cells) three-dimensionally. X-ray imaging at high resolutions provides very distinct visual insight into the xylem structure. Numerical analyses performed through semi-automatic procedures made it possible to quickly quantify cell characteristics (length, diameter, and volume of cells). Use of various spatial resolutions (0.87-5 μm) revealed boundaries users should be aware of. Nevertheless, our findings, both qualitative and quantitative, demonstrate XμCT to be a valuable tool for studying the spatial cell morphology of F. excelsior. Copyright © 2018. Published by Elsevier Ltd.

Bionic Nanosystems

NASA Astrophysics Data System (ADS)

Sebastian Mannoor, Manu

Direct multidimensional integration of functional electronics and mechanical elements with viable biological systems could allow for the creation of bionic systems and devices possessing unique and advanced capabilities. For example, the ability to three dimensionally integrate functional electronic and mechanical components with biological cells and tissue could enable the creation of bionic systems that can have tremendous impact in regenerative medicine, prosthetics, and human-machine interfaces. However, as a consequence of the inherent dichotomy in material properties and limitations of conventional fabrication methods, the attainment of truly seamless integration of electronic and/or mechanical components with biological systems has been challenging. Nanomaterials engineering offers a general route for overcoming these dichotomies, primarily due to the existence of a dimensional compatibility between fundamental biological functional units and abiotic nanomaterial building blocks. One area of compelling interest for bionic systems is in the field of biomedical sensing, where the direct interfacing of nanosensors onto biological tissue or the human body could stimulate exciting opportunities such as on-body health quality monitoring and adaptive threat detection. Further, interfacing of antimicrobial peptide based bioselective probes onto the bionic nanosensors could offer abilities to detect pathogenic bacteria with bio-inspired selectivity. Most compellingly, when paired with additive manufacturing techniques such as 3D printing, these characteristics enable three dimensional integration and merging of a variety of functional materials including electronic, structural and biomaterials with viable biological cells, in the precise anatomic geometries of human organs, to form three dimensionally integrated, multi-functional bionic hybrids and cyborg devices with unique capabilities. In this thesis, we illustrate these approaches using three representative bionic systems: 1) Bionic Nanosensors: featuring bio-integrated graphene nanosensors for ubiquitous sensing, 2) Bionic Organs: featuring 3D printed bionic ears with three dimensionally integrated electronics and 3) Bionic Leaves: describing ongoing work in the direction of the creation of a bionic leaf enabled by the integration of plant derived photosynthetic functional units with electronic materials and components into a leaf-shaped hierarchical structure for harvesting photosynthetic bioelectricity.

Chondrogenic induction of mesenchymal stromal/stem cells from Wharton's jelly embedded in alginate hydrogel and without added growth factor: an alternative stem cell source for cartilage tissue engineering.

PubMed

Reppel, Loïc; Schiavi, Jessica; Charif, Naceur; Leger, Léonore; Yu, Hao; Pinzano, Astrid; Henrionnet, Christel; Stoltz, Jean-François; Bensoussan, Danièle; Huselstein, Céline

2015-12-30

Due to their intrinsic properties, stem cells are promising tools for new developments in tissue engineering and particularly for cartilage tissue regeneration. Although mesenchymal stromal/stem cells from bone marrow (BM-MSC) have long been the most used stem cell source in cartilage tissue engineering, they have certain limits. Thanks to their properties such as low immunogenicity and particularly chondrogenic differentiation potential, mesenchymal stromal/stem cells from Wharton's jelly (WJ-MSC) promise to be an interesting source of MSC for cartilage tissue engineering. In this study, we propose to evaluate chondrogenic potential of WJ-MSC embedded in alginate/hyaluronic acid hydrogel over 28 days. Hydrogels were constructed by the original spraying method. Our main objective was to evaluate chondrogenic differentiation of WJ-MSC on three-dimensional scaffolds, without adding growth factors, at transcript and protein levels. We compared the results to those obtained from standard BM-MSC. After 3 days of culture, WJ-MSC seemed to be adapted to their new three-dimensional environment without any detectable damage. From day 14 and up to 28 days, the proportion of WJ-MSC CD73(+), CD90(+), CD105(+) and CD166(+) decreased significantly compared to monolayer marker expression. Moreover, WJ-MSC and BM-MSC showed different phenotype profiles. After 28 days of scaffold culture, our results showed strong upregulation of cartilage-specific transcript expression. WJ-MSC exhibited greater type II collagen synthesis than BM-MSC at both transcript and protein levels. Furthermore, our work highlighted a relevant result showing that WJ-MSC expressed Runx2 and type X collagen at lower levels than BM-MSC. Once seeded in the hydrogel scaffold, WJ-MSC and BM-MSC have different profiles of chondrogenic differentiation at both the phenotypic level and matrix synthesis. After 4 weeks, WJ-MSC, embedded in a three-dimensional environment, were able to adapt to their environment and express specific cartilage-related genes and matrix proteins. Today, WJ-MSC represent a real alternative source of stem cells for cartilage tissue engineering.

Multiscale modelling of palisade formation in gliobastoma multiforme.

PubMed

Caiazzo, Alfonso; Ramis-Conde, Ignacio

2015-10-21

Palisades are characteristic tissue aberrations that arise in glioblastomas. Observation of palisades is considered as a clinical indicator of the transition from a noninvasive to an invasive tumour. In this paper we propose a computational model to study the influence of the hypoxic switch in palisade formation. For this we produced three-dimensional realistic simulations, based on a multiscale hybrid model, coupling the evolution of tumour cells and the oxygen diffusion in tissue, that depict the shape of palisades during its formation. Our results can be summarized as follows: (1) the presented simulations can provide clinicians and biologists with a better understanding of three-dimensional structure of palisades as well as of glioblastomas growth dynamics; (2) we show that heterogeneity in cell response to hypoxia is a relevant factor in palisade and pseudopalisade formation; (3) we show how selective processes based on the hypoxia switch influence the tumour proliferation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Clinical application of three-dimensional printing technology in craniofacial plastic surgery.

PubMed

Choi, Jong Woo; Kim, Namkug

2015-05-01

Three-dimensional (3D) printing has been particularly widely adopted in medical fields. Application of the 3D printing technique has even been extended to bio-cell printing for 3D tissue/organ development, the creation of scaffolds for tissue engineering, and actual clinical application for various medical parts. Of various medical fields, craniofacial plastic surgery is one of areas that pioneered the use of the 3D printing concept. Rapid prototype technology was introduced in the 1990s to medicine via computer-aided design, computer-aided manufacturing. To investigate the current status of 3D printing technology and its clinical application, a systematic review of the literature was conducted. In addition, the benefits and possibilities of the clinical application of 3D printing in craniofacial surgery are reviewed, based on personal experiences with more than 500 craniofacial cases conducted using 3D printing tactile prototype models.

Solving the forward problem of magnetoacoustic tomography with magnetic induction by means of the finite element method

NASA Astrophysics Data System (ADS)

Li, Xun; Li, Xu; Zhu, Shanan; He, Bin

2009-05-01

Magnetoacoustic tomography with magnetic induction (MAT-MI) is a recently proposed imaging modality to image the electrical impedance of biological tissue. It combines the good contrast of electrical impedance tomography with the high spatial resolution of sonography. In this paper, a three-dimensional MAT-MI forward problem was investigated using the finite element method (FEM). The corresponding FEM formulae describing the forward problem are introduced. In the finite element analysis, magnetic induction in an object with conductivity values close to biological tissues was first carried out. The stimulating magnetic field was simulated as that generated from a three-dimensional coil. The corresponding acoustic source and field were then simulated. Computer simulation studies were conducted using both concentric and eccentric spherical conductivity models with different geometric specifications. In addition, the grid size for finite element analysis was evaluated for the model calibration and evaluation of the corresponding acoustic field.

Clinical Application of Three-Dimensional Printing Technology in Craniofacial Plastic Surgery

PubMed Central

Kim, Namkug

2015-01-01

Three-dimensional (3D) printing has been particularly widely adopted in medical fields. Application of the 3D printing technique has even been extended to bio-cell printing for 3D tissue/organ development, the creation of scaffolds for tissue engineering, and actual clinical application for various medical parts. Of various medical fields, craniofacial plastic surgery is one of areas that pioneered the use of the 3D printing concept. Rapid prototype technology was introduced in the 1990s to medicine via computer-aided design, computer-aided manufacturing. To investigate the current status of 3D printing technology and its clinical application, a systematic review of the literature was conducted. In addition, the benefits and possibilities of the clinical application of 3D printing in craniofacial surgery are reviewed, based on personal experiences with more than 500 craniofacial cases conducted using 3D printing tactile prototype models. PMID:26015880

Image processing and 3D visualization in forensic pathologic examination

NASA Astrophysics Data System (ADS)

Oliver, William R.; Altschuler, Bruce R.

1996-02-01

The use of image processing is becoming increasingly important in the evaluation of violent crime. While much work has been done in the use of these techniques for forensic purposes outside of forensic pathology, its use in the pathologic examination of wounding has been limited. We are investigating the use of image processing and three-dimensional visualization in the analysis of patterned injuries and tissue damage. While image processing will never replace classical understanding and interpretation of how injuries develop and evolve, it can be a useful tool in helping an observer notice features in an image, may help provide correlation of surface to deep tissue injury, and provide a mechanism for the development of a metric for analyzing how likely it may be that a given object may have caused a given wound. We are also exploring methods of acquiring three-dimensional data for such measurements, which is the subject of a second paper.

Hydrogel-Tissue Chemistry: Principles and Applications.

PubMed

Gradinaru, Viviana; Treweek, Jennifer; Overton, Kristin; Deisseroth, Karl

2018-05-20

Over the past five years, a rapidly developing experimental approach has enabled high-resolution and high-content information retrieval from intact multicellular animal (metazoan) systems. New chemical and physical forms are created in the hydrogel-tissue chemistry process, and the retention and retrieval of crucial phenotypic information regarding constituent cells and molecules (and their joint interrelationships) are thereby enabled. For example, rich data sets defining both single-cell-resolution gene expression and single-cell-resolution activity during behavior can now be collected while still preserving information on three-dimensional positioning and/or brain-wide wiring of those very same neurons-even within vertebrate brains. This new approach and its variants, as applied to neuroscience, are beginning to illuminate the fundamental cellular and chemical representations of sensation, cognition, and action. More generally, reimagining metazoans as metareactants-or positionally defined three-dimensional graphs of constituent chemicals made available for ongoing functionalization, transformation, and readout-is stimulating innovation across biology and medicine.

Paleo-tribology: development of wear measurement techniques and a three-dimensional model revealing how grinding dentitions self-wear to enable functionality

NASA Astrophysics Data System (ADS)

Erickson, Gregory M.; Sidebottom, Mark A.; Curry, John F.; Kay, David Ian; Kuhn-Hendricks, Stephen; Norell, Mark A.; Sawyer, W. Gregory; Krick, Brandon A.

2016-06-01

In most mammals and a rare few reptilian lineages the evolution of precise dental occlusion led to the capacity to form functional chewing surfaces due to pressures generated while feeding. The complex dental architectures of such teeth and the biomechanics of their self-wearing nature are poorly understood. Our research team composed of paleontologists, evolutionary biologists, and engineers have developed a protocol to: (1) determine the histological make-up of grinding dentitions in extant and fossil taxa; (2) ascertain wear-relevant material properties of the tissues; (3) determine how those properties relate to inter-tissue-biomechanics leading the dental functionality using a three-dimensional Archard’s wear model developed specifically for dental applications; (4) analyze those data in phylogenetic contexts to infer evolutionary patterns as they relate to feeding. Finally we discuss industrial applications that are emerging from our paleontologically-inspired research.

Solving the Forward Problem of Magnetoacoustic Tomography with Magnetic Induction by Means of the Finite Element Method

PubMed Central

Li, Xun; Li, Xu; Zhu, Shanan; He, Bin

2010-01-01

Magnetoacoustic Tomography with Magnetic Induction (MAT-MI) is a recently proposed imaging modality to image the electrical impedance of biological tissue. It combines the good contrast of electrical impedance tomography with the high spatial resolution of sonography. In this paper, three-dimensional MAT-MI forward problem was investigated using the finite element method (FEM). The corresponding FEM formulas describing the forward problem are introduced. In the finite element analysis, magnetic induction in an object with conductivity values close to biological tissues was first carried out. The stimulating magnetic field was simulated as that generated from a three-dimensional coil. The corresponding acoustic source and field were then simulated. Computer simulation studies were conducted using both concentric and eccentric spherical conductivity models with different geometric specifications. In addition, the grid size for finite element analysis was evaluated for model calibration and evaluation of the corresponding acoustic field. PMID:19351978

Embryonic stem cells in scaffold-free three-dimensional cell culture: osteogenic differentiation and bone generation.

PubMed

Handschel, Jörg; Naujoks, Christian; Depprich, Rita; Lammers, Lydia; Kübler, Norbert; Meyer, Ulrich; Wiesmann, Hans-Peter

2011-07-14

Extracorporeal formation of mineralized bone-like tissue is still an unsolved challenge in tissue engineering. Embryonic stem cells may open up new therapeutic options for the future and should be an interesting model for the analysis of fetal organogenesis. Here we describe a technique for culturing embryonic stem cells (ESCs) in the absence of artificial scaffolds which generated mineralized miromasses. Embryonic stem cells were harvested and osteogenic differentiation was stimulated by the addition of dexamethasone, ascorbic acid, and ß-glycerolphosphate (DAG). After three days of cultivation microspheres were formed. These spherical three-dimensional cell units showed a peripheral zone consisting of densely packed cell layers surrounded by minerals that were embedded in the extracellular matrix. Alizarine red staining confirmed evidence of mineralization after 10 days of DAG stimulation in the stimulated but not in the control group. Transmission electron microscopy demonstrated scorching crystallites and collagenous fibrils as early indication of bone formation. These extracellular structures resembled hydroxyl apatite-like crystals as demonstrated by distinct diffraction patterns using electron diffraction analysis. The micromass culture technique is an appropriate model to form three-dimensional bone-like micro-units without the need for an underlying scaffold. Further studies will have to show whether the technique is applicable also to pluripotent stem cells of different origin. © 2011 Handschel et al; licensee BioMed Central Ltd.

Electromechanical vortex filaments during cardiac fibrillation

NASA Astrophysics Data System (ADS)

Christoph, J.; Chebbok, M.; Richter, C.; Schröder-Schetelig, J.; Bittihn, P.; Stein, S.; Uzelac, I.; Fenton, F. H.; Hasenfuß, G.; Gilmour, R. F., Jr.; Luther, S.

2018-03-01

The self-organized dynamics of vortex-like rotating waves, which are also known as scroll waves, are the basis of the formation of complex spatiotemporal patterns in many excitable chemical and biological systems. In the heart, filament-like phase singularities that are associated with three-dimensional scroll waves are considered to be the organizing centres of life-threatening cardiac arrhythmias. The mechanisms that underlie the onset, maintenance and control of electromechanical turbulence in the heart are inherently three-dimensional phenomena. However, it has not previously been possible to visualize the three-dimensional spatiotemporal dynamics of scroll waves inside cardiac tissues. Here we show that three-dimensional mechanical scroll waves and filament-like phase singularities can be observed deep inside the contracting heart wall using high-resolution four-dimensional ultrasound-based strain imaging. We found that mechanical phase singularities co-exist with electrical phase singularities during cardiac fibrillation. We investigated the dynamics of electrical and mechanical phase singularities by simultaneously measuring the membrane potential, intracellular calcium concentration and mechanical contractions of the heart. We show that cardiac fibrillation can be characterized using the three-dimensional spatiotemporal dynamics of mechanical phase singularities, which arise inside the fibrillating contracting ventricular wall. We demonstrate that electrical and mechanical phase singularities show complex interactions and we characterize their dynamics in terms of trajectories, topological charge and lifetime. We anticipate that our findings will provide novel perspectives for non-invasive diagnostic imaging and therapeutic applications.

A new technique for calculating individual dermal fibroblast contractile forces generated within collagen-GAG scaffolds.

PubMed

Harley, Brendan A; Freyman, Toby M; Wong, Matthew Q; Gibson, Lorna J

2007-10-15

Cell-mediated contraction plays a critical role in many physiological and pathological processes, notably organized contraction during wound healing. Implantation of an appropriately formulated (i.e., mean pore size, chemical composition, degradation rate) three-dimensional scaffold into an in vivo wound site effectively blocks the majority of organized wound contraction and results in induced regeneration rather than scar formation. Improved understanding of cell contraction within three-dimensional constructs therefore represents an important area of study in tissue engineering. Studies of cell contraction within three-dimensional constructs typically calculate an average contractile force from the gross deformation of a macroscopic substrate by a large cell population. In this study, cellular solids theory has been applied to conventional column buckling relationships to quantify the magnitude of individual cell contraction events within a three-dimensional, collagen-glycosaminoglycan scaffold. This new technique can be used for studying cell mechanics with a wide variety of porous scaffolds that resemble low-density, open-cell foams. It extends previous methods for analyzing cell buckling of two-dimensional substrates to three-dimensional constructs. From data available in the literature, the mean contractile force (Fc) generated by individual dermal fibroblasts within the collagen-glycosaminoglycan scaffold was calculated to range between 11 and 41 nN (Fc=26+/-13 nN, mean+/-SD), with an upper bound of cell contractility estimated at 450 nN.

Introducing 3-Dimensional Printing of a Human Anatomic Pathology Specimen: Potential Benefits for Undergraduate and Postgraduate Education and Anatomic Pathology Practice.

PubMed

Mahmoud, Amr; Bennett, Michael

2015-08-01

Three-dimensional (3D) printing, a rapidly advancing technology, is widely applied in fields such as mechanical engineering and architecture. Three-dimensional printing has been introduced recently into medical practice in areas such as reconstructive surgery, as well as in clinical research. Three-dimensionally printed models of anatomic and autopsy pathology specimens can be used for demonstrating pathology entities to undergraduate medical, dental, and biomedical students, as well as for postgraduate training in examination of gross specimens for anatomic pathology residents and pathology assistants, aiding clinicopathological correlation at multidisciplinary team meetings, and guiding reconstructive surgical procedures. To apply 3D printing in anatomic pathology for teaching, training, and clinical correlation purposes. Multicolored 3D printing of human anatomic pathology specimens was achieved using a ZCorp 510 3D printer (3D Systems, Rock Hill, South Carolina) following creation of a 3D model using Autodesk 123D Catch software (Autodesk, Inc, San Francisco, California). Three-dimensionally printed models of anatomic pathology specimens created included pancreatoduodenectomy (Whipple operation) and radical nephrectomy specimens. The models accurately depicted the topographic anatomy of selected specimens and illustrated the anatomic relation of excised lesions to adjacent normal tissues. Three-dimensional printing of human anatomic pathology specimens is achievable. Advances in 3D printing technology may further improve the quality of 3D printable anatomic pathology specimens.

Three-dimensional graphene foam as a biocompatible and conductive scaffold for neural stem cells

PubMed Central

Li, Ning; Zhang, Qi; Gao, Song; Song, Qin; Huang, Rong; Wang, Long; Liu, Liwei; Dai, Jianwu; Tang, Mingliang; Cheng, Guosheng

2013-01-01

Neural stem cell (NSC) based therapy provides a promising approach for neural regeneration. For the success of NSC clinical application, a scaffold is required to provide three-dimensional (3D) cell growth microenvironments and appropriate synergistic cell guidance cues. Here, we report the first utilization of graphene foam, a 3D porous structure, as a novel scaffold for NSCs in vitro. It was found that three-dimensional graphene foams (3D-GFs) can not only support NSC growth, but also keep cell at an active proliferation state with upregulation of Ki67 expression than that of two-dimensional graphene films. Meanwhile, phenotypic analysis indicated that 3D-GFs can enhance the NSC differentiation towards astrocytes and especially neurons. Furthermore, a good electrical coupling of 3D-GFs with differentiated NSCs for efficient electrical stimulation was observed. Our findings implicate 3D-GFs could offer a powerful platform for NSC research, neural tissue engineering and neural prostheses. PMID:23549373

Use of Interim Scaffolding and Neotissue Development to Produce a Scaffold-Free Living Hyaline Cartilage Graft.

PubMed

Lau, Ting Ting; Leong, Wenyan; Peck, Yvonne; Su, Kai; Wang, Dong-An

2015-01-01

The fabrication of three-dimensional (3D) constructs relies heavily on the use of biomaterial-based scaffolds. These are required as mechanical supports as well as to translate two-dimensional cultures to 3D cultures for clinical applications. Regardless of the choice of scaffold, timely degradation of scaffolds is difficult to achieve and undegraded scaffold material can lead to interference in further tissue development or morphogenesis. In cartilage tissue engineering, hydrogel is the highly preferred scaffold material as it shares many similar characteristics with native cartilaginous matrix. Hence, we employed gelatin microspheres as porogens to create a microcavitary alginate hydrogel as an interim scaffold to facilitate initial chondrocyte 3D culture and to establish a final scaffold-free living hyaline cartilaginous graft (LhCG) for cartilage tissue engineering.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Quinn, Heather; Wirthlin, Michael

A variety of fault emulation systems have been created to study the effect of single-event effects (SEEs) in static random access memory (SRAM) based field-programmable gate arrays (FPGAs). These systems are useful for augmenting radiation-hardness assurance (RHA) methodologies for verifying the effectiveness for mitigation techniques; understanding error signatures and failure modes in FPGAs; and failure rate estimation. For radiation effects researchers, it is important that these systems properly emulate how SEEs manifest in FPGAs. If the fault emulation systems does not mimic the radiation environment, the system will generate erroneous data and incorrect predictions of behavior of the FPGA inmore » a radiation environment. Validation determines whether the emulated faults are reasonable analogs to the radiation-induced faults. In this study we present methods for validating fault emulation systems and provide several examples of validated FPGA fault emulation systems.« less

Emulation as an Integrating Principle for Cognition

PubMed Central

Colder, Brian

2011-01-01

Emulations, defined as ongoing internal representations of potential actions and the futures those actions are expected to produce, play a critical role in directing human bodily activities. Studies of gross motor behavior, perception, allocation of attention, response to errors, interoception, and homeostatic activities, and higher cognitive reasoning suggest that the proper execution of all these functions relies on emulations. Further evidence supports the notion that reinforcement learning in humans is aimed at updating emulations, and that action selection occurs via the advancement of preferred emulations toward realization of their action and environmental prediction. Emulations are hypothesized to exist as distributed active networks of neurons in cortical and sub-cortical structures. This manuscript ties together previously unrelated theories of the role of prediction in different aspects of human information processing to create an integrated framework for cognition. PMID:21660288

Acellular Mouse Kidney ECM can be Used as a Three-Dimensional Substrate to Test the Differentiation Potential of Embryonic Stem Cell Derived Renal Progenitors.

PubMed

Sambi, Manpreet; Chow, Theresa; Whiteley, Jennifer; Li, Mira; Chua, Shawn; Raileanu, Vanessa; Rogers, Ian M

2017-08-01

The development of strategies for tissue regeneration and bio-artificial organ development is based on our understanding of embryogenesis. Differentiation protocols attempt to recapitulate the signaling modalities of gastrulation and organogenesis, coupled with cell selection regimens to isolate the cells of choice. This strategy is impeded by the lack of optimal in vitro culture systems since traditional culture systems do not allow for the three-dimensional interaction between cells and the extracellular matrix. While artificial three-dimensional scaffolds are available, using the natural extracellular matrix scaffold is advantageous because it has a distinct architecture that is difficult to replicate. The adult extracellular matrix is predicted to mediate signaling related to tissue repair not embryogenesis but existing similarities between the two argues that the extracellular matrix will influence the differentiation of stem and progenitor cells. Previous studies using undifferentiated embryonic stem cells grown directly on acellular kidney ECM demonstrated that the acellular kidney supported cell growth but limited differentiation occurred. Using mouse kidney extracellular matrix and mouse embryonic stem cells we report that the extracellular matrix can support the development of kidney structures if the stem cells are first differentiated to kidney progenitor cells before being applied to the acellular organ.

Clinical evaluation of final impressions from three-dimensional printed custom trays.

PubMed

Sun, Yuchun; Chen, Hu; Li, Hong; Deng, Kehui; Zhao, Tian; Wang, Yong; Zhou, Yongsheng

2017-11-02

This study aimed to evaluate the quality of the final impressions taken by three-dimensional printed custom trays for edentulous patients. Custom trays were designed with or without saddle-shaped tissue stops and fabricated by three-dimensional printing techniques. Manually made trays with photocurable materials were produced as controls. Both 3D printed custom trays and manually made ones were used to take impressions from edentulous patients. After 3D scanning of the final impression, the impression materials were removed, thus the underneath tray surfaces were able to be scanned, allowing the thickness of the impression materials to be measured. Final impressions obtained by pre-border-molded 3D printed trays were scanned as references, to which the flange extension deviations and morphology deviations of the impressions taken by both 3D printed trays and manually made ones were calculated. The results showed that (1) impressions from 3D printed custom trays had better thickness distribution than that of manually made ones; (2) impression morphology deviations in non-marginal area were neither statistic different between 3D printed trays and manually made trays, nor between trays with and without tissue stops; and (3) final impressions taken by custom trays without pre-border-molding were tended to have insufficient flange extensions.

Quantitative characterization of 3D deformations of cell interactions with soft biomaterials

NASA Astrophysics Data System (ADS)

Franck, Christian

In recent years, the importance of mechanical forces in directing cellular function has been recognized as a significant factor in biological and physiological processes. In fact, these physical forces are now viewed equally as important as biochemical stimuli in controlling cellular response. Not only do these cellular forces, or cell tractions, play an important role in cell migration, they are also significant to many other physiological and pathological processes, both at the tissue and organ level, including wound healing, inflammation, angiogenesis, and embryogenesis. A complete quantification of cell tractions during cell-material interactions can lead to a deeper understanding of the fundamental role these forces play in cell biology. Thus, understanding the function and role of a cell from a mechanical framework can have important implications towards the development of new implant materials and drug treatments. Previous research has contributed significant descriptions of cell-tissue interactions by quantifying cell tractions in two-dimensional environments; however, most physiological processes are three-dimensional in nature. Recent studies have shown morphological differences in cells cultured on two-dimensional substrates versus three-dimensional matrices, and that the intrinsic extracellular matrix interactions and migration behavior are different in three dimensions versus two dimensions. Hence, measurement techniques are needed to investigate cellular behavior in all three dimensions. This thesis presents a full-field imaging technique capable of quantitatively measuring cell traction forces in all three spatial dimensions, and hence addresses the need of a three-dimensional quantitative imaging technique to gain insight into the fundamental role of physical forces in biological processes. The technique combines laser scanning confocal microscopy (LSCM) with digital volume correlation (DVC) to track the motion of fluorescent particles during cell-induced or externally applied deformations. This method is validated by comparing experimentally measured non-uniform deformation fields near hard and soft spherical inclusions under uniaxial compression with the corresponding analytical solution. Utilization of a newly developed computationally efficient stretch-correlation and deconvolution algorithm is shown to improve the overall measurement accuracy, in particular under large deformations. Using this technique, the full three-dimensional substrate displacement fields are experimentally determined during the migration of individual fibroblast cells on polyacrylamide gels. This is the first study to show the highly three-dimensional structure of cell-induced displacement and traction fields. These new findings suggest a three-dimensional push-pull cell motility, which differs from the traditional theories based on two-dimensional data. These results provide new insight into the dynamic cell-matrix force exchange or mechanotransduction of migrating cells, and will aid in the development of new three-dimensional cell motility and adhesion models. As this study reveals, the mechanical interactions of cells and their extracellular matrix appear to be highly three-dimensional. It also shows that the LSCM-DVC technique is well suited for investigating the mechanics of cell-matrix interactions while providing a platform to access detailed information of the intricate biomechanical coupling for many cellular responses. Thus, this method has the capability to provide direct quantitative experimental data showing how cells interact with their surroundings in three dimensions and might stimulate new avenues of scientific thought in understanding the fundamental role physical forces play in regulating cell behavior.

Multi-photon microfabrication of three-dimensional capillary-scale vascular networks

NASA Astrophysics Data System (ADS)

Skylar-Scott, Mark A.; Liu, Man-Chi; Wu, Yuelong; Yanik, Mehmet Fatih

2017-02-01

Biomimetic models of microvasculature could enable assays of complex cellular behavior at the capillary-level, and enable efficient nutrient perfusion for the maintenance of tissues. However, existing three-dimensional printing methods for generating perfusable microvasculature with have insufficient resolution to recapitulate the microscale geometry of capillaries. Here, we present a collection of multiphoton microfabrication methods that enable the production of precise, three-dimensional, branched microvascular networks in collagen. When endothelial cells are added to the channels, they form perfusable lumens with diameters as small as 10 μm. Using a similar photochemistry, we also demonstrate the micropatterning of proteins embedded in microfabricated collagen scaffolds, producing hybrid scaffolds with both defined microarchitecture with integrated gradients of chemical cues. We provide examples for how these hybrid microfabricated scaffolds could be used in angiogenesis and cell homing assays. Finally, we describe a new method for increasing the micropatterning speed by synchronous laser and stage scanning. Using these technologies, we are working towards large-scale (>1 cm), high resolution ( 1 μm) scaffolds with both microarchitecture and embedded protein cues, with applications in three-dimensional assays of cellular behavior.

Demonstration of emulator-based Bayesian calibration of safety analysis codes: Theory and formulation

DOE PAGES

Yurko, Joseph P.; Buongiorno, Jacopo; Youngblood, Robert

2015-05-28

System codes for simulation of safety performance of nuclear plants may contain parameters whose values are not known very accurately. New information from tests or operating experience is incorporated into safety codes by a process known as calibration, which reduces uncertainty in the output of the code and thereby improves its support for decision-making. The work reported here implements several improvements on classic calibration techniques afforded by modern analysis techniques. The key innovation has come from development of code surrogate model (or code emulator) construction and prediction algorithms. Use of a fast emulator makes the calibration processes used here withmore » Markov Chain Monte Carlo (MCMC) sampling feasible. This study uses Gaussian Process (GP) based emulators, which have been used previously to emulate computer codes in the nuclear field. The present work describes the formulation of an emulator that incorporates GPs into a factor analysis-type or pattern recognition-type model. This “function factorization” Gaussian Process (FFGP) model allows overcoming limitations present in standard GP emulators, thereby improving both accuracy and speed of the emulator-based calibration process. Calibration of a friction-factor example using a Method of Manufactured Solution is performed to illustrate key properties of the FFGP based process.« less

Real-time emulation of neural images in the outer retinal circuit.

PubMed

Hasegawa, Jun; Yagi, Tetsuya

2008-12-01

We describe a novel real-time system that emulates the architecture and functionality of the vertebrate retina. This system reconstructs the neural images formed by the retinal neurons in real time by using a combination of analog and digital systems consisting of a neuromorphic silicon retina chip, a field-programmable gate array, and a digital computer. While the silicon retina carries out the spatial filtering of input images instantaneously, using the embedded resistive networks that emulate the receptive field structure of the outer retinal neurons, the digital computer carries out the temporal filtering of the spatially filtered images to emulate the dynamical properties of the outer retinal circuits. The emulations of the neural image, including 128 x 128 bipolar cells, are carried out at a frame rate of 62.5 Hz. The emulation of the response to the Hermann grid and a spot of light and an annulus of lights has demonstrated that the system responds as expected by previous physiological and psychophysical observations. Furthermore, the emulated dynamics of neural images in response to natural scenes revealed the complex nature of retinal neuron activity. We have concluded that the system reflects the spatiotemporal responses of bipolar cells in the vertebrate retina. The proposed emulation system is expected to aid in understanding the visual computation in the retina and the brain.

Basic physics and doubts about relationship between mammographically determined tissue density and breast cancer risk.

PubMed

Kopans, Daniel B

2008-02-01

Numerous studies have suggested a link between breast tissue patterns, as defined with mammography, and risk for breast cancer. There may be a relationship, but the author believes all of these studies have methodological flaws. It is impossible, with the parameters used in these studies, to accurately measure the percentage of tissues by volume when two-dimensional x-ray mammographic images are used. Without exposure values, half-value layer information, and knowledge of the compressed thickness of the breast, an accurate volume of tissue cannot be calculated. The great variability in positioning the breast for a mammogram is also an uncontrollable factor in measuring tissue density. Computerized segmentation algorithms can accurately assess the percentage of the x-ray image that is "dense," but this does not accurately measure the true volume of tissue. Since the percentage of dense tissue is ultimately measured in relation to the complete volume of the breast, defining the true boundaries of the breast is also a problem. Studies that purport to show small percentage differences between groups are likely inaccurate. Future investigations need to use three-dimensional information. (c) RSNA, 2008.

Production of zebrafish cardiospheres and cardiac progenitor cells in vitro and three-dimensional culture of adult zebrafish cardiac tissue in scaffolds.

PubMed

Zeng, Wendy R; Beh, Siew-Joo; Bryson-Richardson, Robert J; Doran, Pauline M

2017-09-01

The hearts of adult zebrafish (Danio rerio) are capable of complete regeneration in vivo even after major injury, making this species of particular interest for understanding the growth and differentiation processes required for cardiac tissue engineering. To date, little research has been carried out on in vitro culture of adult zebrafish cardiac cells. In this work, progenitor-rich cardiospheres suitable for cardiomyocyte differentiation and myocardial regeneration were produced from adult zebrafish hearts. The cardiospheres contained a mixed population of c-kit + and Mef2c + cells; proliferative peripheral cells of possible mesenchymal lineage were also observed. Cellular outgrowth from cardiac explants and cardiospheres was enhanced significantly using conditioned medium harvested from cultures of a rainbow trout cell line, suggesting that fish-specific trophic factors are required for zebrafish cardiac cell expansion. Three-dimensional culture of zebrafish heart cells in fibrous polyglycolic acid (PGA) scaffolds was carried out under dynamic fluid flow conditions. High levels of cell viability and cardiomyocyte differentiation were maintained within the scaffolds. Expression of cardiac troponin T, a marker of differentiated cardiomyocytes, increased during the first 7 days of scaffold culture; after 15 days, premature disintegration of the biodegradable scaffolds led to cell detachment and a decline in differentiation status. This work expands our technical capabilities for three-dimensional zebrafish cardiac cell culture with potential applications in tissue engineering, drug and toxicology screening, and ontogeny research. Biotechnol. Bioeng. 2017;114: 2142-2148. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Hardware and Software Integration to Support Real-Time Space Link Emulation

NASA Technical Reports Server (NTRS)

Murawski, Robert; Bhasin, Kul; Bittner, David; Sweet, Aaron; Coulter, Rachel; Schwab, Devin

2012-01-01

Prior to operational use, communications hardware and software must be thoroughly tested and verified. In space-link communications, field testing equipment can be prohibitively expensive and cannot test to non-ideal situations. In this paper, we show how software and hardware emulation tools can be used to accurately model the characteristics of a satellite communication channel in a lab environment. We describe some of the challenges associated with developing an emulation lab and present results to demonstrate the channel modeling. We then show how network emulation software can be used to extend a hardware emulation model without requiring additional network and channel simulation hardware.

Hardware and Software Integration to Support Real-Time Space-Link Emulation

NASA Technical Reports Server (NTRS)

Murawski, Robert; Bhasin, Kul; Bittner, David

2012-01-01

Prior to operational use, communications hardware and software must be thoroughly tested and verified. In space-link communications, field testing equipment can be prohibitively expensive and cannot test to non-ideal situations. In this paper, we show how software and hardware emulation tools can be used to accurately model the characteristics of a satellite communication channel in a lab environment. We describe some of the challenges associated with developing an emulation lab and present results to demonstrate the channel modeling. We then show how network emulation software can be used to extend a hardware emulation model without requiring additional network and channel simulation hardware.

A k-space method for large-scale models of wave propagation in tissue.

PubMed

Mast, T D; Souriau, L P; Liu, D L; Tabei, M; Nachman, A I; Waag, R C

2001-03-01

Large-scale simulation of ultrasonic pulse propagation in inhomogeneous tissue is important for the study of ultrasound-tissue interaction as well as for development of new imaging methods. Typical scales of interest span hundreds of wavelengths; most current two-dimensional methods, such as finite-difference and finite-element methods, are unable to compute propagation on this scale with the efficiency needed for imaging studies. Furthermore, for most available methods of simulating ultrasonic propagation, large-scale, three-dimensional computations of ultrasonic scattering are infeasible. Some of these difficulties have been overcome by previous pseudospectral and k-space methods, which allow substantial portions of the necessary computations to be executed using fast Fourier transforms. This paper presents a simplified derivation of the k-space method for a medium of variable sound speed and density; the derivation clearly shows the relationship of this k-space method to both past k-space methods and pseudospectral methods. In the present method, the spatial differential equations are solved by a simple Fourier transform method, and temporal iteration is performed using a k-t space propagator. The temporal iteration procedure is shown to be exact for homogeneous media, unconditionally stable for "slow" (c(x) < or = c0) media, and highly accurate for general weakly scattering media. The applicability of the k-space method to large-scale soft tissue modeling is shown by simulating two-dimensional propagation of an incident plane wave through several tissue-mimicking cylinders as well as a model chest wall cross section. A three-dimensional implementation of the k-space method is also employed for the example problem of propagation through a tissue-mimicking sphere. Numerical results indicate that the k-space method is accurate for large-scale soft tissue computations with much greater efficiency than that of an analogous leapfrog pseudospectral method or a 2-4 finite difference time-domain method. However, numerical results also indicate that the k-space method is less accurate than the finite-difference method for a high contrast scatterer with bone-like properties, although qualitative results can still be obtained by the k-space method with high efficiency. Possible extensions to the method, including representation of absorption effects, absorbing boundary conditions, elastic-wave propagation, and acoustic nonlinearity, are discussed.

High-contrast fast Fourier transform acousto-optical tomography of phantom tissues with a frequency-chirp modulation of the ultrasound.

PubMed

Forget, Benoît-Claude; Ramaz, François; Atlan, Michaël; Selb, Juliette; Boccara, Albert-Claude

2003-03-01

We report new results on acousto-optical tomography in phantom tissues using a frequency chirp modulation and a CCD camera. This technique allows quick recording of three-dimensional images of the optical contrast with a two-dimensional scan of the ultrasound source in a plane perpendicular to the ultrasonic path. The entire optical contrast along the ultrasonic path is concurrently obtained from the capture of a film sequence at a rate of 200 Hz. This technique reduces the acquisition time, and it enhances the axial resolution and thus the contrast, which are usually poor owing to the large volume of interaction of the ultrasound perturbation.

Medical Research System

NASA Technical Reports Server (NTRS)

1993-01-01

Based on Johnson Space Flight Center's development of a rotating bioreactor cell culture apparatus for Space Shuttle medical research, Johnson Space Flight Center engineers who worked on the original project formed a company called Synthecon, with the intention of commercializing the bioreactor technology. Synthecon grows three dimensional tissues in the bioreactor. These are superior to previous two-dimensional tissue samples in the study of human cell growth. A refined version of the Johnson Space Center technology, Synthecon's Rotary Cell Culture System includes a cell culture chamber that rotates around a horizontal axis. The cells establish an orbit that approximates free fall through the liquid medium in the chamber. The technology has significant applications for cancer research and treatment as well as AIDS research.

Three-Dimensional Organotypic Co-Culture Model of Intestinal Epithelial Cells and Macrophages to Study "Salmonella Enterica" Colonization Patterns

NASA Technical Reports Server (NTRS)

Ott, Mark; Yang, J; Barilla, J.; Crabbe, A.; Sarker, S. F.; Liu, Y.

2017-01-01

Three-dimensional/3-D organotypic models of human intestinal epithelium mimic the differentiated form and function of parental tissues often not exhibited by 2-D monolayers and respond to Salmonella in ways that reflect in vivo infections. To further enhance the physiological relevance of 3-D models to more closely approximate in vivo intestinal microenvironments during infection, we developed and validated a novel 3-D intestinal co-culture model containing multiple epithelial cell types and phagocytic macrophages, and applied to study enteric infection by different Salmonella pathovars.

Cell culture for three-dimensional modeling in rotating-wall vessels: an application of simulated microgravity

NASA Technical Reports Server (NTRS)

Schwarz, R. P.; Goodwin, T. J.; Wolf, D. A.

1992-01-01

High-density, three-dimensional cell cultures are difficult to grow in vitro. The rotating-wall vessel (RWV) described here has cultured BHK-21 cells to a density of 1.1 X 10(7) cells/ml. Cells on microcarriers were observed to grow with enhanced bridging in this batch culture system. The RWV is a horizontally rotated tissue culture vessel with silicon membrane oxygenation. This design results in a low-turbulence, low-shear cell culture environment with abundant oxygenation. The RWV has the potential to culture a wide variety of normal and neoplastic cells.

Thermal Analysis of the PediaFlow pediatric ventricular assist device.

PubMed

Gardiner, Jeffrey M; Wu, Jingchun; Noh, Myounggyu D; Antaki, James F; Snyder, Trevor A; Paden, David B; Paden, Brad E

2007-01-01

Accurate modeling of heat dissipation in pediatric intracorporeal devices is crucial in avoiding tissue and blood thermotrauma. Thermal models of new Maglev ventricular assist device (VAD) concepts for the PediaFlow VAD are developed by incorporating empirical heat transfer equations with thermal finite element analysis (FEA). The models assume three main sources of waste heat generation: copper motor windings, active magnetic thrust bearing windings, and eddy currents generated within the titanium housing due to the two-pole motor. Waste heat leaves the pump by convection into blood passing through the pump and conduction through surrounding tissue. Coefficients of convection are calculated and assigned locally along fluid path surfaces of the three-dimensional pump housing model. FEA thermal analysis yields a three-dimensional temperature distribution for each of the three candidate pump models. Thermal impedances from the motor and thrust bearing windings to tissue and blood contacting surfaces are estimated based on maximum temperature rise at respective surfaces. A new updated model for the chosen pump topology is created incorporating computational fluid dynamics with empirical fluid and heat transfer equations. This model represents the final geometry of the first generation prototype, incorporates eddy current heating, and has 60 discrete convection regions. Thermal analysis is performed at nominal and maximum flow rates, and temperature distributions are plotted. Results suggest that the pump will not exceed a temperature rise of 2 degrees C during normal operation.

Grating interferometry-based phase microtomography of atherosclerotic human arteries

NASA Astrophysics Data System (ADS)

Buscema, Marzia; Holme, Margaret N.; Deyhle, Hans; Schulz, Georg; Schmitz, Rüdiger; Thalmann, Peter; Hieber, Simone E.; Chicherova, Natalia; Cattin, Philippe C.; Beckmann, Felix; Herzen, Julia; Weitkamp, Timm; Saxer, Till; Müller, Bert

2014-09-01

Cardiovascular diseases are the number one cause of death and morbidity in the world. Understanding disease development in terms of lumen morphology and tissue composition of constricted arteries is essential to improve treatment and patient outcome. X-ray tomography provides non-destructive three-dimensional data with micrometer-resolution. However, a common problem is simultaneous visualization of soft and hard tissue-containing specimens, such as atherosclerotic human coronary arteries. Unlike absorption based techniques, where X-ray absorption strongly depends on atomic number and tissue density, phase contrast methods such as grating interferometry have significant advantages as the phase shift is only a linear function of the atomic number. We demonstrate that grating interferometry-based phase tomography is a powerful method to three-dimensionally visualize a variety of anatomical features in atherosclerotic human coronary arteries, including plaque, muscle, fat, and connective tissue. Three formalin-fixed, human coronary arteries were measured using advanced laboratory μCT. While this technique gives information about plaque morphology, it is impossible to extract the lumen morphology. Therefore, selected regions were measured using grating based phase tomography, sinograms were treated with a wavelet-Fourier filter to remove ring artifacts, and reconstructed data were processed to allow extraction of vessel lumen morphology. Phase tomography data in combination with conventional laboratory μCT data of the same specimen shows potential, through use of a joint histogram, to identify more tissue types than either technique alone. Such phase tomography data was also rigidly registered to subsequently decalcified arteries that were histologically sectioned, although the quality of registration was insufficient for joint histogram analysis.

Engineering three dimensional micro nerve tissue using postnatal stem cells from human dental apical papilla.

PubMed

Kim, Byung-Chul; Jun, Sung-Min; Kim, So Yeon; Kwon, Yong-Dae; Choe, Sung Chul; Kim, Eun-Chul; Lee, Jae-Hyung; Kim, Jinseok; Suh, Jun-Kyo Francis; Hwang, Yu-Shik

2017-04-01

The in vitro generation of cell-based three dimensional (3D) nerve tissue is an attractive subject to improve graft survival and integration into host tissue for neural tissue regeneration or to model biological events in stem cell differentiation. Although 3D organotypic culture strategies are well established for 3D nerve tissue formation of pluripotent stem cells to study underlying biology in nerve development, cell-based nerve tissues have not been developed using human postnatal stem cells with therapeutic potential. Here, we established a culture strategy for the generation of in vitro cell-based 3D nerve tissue from postnatal stem cells from apical papilla (SCAPs) of teeth, which originate from neural crest-derived ectomesenchyme cells. A stem cell population capable of differentiating into neural cell lineages was generated during the ex vivo expansion of SCAPs in the presence of EGF and bFGF, and SCAPs differentiated into neural cells, showing neural cell lineage-related molecular and gene expression profiles, morphological changes and electrophysical property under neural-inductive culture conditions. Moreover, we showed the first evidence that 3D cell-based nerve-like tissue with axons and myelin structures could be generated from SCAPs via 3D organotypic culture using an integrated bioprocess composed of polyethylene glycol (PEG) microwell-mediated cell spheroid formation and subsequent dynamic culture in a high aspect ratio vessel (HARV) bioreactor. In conclusion, the culture strategy in our study provides a novel approach to develop in vitro engineered nerve tissue using SCAPs and a foundation to study biological events in the neural differentiation of postnatal stem cells. Biotechnol. Bioeng. 2017;114: 903-914. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Three-Dimensional Scaffolds for Tissue Engineering Applications: Role of Porosity and Pore Size

PubMed Central

Loh, Qiu Li

2013-01-01

Tissue engineering applications commonly encompass the use of three-dimensional (3D) scaffolds to provide a suitable microenvironment for the incorporation of cells or growth factors to regenerate damaged tissues or organs. These scaffolds serve to mimic the actual in vivo microenvironment where cells interact and behave according to the mechanical cues obtained from the surrounding 3D environment. Hence, the material properties of the scaffolds are vital in determining cellular response and fate. These 3D scaffolds are generally highly porous with interconnected pore networks to facilitate nutrient and oxygen diffusion and waste removal. This review focuses on the various fabrication techniques (e.g., conventional and rapid prototyping methods) that have been employed to fabricate 3D scaffolds of different pore sizes and porosity. The different pore size and porosity measurement methods will also be discussed. Scaffolds with graded porosity have also been studied for their ability to better represent the actual in vivo situation where cells are exposed to layers of different tissues with varying properties. In addition, the ability of pore size and porosity of scaffolds to direct cellular responses and alter the mechanical properties of scaffolds will be reviewed, followed by a look at nature's own scaffold, the extracellular matrix. Overall, the limitations of current scaffold fabrication approaches for tissue engineering applications and some novel and promising alternatives will be highlighted. PMID:23672709

Development of an Indirect Stereolithography Technology for Scaffold Fabrication with a Wide Range of Biomaterial Selectivity

PubMed Central

Kang, Hyun-Wook

2012-01-01

Tissue engineering, which is the study of generating biological substitutes to restore or replace tissues or organs, has the potential to meet current needs for organ transplantation and medical interventions. Various approaches have been attempted to apply three-dimensional (3D) solid freeform fabrication technologies to tissue engineering for scaffold fabrication. Among these, the stereolithography (SL) technology not only has the highest resolution, but also offers quick fabrication. However, a lack of suitable biomaterials is a barrier to applying the SL technology to tissue engineering. In this study, an indirect SL method that combines the SL technology and a sacrificial molding process was developed to address this challenge. A sacrificial mold with an inverse porous shape was fabricated from an alkali-soluble photopolymer by the SL technology. A sacrificial molding process was then developed for scaffold construction using a variety of biomaterials. The results indicated a wide range of biomaterial selectivity and a high resolution. Achievable minimum pore and strut sizes were as large as 50 and 65 μm, respectively. This technology can also be used to fabricate three-dimensional organ shapes, and combined with traditional fabrication methods to construct a new type of scaffold with a dual-pore size. Cytotoxicity tests, as well as nuclear magnetic resonance and gel permeation chromatography analyses, showed that this technology has great potential for tissue engineering applications. PMID:22443315

Conception et mise au point d'un emulateur de machine Synchrone trapezoidale a aimants permanents

NASA Astrophysics Data System (ADS)

Lessard, Francois

The development of technology leads inevitably to higher systems' complexity faced by engineers. Over time, tools are often developed in parallel with the main systems to ensure their sustainability. The work presented in this document provides a new tool for testing motor drives. In general, this project refers to active loads, which are complex dynamic loads emulated electronically with a static converter. Specifically, this document proposes and implements a system whose purpose is to recreate the behaviour of a trapezoidal permanent magnets synchronous machine. The ultimate goal is to connect a motor drive to the three terminal of the motor emulator, as it would with a real motor. The emulator's response then obtained, when subjected to disturbances of the motor drive, is ideally identical to the one of a real motor. The motor emulator led to a significant versatility of a test bench because the electrical and mechanical parameters of the application can be easily modified. The work is divided into two main parts: the static converter and real-rime. Overall, these two entities form a PHIL (Power Hardware-in-the-loop) real-time simulation. The static converter enables the exchange of real power between the drive motor and the real-time simulation. The latter gives the application the intelligence needed to interact with the motor drive in a way which the desired behaviour is recreated. The main partner of this project, Opal-RT, ensures this development. Keywords: virtual machine, PHIL, real-time simulation, electronic load

Rapid fabrication of detachable three-dimensional tissues by layering of cell sheets with heating centrifuge.

PubMed

Haraguchi, Yuji; Kagawa, Yuki; Hasegawa, Akiyuki; Kubo, Hirotsugu; Shimizu, Tatsuya

2018-01-18

Confluent cultured cells on a temperature-responsive culture dish can be harvested as an intact cell sheet by decreasing temperature below 32°C. A three-dimensional (3-D) tissue can be fabricated by the layering of cell sheets. A resulting 3-D multilayered cell sheet-tissue on a temperature-responsive culture dish can be also harvested without any damage by only temperature decreasing. For shortening the fabrication time of the 3-D multilayered constructs, we attempted to layer cell sheets on a temperature-responsive culture dish with centrifugation. However, when a cell sheet was attached to the culture surface with a conventional centrifuge at 22-23°C, the cell sheet hardly adhere to the surface due to its noncell adhesiveness. Therefore, in this study, we have developed a heating centrifuge. In centrifugation (55g) at 36-37°C, the cell sheet adhered tightly within 5 min to the dish without significant cell damage. Additionally, centrifugation accelerated the cell sheet-layering process. The heating centrifugation shortened the fabrication time by one-fifth compared to a multilayer tissue fabrication without centrifugation. Furthermore, the multilayered constructs were finally detached from the dishes by decreasing temperature. This rapid tissue-fabrication method will be used as a valuable tool in the field of tissue engineering and regenerative therapy. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 2018. © 2018 American Institute of Chemical Engineers.

Dynamic 3D culture promotes spontaneous embryonic stem cell differentiation in vitro.

PubMed

Gerlach, Jörg C; Hout, Mariah; Edsbagge, Josefina; Björquist, Petter; Lübberstedt, Marc; Miki, Toshio; Stachelscheid, Harald; Schmelzer, Eva; Schatten, Gerald; Zeilinger, Katrin

2010-02-01

Spontaneous in vitro differentiation of mouse embryonic stem cells (mESC) is promoted by a dynamic, three-dimensional (3D), tissue-density perfusion technique with continuous medium perfusion and exchange in a novel four-compartment, interwoven capillary bioreactor. We compared ectodermal, endodermal, and mesodermal immunoreactive tissue structures formed by mESC at culture day 10 with mouse fetal tissue development at gestational day E9.5. The results show that the bioreactor cultures more closely resemble mouse fetal tissue development at gestational day E9.5 than control mESC cultured in Petri dishes.

3D bio-printing technology for body tissues and organs regeneration.

PubMed

Biazar, Esmaeil; Najafi S, Masoumeh; Heidari K, Saeed; Yazdankhah, Meysam; Rafiei, Ataollah; Biazar, Dariush

2018-04-01

In the last decade, the use of new technologies in the reconstruction of body tissues has greatly developed. Utilising stem cell technology, nanotechnology and scaffolding design has created new opportunities in tissue regeneration. The use of accurate engineering design in the creation of scaffolds, including 3D printers, has been widely considered. Three-dimensional printers, especially high precision bio-printers, have opened up a new way in the design of 3D tissue engineering scaffolds. In this article, a review of the latest applications of this technology in this promising area has been addressed.

Digital avionics design and reliability analyzer

NASA Technical Reports Server (NTRS)

1981-01-01

The description and specifications for a digital avionics design and reliability analyzer are given. Its basic function is to provide for the simulation and emulation of the various fault-tolerant digital avionic computer designs that are developed. It has been established that hardware emulation at the gate-level will be utilized. The primary benefit of emulation to reliability analysis is the fact that it provides the capability to model a system at a very detailed level. Emulation allows the direct insertion of faults into the system, rather than waiting for actual hardware failures to occur. This allows for controlled and accelerated testing of system reaction to hardware failures. There is a trade study which leads to the decision to specify a two-machine system, including an emulation computer connected to a general-purpose computer. There is also an evaluation of potential computers to serve as the emulation computer.

Diagnostic emulation: Implementation and user's guide

NASA Technical Reports Server (NTRS)

Becher, Bernice

1987-01-01

The Diagnostic Emulation Technique was developed within the System Validation Methods Branch as a part of the development of methods for the analysis of the reliability of highly reliable, fault tolerant digital avionics systems. This is a general technique which allows for the emulation of a digital hardware system. The technique is general in the sense that it is completely independent of the particular target hardware which is being emulated. Parts of the system are described and emulated at the logic or gate level, while other parts of the system are described and emulated at the functional level. This algorithm allows for the insertion of faults into the system, and for the observation of the response of the system to these faults. This allows for controlled and accelerated testing of system reaction to hardware failures in the target machine. This document describes in detail how the algorithm was implemented at NASA Langley Research Center and gives instructions for using the system.

Space Communications Emulation Facility

NASA Technical Reports Server (NTRS)

Hill, Chante A.

2004-01-01

Establishing space communication between ground facilities and other satellites is a painstaking task that requires many precise calculations dealing with relay time, atmospheric conditions, and satellite positions, to name a few. The Space Communications Emulation Facility (SCEF) team here at NASA is developing a facility that will approximately emulate the conditions in space that impact space communication. The emulation facility is comprised of a 32 node distributed cluster of computers; each node representing a satellite or ground station. The objective of the satellites is to observe the topography of the Earth (water, vegetation, land, and ice) and relay this information back to the ground stations. Software originally designed by the University of Kansas, labeled the Emulation Manager, controls the interaction of the satellites and ground stations, as well as handling the recording of data. The Emulation Manager is installed on a Linux Operating System, employing both Java and C++ programming codes. The emulation scenarios are written in extensible Markup Language, XML. XML documents are designed to store, carry, and exchange data. With XML documents data can be exchanged between incompatible systems, which makes it ideal for this project because Linux, MAC and Windows Operating Systems are all used. Unfortunately, XML documents cannot display data like HTML documents. Therefore, the SCEF team uses XML Schema Definition (XSD) or just schema to describe the structure of an XML document. Schemas are very important because they have the capability to validate the correctness of data, define restrictions on data, define data formats, and convert data between different data types, among other things. At this time, in order for the Emulation Manager to open and run an XML emulation scenario file, the user must first establish a link between the schema file and the directory under which the XML scenario files are saved. This procedure takes place on the command line on the Linux Operating System. Once this link has been established the Emulation manager validates all the XML files in that directory against the schema file, before the actual scenario is run. Using some very sophisticated commercial software called the Satellite Tool Kit (STK) installed on the Linux box, the Emulation Manager is able to display the data and graphics generated by the execution of a XML emulation scenario file. The Emulation Manager software is written in JAVA programming code. Since the SCEF project is in the developmental stage, the source code for this type of software is being modified to better fit the requirements of the SCEF project. Some parameters for the emulation are hard coded, set at fixed values. Members of the SCEF team are altering the code to allow the user to choose the values of these hard coded parameters by inserting a toolbar onto the preexisting GUI.

Embryoid bodies formation and differentiation from mouse embryonic stem cells in collagen/Matrigel scaffolds.

PubMed

Zhou, Jin; Zhang, Ye; Lin, Qiuxia; Liu, Zhiqiang; Wang, Haibin; Duan, Cuimi; Wang, Yanmeng; Hao, Tong; Wu, Kuiwu; Wang, Changyong

2010-07-01

Embryonic stem (ES) cells have the potential to develop into any type of tissue and are considered as a promising source of seeding cells for tissue engineering and transplantation therapy. The main catalyst for ES cells differentiation is the growth into embryoid bodies (EBs), which are utilized widely as the trigger of in vitro differentiation. In this study, a novel method for generating EBs from mouse ES cells through culture in collagen/Matrigel scaffolds was successfully established. When single ES cells were seeded in three dimensional collagen/Matrigel scaffolds, they grew into aggregates gradually and formed simple EBs with circular structures. After 7 days' culture, they formed into cystic EBs that would eventually differentiate into the three embryonic germ layers. Evaluation of the EBs in terms of morphology and potential to differentiate indicated that they were typical in structure and could generate various cell types; they were also able to form into tissue-like structures. Moreover, with introduction of ascorbic acid, ES cells differentiated into cardiomyocytes efficiently and started contracting synchronously at day 19. The results demonstrated that collagen/Matrigel scaffolds supported EBs formation and their subsequent differentiation in a single three dimensional environment. Copyright 2010 Institute of Genetics and Developmental Biology and the Genetics Society of China. Published by Elsevier Ltd. All rights reserved.

Organoids as Models for Neoplastic Transformation | Office of Cancer Genomics

Cancer.gov

Cancer models strive to recapitulate the incredible diversity inherent in human tumors. A key challenge in accurate tumor modeling lies in capturing the panoply of homo- and heterotypic cellular interactions within the context of a three-dimensional tissue microenvironment. To address this challenge, researchers have developed organotypic cancer models (organoids) that combine the 3D architecture of in vivo tissues with the experimental facility of 2D cell lines.