-
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 -
Tissue Engineering. Part B, Reviews Feb 2022It is estimated that almost one-third of the United States population will be affected by a vocal fold (VF) disorder during their lifespan. Promising therapies to treat... (Review)
Review
It is estimated that almost one-third of the United States population will be affected by a vocal fold (VF) disorder during their lifespan. Promising therapies to treat VF injury and scarring are mostly centered on VF tissue engineering strategies such as the injection of engineered biomaterials and cell therapy. VF tissue engineering, however, is a challenging field as the biomechanical properties, structure, and composition of the VF tissue change upon exposure to mechanical stimulation. As a result, the development of long-term VF treatment strategies relies on the characterization of engineered tissues under a controlled mechanical environment. In this review, we highlight the importance of bioreactors as a powerful tool for VF tissue engineering with a focus on the current state of the art of bioreactors designed to mimic phonation We discuss the influence of the phonatory environment on the development, function, injury, and healing of the VF tissue and its importance for the development of efficient therapeutic strategies. A concise and comprehensive overview of bioreactor designs, principles, operating parameters, and scalability are presented. An in-depth analysis of VF bioreactor data to date reveals that mechanical stimulation significantly influences cell viability and the expression of proinflammatory and profibrotic genes . Although the precision and accuracy of bioreactors contribute to generating reliable results, diverse gene expression profiles across the literature suggest that future efforts should focus on the standardization of bioreactor parameters to enable direct comparisons between studies. Impact statement We present a comprehensive review of bioreactors for vocal fold (VF) tissue engineering with a focus on the influence of the phonatory environment on the development, function, injury, and healing of the VFs and the importance of mimicking phonation on engineered VF tissues . Furthermore, we put forward a strong argument for the continued development of bioreactors in this area with an emphasis on the standardization of bioreactor designs, principles, operating parameters, and oscillatory regimes to enable comparisons between studies.
Topics: Biocompatible Materials; Bioreactors; Cicatrix; Humans; Tissue Engineering; Vocal Cords
PubMed: 33446061
DOI: 10.1089/ten.TEB.2020.0285 -
Ecotoxicology and Environmental Safety Oct 2014The wastewater originating from simultaneous production of styrene and propylene oxide (SPO) is classified as highly polluted with chemical oxygen demand level in the...
The wastewater originating from simultaneous production of styrene and propylene oxide (SPO) is classified as highly polluted with chemical oxygen demand level in the range 5965 to 9137mgL(-1)-as well as highly toxic. The dilution factor providing for a 10 percent toxic effect of wastewater samples in a test with Paramecium caudatum was 8.0-9.5. Biological approach for pretreatment and detoxification of the wastewater under full-scale bioreactor conditions was investigated. The number of suspended microorganisms and the clean up efficiency were increased up to 5.5-6.58×10(8)CFUmL(-1) and 88 percent, respectively during the bioreactor's operation. Isolates in the Citrobacter, Burkholderia, Pseudomonas, and Paracoccus genera were dominant in the mature suspended, as well as the immobilized microbial community of the bioreactor. The most dominant representatives were tested for their ability to biodegrade the major components of the SPO wastewater and evidence of their role in the treatment process was demonstrated. The investigated pretreatment process allowed the wastewater to be detoxified for conventional treatment with activated sludge and was closely related to the maturation of the bioreactor's microbial community.
Topics: Biodegradation, Environmental; Biological Oxygen Demand Analysis; Bioreactors; Epoxy Compounds; Hazardous Waste; Microbial Consortia; Styrene; Waste Disposal, Fluid; Wastewater
PubMed: 25086231
DOI: 10.1016/j.ecoenv.2014.07.012 -
Cell Proliferation Aug 2022For use in regenerative medicine, large-scale manufacturing of human pluripotent stem cells (hPSCs) under current good manufacturing practice (cGMPs) is required. Much... (Review)
Review
For use in regenerative medicine, large-scale manufacturing of human pluripotent stem cells (hPSCs) under current good manufacturing practice (cGMPs) is required. Much progress has been made since culturing under static two-dimensional (2D) conditions on feeders, including feeder-free cultures, conditioned and xeno-free media, and three-dimensional (3D) dynamic suspension expansion. With the advent of horizontal-blade and vertical-wheel bioreactors, scale-out for large-scale production of differentiated hPSCs became possible; control of aggregate size, shear stress, fluid hydrodynamics, batch-feeding strategies, and other process parameters became a reality. Moving from substantially manipulated processes (i.e., 2D) to more automated ones allows easer compliance to current good manufacturing practices (cGMPs), and thus easier regulatory approval. Here, we review the current advances in the field of hPSC culturing, advantages, and challenges in bioreactor use, and regulatory areas of concern with respect to these advances. Manufacturing trends to reduce risk and streamline large-scale manufacturing will bring about easier, faster regulatory approval for clinical applications.
Topics: Bioreactors; Cell Culture Techniques; Cell Differentiation; Humans; Pluripotent Stem Cells; Regenerative Medicine
PubMed: 35638399
DOI: 10.1111/cpr.13247 -
Journal of Diabetes Science and... Nov 2014The concept of bioreactors in biochemical engineering is a well-established process; however, the idea of applying bioreactor technology to biomedical and tissue... (Review)
Review
The concept of bioreactors in biochemical engineering is a well-established process; however, the idea of applying bioreactor technology to biomedical and tissue engineering issues is relatively novel and has been rapidly accepted as a culture model. Tissue engineers have developed and adapted various types of bioreactors in which to culture many different cell types and therapies addressing several diseases, including diabetes mellitus types 1 and 2. With a rising world of bioreactor development and an ever increasing diagnosis rate of diabetes, this review aims to highlight bioreactor history and emerging bioreactor technologies used for diabetes-related cell culture and therapies.
Topics: Animals; Bioreactors; Diabetes Mellitus; Equipment Design; Humans; Tissue Engineering
PubMed: 25160666
DOI: 10.1177/1932296814548215 -
Journal of Biomedical Materials... Feb 2022The challenges to accommodate multiple tissue formation metrics in conventional bioreactors have resulted in an increased interest to explore novel bioreactor designs.... (Review)
Review
The challenges to accommodate multiple tissue formation metrics in conventional bioreactors have resulted in an increased interest to explore novel bioreactor designs. Bioreactors allow researchers to isolate variables in controlled environments to quantify cell response. While current bioreactor designs can effectively provide either mechanical, electrical, or chemical stimuli to the controlled environment, these systems lack the ability to combine all these stimuli simultaneously to better recapitulate the physiological environment. Introducing a dynamic and systematic combination of biomimetic stimuli bioreactor systems could tremendously enhance its clinical relevance in research. Thus, cues from different tissue responses should be studied collectively and included in the design of a biomimetic bioreactor platform. This review begins by providing a summary on the progression of bioreactors from simple to complex designs, focusing on the major advances in bioreactor technology and the approaches employed to better simulate in vivo conditions. The current state of bioreactors in terms of their clinical relevance is also analyzed. Finally, this review provides a comprehensive overview of individual biophysical stimuli and their role in establishing a biomimetic microenvironment for tissue engineering. To date, the most advanced bioreactor designs only incorporate one or two stimuli. Thus, the cell response measured is likely unrelated to the actual clinical performance. Integrating clinically relevant stimuli in bioreactor designs to study cell response can further advance the understanding of physical phenomenon naturally occurring in the body. In the future, the clinically informed biomimetic bioreactor could yield more efficiently translatable results for improved patient care.
Topics: Biomimetics; Bioreactors; Humans; Orthopedic Procedures; Orthopedics; Tissue Engineering
PubMed: 34510706
DOI: 10.1002/jbm.b.34929 -
Molecules (Basel, Switzerland) Jan 2022In recent years, there has been a considerable increase in interest in the use of transgenic plants as sources of valuable secondary metabolites or recombinant proteins.... (Review)
Review
In recent years, there has been a considerable increase in interest in the use of transgenic plants as sources of valuable secondary metabolites or recombinant proteins. This has been facilitated by the advent of genetic engineering technology with the possibility for direct modification of the expression of genes related to the biosynthesis of biologically active compounds. A wide range of research projects have yielded a number of efficient plant systems that produce specific secondary metabolites or recombinant proteins. Furthermore, the use of bioreactors allows production to be increased to industrial scales, which can quickly and cheaply deliver large amounts of material in a short time. The resulting plant production systems can function as small factories, and many of them that are targeted at a specific operation have been patented. This review paper summarizes the key research in the last ten years regarding the use of transgenic plants as small, green biofactories for the bioreactor-based production of secondary metabolites and recombinant proteins; it simultaneously examines the production of metabolites and recombinant proteins on an industrial scale and presents the current state of available patents in the field.
Topics: Bioreactors; Biotechnology; Cell Culture Techniques; Industry; Plants, Genetically Modified; Recombinant Proteins
PubMed: 35164060
DOI: 10.3390/molecules27030795 -
Water Environment Research : a Research... Sep 2022The mobile-organic biofilm (MOB) process includes mobile biofilms and their retention screens with a bioreactor and liquid and solid separation. The MOB process is...
The mobile-organic biofilm (MOB) process includes mobile biofilms and their retention screens with a bioreactor and liquid and solid separation. The MOB process is inexpensive and easy to integrate with wastewater treatment (WWT) processes, and it provides for high-rate WWT in biofilm or hybrid bioreactors. This paper describes three modes of MOB process operation. The first mode of operation, Mode I, has a mobile-biofilm reactor and a mobile-biofilm retention screen that is downstream of and external to a bioreactor and upstream of liquid and solid separation. Modes II and III have a hybrid (i.e., mobile biofilms and accumulated suspended biomass) bioreactor and liquid and solid separation. Mode II includes a mobile-biofilm retention screen that is downstream of and external to a hybrid bioreactor and upstream of liquid and solid separation. Mode III includes mobile-biofilm retention screening that is external to a hybrid bioreactor and liquid and solid separation, receives waste solids, and relies on environmental conditions and wastewater characteristics that are favorable for aerobic-granular sludge formation. This paper presents a mechanistic approach to design and evaluate MOB processes and describes MOB process: (1) modes of operation, (2) design and analysis methodology, (3) process and mechanical design criteria, (4) mathematical modeling, (5) design equations, and (6) mobile-biofilm settling characteristics and return. A mathematical model was applied to describe a fixed bioreactor volume and secondary-clarifier area with Modes I, II, and III. The mathematical modeling identified key differences between MOB process modes of operation, which are described in this paper. PRACTITIONER POINTS: MOB is a municipal and industrial wastewater treatment (WWT) process that reduces bioreactor and liquid and solids separation process volumes. It may operate with a mobile-biofilm reactor or a hybrid (mobile biofilms and suspended biomass) bioreactor. This paper provides a mechanistic basis for the selection and design of a MOB process mode of operation, and it describes MOB process modes of operation, design criteria, design equations, mathematical modeling, and mobile-biofilm settling characteristics. MOB integrated WWT plants exist at full scale and reliably meet their treatment objectives. The MOB process is an emerging environmental biotechnology for cost-effective WWT.
Topics: Biofilms; Bioreactors; Sewage; Wastewater; Water Purification
PubMed: 36114754
DOI: 10.1002/wer.10792 -
Scientific Reports Sep 2019In regenerative medicine, techniques which control stem cell lineage commitment are a rapidly expanding field of interest. Recently, nanoscale mechanical stimulation of...
In regenerative medicine, techniques which control stem cell lineage commitment are a rapidly expanding field of interest. Recently, nanoscale mechanical stimulation of mesenchymal stem cells (MSCs) has been shown to activate mechanotransduction pathways stimulating osteogenesis in 2D and 3D culture. This has the potential to revolutionise bone graft procedures by creating cellular graft material from autologous or allogeneic sources of MSCs without using chemical induction. With the increased interest in mechanical stimulation of cells and huge potential for clinical use, it is apparent that researchers and clinicians require a scalable bioreactor system that provides consistently reproducible results with a simple turnkey approach. A novel bioreactor system is presented that consists of: a bioreactor vibration plate, calibrated and optimised for nanometre vibrations at 1 kHz, a power supply unit, which supplies a 1 kHz sine wave signal necessary to generate approximately 30 nm of vibration amplitude, and custom 6-well cultureware with toroidal shaped magnets incorporated in the base of each well for conformal attachment to the bioreactor's magnetic vibration plate. The cultureware and vibration plate were designed using finite element analysis to determine the modal and harmonic responses, and validated by interferometric measurement. This helps ensure that the vibration plate and cultureware, and thus collagen and MSCs, all move as a rigid body, avoiding large deformations close to the resonant frequency of the vibration plate and vibration damping beyond the resonance. Assessment of osteogenic protein expression was performed to confirm differentiation of MSCs after initial biological experiments with the system, as well as atomic force microscopy of the 3D gel constructs during vibrational stimulation to verify that strain hardening of the gel did not occur. This shows that cell differentiation was the result of the nanovibrational stimulation provided by the bioreactor alone, and that other cell differentiating factors, such as stiffening of the collagen gel, did not contribute.
Topics: Bioreactors; Cell Culture Techniques; Cell Differentiation; Cells, Cultured; Equipment Design; Humans; Mechanotransduction, Cellular; Mesenchymal Stem Cells; Osteogenesis; Tissue Engineering
PubMed: 31506561
DOI: 10.1038/s41598-019-49422-4 -
Biotechnology and Bioengineering Aug 2021This analysis examines the potential of "cultured meat" products made from edible animal cell culture to measurably displace the global consumption of conventional meat....
This analysis examines the potential of "cultured meat" products made from edible animal cell culture to measurably displace the global consumption of conventional meat. Recognizing that the scalability of such products must in turn depend on the scale and process intensity of animal cell production, this study draws on technoeconomic analysis perspectives in industrial fermentation and upstream biopharmaceuticals to assess the extent to which animal cell culture could be scaled like a fermentation process. Low growth rate, metabolic inefficiency, catabolite inhibition, and shear-induced cell damage will all limit practical bioreactor volume and attainable cell density. Equipment and facilities with adequate microbial contamination safeguards have high capital costs. The projected costs of suitably pure amino acids and protein growth factors are also high. The replacement of amino-acid media with plant protein hydrolysates is discussed and requires further study. Capital- and operating-cost analyses of conceptual cell-mass production facilities indicate economics that would likely preclude the affordability of their products as food. The analysis concludes that metabolic efficiency enhancements and the development of low-cost media from plant hydrolysates are both necessary but insufficient conditions for displacement of conventional meat by cultured meat.
Topics: Animals; Bioreactors; CHO Cells; Cell Culture Techniques; Cricetulus; Culture Media; Meat
PubMed: 34101164
DOI: 10.1002/bit.27848