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International Journal of Molecular... Jul 2023An organoid is a 3D organization of cells that can recapitulate some of the structure and function of native tissue. Recent work has seen organoids gain prominence as a... (Review)
Review
An organoid is a 3D organization of cells that can recapitulate some of the structure and function of native tissue. Recent work has seen organoids gain prominence as a valuable model for studying tissue development, drug discovery, and potential clinical applications. The requirements for the successful culture of organoids in vitro differ significantly from those of traditional monolayer cell cultures. The generation and maturation of high-fidelity organoids entails developing and optimizing environmental conditions to provide the optimal cues for growth and 3D maturation, such as oxygenation, mechanical and fluidic activation, nutrition gradients, etc. To this end, we discuss the four main categories of bioreactors used for organoid culture: stirred bioreactors (SBR), microfluidic bioreactors (MFB), rotating wall vessels (RWV), and electrically stimulating (ES) bioreactors. We aim to lay out the state-of-the-art of both commercial and in-house developed bioreactor systems, their benefits to the culture of organoids derived from various cells and tissues, and the limitations of bioreactor technology, including sterilization, accessibility, and suitability and ease of use for long-term culture. Finally, we discuss future directions for improvements to existing bioreactor technology and how they may be used to enhance organoid culture for specific applications.
Topics: Cell Culture Techniques; Organoids; Bioreactors
PubMed: 37511186
DOI: 10.3390/ijms241411427 -
Trends in Biotechnology Aug 2023The robustness of bioprocesses is becoming increasingly important. The main driving forces of this development are, in particular, increasing demands on product purities... (Review)
Review
The robustness of bioprocesses is becoming increasingly important. The main driving forces of this development are, in particular, increasing demands on product purities as well as economic aspects. In general, bioprocesses exhibit extremely high complexity and variability. Biological systems often have a much higher intrinsic variability compared with chemical processes, which makes the development and characterization of robust processes tedious task. To predict and control robustness, a clear understanding of interactions between input and output variables is necessary. Robust bioprocesses can be realized, for example, by using advanced control strategies for the different unit operations. In this review, we discuss the different biological, technical, and mathematical tools for the analysis and control of bioprocess robustness.
Topics: Bioreactors
PubMed: 36959084
DOI: 10.1016/j.tibtech.2023.03.002 -
Biotechnology Advances Oct 2023In order to meet the rising demand for biologics and become competitive on the developing biosimilar market, there is a need for process intensification of... (Review)
Review
In order to meet the rising demand for biologics and become competitive on the developing biosimilar market, there is a need for process intensification of biomanufacturing processes. Process development of biologics has historically relied on extensive experimentation to develop and optimize biopharmaceutical manufacturing. Experimentation to optimize media formulations, feeding schedules, bioreactor operations and bioreactor scale up is expensive, labor intensive and time consuming. Mathematical modeling frameworks have the potential to enable process intensification while reducing the experimental burden. This review focuses on mathematical modeling of cellular metabolism and N-linked glycosylation as applied to upstream manufacturing of biologics. We review developments in the field of modeling cellular metabolism of mammalian cells using kinetic and stoichiometric modeling frameworks along with their applications to simulate, optimize and improve mechanistic understanding of the process. Interest in modeling N-linked glycosylation has led to the creation of various types of parametric and non-parametric models. Most published studies on mammalian cell metabolism have performed experiments in shake flasks where the pH and dissolved oxygen cannot be controlled. Efforts to understand and model the effect of bioreactor-specific parameters such as pH, dissolved oxygen, temperature, and bioreactor heterogeneity are critically reviewed. Most modeling efforts have focused on the Chinese Hamster Ovary (CHO) cells, which are most commonly used to produce monoclonal antibodies (mAbs). However, these modeling approaches can be generalized and applied to any mammalian cell-based manufacturing platform. Current and potential future applications of these models for Vero cell-based vaccine manufacturing, CAR-T cell therapies, and viral vector manufacturing are also discussed. We offer specific recommendations for improving the applicability of these models to industrially relevant processes.
Topics: Cricetinae; Animals; Glycosylation; Cricetulus; CHO Cells; Cell Culture Techniques; Bioreactors; Biological Products
PubMed: 37257729
DOI: 10.1016/j.biotechadv.2023.108179 -
Applied Microbiology and Biotechnology Nov 2023Microalgae are excellent sources of biomass containing several important compounds for human and animal nutrition-proteins, lipids, polysaccharides, pigments and... (Review)
Review
Microalgae are excellent sources of biomass containing several important compounds for human and animal nutrition-proteins, lipids, polysaccharides, pigments and antioxidants as well as bioactive secondary metabolites. In addition, they have a great biotechnological potential for nutraceuticals, and pharmaceuticals as well as for CO sequestration, wastewater treatment, and potentially also biofuel and biopolymer production. In this review, the industrial production of the most frequently used microalgae genera-Arthrospira, Chlorella, Dunaliella, Haematococcus, Nannochloropsis, Phaeodactylum, Porphyridium and several other species is discussed as concerns the applicability of the most widely used large-scale systems, solar bioreactors (SBRs)-open ponds, raceways, cascades, sleeves, columns, flat panels, tubular systems and others. Microalgae culturing is a complex process in which bioreactor operating parameters and physiological variables closely interact. The requirements of the biological system-microalgae culture are crucial to select the suitable type of SBR. When designing a cultivation process, the phototrophic production of microalgae biomass, it is necessary to employ SBRs that are adequately designed, built and operated to satisfy the physiological requirements of the selected microalgae species, considering also local climate. Moreover, scaling up microalgae cultures for commercial production requires qualified staff working out a suitable cultivation regime. KEY POINTS: • Large-scale solar bioreactors designed for microalgae culturing. • Most frequently used microalgae genera for commercial production. • Scale-up requires suitable cultivation conditions and well-elaborated protocols.
Topics: Animals; Humans; Microalgae; Chlorella; Bioreactors; Biotechnology; Chlorophyceae; Biomass; Biofuels
PubMed: 37725140
DOI: 10.1007/s00253-023-12733-8 -
Stem Cell Research & Therapy Oct 2023Human umbilical cord mesenchymal stem cells (hUC-MSCs) are widely used in cell therapy due to their robust immunomodulatory and tissue regenerative capabilities....
BACKGROUND
Human umbilical cord mesenchymal stem cells (hUC-MSCs) are widely used in cell therapy due to their robust immunomodulatory and tissue regenerative capabilities. Currently, the predominant method for obtaining hUC-MSCs for clinical use is through planar culture expansion, which presents several limitations. Specifically, continuous cell passaging can lead to cellular aging, susceptibility to contamination, and an absence of process monitoring and control, among other limitations. To overcome these challenges, the technology of microcarrier-bioreactor culture was developed with the aim of ensuring the therapeutic efficacy of cells while enabling large-scale expansion to meet clinical requirements. However, there is still a knowledge gap regarding the comparison of biological differences in cells obtained through different culture methods.
METHODS
We developed a culture process for hUC-MSCs using self-made microcarrier and stirred bioreactor. This study systematically compares the biological properties of hUC-MSCs amplified through planar culture and microcarrier-bioreactor systems. Additionally, RNA-seq was employed to compare the differences in gene expression profiles between the two cultures, facilitating the identification of pathways and genes associated with cell aging.
RESULTS
The findings revealed that hUC-MSCs expanded on microcarriers exhibited a lower degree of cellular aging compared to those expanded through planar culture. Additionally, these microcarrier-expanded hUC-MSCs showed an enhanced proliferation capacity and a reduced number of cells in the cell cycle retardation period. Moreover, bioreactor-cultured cells differ significantly from planar cultures in the expression of genes associated with the cytoskeleton and extracellular matrix.
CONCLUSIONS
The results of this study demonstrate that our microcarrier-bioreactor culture method enhances the proliferation efficiency of hUC-MSCs. Moreover, this culture method exhibits the potential to delay the process of cell aging while preserving the essential stem cell properties of hUC-MSCs.
Topics: Humans; Mesenchymal Stem Cells; Cells, Cultured; Cellular Senescence; Stem Cells; Bioreactors; Umbilical Cord; Cell Differentiation; Mesenchymal Stem Cell Transplantation
PubMed: 37794520
DOI: 10.1186/s13287-023-03514-1 -
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 -
Biotechnology Journal Jan 2024Laccases have shown to be efficient biocatalysts for the removal of recalcitrant pollutants from wastewater. Thus, they catalyze the oxidation of a wide variety of... (Review)
Review
Laccases have shown to be efficient biocatalysts for the removal of recalcitrant pollutants from wastewater. Thus, they catalyze the oxidation of a wide variety of organic compounds by reducing molecular oxygen to water. However, the use of free laccases holds several drawbacks such as poor reusability, high cost, low stability and sensitivity to different denaturing agents that may occur in wastewater. Such drawbacks can be circumvented by immobilizing laccase enzymes in/on solid carriers. Hence, during the last decades different approaches considering various techniques and solid carriers to immobilize laccase enzymes have been developed and tested for the removal of pollutants from wastewater. To scale up wastewater treatment bioprocesses, immobilized laccases are placed in different reactor configurations.
Topics: Enzymes, Immobilized; Wastewater; Laccase; Bioreactors; Water Purification; Environmental Pollutants
PubMed: 37750809
DOI: 10.1002/biot.202300354 -
Bioresource Technology Nov 2023Mixed pollutant wastewater has been a difficult problem due to the high toxicity of water bodies and the difficulty of treatment. Rice husk biochar modified with...
Mixed pollutant wastewater has been a difficult problem due to the high toxicity of water bodies and the difficulty of treatment. Rice husk biochar modified with nano-iron tetroxide (RBC-nFeO) by polyvinyl alcohol cross-linking internal doping was used to introduce iron-reducing bacteria Klebsiella sp. FC61 to construct a bioreactor. The results of the long-term operation of the bioreactor showed that the removal efficiency of ammonia nitrogen (NH-N) and chemical oxygen demand best reached 90.18 and 98.49%, respectively. In addition, in the co-presence of Ni, Cd, and ciprofloxacin, the bioreactor was still able to remove pollutants efficiently by RBC-nFeO and bio-iron precipitation inside the biocarrier. During the long-term operation, Klebsiella was always the dominant species in the bioreactor. And the sequencing data for functional prediction showed that the biocarrier contained a variety of enzymes and proteins involved in Feammox-related activities to ensure the stable and efficient operation of the bioreactor.
Topics: Hydrogels; Wastewater; Microbiota; Iron; Bioreactors; Nitrogen; Bacteria; Klebsiella
PubMed: 37544543
DOI: 10.1016/j.biortech.2023.129604 -
International Journal of Biological... Jun 2023Hyaluronic acid (HA), an anionic and nonsulfated glycosaminoglycan, is the main structural component of various tissues and plays an important role in various biological... (Review)
Review
Hyaluronic acid (HA), an anionic and nonsulfated glycosaminoglycan, is the main structural component of various tissues and plays an important role in various biological processes. Given the promising properties of HA, such as high cellular compatibility, moisture retention, antiaging, proper interaction with cells, and CD44 targeting, HA can be widely used extensively in drug delivery, tissue engineering, wound healing, and cancer therapy. HA can obtain from animal tissues and microbial fermentation, but its applications depend on its molecular weight. Microbial fermentation is a common method for HA production on an industrial scale and S. zooepidemicus is the most frequently used strain in HA production. Culture conditions including pH, temperature, agitation rate, aeration speed, shear stress, dissolved oxygen, and bioreactor type significantly affect HA biosynthesis properties. In this review all the HA production methods and purification techniques to improve its physicochemical and biological properties for various biomedical applications are discussed in details. In addition, we showed that how HA molecular weight can significantly affect its properties and applications.
Topics: Animals; Hyaluronic Acid; Molecular Weight; Streptococcus equi; Fermentation; Bioreactors
PubMed: 37068534
DOI: 10.1016/j.ijbiomac.2023.124484 -
Water Research Feb 2024Microbially driven anaerobic digestion (AD) processes are of immense interest due to their role in the biovalorization of biowastes into renewable energy resources. The... (Review)
Review
Microbially driven anaerobic digestion (AD) processes are of immense interest due to their role in the biovalorization of biowastes into renewable energy resources. The function-versatile microbiome, interspecies syntrophic interactions, and trophic-level metabolic pathways are important microbial components of AD. However, the lack of a comprehensive understanding of the process hampers efforts to improve AD efficiency. This study presents a holistic review of research on the microbial and metabolic "black box" of AD processes. Recent research on microbiology, functional traits, and metabolic pathways in AD, as well as the responses of functional microbiota and metabolic capabilities to optimization strategies are reviewed. The diverse ecophysiological traits and cooperation/competition interactions of the functional guilds and the biomanipulation of microbial ecology to generate valuable products other than methane during AD are outlined. The results show that AD communities prioritize cooperation to improve functional redundancy, and the dominance of specific microbes can be explained by thermodynamics, resource allocation models, and metabolic division of labor during cross-feeding. In addition, the multi-omics approaches used to decipher the ecological principles of AD consortia are summarized in detail. Lastly, future microbial research and engineering applications of AD are proposed. This review presents an in-depth understanding of microbiome-functionality mechanisms of AD and provides critical guidance for the directional and efficient bioconversion of biowastes into methane and other valuable products.
Topics: Anaerobiosis; Bioreactors; Microbiota; Methane; Metabolic Networks and Pathways
PubMed: 38016221
DOI: 10.1016/j.watres.2023.120891