scholarly journals A Computational Model of Bidirectional Axonal Growth in Micro-Tissue Engineered Neuronal Networks (micro-TENNs)

2018 ◽  
Author(s):  
Toma Marinov ◽  
Liang Yuchi ◽  
Dayo O. Adewole ◽  
D. Kacy Cullen ◽  
Reuben H. Kraft
Keyword(s):  
White Matter ◽  
Computational Model ◽  
Large Scale ◽  
Three Dimensional ◽  
Growth Conditions ◽  
Growth Time ◽  
Directional Growth ◽  
System Reconstruction ◽  
Realistic Neuron

AbstractMicro-Tissue Engineered Neural Networks (Micro-TENNs) are living three-dimensional constructs designed to replicate the neuroanatomy of white matter pathways in the brain, and are being developed as implantable microtissue for axon tract reconstruction or as anatomically-relevant in vitro experimental platforms. Micro-TENNs are composed of discrete neuronal aggregates connected by bundles of long-projecting axonal tracts within miniature tubular hydrogels. In order to help design and optimize micro-TENN performance, we have created a new computational model including geometric and functional properties. The model is built upon the three-dimensional diffusion equation and incorporates large-scale uni- and bi-directional growth that simulates realistic neuron morphologies. The model captures unique features of 3D axonal tract development that are not apparent in planar outgrowth, and may be insightful for how white matter pathways form during brain development. The processes of axonal outgrowth, branching, turning and aggregation/bundling from each neuron are described through functions built on concentration equations and growth time distributed across the growth segments. Once developed we conducted multiple parametric studies to explore the applicability of the method and conducted preliminary validation via comparisons to experimentally grown micro-TENNs for a range of growth conditions. Using this framework, this model can be applied to study micro-TENN growth processes and functional characteristics using spiking network or compartmental network modeling. This model may be applied to improve our understanding of axonal tract development and functionality, as well as to optimize the fabrication of implantable tissue engineered brain pathways for nervous system reconstruction and/or modulation.

scholarly journals Modelling human skull growth: a validated computational model

2017 ◽  
Vol 14 (130) ◽  
pp. 20170202 ◽  
Author(s):  
Joseph Libby ◽  
Arsalan Marghoub ◽  
David Johnson ◽  
Roman H. Khonsari ◽  
Michael J. Fagan ◽  
...  
Keyword(s):  
Computational Model ◽  
Three Dimensional ◽  
Basic Knowledge ◽  
Fe Model ◽  
Adult Size ◽  
Fe Method ◽  
Percentage Difference ◽  
Skull Growth

During the first year of life, the brain grows rapidly and the neurocranium increases to about 65% of its adult size. Our understanding of the relationship between the biomechanical forces, especially from the growing brain, the craniofacial soft tissue structures and the individual bone plates of the skull vault is still limited. This basic knowledge could help in the future planning of craniofacial surgical operations. The aim of this study was to develop a validated computational model of skull growth, based on the finite-element (FE) method, to help understand the biomechanics of skull growth. To do this, a two-step validation study was carried out. First, an in vitro physical three-dimensional printed model and an in silico FE model were created from the same micro-CT scan of an infant skull and loaded with forces from the growing brain from zero to two months of age. The results from the in vitro model validated the FE model before it was further developed to expand from 0 to 12 months of age. This second FE model was compared directly with in vivo clinical CT scans of infants without craniofacial conditions ( n = 56). The various models were compared in terms of predicted skull width, length and circumference, while the overall shape was quantified using three-dimensional distance plots. Statistical analysis yielded no significant differences between the male skull models. All size measurements from the FE model versus the in vitro physical model were within 5%, with one exception showing a 7.6% difference. The FE model and in vivo data also correlated well, with the largest percentage difference in size being 8.3%. Overall, the FE model results matched well with both the in vitro and in vivo data. With further development and model refinement, this modelling method could be used to assist in preoperative planning of craniofacial surgery procedures and could help to reduce reoperation rates.

scholarly journals Seismic performance analysis and assessment of a precast bridge computational model

DYNA ◽  
2020 ◽  
Vol 87 (212) ◽  
pp. 80-89
Author(s):  
José Benjumea ◽  
Mehdi Saiidi ◽  
Ahmad Itani
Keyword(s):  
Performance Analysis ◽  
Computational Model ◽  
Seismic Performance ◽  
Earthquake Engineering ◽  
Large Scale ◽  
Three Dimensional ◽  
Shake Table ◽  
Bridge Model ◽  
Precast Elements ◽  
The University

A large-scale, two-span bridge model constructed by assembling precast elements was tested under a series of bi-axial ground motionssimulated on a shake table at the Earthquake Engineering Laboratory at the University of Nevada, Reno. The response of the bridge wasestimated before the tests using a three-dimensional computational model developed in OpenSees software. After the tests, key measuredseismic responses were compared to those predicted by the computational model to assess the modeling assumptions. Relatively largeerrors for the displacements, base shears, and hysteretic response of the bridge were observed. The influence of the earthquake loading,materials, connectivity of the precast elements, and boundary conditions in the computational model on the errors are discussed in thispaper. Future modeling directions are proposed to reduce these errors.

scholarly journals Impedance-based cellular assays for regenerative medicine

2018 ◽  
Vol 373 (1750) ◽  
pp. 20170226 ◽  
Author(s):  
W. Gamal ◽  
H. Wu ◽  
I. Underwood ◽  
J. Jia ◽  
S. Smith ◽  
...  
Keyword(s):  
Stem Cell ◽  
Regenerative Medicine ◽  
Large Scale ◽  
Three Dimensional ◽  
Cell Renewal ◽  
Label Free ◽  
Impedance Tomography ◽  
Cellular Assays ◽  
Automation And Control

Therapies based on regenerative techniques have the potential to radically improve healthcare in the coming years. As a result, there is an emerging need for non-destructive and label-free technologies to assess the quality of engineered tissues and cell-based products prior to their use in the clinic. In parallel, the emerging regenerative medicine industry that aims to produce stem cells and their progeny on a large scale will benefit from moving away from existing destructive biochemical assays towards data-driven automation and control at the industrial scale. Impedance-based cellular assays (IBCA) have emerged as an alternative approach to study stem-cell properties and cumulative studies, reviewed here, have shown their potential to monitor stem-cell renewal, differentiation and maturation. They offer a novel method to non-destructively assess and quality-control stem-cell cultures. In addition, when combined with in vitro disease models they provide complementary insights as label-free phenotypic assays. IBCA provide quantitative and very sensitive results that can easily be automated and up-scaled in multi-well format. When facing the emerging challenge of real-time monitoring of three-dimensional cell culture dielectric spectroscopy and electrical impedance tomography represent viable alternatives to two-dimensional impedance sensing. This article is part of the theme issue ‘Designer human tissue: coming to a lab near you’.

scholarly journals C-STEM: ENGINEERING NICHE-LIKE MICRO-COMPARTMENTS FOR OPTIMAL AND SCALE-INDEPENDENT EXPANSION OF HUMAN PLURIPOTENT STEM CELLS IN BIOREACTORS

2021 ◽  
Author(s):  
Philippe J.R. Cohen ◽  
Elisa Luquet ◽  
Justine Pletenka ◽  
Andrea Leonard ◽  
Elise Warter ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Large Scale ◽  
Scale Up ◽  
Three Dimensional ◽  
Culture Conditions ◽  
Human Pluripotent Stem Cells ◽  
Cell Therapies ◽  
Cellular Source

Human pluripotent stem cells (hPSCs) have emerged as the most promising cellular source for cell therapies. To overcome scale up limitations of classical 2D culture systems, suspension cultures have been developed to meet the need of large-scale culture in regenerative medicine. Despite constant improvements, current protocols relying on the generation of micro-carriers or cell aggregates only achieve moderate amplification performance. Here, guided by reports showing that hPSCs can self-organize in vitro into cysts reminiscent of the epiblast stage in embryo development, we developed a physio-mimetic approach for hPSC culture. We engineered stem cell niche microenvironments inside microfluidics-assisted core-shell microcapsules. We demonstrate that lumenized three-dimensional colonies maximize viability and expansion rates while maintaining pluripotency. By optimizing capsule size and culture conditions, we scale-up this method to industrial scale stirred tank bioreactors and achieve an unprecedented hPSC amplification rate of 282-fold in 6.5 days.

scholarly journals Altered swelling and ion fluxes in articular cartilage as a biomarker in osteoarthritis and joint immobilization: a computational analysis

2015 ◽  
Vol 12 (102) ◽  
pp. 20141090 ◽  
Author(s):  
Sara Manzano ◽  
Raquel Manzano ◽  
Manuel Doblaré ◽  
Mohamed Hamdy Doweidar
Keyword(s):  
Articular Cartilage ◽  
Computational Model ◽  
Three Dimensional ◽  
Ion Distribution ◽  
Tissue Degeneration ◽  
Structural Deterioration ◽  
Healthy Cartilage ◽  
Tissue Degradation

In healthy cartilage, mechano-electrochemical phenomena act together to maintain tissue homeostasis. Osteoarthritis (OA) and degenerative diseases disrupt this biological equilibrium by causing structural deterioration and subsequent dysfunction of the tissue. Swelling and ion flux alteration as well as abnormal ion distribution are proposed as primary indicators of tissue degradation. In this paper, we present an extension of a previous three-dimensional computational model of the cartilage behaviour developed by the authors to simulate the contribution of the main tissue components in its behaviour. The model considers the mechano-electrochemical events as concurrent phenomena in a three-dimensional environment. This model has been extended here to include the effect of repulsion of negative charges attached to proteoglycans. Moreover, we have studied the fluctuation of these charges owning to proteoglycan variations in healthy and pathological articular cartilage. In this sense, standard patterns of healthy and degraded tissue behaviour can be obtained which could be a helpful diagnostic tool. By introducing measured properties of unhealthy cartilage into the computational model, the severity of tissue degeneration can be predicted avoiding complex tissue extraction and subsequent in vitro analysis. In this work, the model has been applied to monitor and analyse cartilage behaviour at different stages of OA and in both short (four, six and eight weeks) and long-term (11 weeks) fully immobilized joints. Simulation results showed marked differences in the corresponding swelling phenomena, in outgoing cation fluxes and in cation distributions. Furthermore, long-term immobilized patients display similar swelling as well as fluxes and distribution of cations to patients in the early stages of OA, thus, preventive treatments are highly recommended to avoid tissue deterioration.

Tubulogenesis from isolated single cells of adult mammalian kidney: clonal analysis with a recombinant retrovirus

1996 ◽  
Vol 271 (1) ◽  
pp. F42-F49 ◽  
Author(s):  
H. D. Humes ◽  
J. C. Krauss ◽  
D. A. Cieslinski ◽  
A. J. Funke
Keyword(s):  
Single Cells ◽  
Three Dimensional ◽  
High Capacity ◽  
Cell Lineage ◽  
Growth Conditions ◽  
Rabbit Kidney ◽  
Adult Rabbit ◽  
Collagen Gels ◽  
Mammalian Kidney

The adult mammalian kidney tubule epithelium exists in a relatively dormant, slowly replicative state but has a large potential for regenerative morphogenesis following severe ischemic or toxic injury. Under selective serum-free growth conditions, which included epidermal growth factor and retinoic acid, a subpopulation of renal proximal tubule cells isolated from adult rabbit kidney were grown in cell culture. These cells possessed two important characteristics: 1) an ability to differentiate morphogenically into tubule structures when grown in three-dimensional collagen gels and 2) a high capacity for self-renewal, since cell lineage analysis with a recombinant retrovirus demonstrated that in vitro tubulogenesis arose from clonal expansion of a single cell. Thus individual cells in the adult kidney have retained the ability for kidney tubulogenesis in vitro.

scholarly journals Storage of proliferating gooseberry cultures under slow growth conditions

2021 ◽  
Author(s):  
Danuta Kucharska ◽  
Robert Maciorowski ◽  
Małgorzata Kunka ◽  
Angelika Niewiadomska-Wnuk
Keyword(s):  
Large Scale ◽  
Slow Growth ◽  
Shoot Proliferation ◽  
Growth Conditions ◽  
Storage Conditions ◽  
In Vitro Cultures ◽  
Slowing Down ◽  
Growth Room

Short storage of in vitro cultures under slow-growth conditions is included in the commercial large-scale micropropagation process. It is dictated by the organizational scheme that provides temporary stop multiplication of shoots for some months. To avoid subculturing to fresh media every 4 weeks, which is obligatory for gooseberry, they can be kept in conditions that protect them from ageing, by slowing down their metabolism. To develop a rational schedule of gooseberry micropropagation, two experiments were used to adopt a temperature and length of time for storage. The best results were obtained with storage conditions at 2 °C for two or four months for proliferating cultures. Under these conditions, the percentage of necrotic shoots was low (< 10%), and shoot proliferation in the subsequent passages was at a level similar to proliferation cultures incubated in the growth room and sub-cultured monthly. The rate of shoots > 1 cm was higher than in the control in the growth room. Storage at 4 °C increased the probability of necrotic shoots up to 80% and decreased the number of all shoots and shoots > 1 cm in subsequent passages.

scholarly journals Bioengineering Approaches to Improve In Vitro Performance of Prepubertal Lamb Oocytes

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1458
Author(s):  
Antonella Mastrorocco ◽  
Ludovica Cacopardo ◽  
Daniela Lamanna ◽  
Letizia Temerario ◽  
Giacomina Brunetti ◽  
...  
Keyword(s):  
Oocyte Maturation ◽  
Large Scale ◽  
Type I Collagen ◽  
3D Structure ◽  
Three Dimensional ◽  
Basal Membrane ◽  
Type I ◽  
Animal Reproduction ◽  
Blastocyst Quality

Juvenile in vitro embryo technology (JIVET) provides exciting opportunities in animal reproduction by reducing the generation intervals. Prepubertal oocytes are also relevant models for studies on oncofertility. However, current JIVET efficiency is still unpredictable, and further improvements are needed in order for it to be used on a large-scale level. This study applied bioengineering approaches to recreate: (1) the three-dimensional (3D) structure of the cumulus–oocyte complex (COC), by constructing—via bioprinting technologies—alginate-based microbeads (COC-microbeads) for 3D in vitro maturation (3D-IVM); (2) dynamic IVM conditions, by culturing the COC in a millifluidic bioreactor; and (3) an artificial follicular wall with basal membrane, by adding granulosa cells (GCs) and type I collagen (CI) during bioprinting. The results show that oocyte nuclear and cytoplasmic maturation, as well as blastocyst quality, were improved after 3D-IVM compared to 2D controls. The dynamic 3D-IVM did not enhance oocyte maturation, but it improved oocyte bioenergetics compared with static 3D-IVM. The computational model showed higher oxygen levels in the bioreactor with respect to the static well. Microbead enrichment with GCs and CI improved oocyte maturation and bioenergetics. In conclusion, this study demonstrated that bioengineering approaches that mimic the physiological follicle structure could be valuable tools to improve IVM and JIVET.

scholarly journals Eigenstrain Boundary Integral Equations with Local Eshelby Matrix for Stress Analysis of Ellipsoidal Particles

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Hang Ma ◽  
Cheng Yan ◽  
Qing-hua Qin
Keyword(s):  
Numerical Simulation ◽  
Computational Model ◽  
Large Scale ◽  
High Efficiency ◽  
Boundary Integral Equations ◽  
Three Dimensional ◽  
Solution Procedure ◽  
Boundary Integral ◽  
Ellipsoidal Particles ◽  
Reinforced Materials

Aiming at the large scale numerical simulation of particle reinforced materials, the concept of local Eshelby matrix has been introduced into the computational model of the eigenstrain boundary integral equation (BIE) to solve the problem of interactions among particles. The local Eshelby matrix can be considered as an extension of the concepts of Eshelby tensor and the equivalent inclusion in numerical form. Taking the subdomain boundary element method as the control, three-dimensional stress analyses are carried out for some ellipsoidal particles in full space with the proposed computational model. Through the numerical examples, it is verified not only the correctness and feasibility but also the high efficiency of the present model with the corresponding solution procedure, showing the potential of solving the problem of large scale numerical simulation of particle reinforced materials.

Development of novel metastatic prostate cancer cell lines by “organoid” in vitro culture technology.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 33-33
Author(s):  
Ian Vela ◽  
Dong Gao ◽  
Anuradha Gopalan ◽  
Andrea Sboner ◽  
Eva Undvall ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Culture Media ◽  
Three Dimensional ◽  
Genomic Analysis ◽  
Growth Conditions ◽  
In Vitro Models ◽  
Culture Technique

33 Background: The inability to propagate patient-derived prostate cancer cells in vitro is a major impediment in the mechanistic understanding of tumorigenesis and therapeutic response. In order to generate accurate in vitro models that represent the diversity of in situ prostate cancer, we have developed a three-dimensional “organoid” system to culture metastasis samples and integrated it into our precision medicine workflow of attaining and characterizing pre-treatment biopsies. Methods: Biopsy samples of prostate cancer metastases, both soft tissue and bone, acquired at the time of therapeutic or diagnostic interventions following informed consent and institutional review board approval were obtained from two institutions. Samples were digested in Type II Collagenase (Gibco) and re-suspended in growth factor reduced Matrigel (BD), plated on plastic, and overlaid with prostate culture media (PCM). PCM consists of serum free Advanced DMEM/F12 (Gibco) with multiple growth factors optimized to propagate benign primary prostate cells. Cultures were maintained at 37°C in 5% CO2. Results: In the initial 51 samples, 15 continuous organoid cultures (29%) were established from distinct sites (9 of 32 bone, 6 of 19 soft). Tumor content of the biopsy represents a major determinant of organoid growth. Once established, organoids propagate indefinitely with different kinetics (approximately 48 hours to 1 week doubling time), and can be cryopreserved. Histological analysis shows that the organoids recapitulate the structure of the in situ cancer and genomic analysis using array CGH and whole-exome sequencing (WES) shows the presence of typical copy number alterations including TMPRSS2-ERG interstitial deletion, PTEN loss, CHD1 loss, and AR amplification. WES of two organoid/metastasis pairs shows that the growth conditions do not generate additional mutations. Conclusions: This novel tissue culture technique enables the development of new cell lines derived from metastatic deposits. This advance will facilitate research by availing new and varied cell lines, which will hopefully be more closely aligned to the spectrum of behavior of the clinical disease in comparison to the limited and problematic cell line models currently available.

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