736 research outputs found
Modeling the growth of multicellular cancer spheroids in a\ud bioengineered 3D microenvironment and their treatment with an\ud anti-cancer drug
A critical step in the dissemination of ovarian cancer cells is the formation of multicellular spheroids from cells shed from the primary tumor. The objectives of this study were to establish and validate bioengineered three-dimensional (3D) microenvironments for culturing ovarian cancer cells in vitro and simultaneously to develop computational models describing the growth of multicellular spheroids in these bioengineered matrices. Cancer cells derived from human epithelial ovarian carcinoma were embedded within biomimetic hydrogels of varying stiffness and cultured for up to 4 weeks. Immunohistochemistry was used to quantify the dependence of cell proliferation and apoptosis on matrix stiffness, long-term culture and treatment with the anti-cancer drug paclitaxel.\ud
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Two computational models were developed. In the first model, each spheroid was treated as an incompressible porous medium, whereas in the second model the concept of morphoelasticity was used to incorporate details about internal stresses and strains. Each model was formulated as a free boundary problem. Functional forms for cell proliferation and apoptosis motivated by the experimental work were applied and the predictions of both models compared with the output from the experiments. Both models simulated how the growth of cancer spheroids was influenced by mechanical and biochemical stimuli including matrix stiffness, culture time and treatment with paclitaxel. Our mathematical models provide new perspectives on previous experimental results and have informed the design of new 3D studies of multicellular cancer spheroids
Growth of confined cancer spheroids: a combined experimental and mathematical modelling approach
We have integrated a bioengineered three-dimensional platform by generating multicellular cancer spheroids in a controlled microenvironment with a mathematical model to investigate\ud
confined tumour growth and to model its impact on cellular processes
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Rapid Prototyping of 3D Scaffolds for Tissue Engineering Using a Four-Axis Multiple-Dispenser Robotic System
A desktop rapid prototyping (RP) system has been developed to fabricate scaffolds for tissue
engineering (TE) applications. The system is a computer-controlled four-axis machine with a
multiple-dispenser head. This paper presents the scaffold fabrication process to build free-form
scaffolds from relevant features extracted from given CT-scan images for TE applications. This
involves obtaining the required geometric data for the scaffold in the form of a solid model from
CT-scan images. The extracted scaffold model is then sliced into consecutive two-dimensional
(2D) layers to generate appropriately formatted data for the desktop RP system to fabricate the
scaffolds. The basic material processing involves the sequential dispensing of two or more
materials to form a strand. The four-axis system enables strands to be laid in a different direction
at each layer to form suitable interlacing 3D free-form scaffold structures. The multipledispenser head also allows the introduction of living cells and additional materials during the
scaffold building. The building of the scaffolds with the desktop RP system is described based on
the sequential dispensing of chitosan dissolved in acetic acid and sodium hydroxide solution.
Neutralization of the acetic acid by the sodium hydroxide results in a precipitate to form a gellike chitosan strand.Mechanical Engineerin
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Fungal community assembly in drought-stressed sorghum shows stochasticity, selection, and universal ecological dynamics.
Community assembly of crop-associated fungi is thought to be strongly influenced by deterministic selection exerted by the plant host, rather than stochastic processes. Here we use a simple, sorghum system with abundant sampling to show that stochastic forces (drift or stochastic dispersal) act on fungal community assembly in leaves and roots early in host development and when sorghum is drought stressed, conditions when mycobiomes are small. Unexpectedly, we find no signal for stochasticity when drought stress is relieved, likely due to renewed selection by the host. In our experimental system, the host compartment exerts the strongest effects on mycobiome assembly, followed by the timing of plant development and lastly by plant genotype. Using a dissimilarity-overlap approach, we find a universality in the forces of community assembly of the mycobiomes of the different sorghum compartments and in functional guilds of fungi
Biofabrication of customized bone grafts by combination of additive manufacturing and bioreactor knowhow
This study reports on an original concept of additive manufacturing for the fabrication of
tissue engineered constructs (TEC), offering the possibility of concomitantly manufacturing a
customized scaffold and a bioreactor chamber to any size and shape. As a proof of concept
towards the development of anatomically relevant TECs, this concept was utilized for the
design and fabrication of a highly porous sheep tibia scaffold around which a bioreactor
chamber of similar shape was simultaneously built. The morphology of the bioreactor/scaffold
device was investigated by micro-computed tomography and scanning electron microscopy
confirming the porous architecture of the sheep tibiae as opposed to the non-porous nature of
the bioreactor chamber. Additionally, this study demonstrates that both the shape, as well as
the inner architecture of the device can significantly impact the perfusion of fluid within the
scaffold architecture. Indeed, fluid flow modelling revealed that this was of significant
importance for controlling the nutrition flow pattern within the scaffold and the bioreactor
chamber, avoiding the formation of stagnant flow regions detrimental for in vitro tissue
development. The bioreactor/scaffold device was dynamically seeded with human primary
osteoblasts and cultured under bi-directional perfusion for two and six weeks. Primary human
osteoblasts were observed homogenously distributed throughout the scaffold, and were viable
for the six week culture period. This work demonstrates a novel application for additive
manufacturing in the development of scaffolds and bioreactors. Given the intrinsic flexibility
of the additive manufacturing technology platform developed, more complex culture systems
can be fabricated which would contribute to the advances in customized and patient-specific
tissue engineering strategies for a wide range of applications.This work was supported by the NHMRC, the Australian Research Council and Hans Fischer Senior Fellowship, IAS-TUM. Pedro Costa acknowledges the Portuguese Foundation for Science and Technology for his PhD grant (SFRH/BD/62452/2009)
Transcriptomic analysis of field-droughted sorghum from seedling to maturity reveals biotic and metabolic responses.
Drought is the most important environmental stress limiting crop yields. The C4 cereal sorghum [Sorghum bicolor (L.) Moench] is a critical food, forage, and emerging bioenergy crop that is notably drought-tolerant. We conducted a large-scale field experiment, imposing preflowering and postflowering drought stress on 2 genotypes of sorghum across a tightly resolved time series, from plant emergence to postanthesis, resulting in a dataset of nearly 400 transcriptomes. We observed a fast and global transcriptomic response in leaf and root tissues with clear temporal patterns, including modulation of well-known drought pathways. We also identified genotypic differences in core photosynthesis and reactive oxygen species scavenging pathways, highlighting possible mechanisms of drought tolerance and of the delayed senescence, characteristic of the stay-green phenotype. Finally, we discovered a large-scale depletion in the expression of genes critical to arbuscular mycorrhizal (AM) symbiosis, with a corresponding drop in AM fungal mass in the plants' roots
In vivo characterization of 3D-printed polycaprolactone-hydroxyapatite scaffolds with Voronoi design to advance the concept of scaffold-guided bone regeneration
Three-dimensional (3D)-printed medical-grade polycaprolactone (mPCL) composite scaffolds have been the first to enable the concept of scaffold-guided bone regeneration (SGBR) from bench to bedside. However, advances in 3D printing technologies now promise next-generation scaffolds such as those with Voronoi tessellation. We hypothesized that the combination of a Voronoi design, applied for the first time to 3D-printed mPCL and ceramic fillers (here hydroxyapatite, HA), would allow slow degradation and high osteogenicity needed to regenerate bone tissue and enhance regenerative properties when mixed with xenograft material. We tested this hypothesis in vitro and in vivo using 3D-printed composite mPCL-HA scaffolds (wt 96%:4%) with the Voronoi design using an ISO 13485 certified additive manufacturing platform. The resulting scaffold porosity was 73% and minimal in vitro degradation (mass loss <1%) was observed over the period of 6Â months. After loading the scaffolds with different types of fresh sheep xenograft and ectopic implantation in rats for 8Â weeks, highly vascularized tissue without extensive fibrous encapsulation was found in all mPCL-HA Voronoi scaffolds and endochondral bone formation was observed, with no adverse host-tissue reactions. This study supports the use of mPCL-HA Voronoi scaffolds for further testing in future large preclinical animal studies prior to clinical trials to ultimately successfully advance the SGBR concept
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