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Journal of Visualized Experiments : JoVE Apr 2022Repeated injury to airway tissue can impair lung function and cause chronic lung disease, such as chronic obstructive pulmonary disease. Advances in regenerative...
Repeated injury to airway tissue can impair lung function and cause chronic lung disease, such as chronic obstructive pulmonary disease. Advances in regenerative medicine and bioreactor technologies offer opportunities to produce lab-grown functional tissue and organ constructs that can be used to screen drugs, model disease, and engineer tissue replacements. Here, a miniaturized bioreactor coupled with an imaging modality that allows in situ visualization of the inner lumen of explanted rat trachea during in vitro tissue manipulation and culture is described. Using this bioreactor, the protocol demonstrates imaging-guided selective removal of endogenous cellular components while preserving the intrinsic biochemical features and ultrastructure of the airway tissue matrix. Furthermore, the delivery, uniform distribution, and subsequent prolonged culture of exogenous cells on the decellularized airway lumen with optical monitoring in situ are shown. The results highlight that the imaging-guided bioreactor can potentially be used to facilitate the generation of functional in vitro airway tissues.
Topics: Animals; Biomedical Engineering; Bioreactors; Rats; Tissue Engineering
PubMed: 35467661
DOI: 10.3791/63544 -
Trends in Microbiology Jun 2019Systems biology and synthetic biology are increasingly used to examine and modulate complex biological systems. As such, many issues arising during scaling-up microbial... (Review)
Review
Systems biology and synthetic biology are increasingly used to examine and modulate complex biological systems. As such, many issues arising during scaling-up microbial production processes can be addressed using these approaches. We review differences between laboratory-scale cultures and larger-scale processes to provide a perspective on those strain characteristics that are especially important during scaling. Systems biology has been used to examine a range of microbial systems for their response in bioreactors to fluctuations in nutrients, dissolved gases, and other stresses. Synthetic biology has been used both to assess and modulate strain response, and to engineer strains to improve production. We discuss these approaches and tools in the context of their use in engineering robust microbes for applications in large-scale production.
Topics: Bioengineering; Bioreactors; Fermentation; Genetic Association Studies; Microbiological Techniques; Systems Biology
PubMed: 30819548
DOI: 10.1016/j.tim.2019.01.006 -
Bulletin of Mathematical Biology Nov 2021A multiscale mathematical model is presented to describe de novo granulation, and the evolution of multispecies granular biofilms, in a continuously fed bioreactor. The...
A multiscale mathematical model is presented to describe de novo granulation, and the evolution of multispecies granular biofilms, in a continuously fed bioreactor. The granule is modelled as a spherical free boundary domain with radial symmetry. The equation governing the free boundary is derived from global mass balance considerations and takes into account the growth of sessile biomass as well as exchange fluxes with the bulk liquid. Starting from a vanishing initial value, the expansion of the free boundary is initiated by the attachment process, which depends on the microbial species concentrations within the bulk liquid and their specific attachment velocity. Nonlinear hyperbolic PDEs model the growth of the sessile microbial species, while quasi-linear parabolic PDEs govern the dynamics of substrates and invading species within the granular biofilm. Nonlinear ODEs govern the evolution of soluble substrates and planktonic biomass within the bulk liquid. The model is applied to an anaerobic, granular-based bioreactor system, and solved numerically to test its qualitative behaviour and explore the main aspects of de novo anaerobic granulation: ecology, biomass distribution, relative abundance, dimensional evolution of the granules and soluble substrates, and planktonic biomass dynamics within the bioreactor. The numerical results confirm that the model accurately describes the ecology and the concentrically layered structure of anaerobic granules observed experimentally, and that it can predict the effects on the process of significant factors, such as influent wastewater composition; granulation properties of planktonic biomass; biomass density; detachment intensity; and number of granules.
Topics: Anaerobiosis; Biofilms; Biomass; Bioreactors; Mathematical Concepts; Models, Biological
PubMed: 34741191
DOI: 10.1007/s11538-021-00951-y -
Biotechnology Letters Sep 2021With generation times of less than 10 min under optimal conditions, the halophilic Vibrio natriegens is the fastest growing non-pathogenic bacterium isolated so far. The...
OBJECTIVES
With generation times of less than 10 min under optimal conditions, the halophilic Vibrio natriegens is the fastest growing non-pathogenic bacterium isolated so far. The availability of the full genome and genetic engineering tools and its ability to utilize a wide range of carbon sources make V. natriegens an attractive host for biotechnological production processes. However, high-cell-density cultivations, which are desired at industrial-scale have not been described so far.
RESULTS
In this study we report fed-batch cultivations of V. natriegens in deep-well plates and lab-scale bioreactor cultivations at different temperatures in mineral salt medium (MSM). Upon switching from exponential glucose to constant glucose-feeding cell death was induced. Initial NaCl concentrations of 15-18 g L and a temperature reduction from 37 to 30 °C had a positive effect on cell growth. The maximal growth rate in MSM with glucose was 1.36 h with a specific oxygen uptake rate of 22 mmol g h. High biomass yields of up to 55 g L after only 12 h were reached.
CONCLUSIONS
The shown fed-batch strategies demonstrate the potential of V. natriegens as a strong producer in industrial biotechnology.
Topics: Batch Cell Culture Techniques; Bioreactors; Culture Media; Sodium Chloride; Temperature; Vibrio
PubMed: 34009528
DOI: 10.1007/s10529-021-03147-5 -
World Journal of Microbiology &... Dec 2023Increased production of renewable energy sources is becoming increasingly needed. Amidst other strategies, one promising technology that could help achieve this goal is... (Review)
Review
Increased production of renewable energy sources is becoming increasingly needed. Amidst other strategies, one promising technology that could help achieve this goal is biological hydrogen production. This technology uses micro-organisms to convert organic matter into hydrogen gas, a clean and versatile fuel that can be used in a wide range of applications. While biohydrogen production is in its early stages, several challenges must be addressed for biological hydrogen production to become a viable commercial solution. From an experimental perspective, the need to improve the efficiency of hydrogen production, the optimization strategy of the microbial consortia, and the reduction in costs associated with the process is still required. From a scale-up perspective, novel strategies (such as modelling and experimental validation) need to be discussed to facilitate this hydrogen production process. Hence, this review considers hydrogen production, not within the framework of a particular production method or technique, but rather outlines the work (bioreactor modes and configurations, modelling, and techno-economic and life cycle assessment) that has been done in the field as a whole. This type of analysis allows for the abstraction of the biohydrogen production technology industrially, giving insights into novel applications, cross-pollination of separate lines of inquiry, and giving a reference point for researchers and industrial developers in the field of biohydrogen production.
Topics: Fermentation; Bioreactors; Microbial Consortia; Hydrogen; Costs and Cost Analysis; Biofuels
PubMed: 38057658
DOI: 10.1007/s11274-023-03845-4 -
Journal of Dental Research Dec 2014Large mandibular defects are difficult to reconstruct with good functional and aesthetic outcomes because of the complex geometry of craniofacial bone. While the current... (Review)
Review
Large mandibular defects are difficult to reconstruct with good functional and aesthetic outcomes because of the complex geometry of craniofacial bone. While the current gold standard is free tissue flap transfer, this treatment is limited in fidelity by the shape of the harvested tissue and can result in significant donor site morbidity. To address these problems, in vivo bioreactors have been explored as an approach to generate autologous prefabricated tissue flaps. These bioreactors are implanted in an ectopic site in the body, where ossified tissue grows into the bioreactor in predefined geometries and local vessels are recruited to vascularize the developing construct. The prefabricated flap can then be harvested with vessels and transferred to a mandibular defect for optimal reconstruction. The objective of this review article is to introduce the concept of the in vivo bioreactor, describe important preclinical models in the field, summarize the human cases that have been reported through this strategy, and offer future directions for this exciting approach.
Topics: Bioreactors; Guided Tissue Regeneration; Humans; Mandibular Diseases; Mandibular Reconstruction; Plastic Surgery Procedures; Tissue Engineering
PubMed: 25139360
DOI: 10.1177/0022034514547763 -
Journal of Orthopaedic Research :... Nov 2020Bioreactors are powerful tools with the potential to model tissue development and disease in vitro. For nearly four decades, bioreactors have been used to create tendon... (Review)
Review
Bioreactors are powerful tools with the potential to model tissue development and disease in vitro. For nearly four decades, bioreactors have been used to create tendon and ligament tissue-engineered constructs in order to define basic mechanisms of cell function, extracellular matrix deposition, tissue organization, injury, and tissue remodeling. This review provides a historical perspective of tendon and ligament bioreactors and their contributions to this advancing field. First, we demonstrate the need for bioreactors to improve understanding of tendon and ligament function and dysfunction. Next, we detail the history and evolution of bioreactor development and design from simple stretching of explants to fabrication and stimulation of two- and three-dimensional constructs. Then, we demonstrate how research using tendon and ligament bioreactors has led to pivotal basic science and tissue-engineering discoveries. Finally, we provide guidance for new basic, applied, and clinical research utilizing these valuable systems, recognizing that fundamental knowledge of cell-cell and cell-matrix interactions combined with appropriate mechanical and chemical stimulation of constructs could ultimately lead to functional tendon and ligament repairs in the coming decades.
Topics: Animals; Biomechanical Phenomena; Bioreactors; Extracellular Matrix; History, 20th Century; History, 21st Century; Humans; In Vitro Techniques; Ligaments; Orthopedics; Regenerative Medicine; Tendon Injuries; Tendons; Tissue Engineering
PubMed: 32579266
DOI: 10.1002/jor.24784 -
Medicina (Kaunas, Lithuania) Oct 2022To test the long-term ability of human ovarian cortex cells to develop in unconventional culture conditions. Ovarian cortex cells from fetuses aged 23 to 39 weeks...
To test the long-term ability of human ovarian cortex cells to develop in unconventional culture conditions. Ovarian cortex cells from fetuses aged 23 to 39 weeks gestation were cultured for 90 days in hollow chitosan hydrogel micro-bioreactors and concurrently in traditional wells. Various cell-type counts were considered. : With intact follicles as a denominator, the percentage of growing intact follicles at Day 0 varied widely between ovaries (0 to 31.7%). This percentage tended to increase or stay relatively constant in bioreactor as in control cultures; it tended more toward an increase over time in bioreactor vs. control cultures. Modeled percentages showed differences (though not significant) in favor of bioreactor cultures (16.12% difference at D50 but only 0.12% difference at D90). With all follicles present as a denominator, the percentage of growing primary and secondary follicles at D0 varied widely between ovaries (0 to 29.3%). This percentage tended to increase over time in bioreactor cultures but to decrease in control cultures. Modeled percentages showed significant differences in favor of bioreactor cultures (8.9% difference at D50 and 11.1% difference at D90). At D50 and D90, there were only few and sparse apoptotic cells in bioreactor cultures vs. no apoptotic cells in control cultures. : Over three months, bioreactor folliculogenesis outperformed slightly traditional culture. This is an interesting perspective for follicle preservation and long-term toxicological studies.
Topics: Female; Humans; Ovary; Chitosan; Hydrogels; Tissue Culture Techniques; Bioreactors
PubMed: 36363522
DOI: 10.3390/medicina58111565 -
Cells, Tissues, Organs 2022To date, the creation of biomimetic devices for the regeneration and repair of injured or diseased tissues and organs remains a crucial challenge in tissue engineering.... (Review)
Review
To date, the creation of biomimetic devices for the regeneration and repair of injured or diseased tissues and organs remains a crucial challenge in tissue engineering. Membrane technology offers advanced approaches to realize multifunctional tools with permissive environments well-controlled at molecular level for the development of functional tissues and organs. Membranes in fiber configuration with precisely controlled, tunable topography, and physical, biochemical, and mechanical cues, can direct and control the function of different kinds of cells toward the recovery from disorders and injuries. At the same time, fiber tools also provide the potential to model diseases in vitro for investigating specific biological phenomena as well as for drug testing. The purpose of this review is to present an overview of the literature concerning the development of hollow fibers and electrospun fiber membranes used in bioartificial organs, tissue engineered constructs, and in vitro bioreactors. With the aim to highlight the main biomedical applications of fiber-based systems, the first part reviews the fibers for bioartificial liver and liver tissue engineering with special attention to their multifunctional role in the long-term maintenance of specific liver functions and in driving hepatocyte differentiation. The second part reports the fiber-based systems used for neuronal tissue applications including advanced approaches for the creation of novel nerve conduits and in vitro models of brain tissue. Besides presenting recent advances and achievements, this work also delineates existing limitations and highlights emerging possibilities and future prospects in this field.
Topics: Bioreactors; Liver; Liver, Artificial; Nanofibers; Tissue Engineering
PubMed: 33849029
DOI: 10.1159/000511680 -
Cytotherapy Oct 2023The Quantum cell expansion system manufactured by Terumo-BCT is perhaps the most widely reported Good Manufacturing Practice-compliant bioreactor used for the expansion... (Review)
Review
The Quantum cell expansion system manufactured by Terumo-BCT is perhaps the most widely reported Good Manufacturing Practice-compliant bioreactor used for the expansion of adherent cell populations, both for research purposes and clinical cell-based therapies/trials. Although the system was originally designed for adherent cell expansion, more recently suspension cultures and extracellular vesicle manufacturing protocols have been published using the Quantum system. Cell therapy research and regenerative medicine in general is a rapidly expanding field and as such it is likely that the use of this system will become even more widespread and perhaps mandatory, for both research and development and in the clinic. The purpose of this review is to describe, compare and discuss the diverse range of research and clinical applications currently using the Quantum system, which to our knowledge has not previously been reviewed. In addition, current and future challenges will also be discussed.
Topics: Cell Culture Techniques; Mesenchymal Stem Cells; Bioreactors; Cell- and Tissue-Based Therapy; Cell Proliferation
PubMed: 37162433
DOI: 10.1016/j.jcyt.2023.04.004