Development of perfusion bioreactor for whole organ engineering — a culture system that enhances cellular engraftment, survival and phenotype of repopulated pancreas

TECHNOLOGY ◽  
2018 ◽  
Vol 06 (03n04) ◽  
pp. 118-134
Author(s):  
Saik-Kia Goh ◽  
Suzanne Bertera ◽  
Vimal Vaidya ◽  
Sam Dumpe ◽  
Sierra Barner ◽  
...  

Whole organ engineering has emerged as a promising alternative avenue to fill the gap of donor organ shortage in organ transplantation. Recent breakthroughs in the decellularization of solid organs and repopulation with desired cell populations have generated neo-organ constructs with promising functional outcomes. The realization of this goal requires engineering advancement in the perfusion-based bioreactors to (i) efficiently deliver decellularization agents, followed by (ii) its reconstruction with relevant cell types and (iii) maintenance of viability and function of the repopulated organ. In this study, we report the development and assembly of a perfusion bioreactor with the potential to enable regenerative reconstruction of pancreas. The assembled bioreactor is versatile to efficiently decellularize multiple organs, as demonstrated by complete decellularization of pancreas, liver and heart in the same set-up. Further, the same system is amenable to support organ repopulation with diverse cell types. Using our in-house bioreactor system, we demonstrate pancreas repopulation with both immortalized MIN-6 beta cells and differentiating human pluripotent stem cells. Importantly, we show the significant advantage of perfusion culture over static culture in enhancing cell engraftment, viability and phenotypic maintenance of the repopulated pancreas. In addition, this study is a significant step forward for whole organ engineering as it will facilitate cost-effective and easy assembly of perfusion bioreactors to enable rapid advancement in regenerative organ reconstruction.

2017 ◽  
Vol 40 (4) ◽  
pp. 150-158 ◽  
Author(s):  
Michele Fedecostante ◽  
Oana G. Onciu ◽  
Koen G.C. Westphal ◽  
Rosalinde Masereeuw

Patients with end-stage renal disease often undergo dialysis as a partial substitute for kidney function while waiting for their only treatment option: a kidney transplant. Several research directions emerged for alternatives in support of the ever-growing numbers of patients. Recent years brought big steps forward in the field, with researchers questioning and improving the current dialysis devices as well as moving towards the design of a bioengineered kidney. Whole-organ engineering is also being explored as a possibility, making use of animal or human kidney scaffolds for engineering a transplantable organ. While this is not a new strategy, having been applied so far for thin tissues, it is a novel approach for complex organs such as the kidneys. Kidneys can be decellularized and the remaining scaffold consisting of an extracellular matrix can be repopulated with (autologous) cells, aiming at growing ex vivo a fully transplantable organ. In a broader view, such organs might also be used for a better understanding of fundamental biological concepts and disease mechanisms, drug screening and toxicological investigations, opening new pathways in the treatment of kidney disease. Decellularization of whole organs has been widely explored and described; therefore, this manuscript only briefly reviews some important considerations with an emphasis on scaffold decontamination, but focuses further on recellularization strategies. Critical aspects, including cell types and sources that can be used for recellularization, seeding strategies and possible applications beyond renal replacement are discussed.


2020 ◽  
Vol 10 (12) ◽  
pp. 4277
Author(s):  
Sogu Sohn ◽  
Maxwell Van Buskirk ◽  
Michael J. Buckenmeyer ◽  
Ricardo Londono ◽  
Denver Faulk

End-stage organ failure remains a leading cause of morbidity and mortality across the globe. The only curative treatment option currently available for patients diagnosed with end-stage organ failure is organ transplantation. However, due to a critical shortage of organs, only a fraction of these patients are able to receive a viable organ transplantation. Those patients fortunate enough to receive a transplant must then be subjected to a lifelong regimen of immunosuppressant drugs. The concept of whole organ engineering offers a promising alternative to organ transplantation that overcomes these limitations. Organ engineering is a discipline that merges developmental biology, anatomy, physiology, and cellular interactions with enabling technologies such as advanced biomaterials and biofabrication to create bioartificial organs that recapitulate native organs in vivo. There have been numerous developments in bioengineering of whole organs over the past two decades. Key technological advancements include (1) methods of whole organ decellularization and recellularization, (2) three-dimensional bioprinting, (3) advanced stem cell technologies, and (4) the ability to genetically modify tissues and cells. These advancements give hope that organ engineering will become a commercial reality in the next decade. In this review article, we describe the foundational principles of whole organ engineering, discuss key technological advances, and provide an overview of current limitations and future directions.


Author(s):  
Yan Pan ◽  
Shining Li ◽  
Qianwu Chen ◽  
Nan Zhang ◽  
Tao Cheng ◽  
...  

Stimulated by the dramatical service demand in the logistics industry, logistics trucks employed in last-mile parcel delivery bring critical public concerns, such as heavy cost burden, traffic congestion and air pollution. Unmanned Aerial Vehicles (UAVs) are a promising alternative tool in last-mile delivery, which is however limited by insufficient flight range and load capacity. This paper presents an innovative energy-limited logistics UAV schedule approach using crowdsourced buses. Specifically, when one UAV delivers a parcel, it first lands on a crowdsourced social bus to parcel destination, gets recharged by the wireless recharger deployed on the bus, and then flies from the bus to the parcel destination. This novel approach not only increases the delivery range and load capacity of battery-limited UAVs, but is also much more cost-effective and environment-friendly than traditional methods. New challenges therefore emerge as the buses with spatiotemporal mobility become the bottleneck during delivery. By landing on buses, an Energy-Neutral Flight Principle and a delivery scheduling algorithm are proposed for the UAVs. Using the Energy-Neutral Flight Principle, each UAV can plan a flying path without depleting energy given buses with uncertain velocities. Besides, the delivery scheduling algorithm optimizes the delivery time and number of delivered parcels given warehouse location, logistics UAVs, parcel locations and buses. Comprehensive evaluations using a large-scale bus dataset demonstrate the superiority of the innovative logistics UAV schedule approach.


Water ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 661
Author(s):  
Luigi Piazzi ◽  
Stefano Acunto ◽  
Francesca Frau ◽  
Fabrizio Atzori ◽  
Maria Francesca Cinti ◽  
...  

Seagrass planting techniques have shown to be an effective tool for restoring degraded meadows and ecosystem function. In the Mediterranean Sea, most restoration efforts have been addressed to the endemic seagrass Posidonia oceanica, but cost-benefit analyses have shown unpromising results. This study aimed at evaluating the effectiveness of environmental engineering techniques generally employed in terrestrial systems to restore the P. oceanica meadows: two different restoration efforts were considered, either exploring non-degradable mats or, for the first time, degradable mats. Both of them provided encouraging results, as the loss of transplanting plots was null or very low and the survival of cuttings stabilized to about 50%. Data collected are to be considered positive as the survived cuttings are enough to allow the future spread of the patches. The utilized techniques provided a cost-effective restoration tool likely affordable for large-scale projects, as the methods allowed to set up a wide bottom surface to restore in a relatively short time without any particular expensive device. Moreover, the mats, comparing with other anchoring methods, enhanced the colonization of other organisms such as macroalgae and sessile invertebrates, contributing to generate a natural habitat.


2021 ◽  
Vol 11 (4) ◽  
pp. 1814
Author(s):  
Min Seong Kim ◽  
Sean Seungwon Lee

Drill and blast is the most cost-effective excavation method for underground construction, however, vibration and noise, induced by blasting, have been consistently reported as problems. Cut blasting has been widely employed to reduce the blast-induced problems during underground excavation. We propose that the large hole boring method using the state-of-the-art MSP (Multi-setting smart-investigation of the ground and pre-large hole boring) machine (“MSP method”) can efficiently improve vibration reduction. The MSP machine will be used to create 382 mm diameter empty holes at the tunnel cut area for this purpose. This study assessed the efficiency of the MSP method in reducing blast-induced vibration in five blasting patterns using a cylinder-cut, which is a traditional cut blasting method. The controlled blasting patterns using the MSP method demonstrated up to 72% reduction in blast-induced vibration, compared to the base case, Pattern B, where only cylinder-cut and smooth blasting method were applied. Therefore, the MSP method proves to be a promising alternative for blasting in sensitive urban areas where non-vibration excavation techniques were initially considered. Geological characteristics of 50 m beyond the excavation face can be acquired through the proposed real-time boring data monitoring system together with a borehole alignment tracking and ground exploration system. The obtained geological information will be a great help in preparing alternative designs, and scheduling of construction equipment and labour during the tunnel construction.


2021 ◽  
pp. 1-9
Author(s):  
Karen Patricia Best ◽  
Judith Gomersall ◽  
Maria Makrides

Worldwide, around 15 million preterm babies are born annually, and despite intensive research, the specific mechanisms triggering preterm birth (PTB) remain unclear. Cost-effective primary prevention strategies to reduce PTB are required, and nutritional interventions offer a promising alternative. Nutrients contribute to a variety of mechanisms that are potentially important to preterm delivery, such as infection, inflammation, oxidative stress, and muscle contractility. Several observational studies have explored the association between dietary nutrients and/or dietary patterns and PTB, often with contrasting results. Randomized trial evidence on the effects of supplementation with zinc, multiple micronutrients (iron and folic acid), and vitamin D is promising; however, results are inconsistent, and many studies are not adequately powered for outcomes of PTB. Large-scale clinical trials with PTB as the primary outcome are needed before any firm conclusions can be drawn for these nutrients. The strongest evidence to date for a nutritional solution exists for omega-3 long-chain polyunsaturated fatty acids (LCPUFAs), key nutrients in fish. In 2018, a Cochrane Review (including 70 studies) showed that prenatal supplementation with omega-3 LCPUFAs reduced the risk of PTB and early PTB (EPTB) compared with no omega-3 supplementation. However, the largest trial of omega-3 supplementation in pregnancy, the Omega-3 to Reduce the Incidence of Prematurity (ORIP) trial (<i>n</i> = 5,544), showed no reduction in EPTB and a reduction in PTB only in a prespecified analysis of singleton pregnancies. Exploratory analyses from the ORIP trial found that women with low baseline total omega-3 status were at higher risk of EPTB, and that this risk was substantially reduced with omega-3 supplementation. In contrast, women with replete or high baseline total omega-3 status were already at low risk of EPTB and additional omega-3 supplementation increased the risk of EPTB compared to control. These findings suggest that determining an individual woman’s PUFA status may be the most precise way to inform recommendations to reduce her risk of PTB.


Author(s):  
Hitesh Chawla ◽  
Megat-Usamah Megat-Johari ◽  
Peter T. Savolainen ◽  
Christopher M. Day

The objectives of this study were to assess the in-service safety performance of roadside culverts and evaluate the potential impacts of installing various safety treatments to mitigate the severity of culvert-involved crashes. Such crashes were identified using standard fields on police crash report forms, as well as through a review of pertinent keywords from the narrative section of these forms. These crashes were then linked to the nearest cross-drainage culvert, which was associated with the nearest road segment. A negative binomial regression model was then estimated to discern how the risk of culvert-involved crashes varied as a function of annual average daily traffic, speed limit, number of travel lanes, and culvert size and offset. The second stage of the analysis involved the use of the Roadside Safety Analysis Program to estimate the expected crash costs associated with various design contexts. A series of scenarios were evaluated, culminating in guidance as to the most cost-effective treatments for different combinations of roadway geometric and traffic characteristics. The results of this study provide an empirical model that can be used to predict the risk of culvert-involved crashes under various scenarios. The findings also suggest that the installation of safety grates on culvert openings provides a promising alternative for most of the cases where the culvert is located within the clear zone. In general, a guardrail is recommended when adverse conditions are present or when other treatments are not feasible at a specific location.


Plant Methods ◽  
2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Peio Ziarsolo ◽  
Tomas Hasing ◽  
Rebeca Hilario ◽  
Victor Garcia-Carpintero ◽  
Jose Blanca ◽  
...  

Abstract Background K-seq, a new genotyping methodology based on the amplification of genomic regions using two steps of Klenow amplification with short oligonucleotides, followed by standard PCR and Illumina sequencing, is presented. The protocol was accompanied by software developed to aid with primer set design. Results As the first examples, K-seq in species as diverse as tomato, dog and wheat was developed. K-seq provided genetic distances similar to those based on WGS in dogs. Experiments comparing K-seq and GBS in tomato showed similar genetic results, although K-seq had the advantage of finding more SNPs for the same number of Illumina reads. The technology reproducibility was tested with two independent runs of the tomato samples, and the correlation coefficient of the SNP coverages between samples was 0.8 and the genotype match was above 94%. K-seq also proved to be useful in polyploid species. The wheat samples generated specific markers for all subgenomes, and the SNPs generated from the diploid ancestors were located in the expected subgenome with accuracies greater than 80%. Conclusion K-seq is an open, patent-unencumbered, easy-to-set-up, cost-effective and reliable technology ready to be used by any molecular biology laboratory without special equipment in many genetic studies.


2021 ◽  
Vol 13 (9) ◽  
pp. 4651
Author(s):  
Ming-Lun Alan Fong

The analysis of ventilation strategies is fundamentally affected by regional climate conditions and local cost databases, in terms of energy consumption, CO2 emission and cost-effective analysis. A systematic approach is covered in this paper to estimate a local economic and environmental impact on a medium-sized space located in two regions during supply-and-installation and operation phases. Three ventilation strategies, including mixing ventilation (MV), displacement ventilation (DV) and stratum ventilation (SV) were applied to medium-sized air-conditioned space with this approach. The trend of the results for three ventilation systems in the life cycle assessment (LCA) and life cycle cost (LCC) analysis is SV < DV < MV. The result of CO2 emission and regional LCC shows that SV is the lowest one in both regional studies. In comparison with the Hong Kong Special Administrative Region (HKSAR) during 20 Service years, the case analysis demonstrates that the percentage differences in LCC analysis of MV, DV & SV in Guangdong are less than 20.5%, 19.4% and 18.82% respectively. Their CO2 emission of MV, DV and SV in Guangdong are more than HKSAR in 10.69%, 11.22% and 12.05%, respectively. The present study could provide information about regional effects in the LCA and LCC analysis of three ventilation strategies emissions, and thereby help set up models for decision-making on high efficiency and cost-effective ventilation strategy plans.


2020 ◽  
Vol 7 (2) ◽  
pp. 36 ◽  
Author(s):  
João P. Cotovio ◽  
Tiago G. Fernandes

Liver disease is one of the leading causes of death worldwide, leading to the death of approximately 2 million people per year. Current therapies include orthotopic liver transplantation, however, donor organ shortage remains a great challenge. In addition, the development of novel therapeutics has been limited due to the lack of in vitro models that mimic in vivo liver physiology. Accordingly, hepatic cell lineages derived from human pluripotent stem cells (hPSCs) represent a promising cell source for liver cell therapy, disease modelling, and drug discovery. Moreover, the development of new culture systems bringing together the multiple liver-specific hepatic cell types triggered the development of hPSC-derived liver organoids. Therefore, these human liver-based platforms hold great potential for clinical applications. In this review, the production of the different hepatic cell lineages from hPSCs, including hepatocytes, as well as the emerging strategies to generate hPSC-derived liver organoids will be assessed, while current biomedical applications will be highlighted.


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