{"title":"Correction to “Regeneration of Spent Culture Media for Sustainable and Continuous mAb Production via Ion Concentration Polarization”","authors":"","doi":"10.1002/bit.70034","DOIUrl":"10.1002/bit.70034","url":null,"abstract":"<p>Wynne, E., Yoon, J., Park, D., Cui, M., Morris, C., Lee, J., Wang, Z., Yoon, S. and Han, J. (2025). Regeneration of Spent Culture Media for Sustainable and Continuous mAb Production via Ion Concentration Polarization. <i>Biotechnology and Bioengineering</i>, 122: 373–381. https://doi.org/10.1002/bit.28888</p><p>During production, Figure 3 was duplicated and appeared as both Figures 3 and 4. The correct Figure 4 appears below.</p><p>We apologize for this error.</p>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 10","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/epdf/10.1002/bit.70034","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144763290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marianne Volkmar, Wolfgang Laudensack, Felix Bartzack, Niklas Erdmann, Sonja Schönrock, Emely Fuderer, Dirk Holtmann, Lars M. Blank, Roland Ulber
{"title":"Low Oxygen Availability Increases Itaconate Production by Ustilago maydis","authors":"Marianne Volkmar, Wolfgang Laudensack, Felix Bartzack, Niklas Erdmann, Sonja Schönrock, Emely Fuderer, Dirk Holtmann, Lars M. Blank, Roland Ulber","doi":"10.1002/bit.70035","DOIUrl":"10.1002/bit.70035","url":null,"abstract":"<p>Itaconic acid is a monomer for high performance polymers. While produced in industry with the filamentous fungi <i>Aspergillus terreus</i>, the production with the smut fungus <i>Ustilago maydis</i> was proposed recently. The strict aerobic process suffers from high power input via gassing and stirring. Here, we investigated in detail possible scenarios for the reduction of energy use during cultivation. In contrast to fermentations with other organic acids, in which even small oxygen concentrations in the medium hinders production, low oxygen availability correlated with increased itaconic acid titer and yield. This is somewhat surprising, as not only the sensitivity of itaconic acid producing <i>U. maydis</i> to oxygen deprivation was previously reported, but also the lower degree of reduction compared to glucose is not directly arguing for improved yield. Scale ups from 0.4 to 30 L using different criteria confirmed the positive impact of low availability of oxygen on itaconic acid production, suggesting a shift in metabolic pathways under restricted oxygen conditions. Oxygen limitation, encountered more likely in industrial fermenters, can be effectively used as a process control strategy to enhance itaconic acid production in <i>U. maydis</i>, offering a new approach for improving the efficiency of industrial-scale biotechnological production.</p>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 11","pages":"3007-3017"},"PeriodicalIF":3.6,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/epdf/10.1002/bit.70035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144763288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Filsan Ahmed Abokor, Safiya Al Yazeedi, Janaeya Zuri Baher, Chung Cheung, Don D. Sin, Emmanuel Twumasi Osei
{"title":"Exploring Multi-Organ Crosstalk via the TissUse HUMIMIC Chip System: Lessons Learnt So Far","authors":"Filsan Ahmed Abokor, Safiya Al Yazeedi, Janaeya Zuri Baher, Chung Cheung, Don D. Sin, Emmanuel Twumasi Osei","doi":"10.1002/bit.70031","DOIUrl":"10.1002/bit.70031","url":null,"abstract":"<p>Three-dimensional (3D) in vitro cell culture models have revolutionized biomedical research by mimicking the complex 3D in vivo environment in the human body. Different types of 3D models have been established, including heterotypic systems such as, organ-on-a-chips which have been further developed into multiorgan-on-chip systems that simulate or mimic the mutual and multiplex physiological communication between (distant) organs that may not be physically connected with each other known as multiorgan crosstalk/interactions. These multiorgan interactions have been shown to be mediated by various factors including cells, soluble mediators (growth factors, cytokines etc.,) and cellular vesicles and are responsible for regulating metabolic, inflammatory, and tissue repair processes in the body. Different multiorgan-on-chip systems have been developed to mimic and study these interactions and their role in various molecular and toxicological processes. Of these, the TissUse HUMIMIC Starter and Chip microphysiological system is a commercially available multiorgan model that has been used to study inter-organ crosstalk between organs such as the gut and liver, liver and brain, liver and kidney, among others and applied in cellular, molecular and toxicology studies to among other things aid in the reduction of animals in drug and toxicological research. In this review, we provide a brief overview of multiorgan systems and summarize studies that have specifically used the TissUse system to investigate multiorgan crosstalk in the human body to deliver an update in the field of multiorgan microphysiological systems.</p>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 11","pages":"2951-2966"},"PeriodicalIF":3.6,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/epdf/10.1002/bit.70031","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144720259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yan Gao, Patrick Perré, Ignacio Fierro, Filipa Lopes, Olivier Bernard
{"title":"Mechanistic Modeling of Rotating Algal Biofilms","authors":"Yan Gao, Patrick Perré, Ignacio Fierro, Filipa Lopes, Olivier Bernard","doi":"10.1002/bit.70028","DOIUrl":"10.1002/bit.70028","url":null,"abstract":"<div>\u0000 \u0000 <p>Biofilm-based microalgal cultivation systems have emerged as a promising alternative to conventional suspended growth methods, offering improved light utilization and biomass productivity. Among these, Rotating Algal Biofilm (RAB) systems are particularly advantageous by subjecting cells to short periodic light/dark (L/D) cycles to mitigate photoinhibition. Through experimental validation and modeling, this study demonstrates that optimized L/D cycles enhance photosynthetic efficiency by temporally diluting high-intensity light. To investigate the impact of light regimes, a model was developed based on Han's photosynthesis framework, incorporating respiration dynamics for broad ranges of cycle times and L/D ratios. Calibrated with experimental data, it accurately predicts biofilm behavior under varying light conditions. A key innovation is the integration of respiration variations during intermittent illumination, providing insights into growth dynamics across frequencies and duty cycles. Key findings show that high light frequencies reduce photoinhibition and enhance growth at given intensities. Increasing the light fraction improves growth rates by reducing peak intensity and shortening dark periods. The model elucidates biofilm responses to fluctuating light and offers strategies for reactor optimization. This study advances algal biofilm photophysiology understanding and provides a predictive tool for optimization and scaling up biofilm-based cultivation systems.</p></div>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 11","pages":"2980-3006"},"PeriodicalIF":3.6,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144715569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Porphyrin-Based Carbon Dots: Navigating the Nanoscale Frontier of Precision Biomedicine","authors":"Qian He","doi":"10.1002/bit.70032","DOIUrl":"10.1002/bit.70032","url":null,"abstract":"<div>\u0000 \u0000 <p>As natural aromatic macrocyclic compounds with an 18-π electron system, porphyrins exhibit key values in multiple fields such as biosensing, imaging, and photothermal/photodynamic therapy due to their unique photophysical properties and chemical tunability. Their integration with low-toxicity carbon dots (CDs) with tunable optical and physicochemical properties has opened diverse innovative pathways for interdisciplinary nanotechnology research. This review presents a critical analysis of porphyrin-based CDs (p-CDs), highlighting their structural versatility and transformative applications in nanomedicine. By integrating porphyrin's photophysical prowess with CDs' biocompatibility, these hybrid materials enable breakthroughs in near-infrared bioimaging, enzymatic-optical dual sensing, and synergistic phototherapies. Synthetic strategies, including covalent π-conjugation, natural precursor carbonization, and metal-nanozyme engineering, are discussed to underscore their structure–activity relationships. In the landscape of biomedicine, p-CDs have emerged as a revolutionary tool, facilitating early disease detection, precise molecular diagnosis, and targeted therapeutic interventions, thereby reshaping the paradigms of clinical practice and patient care. However, challenges remain in large-scale production and biocompatibility assessment. Future research should prioritize biomimetic design and multimodal integration to realize the full potential of p-CDs in precision medicine.</p>\u0000 </div>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 11","pages":"2937-2950"},"PeriodicalIF":3.6,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144701338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Joseph A. E. Morgan, Peter R. Cook, Alfonso A. Castrejón-Pita, Edmond J. Walsh
{"title":"Generation of Clonal Cultures of Adherent or Suspension Cells Using Flat Sessile Drops for Assurance of Monoclonality","authors":"Joseph A. E. Morgan, Peter R. Cook, Alfonso A. Castrejón-Pita, Edmond J. Walsh","doi":"10.1002/bit.70030","DOIUrl":"10.1002/bit.70030","url":null,"abstract":"<p>Single-cell isolation is an essential step in many biomedical workflows, including genetic analyses and drug-based assays. It is commonly attempted through limiting dilution into microtiter wells. However, dark optical edge effects at the well periphery make it difficult to confirm which wells contain just one cell. Consequently, statistical methods are used to obtain the probability that a well contains a single cell. Sessile microdrops can be deposited in the center of wells away from obscuring walls. If these drops have low contact angles, optical edge effects are minimal. A dilute cell suspension can be infused into such drops, which are then imaged to confirm the presence of a single cell with certainty. Subsequently, wells are flooded with media and incubated to allow clonal growth. The fraction of single cells yielding colonies then provides an accurate and non-probabilistic measure of cloning efficiency. We demonstrate average cloning efficiencies between 62% and 78% with human embryonic kidney, cancer, and induced pluripotent stem cells, as well as Chinese-hamster suspension cells. We verify that stem cells continue to express pluripotency markers after cloning and incorporate the method into a gene-editing workflow for cell-line development. This demonstrates the seamless integration of sessile microdrops into established protocols, providing assurance of monoclonality with high cloning efficiency.</p>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 10","pages":"2739-2750"},"PeriodicalIF":3.6,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/epdf/10.1002/bit.70030","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144664181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alexander W. Rogers, Fernando Vega-Ramon, Amanda Lane, Philip Martin, Dongda Zhang
{"title":"Interpretable-AI-Based Model Structural Transfer Learning to Accelerate Bioprocess Model Construction","authors":"Alexander W. Rogers, Fernando Vega-Ramon, Amanda Lane, Philip Martin, Dongda Zhang","doi":"10.1002/bit.70026","DOIUrl":"10.1002/bit.70026","url":null,"abstract":"<p>Determining accurate kinetic models for new biochemical systems is time-intensive, requiring experimental data collection, model construction, validation, and discrimination. Traditional black-box machine learning-based transfer learning methods leverage prior knowledge but lack interpretability and physical insights. To address this, we propose a novel model structural transfer learning approach that combines symbolic regression with artificial neural network feature attribution. The method enables automatic structural modification of an inaccurate or low-fidelity mechanistic model developed for one system when being applied to another system. Through a comprehensive in silico case study, our framework successfully adapted a kinetic model from one biochemical system to a different but related one, improving predictive accuracy. Moreover, the framework can significantly accelerate model identification when being integrated with model-based design of experiments. By comparing the old and new model structures, physical insight can be obtained, altogether highlighting the framework's potential for advancing automated knowledge discovery and facilitating high-fidelity predictive digital twin design for novel biochemical processes.</p>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 10","pages":"2819-2831"},"PeriodicalIF":3.6,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/epdf/10.1002/bit.70026","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144652903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Quyen Nham, Tristan Gordon, Hanna Farnelid, Catherine Legrand, Elin Lindehoff
{"title":"Mitigating Night Biomass Loss in Outdoor Pilot-Scale Mixotrophic Algal Cultivation of Monoraphidium minutum Using Flue Gas Condensate and Cheese Whey","authors":"Quyen Nham, Tristan Gordon, Hanna Farnelid, Catherine Legrand, Elin Lindehoff","doi":"10.1002/bit.70027","DOIUrl":"10.1002/bit.70027","url":null,"abstract":"<p>In algal cultivation, nighttime biomass loss due to respiration and cell mortality can considerably reduce the amount of biomass produced during daylight. The adverse effect can be counteracted by mixotrophic cultivation, where an organic carbon (OC) source is used to supply the energy required for cell maintenance and division during darkness. The potential for mixotrophic cultivation to mitigate night biomass loss has yet to be tested under outdoor, large-scale conditions that use raw industrial waste streams, particularly during low-light seasons. We investigated night biomass loss in cultivation of the strain <i>Monoraphidium minutum</i> KAC90 in outdoor 1 m<sup>3</sup> raceway ponds during the Nordic autumn. Flue gas condensate (nitrogen source) and cheese whey (phosphorus and OC source) were used for the mixotrophic treatment, while potassium monophosphate (phosphorus source) was used for the photoautotrophic control. Results indicate that under high OC availability, the mixotrophic treatment had a night biomass gain of 33% ± 16%, whereas it experienced a night biomass loss of 10% ± 9% under low OC. In contrast, the photoautotrophic control showed a night biomass loss of 5% ± 15%. In the mixotrophic treatment, algal biomass had a higher carbohydrate content, but lower levels of lipids and proteins than the photoautotrophic cultures. The cultivation of algae using cheese whey may increase biomass accumulation in darkness, enhancing the overall production of algal biomass rich in carbohydrates.</p>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 10","pages":"2688-2700"},"PeriodicalIF":3.6,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/epdf/10.1002/bit.70027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144652901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mathematical Model for Measles Virus Production in Batch Bioreactors","authors":"Shiny Samuel, Todd Przybycien","doi":"10.1002/bit.70017","DOIUrl":"10.1002/bit.70017","url":null,"abstract":"<div>\u0000 \u0000 <p>Measles virus (MeV) is a promising vector for vaccines, gene therapy, and oncolytic virus therapy due to its safety, efficacy, and natural ability to target tumor cells. However, MeV production in bioreactors, typically with microcarrier cultures of Vero cells, is challenging because of the sensitivity of the virus to temperature, shear stress, and low pH. At 37°C, the optimal growth temperature of Vero cells, MeV has a short half-life of 1 h, requiring precise control of the harvest time (TOH) to maximize yield. We developed a mathematical model to predict the TOH for recombinant MeV production in Vero cells. Model predictions for TOH were in good agreement with observations across five separate bioreactor runs, despite significant run-to-run performance variations. Parameter analysis revealed that virus attachment parameters and thermal degradation rate significantly influence infection dynamics. Furthermore, the model highlights the critical importance of accurately characterizing seed virus quality, particularly concerning defective interfering particle (DIP) content, to minimize production variability and optimize yield.</p></div>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 10","pages":"2791-2802"},"PeriodicalIF":3.6,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144645986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tom A. Wyrobnik, Laia Miranda, Alan Lam, Steve Oh, Andrea Ducci, Martina Micheletti
{"title":"Scalable, High-Density Expansion of Human Mesenchymal Stem Cells on Microcarriers Using the Bach Impeller in Stirred-Tank Reactors","authors":"Tom A. Wyrobnik, Laia Miranda, Alan Lam, Steve Oh, Andrea Ducci, Martina Micheletti","doi":"10.1002/bit.70025","DOIUrl":"10.1002/bit.70025","url":null,"abstract":"<p>This paper describes the results of process developmental experiments to achieve higher cell densities in the manufacturing of hMSCs using the novel Bach impeller in a stirred-tank bioreactor. Engineering experiments have previously shown that the Bach impeller represents an efficient mixing device that suspends particles in fluids at low power inputs. To assess the impeller during biological experiments, the growth performance of Wharton Jelly (WJ)-hMSCs in a 1 L STR equipped with the Bach impeller was evaluated at a variety of culture conditions. The cells attached to Cytodex 1 microcarriers at a concentration of 5.6 g/L and were cultured for 5–7 days. The growth phase was carried out at varying impeller speeds <span></span><math>\u0000 <semantics>\u0000 <mrow>\u0000 \u0000 <mrow>\u0000 <mi>N</mi>\u0000 </mrow>\u0000 </mrow>\u0000 </semantics></math> = 75, 115, and 150 rpm. Cell growth was additionally evaluated at a microcarrier concentration of 11.2 g/L Cytodex 1. Here, a maximum cell density of up to 1.7 × 10<sup>6</sup> cells/mL and cell viability > 90% was achieved within 5 culture days, which is amongst the highest cell densities ever attained for a hMSC batch culture. Critical cell quality attributes of the WJ-hMSCs were assessed upon completion of the growth phase, that is, FACS to identify stem cell surface markers, tri-lineage differentiation, and capacity of the cells to form colonies. In addition, informed by the previously described engineering characterization, the 1 L process at <span></span><math>\u0000 <semantics>\u0000 <mrow>\u0000 \u0000 <mrow>\u0000 <mi>N</mi>\u0000 </mrow>\u0000 </mrow>\u0000 </semantics></math> = 75 rpm was scaled up to the 5 L scale, where WJ-hMSCs were again confirmed to have retained the relevant cell quality attributes. The reported findings are important to determine the design space to which scale-ups to even larger tank sizes can adhere.</p>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 10","pages":"2803-2818"},"PeriodicalIF":3.6,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/epdf/10.1002/bit.70025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144652904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}