Frontiers in Bioengineering and Biotechnology最新文献

{"title":"Research on rehabilitation robot control based on port-Hamiltonian systems and fatigue dissipation port compensation.","authors":"Jingjing Li, Zhen Chen, Jian Li, Hongyu Yan, Zhen Li, Minshan Feng, Jiawen Zhan, Liwei Shao","doi":"10.3389/fbioe.2025.1609548","DOIUrl":"10.3389/fbioe.2025.1609548","url":null,"abstract":"<p><strong>Introduction: </strong>Upper-limb rehabilitation robots have been demonstrated to effectively promote motor recovery in stroke patients. However, in active training modes, control instability may be induced by the nonlinear and time-varying characteristics of muscle fatigue, increasing the risks of physical human-robot interaction and ultimately limiting rehabilitation outcomes.</p><p><strong>Methods: </strong>A novel control strategy within the port-Hamiltonian framework, incorporating a dynamic muscle fatigue model. Fatigue levels were assessed in real time using surface electromyography (sEMG) signals and mapped to damping parameters in joint space, enabling the port-based modeling of fatigue-related energy dissipation. A hierarchical control architecture was constructed, consisting of outer-loop admittance control and inner-loop energy shaping.</p><p><strong>Results: </strong>Theoretical analysis confirmed that the closed-loop passivity of the system was preserved and stability was ensured. Experimental validation further showed that, compared to fixed damping parameters, the proposed fatigue compensation approach reduced muscle fatigue accumulation by 45% and increased training duration by 40%.</p><p><strong>Discussion: </strong>The proposed fatigue-adaptive control framework was shown to enhance the safety, effectiveness, and physiological adaptability of rehabilitation training. The integration of real-time sEMG feedback and port-Hamiltonian modeling offers a promising solution for personalized robotic rehabilitation.</p>","PeriodicalId":12444,"journal":{"name":"Frontiers in Bioengineering and Biotechnology","volume":"13 ","pages":"1609548"},"PeriodicalIF":4.3,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12141283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innate immune pathway activated mesenchymal stromal cells improve function and histologic outcomes in a rodent osteoarthritis model.","authors":"Cody Plaisance, Lyndah Chow, Renata Impastato, Zoë J Williams, Isabella Sabino, Katie J Sikes, Kelly S Santangelo, Steven Dow, Lynn M Pezzanite","doi":"10.3389/fbioe.2025.1525969","DOIUrl":"10.3389/fbioe.2025.1525969","url":null,"abstract":"<p><strong>Introduction: </strong>Intra-articular administration of mesenchymal stromal cells (MSC) has demonstrated anti-inflammatory and chondroprotective activity in both preclinical models and in randomized clinical trials in patients with osteoarthritis (OA). Nonetheless, precedent from MSC studies in non-OA models suggests that the overall anti-inflammatory effectiveness of MSC can be improved by prior immune activation through cytokines or innate immune pathways.</p><p><strong>Methods: </strong>Therefore, in the current study, we determined whether activation of MSC by two different innate immune pathways (Toll-like receptor 3 (TLR3) pathway or Stimulator of Interferon Genes (STING) pathway could improve their effectiveness for intra-articular treatment of OA, using a murine destabilization of the medial meniscus (DMM) model. Outcome parameters included voluntary gait activity, joint histology and RNA transcriptomic analyses of synovial tissues.</p><p><strong>Results: </strong>We found that activation of MSC via either innate immune pathway improved functional voluntary movement outcomes compared to treatment with non-activated MSC. Moreover, cartilage integrity, including cartilage preservation, was significantly improved in mice receiving activated MSC, with greater benefits observed in animals treated with STING pathway-activated MSC compared to animals treated with non-activated MSC alone. Transcriptomic analysis of joint tissues revealed that treatment with activated MSC upregulated pathways associated with tissue remodeling, angiogenesis, and wound healing compared to tissues from animals treated with non-activated MSC.</p><p><strong>Discussion: </strong>These findings indicate therefore that innate immune activation of MSC prior to intra-articular delivery for treatment of OA can significantly improve functional gait activity and chondroprotective effects compared to non-activated MSC and suggest that this strategy could be evaluated clinically.</p>","PeriodicalId":12444,"journal":{"name":"Frontiers in Bioengineering and Biotechnology","volume":"13 ","pages":"1525969"},"PeriodicalIF":4.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12138259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes in volumetric bone mineral density after ACL reconstruction with single-bundle and double-bundle: a 1-year follow-up study using peripheral quantitative computed tomography.","authors":"Binbin Yin, Chaohua Fang, Ren Hai Feng, Jian Min Wu","doi":"10.3389/fbioe.2025.1606404","DOIUrl":"10.3389/fbioe.2025.1606404","url":null,"abstract":"<p><strong>Background: </strong>The purpose of this study is to quantify changes in volumetric bone mineral density (vBMD) in different regions of the tibial plateau after single-bundle (SB) and double-bundle (DB) anterior cruciate ligament reconstruction (ACLR).</p><p><strong>Methods: </strong>Twenty-six patients with diagnosed anterior cruciate ligament (ACL) rupture were allocated into SB (10) or DB group (16) and completed the last follow-up at 12 months. Peripheral quantitative computed tomography (pQCT) was performed before surgery and at 1, 3, 6, and 12 months after surgery. Four regions of interest (ROI) were identified 2 mm below the medial and lateral subchondral plate of the knee joint, namely, the anteromedial (AM), posteromedial (PM), anterolateral (AL) and posterolateral (PL) regions. The vBMD of each ROI was measured and compared between the groups at different timepoints.</p><p><strong>Results: </strong>For the vBMD, a significant change in all ROIs can be found over time, with the values at all ROIs decreased until 6 months postoperatively and then steadily increased, but the values did not reach preoperative levels. The AM region had the highest vBMD, followed by the PL region, and the vBMD was lowest in the AL region. For the change percent, the decrease magnitude was comparable between AM and PM region at postoperative 1 and 12 months, but it was greater at PM region at postoperative 3 and 6 months. Comparing DB ACLR and SB ACLR, there was no significant difference in the change percent of vBMD in all ROIs, except for in the AL region at 1 month postoperatively.</p><p><strong>Conclusion: </strong>A partially reversible decline in vBMD was found in the proximal tibia at 12 months after ACLR. But the change percent varied among the different regions, which may indicate inadequate restoration of knee kinematics after ACLR. DB and SB ACLR methods may have a similar effect on knee kinematics.</p>","PeriodicalId":12444,"journal":{"name":"Frontiers in Bioengineering and Biotechnology","volume":"13 ","pages":"1606404"},"PeriodicalIF":4.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12142058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regional bone density patterns of the tibial plateau: implications for finite element analysis.","authors":"Pablo Besa, Anselmo Alegría, Nicolás González, Fiorella Biancardi, Catalina Vidal, Pablo Cikutovic, Marcelo E Andia, Joaquín Mura","doi":"10.3389/fbioe.2025.1541536","DOIUrl":"10.3389/fbioe.2025.1541536","url":null,"abstract":"<p><p>The tibial plateau has different anatomical regions and heterogeneous bone densities. Most finite element simulation (FEM) studies of tibial plateau fracture fail to account these regional variations, which may significantly influence biomechanical behavior. This study aimed to quantify the regional density profile of the tibial plateau using Hounsfield Units (HU) from computed tomography (CT) scans and explore associations between density, age, and sex. We developed a novel measurement protocol to compare HU values of the subchondral bone and cancellous bone in eight different regions of the tibial plateau. Results demonstrated that patient age and female sex were associated with reduced bone density. Subchondral bone and medial bone had significantly higher density than metaphyseal and lateral bone, respectively. This findings could have implications on orthopedic modeling of tibial plateau fractures using FEM. Current FEM should consider distinct regions in tibial plateau to improve accuracy. Conclusion: Tibial plateau heterogenous bone density distribution could contribute to explain the low predictive accuracy in FEM models.</p>","PeriodicalId":12444,"journal":{"name":"Frontiers in Bioengineering and Biotechnology","volume":"13 ","pages":"1541536"},"PeriodicalIF":4.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12137267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel approach with modified suture bridge fixation technique for posterior cruciate ligament tibial avulsion fracture in adult.","authors":"Xiong Wang, Qing Gu, Shuming Zi, Wenqiang Wei, Biao Cheng, Liehu Cao","doi":"10.3389/fbioe.2025.1496728","DOIUrl":"10.3389/fbioe.2025.1496728","url":null,"abstract":"<p><strong>Background: </strong>Posterior cruciate ligament (PCL) tibial avulsion fractures are relatively rare injuries that often result in chronic pain, limited range of motion, knee instability, and osteoarthritis. Most cases require surgical intervention to restore the fragment's normal anatomy, the ligament's tension, and the knee joint's stability. In this study, we propose a novel approach utilizing a modified suture bridge fixation technique to treat PCL tibial avulsion fractures and explore the clinical outcome and applicability.</p><p><strong>Methods: </strong>We retrospectively reviewed and collected the clinical data from March 2020 to April 2023. Of the 24 patients (14 males and 10 females) with PCL tibial avulsion fractures who underwent modified suture bridge fixation technique were enrolled in the study. The surgical data of the surgery time and intraoperative blood loss were analyzed. The knee range of motion (ROM), the Lysholm knee scoring scale, and the International Knee Documentation Committee (IKDC) were used to evaluate the recovery of knee joint function.</p><p><strong>Results: </strong>All 24 patients were followed up for a duration ranging from 11 to 16 months, with an average of 13.00 ± 1.32 months. The surgery time was 40∼60 min, with a mean of 50.88 ± 4.85 min. The intraoperative blood loss was approximately 25∼45 mL, averaging 36.75 ± 4.89 mL. No instances of wound infection, neurovascular injuries, fracture nonunion, fixation failure, deep vein thrombosis, or secondary operation were reported during follow-up. The knee joint range of motion (ROM) was 118°∼134°, with an average of 127.46° ± 4.16° at the final follow-up. The Lysholm score was 41.17 ± 3.48 at the preoperative stage and improved to 90.25 ± 2.59 at the final follow-up. The IKDC score was 40.38 ± 2.16 at the preoperative stage, and 88.54 ± 1.77 at the final follow-up.</p><p><strong>Conclusion: </strong>The results indicate that the novel approach utilizing a modified suture bridge fixation technique can provide effective stabilization and favorable clinical outcomes. The suture bridge structure can be applied to displaced posterior cruciate ligament (PCL) tibial avulsion fractures through its compression capabilities, especially in comminuted fractures. This procedure is straightforward, minimizing the risk of injury to peripheral neurovascular structures and eliminating the need for a second operation. Consequently, this technique represents a viable alternative treatment option for primary care facilities or hospitals that lack arthroscopic equipment.</p>","PeriodicalId":12444,"journal":{"name":"Frontiers in Bioengineering and Biotechnology","volume":"13 ","pages":"1496728"},"PeriodicalIF":4.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12137226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cementless long-stem fixation in periprosthetic clamshell fracture: a biomechanical investigation.","authors":"Lingqi Zhu, Li Xie, Mingchang He, Jianyun Miao, Liang Zhou, Lianshui Huang, Hui Liu, Wei Xie, Wenliang Zhai","doi":"10.3389/fbioe.2025.1604441","DOIUrl":"10.3389/fbioe.2025.1604441","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the biomechanical strength of cementless long-stem fixation for the treatment of periprosthetic clamshell fracture.</p><p><strong>Methods: </strong>Eighteen Sawbones artificial femur models were used and divided into three groups. Group A had an intact medial wall. Group B, the proximal periprosthetic femoral medial wall was osteotomized to simulate periprosthetic clamshell fractures. Group C, following identical osteotomy to Group B, cerclage wiring was applied to fix the medial wall fracture fragment. After molding, the cementless long-stem were implanted in all models, which were then evaluated through axial compression tests, torsion tests, and axial failure tests. The axial stiffness, axial displacement, torsional stiffness, torque, and maximum failure load were recorded and statistically analyzed.</p><p><strong>Results: </strong>In the axial compression tests, no statistically significant differences were observed among Groups A, B, and C in terms of axial displacement, axial stiffness, or maximum failure load (the displacement greater than 3 mm). However, in the torsional tests, Group B showed significantly lower torsional stiffness or torque compared to Groups A and C (<i>p</i> < 0.05). No significant differences in torsional stiffness or torque were detected between Groups A and C.</p><p><strong>Conclusion: </strong>The integrity of the femoral medial wall is crucial for femoral stem stability. In case of medial wall fracture, while cementless long-stem implantation can achieve satisfactory axial stability, its torsional stability remains inadequate. The application of supplemental cerclage wiring for medial wall fragment fixation provides reliable improvement in torsional stability of the stem.</p>","PeriodicalId":12444,"journal":{"name":"Frontiers in Bioengineering and Biotechnology","volume":"13 ","pages":"1604441"},"PeriodicalIF":4.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12137322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Laboratory quality management system fundamentals.","authors":"Segaran P Pillai, Elizabeth Fox","doi":"10.3389/fbioe.2025.1578654","DOIUrl":"10.3389/fbioe.2025.1578654","url":null,"abstract":"<p><p>A laboratory quality management system (LQMS) enables the effective operation of laboratories of all types and sizes. With rapid advances in technology (e.g., artificial intelligence and machine learning, advanced manufacturing) comes the need for laboratories worldwide to conduct proper change management and process improvement to meet the continued demand amidst major changes. In order to do so while ensuring that results and data are accurate, timely, and reproducible, it is crucial for laboratories to sustain a foundational LQMS that accommodates laboratory processes, document and records management, and a path for continual improvement in the laboratory itself and within its contextual organization. A foundational LQMS provides a framework to address gaps in process or product performance and risks present throughout the laboratory's workflow, any of which could lead to a critical error that compromises the organization's credibility. There are many LQMS frameworks-benchmarks such as consensus standards or regulations (e.g., Good Laboratory Practices for Nonclinical Laboratory Studies) - that the laboratory can select from to govern its LQMS. While these frameworks vary in applicability, there are several common elements across these frameworks that can serve as the basic components of any LQMS. The aim of this study is to review and assess 12 widely-recognized, fundamental aspects of an LQMS to identify actionable examples and templates that can enable effective implementation of a robust LQMS. A robust LQMS is one that fosters long term success of the laboratory, and which ultimately ensures reliable results, efficient operations, and the protection of public health.</p>","PeriodicalId":12444,"journal":{"name":"Frontiers in Bioengineering and Biotechnology","volume":"13 ","pages":"1578654"},"PeriodicalIF":4.3,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12133829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical evaluation of computer-aided design and three-dimensional printing for completely edentulous mandibular custom tray fabrication: assessing clinician satisfaction.","authors":"Tian Zhao, Yi Weng, Ning Li, Yiming Gao","doi":"10.3389/fbioe.2025.1556651","DOIUrl":"10.3389/fbioe.2025.1556651","url":null,"abstract":"<p><p>This study evaluates prosthodontists' satisfaction and efficiency of custom tray fabrication methods in completely edentulous mandibular jaw patients. A digital workflow was established, incorporating 3D scanning for preliminary impressions, CAD for designing border extensions and ensuring uniform 3D space, and 3D printing for tray fabrication. Three methods were compared: CAD/3D printing, light-cured resin, and impression compound trimming. Prosthodontist satisfaction was assessed using a visual analog scale, and manual fabrication time was analyzed. Dislocation tests were performed to evaluate tray retention. The CAD/3D printing method achieved the highest satisfaction across most parameters (<i>P</i> < 0.05), the best stability and retention (<i>P</i> < 0.05), and significantly reduced manual fabrication time (<i>P</i> < 0.05). The light-cured resin method showed moderate performance, while the impression compound trimming method scored lowest. The CAD/3D printing technique enhances satisfaction, precision, and efficiency, demonstrating significant potential for optimizing prosthodontic workflows. Further exploration in broader clinical applications is recommended.</p>","PeriodicalId":12444,"journal":{"name":"Frontiers in Bioengineering and Biotechnology","volume":"13 ","pages":"1556651"},"PeriodicalIF":4.3,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12133730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Normative isokinetic knee strength values and prediction models in non-athletic Chinese adults.","authors":"Kun Liu, Lulu Yin, Ye Zhang, Gongliang Liu, Ping Fang, Yanhong Ma, Lihua Huang","doi":"10.3389/fbioe.2025.1573267","DOIUrl":"10.3389/fbioe.2025.1573267","url":null,"abstract":"<p><strong>Background: </strong>Establishing normative isokinetic muscle strength values and prediction models for knee joints in non-athletic healthy Chinese adults aids in clinical assessments, diagnosis, and rehabilitation. However, there has been limited research on these normal reference values, particularly involving large sample cohorts. Therefore, this study aimed to develop normative reference values and predictive models for knee joint isokinetic muscle strength across different age groups and genders in non-athletic healthy Chinese adults.</p><p><strong>Methods: </strong>A total of 2,208 participants aged between 20-70 years old were included in the study. The participants were divided into two groups by gender and further divided into five age groups: 20-29, 30-39, 40-49, 50-59 and 60-69 years old, resulting in a total of 10 groups. Key parameters, including peak torque of knee flexors and extensors, relative peak torque, peak torque ratio of flexors to extensors, peak torque angle and work, were collected using an isokinetic dynamometer at angular velocities of 60°/s and 180°/s. Two-way analysis of variance was utilised to analyse the characteristics and differences of these parameters amongst different age groups and genders. Pearson correlation coefficients were calculated to examine the relationships between these parameters and gender, age, height, weight and body mass index. Predictive models were developed using linear regression and various machine learning techniques.</p><p><strong>Results: </strong>Males exhibited significantly higher knee isokinetic strength values than females across all age groups, with knee extensor strength 20.47%-38.01% higher and knee flexor strength 22.91%-43.42% higher at both 60°/s and 180°/s. Muscle strength showed a moderate negative correlation with age, indicating a decline with increasing age. Extension strength values were greater than flexion, and measurements at 180°/s were lower compared to 60°/s. The multilayer perceptron regressor demonstrated the highest predictive capability among the models tested.</p><p><strong>Conclusion: </strong>This study provides comprehensive normative reference values and predictive models for knee joint isokinetic muscle strength in non-athletic healthy Chinese adults. The results highlight significant gender and age differences, offering valuable data for clinical assessments and personalized rehabilitation strategies to improve knee joint health and overall quality of life.</p>","PeriodicalId":12444,"journal":{"name":"Frontiers in Bioengineering and Biotechnology","volume":"13 ","pages":"1573267"},"PeriodicalIF":4.3,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12133959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"mAb production kinetics in CHO batch culture: exploring extracellular and intracellular dynamics.","authors":"Alejandro Avilan Garzon, Bruno Ebel, Cédric Paris, Samuel Schneider, David Pfister, Eric Olmos","doi":"10.3389/fbioe.2025.1546105","DOIUrl":"10.3389/fbioe.2025.1546105","url":null,"abstract":"<p><p>Monoclonal antibodies (mAbs) are complex therapeutic proteins commonly produced by Chinese Hamster Ovary cell culture. Cells are cultivated using a chemically defined medium containing essential nutrients like glucose, amino acids, vitamins, etc., that cells use to grow and produce the target protein among other by-products. Various studies have focused on both extracellular and intracellular culture dynamics, measuring the concentration of various metabolites in the culture medium and inside the cell, but in the vast majority of cases these studies have excluded the intracellular concentration profile of the antibody. To better understand the complexity of the culture process, and the intracellular and extracellular dynamics of the antibody production, the present study focuses on both the extracellular and intracellular biochemical dynamics. A quenching and a lysis protocol were used to obtain the intracellular and the extracellular concentration profiles for the main substrates, metabolites, and mAb during a standard batch culture. The results revealed that three amino acids (glutamine, asparagine, and cystine) were limiting substrates as they were completely depleted almost simultaneously from the culture medium. Intracellular accumulation of different metabolites during the culture process was demonstrated, as well as a 2-day delay between the onset of the intracellular mAb production and its secretion to the culture medium. Finally, a comparison of mass transfer rates across the cell membrane, intracellular production/consumption rates, and accumulation of metabolites in the cell interior revealed that although the intracellular concentrations of the different metabolites changed during the culture process, the dynamics of these variations were much slower than the other two phenomena.</p>","PeriodicalId":12444,"journal":{"name":"Frontiers in Bioengineering and Biotechnology","volume":"13 ","pages":"1546105"},"PeriodicalIF":4.3,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12134900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}