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Feasibility Assessment of a Single‐pH Connected Polishing Train for Monoclonal Antibody Purification Using Mildly Acidic Protein A Elution and an Acidic‐Window Anion Exchange Membrane 使用温和酸性蛋白a洗脱和酸性窗口阴离子交换膜纯化单克隆抗体的单pH连接抛光序列的可行性评估
IF 3.8 2区 生物学
Biotechnology and Bioengineering Pub Date : 2026-10-19 DOI: 10.1002/bit.70415
Takaki Aiso, Hiroshi Muto, Kyota Suzuki, Yumiko Masuda, Hirofumi Kakihara, Masashi Sonoyama
{"title":"Feasibility Assessment of a Single‐pH Connected Polishing Train for Monoclonal Antibody Purification Using Mildly Acidic Protein A Elution and an Acidic‐Window Anion Exchange Membrane","authors":"Takaki Aiso, Hiroshi Muto, Kyota Suzuki, Yumiko Masuda, Hirofumi Kakihara, Masashi Sonoyama","doi":"10.1002/bit.70415","DOIUrl":"https://doi.org/10.1002/bit.70415","url":null,"abstract":"Monoclonal antibody downstream processing often requires multiple pH adjustments between Protein A capture and polishing steps. These adjustments increase process complexity and make direct unit‐operation connection more difficult. We evaluated a connected post‐capture polishing block operated at approximately pH 5.0 using mild‐pH Protein A elution, an acidic‐window anion exchange (AEX) membrane, and cation exchange (CEX) chromatography. Praesto Jetted A50 HipH generated IgG1 eluates near pH 5.0 with conductivity suitable for direct AEX loading. Under standard condition (pH 5.0, 5.0 mS/cm), the AEX membrane reduced xenotropic murine leukemia virus to the assay limit (≥ 3 log10) and minute virus of mice by approximately 2–3 log10. In a connected proof‐of‐concept run without intermediate pH adjustment, the AEX–CEX polishing block reduced host cell proteins from > 25 to < 10 ng/mg‐IgG and high‐molecular‐weight species from 1.3% to < 1% in the final product pool, maintained low‐molecular‐weight species below 1%, and achieved 97.6% product recovery. For two additional IgGs, archived strong‐AEX flow‐through records at pH 7.5 and sequence‐derived charge descriptors supported the plausibility of product flow‐through at pH 5.0. In a same‐IgG1 retrospective comparison, the connected configuration used fewer vessels and conditioning operations and had shorter recipe‐derived programmed chromatography time. These findings support process‐representative evaluation of single‐pH connected polishing.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"81 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149218635","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}
引用次数: 0
Engineering 4‐Vinylcatechol Biosynthesis in Escherichia coli Through Host–Enzyme Combination 通过宿主-酶结合在大肠杆菌中合成乙烯基儿茶酚
IF 3.8 2区 生物学
Biotechnology and Bioengineering Pub Date : 2026-10-19 DOI: 10.1002/bit.70414
Esra Kaynak, Merve Seven, Hüseyin Balcı, Arzu Aysan, Mattheos A. G. Koffas, Hülya Akdemir
{"title":"Engineering 4‐Vinylcatechol Biosynthesis in Escherichia coli Through Host–Enzyme Combination","authors":"Esra Kaynak, Merve Seven, Hüseyin Balcı, Arzu Aysan, Mattheos A. G. Koffas, Hülya Akdemir","doi":"10.1002/bit.70414","DOIUrl":"https://doi.org/10.1002/bit.70414","url":null,"abstract":"<jats:italic>De novo</jats:italic> biosynthesis of 4‐vinylcatechol (VCAT), a valuable bio‐based monomer and potent antioxidant, has emerged as a crucial objective due to its profound industrial and pharmacological significance. However, its biosynthesis is frequently hindered by limited precursor availability. In this study, we developed a highly efficient, dual‐plasmid platform utilizing engineered <jats:italic>Escherichia coli</jats:italic> cell factories to synthesize VCAT directly from glucose without precursor feeding. To establish optimal production cells, we evaluated combinations of different host strains and phenolic acid decarboxylase ( <jats:italic>PAD</jats:italic> ) sources. Our results indicate that BL21(DE3) is less suitable for efficient <jats:italic>de novo</jats:italic> VCAT biosynthesis under the conditions tested. In contrast, the rpoA14(DE3), featuring a reprogrammed shikimate pathway, provided a more favorable host for VCAT production and enabled endogenous tyrosine supply, thereby eliminating the need for exogenous tyrosine supplementation required in BL21(DE3). To maximize this enhanced intracellular flux, we comparatively evaluated <jats:italic>padC</jats:italic> genes from different <jats:italic>Bacillus subtilis</jats:italic> strains. Comparative analysis demonstrated that the rpoA14(DE3)‐10A5 exhibited significantly superior production titers, markedly outperforming both its 168‐PAD counterpart and the standard BL21(DE3) expression hosts. Cultivated in single‐step, aqueous fermentation at mild conditions, this optimal host–enzyme combination achieved <jats:italic>de novo</jats:italic> accumulation of 200 mg/L VCAT, promising scalable biosynthesis.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"64 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149218634","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}
引用次数: 0
Biogenic Magnetic Nanoplatform for Dual Tumor Microenvironment‐Responsive Aripiprazole Delivery in Breast Cancer 双肿瘤微环境响应的乳腺癌阿立哌唑递送生物源磁性纳米平台
IF 3.8 2区 生物学
Biotechnology and Bioengineering Pub Date : 2026-10-19 DOI: 10.1002/bit.70382
S. Ayyanaar, Munusamy Settu, A. Arunkumar, R. Kayalvizhi, M. Sathiyamoorthy, Johnpeter Deepak Rosario, M. P. Kesavan, M. Sampath
{"title":"Biogenic Magnetic Nanoplatform for Dual Tumor Microenvironment‐Responsive Aripiprazole Delivery in Breast Cancer","authors":"S. Ayyanaar, Munusamy Settu, A. Arunkumar, R. Kayalvizhi, M. Sathiyamoorthy, Johnpeter Deepak Rosario, M. P. Kesavan, M. Sampath","doi":"10.1002/bit.70382","DOIUrl":"https://doi.org/10.1002/bit.70382","url":null,"abstract":"Breast cancer remains a major global health challenge, highlighting the need for targeted drug delivery systems with improved therapeutic efficacy and reduced systemic toxicity. In this study, a green‐synthesized dual‐responsive magnetic nanoplatform, Iron oxide@Tween 80‐PEG‐ARI‐NPs, was developed for targeted breast cancer therapy. Iron oxide nanoparticles were synthesized using <jats:italic>Nephelium lappaceum</jats:italic> ( <jats:italic>Rambutan</jats:italic> ) peel extract as an eco‐friendly reducing and stabilizing agent, followed by functionalization with Tween 80, polyethylene glycol (PEG), and aripiprazole (ARI) loading. Comprehensive characterization using FTIR, XRD, SEM‐EDX, HR‐TEM, DLS, TGA/DTA, and VSM confirmed successful surface modification, spherical morphology, preserved crystallinity, superparamagnetic behavior, and enhanced colloidal stability. In vitro drug release studies demonstrated minimal ARI leakage at physiological pH 7.4 and accelerated release under acidic pH 5.5 and oxidative conditions, reaching 70.40% ± 0.55% and 90.35% ± 5.15% cumulative release after 60 h, respectively. Release kinetics followed anomalous non‐Fickian diffusion under acidic conditions and quasi‐Fickian diffusion at physiological pH. The nanoparticles exhibited significant anti‐inflammatory activity and potent cytotoxicity against MCF‐7 breast cancer cells, with an IC <jats:sub>50</jats:sub> of 40.2 ± 2.15 µg/mL, inducing pronounced apoptotic morphological changes. These findings demonstrate the potential of Iron oxide@Tween 80‐PEG‐ARI‐NPs as an effective dual‐responsive magnetic nanocarrier for targeted breast cancer therapy with enhanced therapeutic potential.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"28 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149218633","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}
引用次数: 0
Highly Diastereo‐ and Enantioselective Imine Reductases Engineered for γ‐Piperidinamines Bearing Contiguous Stereocenters 高度非立体选择性和对映选择性亚胺还原酶,用于γ -哌啶胺的连续立体中心
IF 3.8 2区 生物学
Biotechnology and Bioengineering Pub Date : 2026-10-15 DOI: 10.1002/bit.70416
Min‐Min Zhao, Jia‐Neng Xu, Jia‐Hui Chen, Zhe Dou, Ya‐Jun Wang
{"title":"Highly Diastereo‐ and Enantioselective Imine Reductases Engineered for γ‐Piperidinamines Bearing Contiguous Stereocenters","authors":"Min‐Min Zhao, Jia‐Neng Xu, Jia‐Hui Chen, Zhe Dou, Ya‐Jun Wang","doi":"10.1002/bit.70416","DOIUrl":"https://doi.org/10.1002/bit.70416","url":null,"abstract":"Imine reductases (IREDs) represent a highly promising class of biocatalysts for the asymmetric synthesis of chiral amines bearing two stereogenic centers. Herein, we report an IRED‐catalyzed asymmetric reductive amination strategy that converts racemic ketones into γ‐piperidinamines with contiguous stereocenters and operates through a pathway consistent with a dynamic kinetic resolution‐asymmetric reductive amination (DKR‐ARA). The wild‐type <jats:italic>Ac</jats:italic> IRED afforded the 1‐benzyl‐ <jats:italic>N</jats:italic> ‐cyclopropyl‐3‐methylpiperidin‐4‐amine ( 1a ) in 60.8% conversion, but with only 78.5% enantiomeric excess ( <jats:italic>ee</jats:italic> <jats:sub>cis</jats:sub> ) for (3 <jats:italic>S</jats:italic> ,4 <jats:italic>R</jats:italic> )‐ 1a and 23.5% <jats:italic>ee</jats:italic> <jats:sub>trans</jats:sub> for (3 <jats:italic>R</jats:italic> ,4 <jats:italic>R</jats:italic> )‐ 1a , giving an 84:16 diastereomeric ratio ( <jats:italic>dr</jats:italic> ). To enhance stereoselectivity, we employed a “trans‐drop, enantio‐catch” strategy to reshape the pocket architecture of <jats:italic>Ac</jats:italic> IRED. The resulting variant Mut‐5 afforded 99.9% <jats:italic>ee</jats:italic> <jats:sub>cis</jats:sub> for (3 <jats:italic>S</jats:italic> ,4 <jats:italic>R</jats:italic> )‐ 1a and &gt; 99:1 <jats:italic>dr</jats:italic> , along with a 19‐fold increase in specific activity and a 24.7°C elevation in . Remarkably, at a cumulative substrate loading of 700 mM (142.3 g·L <jats:sup>–1</jats:sup> ), Mut‐5 furnished (3 <jats:italic>S</jats:italic> ,4 <jats:italic>R</jats:italic> ) −1a with 95% conversion, a space‐time yield (STY) of 208.7 g·L <jats:sup>–1</jats:sup> ·d <jats:sup>–1</jats:sup> . This strategy not only provided highly efficient imine reductases but also established a robust platform for the atom‐economical synthesis of γ‐piperidinamine building blocks bearing two stereogenic centers.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"13 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149172765","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}
引用次数: 0
Genetically Engineered Whole Virus Biorecognition Units for Cu(II) Sensing 用于Cu(II)传感的基因工程全病毒生物识别单元
IF 3.8 2区 生物学
Biotechnology and Bioengineering Pub Date : 2026-10-15 DOI: 10.1002/bit.70419
Nuriye Korkmaz, Jihoon Kim
{"title":"Genetically Engineered Whole Virus Biorecognition Units for Cu(II) Sensing","authors":"Nuriye Korkmaz, Jihoon Kim","doi":"10.1002/bit.70419","DOIUrl":"https://doi.org/10.1002/bit.70419","url":null,"abstract":"A hybrid filamentous fd virus variant (p9V5‐p8Cu5) was generated with improved gold (Au) and copper (Cu) binding properties through genetic engineering by displaying five copies of Au‐specific V5 peptides (VSGSSPDS) on the head and over 2500 copies of Cu binding Cu5 peptides (HGFANVA) on the elongated body part. Atomic Force Microscopy (AFM) topography imaging revealed the typical filamentous morphology of the engineered p9V5‐p8Cu5 phages with a dry‐state thickness of around 2–3 nm. Gold nanoparticle (AuNP) binding of the viruses was investigated by Scanning Electron Microscopy (SEM) analyses upon exposure to 20 nm PBS‐stabilized AuNPs. The hybrid phages were excessively loaded with AuNPs. Energy Dispersive X‐ray (EDX) analyses showed Au, carbon (C), and nitrogen (N) peaks, confirming the presence of AuNPs and the viral organic material. Quartz crystal microbalance (QCM) analyses, performed using Au‐coated quartz crystal sensors, gave a net frequency decrease of 250.20 ± 14.37 Hz for the engineered bacteriophages versus 31.40 ± 4.47 Hz for wild‐type fd at the 3rd overtone showing their improved Au binding. Enzyme‐Linked Immunosorbent Assay (ELISA) analyses conducted with Cu(II)‐coated magnetic agarose‐based NTA beads revealed the enhanced Cu(II) binding of the hybrid viruses. A colorimetric Cu(II) detection system was validated using 20 nm PBS‐stabilized AuNPs and p9V5‐p8Cu5 phages. Following the Cu(II) exposure, the AuNP–virus complex solution was treated with 10x PBS to induce AuNP aggregation. The level of AuNP aggregation was correlated with the applied Cu(II) concentration. For the case study, a linear relationship ( <jats:italic>R</jats:italic> <jats:sup>2</jats:sup> = 0.9926) was obtained as the absorbance ratios at 600 nm and 525 nm (Abs 600/Abs 525) were plotted against the applied Cu(II) concentration from 0 to 15 µM, with an estimated limit of detection (LOD) of around 260 nM (0.0165 mg/L), well below the WHO drinking‐water guideline of 1.3 mg/L. No significant interference was observed from Ag(I), Al(III), Au(III), Cd(II), Co(II), Cr(III), Fe(III), Mn(II), Ni(II), Pb(II), Zn(II), Na(I), Ca(II), or Mg(II) at 5 µM. In mixed samples containing Cu(II) together with each competing ion, the response was likewise unaffected, with the exception of Pb(II), which partially suppressed the Cu(II) signal. This study demonstrates the potential of genetically reprogrammed biomaterials as biorecognition units, offering a biocompatible, easily produced, and cost‐effective alternative to synthetic peptides in biosensor development.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"53 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149172764","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}
引用次数: 0
A Biomanufacturing Digital Twin for Consistent N‐1 Seed Bioreactor Transfers for Commercial Monoclonal Antibody Production 用于商业单克隆抗体生产的一致N‐1种子生物反应器转移的生物制造数字双胞胎
IF 3.8 2区 生物学
Biotechnology and Bioengineering Pub Date : 2026-10-14 DOI: 10.1002/bit.70400
Yu Luo, Sumit Pareek, Carolyn Zhang, Kelly Sarnese, Diana Ritz, Sameer Talwar
{"title":"A Biomanufacturing Digital Twin for Consistent N‐1 Seed Bioreactor Transfers for Commercial Monoclonal Antibody Production","authors":"Yu Luo, Sumit Pareek, Carolyn Zhang, Kelly Sarnese, Diana Ritz, Sameer Talwar","doi":"10.1002/bit.70400","DOIUrl":"https://doi.org/10.1002/bit.70400","url":null,"abstract":"Process consistency in biomanufacturing, particularly for commercial products, is critical for achieving consistent yield and product quality. The N‐1 seed bioreactor stage, where cells grow before the transfer to a production bioreactor, often faces variability in final viable cell density (VCD), which leads to variable seeding densities in the production bioreactor and subsequent variability in total protein output per batch. In this study, we address the challenge of precise batch transfer by developing an upstream, stage‐specific, level‐2 digital twin (digital shadow). Here we show that a cell growth process model predicts growth accurately and updates forecasts using off‐line and in‐line measurements, enabling precise determination of the final sample time. Deployment of this seed transfer digital twin led to all N‐1 to production transfers falling within acceptable limits and resulted in statistically significant increases in harvest yield relative to historical batches. This improvement is attributed to significantly higher on‐target accuracy of final N‐1 VCDs and significantly higher working volumes in the production bioreactors. Our findings demonstrate that such digital twins ensure consistent cell density during transfer, improve overall upstream process consistency, and lay a foundation for more advanced process control strategies.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"38 5 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149172766","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}
引用次数: 0
A Behavior-Integrated Potency Assay for Quantitative Evaluation of Extracellular Matrix Remodeling by Mesenchymal Stem/Stromal Cells 间充质干细胞/基质细胞细胞外基质重塑的行为综合效价定量评价。
IF 3.9 2区 生物学
Biotechnology and Bioengineering Pub Date : 2026-10-14 Epub Date: 2026-07-05 DOI: 10.1002/bit.70298
Shao Ying Tan, Mee-Hae Kim, Masahiro Kino-oka
{"title":"A Behavior-Integrated Potency Assay for Quantitative Evaluation of Extracellular Matrix Remodeling by Mesenchymal Stem/Stromal Cells","authors":"Shao Ying Tan,&nbsp;Mee-Hae Kim,&nbsp;Masahiro Kino-oka","doi":"10.1002/bit.70298","DOIUrl":"10.1002/bit.70298","url":null,"abstract":"<p>Reliable potency assays are critical for ensuring the therapeutic consistency and manufacturing quality of mesenchymal stem/stromal cells (MSCs). Conventional assays based on soluble factor quantification often fail to capture extracellular matrix (ECM) remodeling capacity and exhibit high variability. We developed a biologically relevant, image-based potency assay that directly quantifies MSCs-mediated ECM remodeling under defined biophysical conditions. A collagen-coated (CL) surface that provides a stable, proliferation-suppressive microenvironment, enabling single-cell quantification of remodeling activity using collagen hybridizing peptide staining. The ECM remodeling index (<i>I</i><sub>CHP+</sub>) defined an optimal working range (3.0 × 10<sup>3</sup> ≤ cells/cm<sup>2</sup> ≤ 4.5 × 10<sup>3</sup>), where spatially separated MSCs achieved high analytical precision (CV &lt; 10%). The CL-based assay demonstrated robust repeatability across MSCs sources and biologically relevant quantitation limits. Integration of <i>I</i><sub>CHP+</sub> with γH2AX, enabled simultaneous assessment of functional potency and cell health. Response surface methodology modeling of culture duration, seeding density, and passage number revealed a dome-shaped relationship, with maximal remodeling at early passages (<i>N</i><sub>p</sub>1–<i>N</i><sub>p</sub>3) and 3–5 days of culture, whereas extended culture (&gt; 6 days) decreased potency alongside elevated γH2AX expression. The model exhibited strong predictive performance (R<sup>2</sup> &gt; 0.95), supporting its utility for process optimization. Collectively, this mechanism-based potency assay enables standardized platform for potency evaluation and manufacturing control for consistent, high-quality MSCs therapeutics.</p>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"123 11","pages":"2984-2998"},"PeriodicalIF":3.9,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bit.70298","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148388751","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}
引用次数: 0
Inventory Replenishment and Transshipment for Distributed Autologous Cell Therapy Manufacturing Networks 分布式自体细胞治疗制造网络的库存补充和转运。
IF 3.9 2区 生物学
Biotechnology and Bioengineering Pub Date : 2026-10-14 Epub Date: 2026-07-26 DOI: 10.1002/bit.70316
Zhaowei Li, Chelsea C. White III, Kan Wang, Ben Wang
{"title":"Inventory Replenishment and Transshipment for Distributed Autologous Cell Therapy Manufacturing Networks","authors":"Zhaowei Li,&nbsp;Chelsea C. White III,&nbsp;Kan Wang,&nbsp;Ben Wang","doi":"10.1002/bit.70316","DOIUrl":"10.1002/bit.70316","url":null,"abstract":"<p>Autologous cell therapy (AuCT) manufacturing networks must balance two competing objectives: reducing cost and improving patient access to time-sensitive therapy. This study compares three AuCT manufacturing network designs: a centralized network with a single manufacturing facility, a coordinated point-of-care (POC) network in which POCs can coordinate and transship specimens and consumables when needed, and an independent POC network in which each POC operates separately. Minimizing the time from specimen harvest to therapy infusion is used as an operational proxy for patient benefit. The analysis considers reagent replenishment, specimen and reagent transshipment, patient deterioration while waiting for therapy manufacturing to begin or during the therapy manufacturing process, and bioreactor capacity planning under a high patient service-level requirement. Using data based on a commercial-style AuCT network with one manufacturing site, 20 geographically distributed POCs, and two consumable suppliers, the results show that the coordinated POC network can achieve total cost close to that of the centralized network while maintaining turnaround time close to that of the independent POC network. These findings provide decision-support insight for commercialization and industrialization of AuCT manufacturing by quantifying when coordinated distributed manufacturing may offer a practical compromise between the economic efficiency of centralized production and the responsiveness of local manufacturing.</p>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"123 11","pages":"3134-3151"},"PeriodicalIF":3.9,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bit.70316","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148590085","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}
引用次数: 0
Osteoimmunoengineering With Exosome-Functionalized Biomaterials: Rewriting the Immune–Bone Regeneration Interface 外泌体功能化生物材料的骨免疫工程:改写免疫-骨再生界面
IF 3.9 2区 生物学
Biotechnology and Bioengineering Pub Date : 2026-10-14 Epub Date: 2026-07-16 DOI: 10.1002/bit.70315
Asrin Emami, Iman Menbari Oskouie
{"title":"Osteoimmunoengineering With Exosome-Functionalized Biomaterials: Rewriting the Immune–Bone Regeneration Interface","authors":"Asrin Emami,&nbsp;Iman Menbari Oskouie","doi":"10.1002/bit.70315","DOIUrl":"10.1002/bit.70315","url":null,"abstract":"<div>\u0000 \u0000 <p>Bone regeneration is a highly coordinated, multistep process governed by interactions among skeletal cells, immune components, and the vascular system. Although bone exhibits an intrinsic capacity for self-repair, critical-sized defects caused by trauma, tumor resection, infection, or chronic diseases often exceed this regenerative potential and necessitate therapeutic intervention. Conventional bone tissue engineering strategies have predominantly focused on promoting osteogenesis and angiogenesis; however, their limited clinical translation indicates that essential regulatory mechanisms remain insufficiently addressed. Advances in osteoimmunology have revealed that immune responses—particularly the initiation, intensity, and resolution of early inflammation—play an instructive role in determining bone healing outcomes. In parallel, exosomes have emerged as mediators of intercellular communication, capable of transferring bioactive cargos that regulate immune cell polarization, angiogenesis, and osteogenic differentiation. Integrating exosomes with biomaterial scaffolds has led to the concept of osteoimmunoengineering, in which scaffolds are designed not only to provide mechanical support but also to modulate the immune microenvironment in a spatiotemporally controlled manner. This review systematically discusses how exosome-functionalized biomaterials can reprogram immune responses to enhance bone regeneration. We outline the immune landscape of bone healing, highlighting key immune cell populations and cytokine signaling pathways involved in inflammation resolution and tissue reconstruction. We also examine immunomodulatory mechanisms of exosomes, material-based strategies for regulating exosome immobilization and release kinetics, and major translational challenges, including exosome heterogeneity, manufacturing standardization, and clinical product classification.</p>\u0000 </div>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"123 11","pages":"2953-2967"},"PeriodicalIF":3.9,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148459642","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}
引用次数: 0
Computational Resources for Designing and Evaluating Genetically Modified Crops 转基因作物设计与评价的计算资源。
IF 3.9 2区 生物学
Biotechnology and Bioengineering Pub Date : 2026-10-14 Epub Date: 2026-07-21 DOI: 10.1002/bit.70314
Pushpendra Singh Gahlot, Ritu Tomer, Ruchir Sahni, Anand Singh Rathore, Gajendra P. S. Raghava
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