{"title":"Proof-of-concept engineering of Escherichia coli expressing a bee-derived cytochrome P450 monooxygenase for thiamethoxam detoxification.","authors":"Pachara Sattayawat, Kasimaporn Promubon, Kritapas Sripinta, Warisa Chunguaongsuk, Chonlaphon Juntama, Nuttapol Noirungsee, Aussara Panya, Terd Disayathanoowat","doi":"10.1186/s13036-026-00686-1","DOIUrl":"10.1186/s13036-026-00686-1","url":null,"abstract":"<p><p>Bees are unintentionally exposed to pesticides applied to control other insect pests. Although bees possess endogenous detoxification mechanisms, their efficiency may not always be sufficient. To this end, the use of probiotics that can assist in pesticide detoxification may offer an additional layer of protection. In this study, we engineered Escherichia coli BL21(DE3) to heterologously express the bee-derived cytochrome P450 monooxygenase (CYP450), CYP9Q1, from Apis mellifera as a proof-of-concept microbial platform for thiamethoxam biotransformation and future microbiome-assisted pesticide detoxification strategies. We first assessed the toxicity of thiamethoxam, a systemic insecticide, on E. coli, which showed obvious impaired growth at relatively high concentrations (5 and 10 g/L). Subsequently, we computationally modeled the 3D structure and modified the CYP450 to improve its solubility when expressed in E. coli. Molecular docking of the CYP450 and thiamethoxam was also performed to confirm their potential interaction. pRSFDuet-1 plasmid was used to carry the modified CYP450 gene for expression in E. coli and the induction condition was optimized, with 0.5 mM isopropyl 𝛽-D-1-thiogalactopyranoside (IPTG) yielding the most favorable expression level. A whole-cell detoxification assay subsequently showed reduced concentrations of thiamethoxam after 46 h of biocatalytic activity, as monitored by High-Performance Liquid Chromatography (HPLC). Liquid Chromatography-Mass Spectrometry (LC-MS) analysis further revealed the presence of desnitro thiamethoxam corresponding to m/z 247.04105 confirming enzymatic transformation of thiamethoxam. To our knowledge, this study provides the first demonstration of bee CYP9Q1 heterologous expression in E. coli for whole-cell thiamethoxam biotransformation, highlighting its potential as a platform for developing probiotic or gut microbiome-based detoxification strategies to support bee pesticide tolerance.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13321449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
David Wollborn, Carol J Hartley, Andreas Schulte, Juan C P Correa
{"title":"Early bioprocess development using Komagataella phaffii: application scenarios for the microTOM mini bioreactor system.","authors":"David Wollborn, Carol J Hartley, Andreas Schulte, Juan C P Correa","doi":"10.1186/s13036-026-00691-4","DOIUrl":"10.1186/s13036-026-00691-4","url":null,"abstract":"<p><p>Developing novel bioprocesses usually starts with an iterative cycle to engineer genetically modified organisms. This leads to large strain libraries that differ in their genetic makeup, showing different growth and production performance. Finding the optimal production strain requires extensive screening and is arguably one of the most important steps for large-scale productivity. For aerobic processes, it is important to ensure the cultivation conditions avoid oxygen limitation. The oxygen transfer rate (OTR) is a parameter to monitor metabolic activity. The micro-scale Transfer rate Online Measurement (microTOM) system allows online monitoring of the respiration activity in 96-individual wells of a microtiter plate. This novel late-stage beta version prototype, provided by Kuhner Shaker, was trialled with the common microbial host Komagataella phaffii. It is demonstrated how the microTOM system can be applied to rapidly determine essential parameters for bioprocess design. Using a 96-well microtiter plate format enabled high-throughput investigation of three strains in parallel. The methanol uptake and growth rate was estimated, which can be used in process models to guide scale-up and decisions regarding feeding rates in fed-batch operation mode. Further, we assessed seven media formulations with two carbon sources, the impact of filling volume on the maximum oxygen transfer capacity, eight different antifoam agents, and growth rates were estimated at five different temperatures. These findings can help select screening conditions and demonstrate how the microTOM system can accelerate bioprocess development. Until now, obtaining high-resolution OTR datasets at high-throughput, suitable for deriving critical process parameters, has not been feasible. Thus, the microTOM supports robust, data-driven bioprocess development.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13317299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marcos Sforza, Olga Ivanenko, Nazanin Biabani, Lara Sforza, Deepak M Kalaskar, Zahra Mohri, Afshin Mosahebi
{"title":"Mechanical isolation of stromal vascular fraction using a spiral-based device: cellular outcomes and point-of-care workflow considerations.","authors":"Marcos Sforza, Olga Ivanenko, Nazanin Biabani, Lara Sforza, Deepak M Kalaskar, Zahra Mohri, Afshin Mosahebi","doi":"10.1186/s13036-026-00688-z","DOIUrl":"10.1186/s13036-026-00688-z","url":null,"abstract":"<p><strong>Background: </strong>Stromal vascular fraction (SVF) from adipose tissue represents a promising source of regenerative cells. A major trend in SVF isolation is the increasing use of dedicated devices and systems to enhance standardization and reproducibility. Real-world implementation of new technologies requires consideration of workflow-related factors alongside biological results. This study primarily aimed to characterize the novel BMC Uniq® SVF device, describe a mechanical isolation approach (MI-SVF) with this device, and evaluate the cellular outcomes of MI-SVF. Enzymatic isolation (EI-SVF) was included as a reference method for comparison of selected cellular parameters.</p><p><strong>Results: </strong>The BMC Uniq® SVF device is a spiral-based, closed system composed of two housings and three filters, designed as a sterile disposable unit. Lipoaspirate samples from 10 healthy female donors were equally divided and handled using MI-SVF (decantation, device processing, centrifugation) or EI-SVF (adding collagenase and post-digestion steps to the MI-SVF protocol). Total cell yield was significantly greater in the EI-SVF group (mean ± standard error (SE) 94.9 × 10<sup>4</sup> ± 6.4 × 10<sup>4</sup> versus 37.5 × 10<sup>4</sup> ± 2.7 × 10<sup>4</sup> for MI-SVF; p = 0.002). The flow cytometry demonstrated significantly higher relative proportions of CD90+ (10.3 ± 1.3% versus 5.4 ± 0.9%; p = 0.014) and CD73+ cells (10.7 ± 0.7% versus 6.6 ± 0.7%; p = 0.010) in MI-SVF compared with EI-SVF, with no significant differences in CD105+ percentage. There were no differences in cell viability (MI-SVF: mean 87.0%; EI-SVF: 83.9%). MI-SVF samples showed a CFU-F frequency of 5.0 ± 0.3% and consistently demonstrated adipogenic, chondrogenic, and osteogenic differentiation potential.</p><p><strong>Conclusions: </strong>The BMC Uniq® SVF device is a simple closed single-use system for mechanical SVF extraction in point-of-care applications. Fresh MI-SVF samples derived in such a way had one of the highest reported cell yields and demonstrated viability, immunophenotype, clonogenic capacity, and multilineage differentiation potential that were comparable to, and in some cases exceeded, those of previously described non-enzymatic protocols. Relative to EI-SVF, the mechanical approach showed a lower total cell count but a higher relative percentage of CD73+ and CD90+ cells. In general, this work contributes to a broader framework for assessing SVF isolation methods by integrating biological performance with practical aspects of clinical workflow.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13312744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amir Hossein Aghayan, Davood Mohammadi, Hamed Soleimani Samarkhazan, Amir Atashi, Zahra Jamalpoor
{"title":"Therapeutic efficacy of mesenchymal stem cell-derived extracellular vesicles combined with injectable hydrogels in bone defect repair: a systematic review and meta-analysis of preclinical studies.","authors":"Amir Hossein Aghayan, Davood Mohammadi, Hamed Soleimani Samarkhazan, Amir Atashi, Zahra Jamalpoor","doi":"10.1186/s13036-026-00684-3","DOIUrl":"10.1186/s13036-026-00684-3","url":null,"abstract":"<p><p>BACKGROUND: Critical-sized bone defects represent a major clinical challenge due to their limited intrinsic regenerative potential and the considerable limitations of existing surgical interventions. In recent years, the integration of mesenchymal stem cell-derived extracellular vesicles (MSCEVs) with injectable hydrogels (IHs) has gained attention as a promising, cell-free regenerative approach. Although each component independently confers therapeutic benefits, their combined efficacy has not yet been thoroughly evaluated. METHODS: This systematic review and meta-analysis was conducted in accordance with PRISMA 2020 guidelines. Relevant studies were identified through comprehensive searches in PubMed, Embase, Scopus, Web of Science, and ProQuest. Standardized mean differences (SMD) were calculated using a random-effects model. Risk of bias was assessed using the SYRCLE tool, and sensitivity analysis, publication bias assessment, and subgroup analyses were conducted. RESULTS: A quantitative analysis of the included literature revealed that MSCEV-IHs constructs significantly enhanced bone regeneration compared with the control groups, with improved BV/TV at 4 weeks (SMD = 3.52) and 8 weeks (SMD = 6.30), BMD (SMD = 5.45), trabecular number (SMD = 7.52), and thickness (SMD = 6.46). Angiogenesis (SMD = 3.53) and osteogenic markers RUNX2 (SMD = 5.86), BMP2 (SMD = 2.57), OPN (SMD = 7.22), and OCN (SMD = 7.66) were significantly upregulated. CONCLUSION: The use of MSCEVs in combination with IHs has demonstrated substantial potential to enhance both angiogenesis and osteogenic activity in bone defects. However, the considerable heterogeneity across existing studies presents a major barrier to clinical translation. To advance this strategy toward clinical application, harmonized protocols and standardized methodologies are critically needed for consistent validation and optimization. </p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13267703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147771901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Trends of nucleic acid - based point-of-care diagnostics for infectious diseases.","authors":"Hossam Hatem, Mohamed Mysara, Raghda Ramadan","doi":"10.1186/s13036-026-00681-6","DOIUrl":"10.1186/s13036-026-00681-6","url":null,"abstract":"<p><p>The global emergence and spread of infectious diseases highlights the importance of having an easily accessible, decentralized testing modality that is adept at quickly identifying the nucleic acids present in a Point-of-Care (PoC) setting. PoC-based nucleic acid diagnostics encompass a broad range of platforms, such as lateral flow, biochips, and biosensors, whose primary goal has always been to offer sensitive, selective, and economically viable testing beyond conventional laboratory facilities. The current review illustrates a comprehensive overview of PoC-based nucleic acid diagnostics for infectious diseases, as it is divided into three major operational steps: nucleic acid extraction, amplification, and detection. Firstly, it describes strategies that could effectively work as a PoC, such as magnetic bead-based, paper-based, and integrated microfluidic approaches, while further focusing on their ability to remain simplified, rugged, and equipment-free. Secondly, it summarizes key amplification methods, such as Polymerase Chain Reaction (PCR), Nucleic Acid Sequence-Based Amplification (NASBA), Recombinase Polymerase Amplification (RPA), and Loop-Mediated Isothermal Amplification (LAMP), as they have all been modified to effectively work under more rapid, low-power, and portable conditions. Lastly, it introduces all presently known detection platforms, starting from simpler colorimetric and fluorescent assays present in lateral flow or device platforms, to innovative and advanced biosensors like those exploiting CRISPR/Cas systems and toehold switch principles, as these detectively offer highly sensitive and highly programmable nucleic acid recognition.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":"20 1","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13130695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147771882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dae-Yeol Ye, Myeongwon Min, Ga Yeon Lim, Hyun Gyu Hwang, Gyoo Yeol Jung, Hyun Gyu Lim
{"title":"Metabolic rewiring for enhanced itaconate yield through heterotrophic CO<sub>2</sub> fixation in Escherichia coli.","authors":"Dae-Yeol Ye, Myeongwon Min, Ga Yeon Lim, Hyun Gyu Hwang, Gyoo Yeol Jung, Hyun Gyu Lim","doi":"10.1186/s13036-026-00687-0","DOIUrl":"10.1186/s13036-026-00687-0","url":null,"abstract":"<p><p>BACKGROUND: It is crucial to obtain high production yields in the microbial production of diverse biochemicals to maximize economic viability. However, microorganisms, particularly heterotrophs, release carbon dioxide (CO2) during the oxidation of organic compounds for energy and building blocks. This metabolism limits the theoretical maximum carbon yield and constrains the development of efficient microbial cell factories. Specifically, metabolite production from tricarboxylic acid (TCA)-cycle intermediates involves major CO2 emission steps, leading to unavoidable carbon loss. RESULTS: Central carbon metabolism in Escherichia coli, a model heterotroph, was synthetically rewired to facilitate CO2 fixation and escalate carbon yields. Specifically, we blocked multiple routes to prevent pyruvate oxidation to acetyl-CoA, which was identified as a major CO2 emission step, and promoted CO2 incorporation into TCA cycle intermediates by reengineering endogenous pathways for co-utilization of glucose and acetate. This strategy was applied to produce itaconate, a promising bioplastic precursor, achieving a yield of 0.81 C mol/C substrate mol, a value near the theoretical maximum yield obtainable from glucose (0.83 C mol/C mol). CONCLUSIONS: This heterotrophic CO2 fixation strategy can be used to produce TCA-derived chemicals and enhance the economic viability of microbial production. This study demonstrates that synthetically rewiring central carbon metabolism enables direct incorporation of CO₂ into the product, thereby increasing carbon yields approaching the conventional maximum value. This heterotrophic CO2 fixation strategy not only provides a breakthrough for efficient itaconate production but also serves as a versatile platform for engineering microbial cell factories to produce various TCA-derived chemicals with amplified carbon yield. </p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13262084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147771923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Le Guo, Pihong Zhang, Minghua Zhang, Pengfei Liang, Situo Zhou
{"title":"pH/glucose dual-responsive drug release hydrogel loaded with tannic acid and gallium ions enhances diabetic wound healing upon bacterial infection.","authors":"Le Guo, Pihong Zhang, Minghua Zhang, Pengfei Liang, Situo Zhou","doi":"10.1186/s13036-025-00581-1","DOIUrl":"10.1186/s13036-025-00581-1","url":null,"abstract":"<p><p>Chronic infected diabetic wounds pose a significant global health challenge. This study explores a novel therapeutic approach using a [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (SBMA), 3-(acrylamidophenyl)boronic acid (AAPBA) and tannic acid (TA) based pH/glucose dual-responsive drug release hydrogel loaded with gallium ions (Ga3+) (named “STAG hydrogel”) to enhance the treatment of Staphylococcus aureus (S. aureus) -infected diabetic wounds. The hydrogel was designed to respond to the acidic and hyperglycemic microenvironment typical of chronic diabetic wounds, ensuring controlled release of its antimicrobial components. In vitro, the hydrogel demonstrated significant antibacterial activity against S. aureus and Escherichia coli (E. coli), reducing bacterial viability and inhibiting biofilm formation. Furthermore, the hydrogel exhibited excellent biocompatibility, promoting fibroblast viability and migration, crucial for wound healing. In vivo studies using a diabetic mouse model confirmed the hydrogel’s efficacy in accelerating wound closure, reducing bacterial load, and enhancing collagen deposition and CD31 and VEGF levels. The dual-responsive drug release hydrogel also modulated the inflammatory response, promoting M2 macrophage polarization, which is essential for tissue repair and regeneration. These findings highlight the potential of the STAG hydrogel as an effective therapeutic strategy for managing chronic infected diabetic wounds.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13251176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147771903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Minse Kim, Jaewon Choi, Kisung Lee, Subin Lee, Jaewon Lee, Jeong-Ann Park, Kwang Suk Lim, Suk-Jin Ha, Hyun-Ouk Kim
{"title":"Waste-to-sensor upcycling of polyethylene terephthalate over Ag/Zr-MOF photocatalyst for microplastic degradation and AI-assisted heavy metal detection.","authors":"Minse Kim, Jaewon Choi, Kisung Lee, Subin Lee, Jaewon Lee, Jeong-Ann Park, Kwang Suk Lim, Suk-Jin Ha, Hyun-Ouk Kim","doi":"10.1186/s13036-026-00683-4","DOIUrl":"10.1186/s13036-026-00683-4","url":null,"abstract":"<p><p>This study aims to develop an integrated waste to sensor platform that couples photocatalytic PET depolymerization with on stream quantification of coexisting heavy metals. We achieve this by preparing AIM-202 through surface coordination of Ag to a water stable Zr-aspartate MOF (MIP-202), creating Ag<sup>0</sup>/Ag<sup>δ+</sup> electron sink sites that enhance charge separation and reactive oxygen species generation while preserving the parent framework. The material was characterized by FT-IR, XRD, XPS, photoluminescence, KPFM, and EPR, and its photocatalytic activity was evaluated under Xe lamp irradiation. AIM-202 (5 mg mL-1) oxidized PET with increased FT-IR oxidation indices and surface pitting, and generated soluble products that increased from 151.40 µmol (week 1) to 277.27 µmol (week 2), corresponding to 11.63% and 28.68% conversion to quantified byproducts. The PET derived fluorophore 2-hydroxyterephthalate enabled fluorescence quenching based Cu<sup>2+</sup> and Fe<sup>3+</sup> sensing, and physics guided models refined with lightweight machine learning provided robust concentration back calculation. The novelty lies in a closed loop design in which MOF mediated depolymerization simultaneously produces the sensing reporter and enables data assisted quantification, supporting scalable remediation and monitoring within a single integrated scheme.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13248307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147771895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Justin Sargunas, Bradley Priem, Dylan Carman, Taravat Sarvari, Natalie M Nold, Vaishali Sharma, Andrew Pekosz, Caryn L Heldt, Michael Betenbaugh
{"title":"A continuous viral vaccine biomanufacturing platform utilizing multiple bioreactor configurations.","authors":"Justin Sargunas, Bradley Priem, Dylan Carman, Taravat Sarvari, Natalie M Nold, Vaishali Sharma, Andrew Pekosz, Caryn L Heldt, Michael Betenbaugh","doi":"10.1186/s13036-026-00680-7","DOIUrl":"10.1186/s13036-026-00680-7","url":null,"abstract":"<p><p>Scalable, continuous biomanufacturing processes have grown in importance to meet demand for smaller bioreactor sizes, lowered production costs, and improved quality attribute consistency. The Sf9/recombinant baculovirus (rBV) expression system demonstrates promise for virus-like particle (VLP) vaccine and gene therapy production. Here, we present a continuous rBV platform integrating an infection plug flow reactor (PFR) between stirred tank growth (gCSTR) and production (pCSTR) bioreactors. Cell expansion in the gCSTR included a ramp-up stage followed by continuous growth, reaching a steady state of 5×10<sup>6</sup> cells/mL and >90% viability. Péclet number-fit tracer studies confirmed near-ideal plug flow in the PFR, yielding a 10 h residence time and progressive infection as measured by gp64 signaling. Finally, a pCSTR with a residence time of 48 h exhibited sustained recombinant protein production. An integrated pilot cascade incorporating all reactors ran continuously for 5 days, maintaining stable CSTR cell densities and a measurable increase in infected cell diameter from 14.5 μm to 16.1 μm. Western blotting and EM of ~ 100 nm VLPs in pCSTR effluent demonstrated platform success. Digital twin mechanistic models across four distinct stages of bioreactor operation and Hill-type relationships for rBV infection kinetics predicted cell growth and death for a 7-day run, demonstrating promise for designing continuous systems in silico and building a quantitative framework for scale-up and optimization. Our multi-stage reactor configuration represents a cell host- and product-agnostic production scheme, particularly for processes prone to product heterogeneity, and paves the way towards a true end-to-end continuous platform for myriad modalities in the future.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13244601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147771879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Application of microneedle patches in the alleviation of cardiac infarction in animal models: a systematic review and meta-analysis.","authors":"Samaneh Narimani, Hanieh Salehipourmehr, Ali Baradar Khoshfetrat, Elham Dehghani, Hassan Amini, Zeinab Aliyari Serej, Emel Sokullu, Reza Rahbarghazi","doi":"10.1186/s13036-026-00679-0","DOIUrl":"10.1186/s13036-026-00679-0","url":null,"abstract":"<p><p>BACKGROUND: Myocardial infarction (MI) is associated with high mortality rates in the clinical setting. Microneedle patches (MNP) are sophisticated platforms for delivering various cargoes into target tissues with high efficiency rates. This systematic review aimed to evaluate the potential regenerative outcomes of MNP application, with or without cargo, in animal models of experimentally induced MI. METHODS: A comprehensive systematic search was performed using computerized databases, including Embase, PubMed, Scopus, WOS, and Google Scholar without language limitation, up to Dec 2025, to identify animal studies using MNP in various MI models. Two authors independently evaluated methodological quality according to the modified CAMARADES (Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies) checklist. Data were extracted and reported by theme for both the control and experimental groups. RESULTS: Of A total of 458 studies, 21 papers preliminarily met the inclusion criteria for the systematic review, and subsequently, 18 studies were included in the meta-analysis. The overall effect size observed in the groups transplanting cargo containing MNP was compared to the matched control group. Data revealed enhanced ejection fraction (EF) (Standard difference in mean (SMD): 19.84; confidence interval (CI) 95%: 15.94–23.73), fractional shortening (FS) (SMD: 11.24; 95% CI: 8.91–13.56), angiogenesis (SMD: 14.32; CI 95%: 9.57–19.07), and reduced fibrosis (SMD: −11.12; 95% CI: −13.46, −8.78). CONCLUSION: Our results indicated that MNP could be an alternative therapy to promote ischemic cardiac tissue healing, mainly by enhancing myocardial angiogenesis, and the reduction of fibrosis coincided with improved EF and FS. However, statistically significant heterogeneity was observed among studies. OTHERS: the current study was supported by a grant from Tabriz University of Medical Sciences under grant number 73569 and ethical code of IR.TBZMED.AEC.1403.022. The protocol used was registered on PROSPERO (CRD42025615993) CLINICAL TRIAL NUMBER: Not applicable. </p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13430712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147698899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}