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Next Generation Tissue Engineering Strategies by Combination of Organoid Formation and 3D Bioprinting
Published in Naznin Sultana, Sanchita Bandyopadhyay-Ghosh, Chin Fhong Soon, Tissue Engineering Strategies for Organ Regeneration, 2020
Shikha Chawla, Juhi Chakraborty, Sourabh Ghosh
Bioreactors play a crucial role in maintaining precise culture conditions like pH, osmolality, temperature, and oxygen concentration required for cell proliferation and differentiation. Furthermore, there is a possibility to facilitate even mass and nutrient transfer for the cultured cells. Bioreactors have been utilized since long to provide additional control over physical signals corresponding to tissue of interest (physiological mechanical loading, compression, shear and interstitial fluid flow). Development of anatomically relevant intervertebral tissue construct is an interesting example, where bioreactor induced fluid flow modulated the constructs towards attaining an in vivo like tissue gradient. The interior region of the constructs showed stiffer compression along with the overexpression of collagen II, GAG, while the outer region showed stiffer tension and overexpressed collagen I (Bhattacharjee et al. 2014). Proper combination of cell-scaffold-bioreactor system has been also used to develop some disease models like the 3D tumor models, where this system helps in stimulating tumor characteristics in vitro for an extended time (Guller et al. 2016). Such successful models could be utilized for the research, development and diagnosis of new strategies for cancer treatment.
Open Cultivation Systems and Closed Photobioreactors for Microalgal Cultivation and Biomass Production
Published in Gokare A. Ravishankar, Ranga Rao Ambati, Handbook of Algal Technologies and Phytochemicals, 2019
C.K. Madhubalaji, Ajam Shekh, P.V. Sijil, Sandeep Mudliar, Vikas Singh Chauhan, Ravi Sarada, Ambati Ranga Rao, Gokare A. Ravishankar
Closed bioreactors of various designs are being developed and adapted for controlled cultivation of the biomass with higher precision in providing the adequate quantity and quality of light; mixing of nutrients and dosing; regulation of pH, temperature, in addition to programmed harvesting of the biomass. The configuration of the photobioreactor has a great influence on CO2 capture and biomass production by microalgae. Various closed photobioreactors (flat panel, airlift, bubble column, stirred tank reactors) are considered for microalgae cultivation (Ranga Rao et al. 2016). In order to utilize the advantages of both open cultivation and closed bioreactors, hybrid reactors are in use.
3D In Vitro/Ex Vivo Systems
Published in Anthony J. Hickey, Sandro R.P. da Rocha, Pharmaceutical Inhalation Aerosol Technology, 2019
Bethany M. Young, Alexandria Ritchie, Laleh Golshahi, Rebecca L. Heise
Recellularization of decellularized lung scaffolds is improved by culturing in a dynamic bioreactor system to simulate the physiological environment and innovative protocols that allow for the most effective seeding of cells (Ren et al. 2015; Gilpin et al. 2017; Le et al. 2017). Bioreactor designs began with hollow fiber bioreactors that allow for basic perfusion of media around the tube and air within the tube for lung cell differentiation (Guyot and Hanrahan 2002) to more complex and regulated whole lung perfusion systems. Bioreactors have been developed for both decellularization and recellularization procedures to ensure reproducibility. The most common system performs cell seeding and culture with pulsatile or continuous vascular perfusion and negative pressure breathing (Ott et al. 2010; Bonvillain et al. 2013). This system can be outfitted with various aerosol delivery systems such as pressure metered-dose inhaler, dry powder inhalers, nebulizers, solution mist inhalers, or nasal sprays (Cheng 2014) at the inlet of the tracheal canula to test pharmacokinetics and toxicity.
Development and Clinical Translation Considerations for the Next Wave of Gene Modified Hematopoietic Stem and Progenitor Cells Therapies
Published in Expert Opinion on Biological Therapy, 2022
Matthew Li, Brent Morse, Sadik Kassim
While autologous HSPC therapies may not require the scale seen in bioprocessing, the merging of fields has been explored in the realm of bioreactors. Innately more complicated in nature, bioreactors offer the advantage of increased process monitoring (e.g. direct temp, O2, pH, etc. measurements) and controls (e.g. media feeds). However, the effect of mechanical cues and culture conditions on HSPC stemness, function, and overall impact on drug product potency should be understood [127–129]. For instance, it has been shown that autocrine factors during culture can affect HSPC biology and that the development of a bioreactor to control media removal and feed rates could control this [130]. Cell therapy-specific devices, such as the CliniMACS® Prodigy, have demonstrated promise for an all-in-one, cGMP compliant system for HSPC therapies [131].
Manufacturing T cells in hollow fiber membrane bioreactors changes their programming and enhances their potency
Published in OncoImmunology, 2021
Seung Mi Yoo, Vivan W.C. Lau, Craig Aarts, Bojana Bojovic, Gregory Steinberg, Joanne A. Hammill, Anna Dvorkin-Gheva, Raja Ghosh, Jonathan L. Bramson
A central component of the process used to manufacture T cells is the vessel, or bioreactor, used to culture the T cells. In most cases, the bioreactor is a plastic dish or culture bag, which requires an operator to manipulate cells and medium. We believe the ideal bioreactor should allow all unit operations to be carried out within a single device in an integrated fashion, thereby overcoming the need for multiple transfer steps typically required for cell expansion, and downstream processing steps such as centrifugation. Additionally, as personalized cell therapies present a scale-out, rather than a scale-up, challenge, the bioreactor and associated equipment should occupy as small a footprint as possible to enable the installation of multiple closed units within a single manufacturing suite. Hollow fiber membrane bioreactors (HFMBR) are ideally suited for this purpose. They are perfusion-based, protect cells from high shear stresses, ensure adequate oxygen transport to cells, aid in achieving high cell density and productivity, reduce media requirement, and allow integration of cell culture with downstream processing; all in a small footprint. Nutrients can be added to, and toxic metabolites can be removed from, HFMBRs in a controllable manner allowing all unit operations associated with the T cell culture to be performed in a single bioreactor, which reduces the number of human interventions and will facilitate the ultimate automation of the manufacturing process.
Study of tissue engineered vascularised oral mucosa-like structures based on ACVM-0.25% HLC-I scaffold in vitro and in vivo
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2020
Minyue Zhou, Xiao Chen, Yanling Qiu, He Chen, Yaoqiang Liu, Yali Hou, Minhai Nie, Xuqian Liu
The realisation of vascularisation in vivo depends on the bioreactor. Bioreactor is a new type of equipment that has appeared in the field of biological engineering in recent years, which was used in many fields due to their diverse functions [26–28]. In this study, the skin of nude mice was used as a bioreactor to simulate human oral mucosa defect, and the HGECs-HGFs-VECs-ACVM-0.25% HLC-I complex was implanted in the skin defect of nude mice to induce the formation of new tissues, so as to explore the feasibility of constructing tissue-engineered vascularised oral mucosa after implantation of the tissue-engineered vascularised tissue complex in vitro. Enhancement experiments in vivo showed that no obvious scar repair was observed at the wound surface of the nude mice in the experimental group after 28 days, and the implanted tissue had a good connection with the surrounding normal skin. The presence of hard tissue of the scaffold could be sensed by pressure, but the scaffold could not be removed by pulling, indicating that the cellular scaffold complex had a good compatibility with the tissue of the nude mice. EDU tracer staining results indicated that the seed cells with epithelioid-like structure, lamina propria-like structure and vascular-like structure were derived from HGECs, HGFs and VEC-like cells cultured in vitro.