Haolin Xin, Zilin Wei, Yingkai Qin, Aili Wei, Kang Chen, Longfei Xu, Bin Li, Kun Wang, Tianhui Wang
{"title":"A novel non-invasive sweat lactate biosensor and its application in human exercise monitoring.","authors":"Haolin Xin, Zilin Wei, Yingkai Qin, Aili Wei, Kang Chen, Longfei Xu, Bin Li, Kun Wang, Tianhui Wang","doi":"10.3389/fbioe.2025.1661224","DOIUrl":"10.3389/fbioe.2025.1661224","url":null,"abstract":"<p><strong>Introduction: </strong>Lactate is a key biomarker for clinical diagnostics and athletic performance monitoring. Conventional blood-based assays are invasive and not ideal for real-time applications. Sweat, as a non-invasive alternative, offers significant advantages for dynamic lactate tracking.</p><p><strong>Methods: </strong>We developed a highly sensitive fluorescence resonance energy transfer (FRET)-based aptasensor for lactate detection in sweat. The sensing platform utilizes aptamer-functionalized core-shell upconversion nanoparticles (APT-CS-UCNPs) as energy donors and Fe<sub>3</sub>O<sub>4</sub>-decorated molybdenum disulfide (MoS<sub>2</sub>) nanosheets as quenchers. In the absence of lactate, efficient FRET occurs due to the close proximity (<10 nm) between the donor and acceptor, quenching fluorescence at 545 nm. Lactate binding induces conformational changes in the aptamer, increasing donor-acceptor distance and restoring fluorescence intensity.</p><p><strong>Results: </strong>The aptasensor exhibited a broad linear detection range (0-30 mM, <i>R</i> <sup>2</sup> = 0.9981) and an ultralow detection limit (0.07785 mM), outperforming most reported electrochemical sensors. In spiked sweat samples, recovery rates ranged from 98.45% to 104.28%, with negligible cross-reactivity to common interferents. Comparative analysis with commercial kits and previously published methods confirmed superior sensitivity and ease of operation.</p><p><strong>Discussion: </strong>This FRET-based aptasensor enables accurate, rapid, and non-invasive lactate quantification using standard laboratory instrumentation. Its successful application in real human sweat samples highlights strong potential for both clinical diagnostics and athletic performance monitoring.</p>","PeriodicalId":12444,"journal":{"name":"Frontiers in Bioengineering and Biotechnology","volume":"13 ","pages":"1661224"},"PeriodicalIF":4.8,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12479049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198665","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}
Martin Saballus, Lucas Nik Reger, Robin Obser, Julia Niemann, Rene H Wijffels, Dirk E Martens, Markus Kampmann
{"title":"Viable cell sorting by fluidized bed centrifugation enables novel cultivation strategies.","authors":"Martin Saballus, Lucas Nik Reger, Robin Obser, Julia Niemann, Rene H Wijffels, Dirk E Martens, Markus Kampmann","doi":"10.3389/fbioe.2025.1667343","DOIUrl":"https://doi.org/10.3389/fbioe.2025.1667343","url":null,"abstract":"<p><p>In biopharmaceutical manufacturing, continuous perfusion cultivation enables high space-time yields and increased plant utilization, which are critical targets for modern upstream process intensification. However, filter-based cell retention devices, utilized in these processes, have significant disadvantages: Significant sieving effects and the risk of filter blockage alongside the retention of harmful substances and non-viable cells, represent a major challenge and often reduce the viability of the culture. To enable the next-generation of continuous processes, novel cell retention strategies are required. Therefore, the aim of this study was to develop an approach for large-scale sorting of viable and non-viable cells and to investigate its applicability for novel continuous cultivation strategies. To remove non-viable cells and thus to enrich viable cells in the culture, a single-use fluidized bed centrifuge (FBC) was used, which is usually applied for concentration and washing of mammalian cells. A novel FBC method was introduced by overloading the centrifuge chambers that allows high throughput sorting depending on the culture´s viability. The impact of the sorting on the subsequent cultivation and productivity of the cells was investigated in a multi-parallel 15 mL bioreactor setup. Cell sorting after regular fed-batch cultivation showed +14% increase of viability, continued cell growth, and thus +13% higher titers. Thereafter, periodic cell sorting was tested on a 5-L scale bioreactor, combining the advantageous characteristics of fed-batch and perfusion cultivation. The feasibility was successfully demonstrated for 20 days, achieving a high average space-time yield of 0.75 g/L/d. In both cultivation trials, up to +38% higher cell specific antibody productivities were found after cell sorting. Overall, the FBC sorting method in combination with innovative cultivation concepts addresses current limitations and challenges of continuous biopharmaceutical manufacturing and has great potential to further advance modern process intensification.</p>","PeriodicalId":12444,"journal":{"name":"Frontiers in Bioengineering and Biotechnology","volume":"13 ","pages":"1667343"},"PeriodicalIF":4.8,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12481202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206099","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":"Effect of cobalt ions on TNF-α and IL-6 secretion by fibroblasts surrounding hip periprosthetic membrane.","authors":"Ying Cai, Ang Li, Yebin Qian","doi":"10.3389/fbioe.2025.1651049","DOIUrl":"https://doi.org/10.3389/fbioe.2025.1651049","url":null,"abstract":"<p><strong>Aims: </strong>The periprosthetic fibroblast-like cells (PPFs) play an important role in aseptic loosening after total hip arthroplasty (THA). However, little is known about fibroblast metabolism in aseptic loosening. Proinflammatory cytokines such as tumor necrosis factor-α (TNF-α) and il-6 interleukin-6 (IL-6) are involved in periprosthetic osteolysis. Cobalt (Co) ions are capable of inducing cytokines from macrophage. In this study, we investigated the effects of Co<sup>2+</sup> on glycolysis and secretion of TNF-α and IL-6 in PPFs.</p><p><strong>Materials and methods: </strong>Fibroblasts were isolated from synovial tissues of osteoarthritis (OA) and rheumatoid arthritis (RA) patients, as well as from the periprosthetic pseudomembrane of patients undergoing revision surgery for aseptic loosening. Cells were cultured with or without Co<sup>2+</sup>. Following treatment, fibroblast viability was assessed using the MTT assay. To evaluate glycolysis, glucose uptake and lactate secretion were measured using specific assay kits. Furthermore, gene expression of key glycolysis enzymes (glucose transporter -1(GLUT1), hexokinase-2(HK2)) was analyzed by quantitative real-time PCR (qPCR), while protein expression of protein kinase B (AKT) and phosphorylated AKT (pAKT) was detected via Western blotting. Finally, TNF-α and IL-6 secretion into the culture supernatant was quantified using enzyme-linked immunosorbent assay (ELISA) kits.</p><p><strong>Results: </strong>Increased glucose uptake and lactic acid secretion occurred in PPFs. Exposure to Co<sup>2+</sup> significantly increased glucose uptake, lactate secretion, GLUT1/HK2 mRNA expression, and TNF-α/IL-6 levels in PPFs. This Co<sup>2+</sup>-induced enhancement of glycolysis and cytokine secretion was dependent on glycolytic activity, as inhibition with 2-deoxy-D-glucose (2-DG) reduced all measured parameters. Furthermore, Co<sup>2+</sup> stimulation increased pAKT protein expression in PPFs, indicating activation of the PI3K/AKT pathway. Consistent with this, treatment with the phosphatidylinositol three kinase/protein kinase B (PI3K/AKT) inhibitor LY294002 attenuated the Co<sup>2+</sup>-induced increases in glucose uptake, lactate secretion, GLUT1/HK2 mRNA, and TNF-α/IL-6 levels.</p><p><strong>Conclusion: </strong>Our findings suggest that Co<sup>2+</sup> enhances TNF-α and IL-6 secretion in PPFs by upregulating glycolysis. This glycolytic regulation of cytokine production appears to be mediated by the PI3K/AKT signaling pathway, identifying it as a potential novel therapeutic target for preventing aseptic loosening.</p>","PeriodicalId":12444,"journal":{"name":"Frontiers in Bioengineering and Biotechnology","volume":"13 ","pages":"1651049"},"PeriodicalIF":4.8,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12479478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206040","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":"Advances in tissue engineering for the repair of growth plate injuries.","authors":"Wenla Wang, Wenxiang Zeng, Qingyu Tu, Qing Li, Jindi Xu, Wei Zhuang","doi":"10.3389/fbioe.2025.1608923","DOIUrl":"https://doi.org/10.3389/fbioe.2025.1608923","url":null,"abstract":"<p><p>The growth plate is a cartilage tissue located between the epiphysis and diaphysis of long bones, responsible for the longitudinal growth of the skeleton. Due to its limited regenerative capacity, when the growth plate is damaged, it is typically replaced by inappropriate bone tissue, leading to the formation of bony bridges. These bony bridges not only restrict normal skeletal growth but may also cause limb length discrepancies, angular deformities, and functional impairments. Although traditional clinical treatments have shown some effectiveness, they are often associated with severe complications and poor prognoses. Therefore, the development of effective therapeutic strategies to prevent the formation of bony bridges and promote the repair and regeneration of the growth plate has become a current research focus. Cartilage tissue engineering, as an emerging therapeutic approach, restore the function of the growth plate through the substitution or repair of damaged cartilage tissue, has been widely applied in the repair of growth plate injuries. Cartilage tissue engineering for growth plate injury primarily relies on three key components: seed cells, growth factors, and scaffold materials. Seed cells provide the basis for cartilage regeneration, typically using autologous or allogeneic chondrocytes, mesenchymal stem cells, etc.,; growth factors such as bone morphogenetic proteins (BMPs) and transforming growth factor-beta (TGF-β) promote cell proliferation and differentiation, while regulating the synthesis of cartilage matrix; scaffold materials provide three-dimensional structural support, offering a platform for directed cell growth and tissue repair. In recent years, with continuous advancements in biomaterials and innovations in tissue engineering techniques, cartilage tissue engineering has shown promising prospects for application. This article systematically reviews the latest research progress on cartilage tissue engineering in the repair of growth plate injuries, based on a comprehensive search and analysis of relevant literature from databases such as PubMed and CNKI. The paper focuses on the classification and stages of growth plate injuries and discusses the three essential elements of tissue engineering treatment for growth plate injury.</p>","PeriodicalId":12444,"journal":{"name":"Frontiers in Bioengineering and Biotechnology","volume":"13 ","pages":"1608923"},"PeriodicalIF":4.8,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12479520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206045","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":"Metabolome profile and microbial community structure of <i>Cenchrus fungigraminus</i> silage under different moisture gradients.","authors":"Xiaohan Hou, Xiaohui Chu, Yang Yang, Xue Xiao, Qiongmei Niu, Guilian Shan","doi":"10.3389/fbioe.2025.1657657","DOIUrl":"10.3389/fbioe.2025.1657657","url":null,"abstract":"<p><p>Due to its high biomass yield, <i>Cenchrus fungigraminus</i> is widely cultivated in Yunnan. Local herders often adjust the moisture content of fresh grass by sun-drying to improve its suitability for silage. However, the spatiotemporal dynamics of microbial communities and metabolites during its fermentation process remain unclear. In this study, fresh grass was subjected to natural sun-drying for 0, 12, 24, and 36 h, achieving moisture contents of approximately 88%, 77%, 66%, and 50%, respectively, before ensiling. We combined 16S rRNA high-throughput sequencing and LC-MS-based metabolomics to investigate changes in microbial diversity, community structure, and metabolic pathways under different moisture conditions. The results showed that, with prolonged sun exposure, the water-soluble carbohydrate (WSC) and ether extract (EE) of the raw material decreased, and the acid-insoluble fiber (ADF) also decreased; the richness and diversity of the microbial community in the low-moisture group (50%) after silage were significantly higher than those in the high-moisture group, accompanied by an increase in harmful bacteria such as <i>Clostridium</i>. In contrast, the abundance of lactic acid bacteria (LAB), including <i>Lactobacillus</i> and <i>Weissella</i>, showed a significant positive correlation with moisture content. Metabolomics analysis showed that essential amino acid-related pathways (aspartic acid and glutamic acid) were upregulated, while phenolic acid metabolism (protocatechuic acid and gallic acid) was downregulated, reflecting the differential regulation of fermentation products under different moisture conditions. In summary, although excessive sun-drying can optimize the fiber structure and palatability of raw materials, overly low moisture levels are unfavorable for the proliferation of probiotics and may compromise silage quality. Maintaining a higher moisture content (≥75%) for silage is more conducive to fermentation stability and nutritional value, providing a theoretical basis for optimizing the silage process of <i>Cenchrus fungigraminus</i>.</p>","PeriodicalId":12444,"journal":{"name":"Frontiers in Bioengineering and Biotechnology","volume":"13 ","pages":"1657657"},"PeriodicalIF":4.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198739","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}
Xiaogang Li, Zeqing Zhao, Shi Chen, Ye Guo, Hui Pan, Xiao Yang
{"title":"Quantitative absorptive micro-sampling for decentralized monitoring of insulin-like growth factor 1.","authors":"Xiaogang Li, Zeqing Zhao, Shi Chen, Ye Guo, Hui Pan, Xiao Yang","doi":"10.3389/fbioe.2025.1648347","DOIUrl":"10.3389/fbioe.2025.1648347","url":null,"abstract":"<p><strong>Introduction: </strong>This study establishes a novel quantitative acoustic mass spectrometry (QAMS) methodology for insulin-like growth factor 1 (IGF-1) detection.</p><p><strong>Methods: </strong>Chromatographic separation utilized a Peptide C18 column (1.8 μm, 50 mm) with 0.1% formic acid/acetonitrile gradient elution, coupled to tandem mass spectrometry operated in scheduled multiple reaction monitoring (sMRM) mode.</p><p><strong>Results: </strong>The method demonstrated a lower limit of quantification (LOQ) of 10 ng/mL with linear dynamic range spanning 10-500 ng/mL. Comparative analysis of 74 paired plasma specimens revealed strong inter-matrix correlation with quantifiable bias.</p><p><strong>Discussion: </strong>These advancements position QAMS- as a robust tool for decentralized IGF-1 monitoring, particularly valuable in pediatric growth disorder studies and resource-limited settings. Longitudinal stability validation and isoform differentiation remain focal points for future optimization.</p>","PeriodicalId":12444,"journal":{"name":"Frontiers in Bioengineering and Biotechnology","volume":"13 ","pages":"1648347"},"PeriodicalIF":4.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198683","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}
Yu Chen, Yangfei Ou, Chunxing Xian, Hao Wu, Guoqing Pei, Wei Li, Ling Wang, Lei Shi
{"title":"The effect of barium titanate-coated titanium alloy scaffolds on bone regeneration in osteonecrosis of the femoral head models: a comprehensive analysis based on <i>in vitro</i> and <i>in vivo</i> experiments.","authors":"Yu Chen, Yangfei Ou, Chunxing Xian, Hao Wu, Guoqing Pei, Wei Li, Ling Wang, Lei Shi","doi":"10.3389/fbioe.2025.1671695","DOIUrl":"10.3389/fbioe.2025.1671695","url":null,"abstract":"<p><p>Osteonecrosis of the femoral head (ONFH) is a common condition that greatly affects patients' quality of life, yet current treatments often have limited effectiveness. This study aimed to explore how a porous titanium alloy scaffold coated with barium titanate (BaTiO<sub>3</sub>) could promote bone regeneration in ONFH. We employed various research methods including cell culture, piezoelectric property measurements, tissue-engineered scaffold fabrication, and <i>in vitro</i> and <i>in vivo</i> biocompatibility assessments. Our results showed that macrophages had better attachment and growth on the BaTiO<sub>3</sub>-coated porous titanium alloy (PTB) scaffold than on the uncoated porous titanium alloy (PT) scaffold, with no significant differences in apoptosis rates between the two groups. Furthermore, the PTB scaffolds reduced the expression of bone resorption markers, such as Cathepsin K, TRAP, and RANK, under dynamic loading conditions. This finding indicates their potential to inhibit osteoclast differentiation. Moreover, the BaTiO<sub>3</sub> coating enhanced the mechanical properties and biocompatibility of the scaffolds, evidenced by significantly higher alkaline phosphatase activity and calcium nodule formation in MC3T3-E1 osteoblasts cultured on PTB scaffolds. These findings underscore the dual role of BaTiO<sub>3</sub> in facilitating cellular responses and modulating signaling pathways involved in bone metabolism. Our study highlights the promise of BaTiO<sub>3</sub>-coated titanium alloy scaffolds as an innovative approach to enhance bone regeneration in ONFH, paving the way for future clinical applications and the development of advanced biomaterials for bone healing.</p>","PeriodicalId":12444,"journal":{"name":"Frontiers in Bioengineering and Biotechnology","volume":"13 ","pages":"1671695"},"PeriodicalIF":4.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185239","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}
Jing Dai, Jian-Xiong Ma, Bin Lu, Hao-Hao Bai, Hongjie Zhang, Xin-Long Ma
{"title":"Foot progression angle asymmetry as a potential biomechanical marker of radiographic severity in knee osteoarthritis.","authors":"Jing Dai, Jian-Xiong Ma, Bin Lu, Hao-Hao Bai, Hongjie Zhang, Xin-Long Ma","doi":"10.3389/fbioe.2025.1667271","DOIUrl":"10.3389/fbioe.2025.1667271","url":null,"abstract":"<p><strong>Introduction: </strong>Knee osteoarthritis (OA) induces asymmetric gait adaptations, yet the role of foot progression angle (FPA) remains unquantified. This study aimed to: (1) compare FPA differences between affected and contralateral limbs in knee OA patients, (2) characterize FPA asymmetry patterns, and (3) identify factors associated with inter-limb FPA differences.</p><p><strong>Methods: </strong>FPA asymmetry was quantified in 127 patients scheduled for unilateral high tibial osteotomy (HTO). FPA was measured bilaterally during natural walking. Multivariable logistic regression identified factors associated with asymmetry patterns.</p><p><strong>Results: </strong>FPA was significantly larger on contralateral limbs versus affected limbs (15.21° ± 7.72° vs 11.38° ± 8.13°, *p* < 0.001). Adjusted for covariates, patients with Kellgren-Lawrence (K&L) grade 1/2 OA had 70.2% lower odds (OR = 0.298, 95%CI:0.091-0.982) and grade 3 OA had 76.2% lower odds (OR = 0.238, 95%CI:0.081-0.700) of exhibiting contralateral-dominant FPA asymmetry compared to grade 4 OA (<i>P</i> < 0.05).</p><p><strong>Conclusion: </strong>Knee OA patients exhibit FPA asymmetry characterized by greater toe-out on the contralateral limb, correlating positively with higher radiographic severity (K&L grade) in the affected knee. FPA asymmetry may serve as a potential biomechanical marker of OA severity.</p>","PeriodicalId":12444,"journal":{"name":"Frontiers in Bioengineering and Biotechnology","volume":"13 ","pages":"1667271"},"PeriodicalIF":4.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185242","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}
Asier Muñoz, Annalisa De Paolis, Luis Cardoso, Alessandra Carriero
{"title":"Mechanical deformations of bone generate interstitial fluid flow at nanoscale velocities around osteocytes.","authors":"Asier Muñoz, Annalisa De Paolis, Luis Cardoso, Alessandra Carriero","doi":"10.3389/fbioe.2025.1639788","DOIUrl":"10.3389/fbioe.2025.1639788","url":null,"abstract":"<p><p>Osteocytes play a critical role in bone mechanobiology, sensing and responding to mechanical loading through fluid flow within the lacunar-canalicular network (LCN). Experimental measurements of interstitial fluid flow in bone are difficult due to the embedded nature of osteocytes in the dense mineralized matrix. Therefore, accurate computer simulations of these processes are essential for understanding bone mechanobiology. Two computational approaches have mostly been used to characterize convective interstitial fluid flow in bone: poroelastic finite element (FE) models, which treat bone as a homogenized porous medium, and fluid-structure interaction (FSI) models, which incorporate explicit LCN microarchitecture. However, these approaches have predicted fluid velocities that differ by three to four orders of magnitude. Here, we investigate the reasons for this discrepancy and demonstrate how imposed pressure gradients influence the predicted fluid velocities. Using an FSI model of a single osteocyte embedded in the mineralized matrix, we show that when an imposed pore pressure gradient is smaller than that generated by bone matrix deformation under mechanical loading, the convective fluid velocities in the canaliculi reach ∼100 nm/s and scale with the applied strain. In contrast, applying higher pressure gradients decouples fluid flow from the solid bone matrix deformation, resulting in fluid velocities bigger than 100 μm/s that are insensitive to loading conditions. Future studies investigating the effect of load-induced convection flow on osteocyte mechanobiology should therefore apply small imposed pressure gradients to avoid overestimating interstitial flow and more realistically capture load-induced convective flow.</p>","PeriodicalId":12444,"journal":{"name":"Frontiers in Bioengineering and Biotechnology","volume":"13 ","pages":"1639788"},"PeriodicalIF":4.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185259","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}
Jenny S Choy, Lei Fan, Yousif Awakeem, Chenghan Cai, Farshad Raissi, Lik Chuan Lee, Ghassan S Kassab
{"title":"Acute effects of mechanical dyssynchrony on left ventricular function and coronary perfusion.","authors":"Jenny S Choy, Lei Fan, Yousif Awakeem, Chenghan Cai, Farshad Raissi, Lik Chuan Lee, Ghassan S Kassab","doi":"10.3389/fbioe.2025.1630854","DOIUrl":"10.3389/fbioe.2025.1630854","url":null,"abstract":"<p><strong>Background: </strong>Patients with heart failure frequently develop mechanical dyssynchrony, which impairs ventricular function, coronary perfusion and their interactions. The underlying mechanisms, however, remain poorly understood due to numerous confounding factors. The objective of this study was to determine the acute effects of mechanical dyssynchrony on global and regional left ventricular (LV) function, coronary perfusion and their interactions based on experimental and computational approaches.</p><p><strong>Methods: </strong>Mechanical dyssynchrony was created with right ventricular apical pacing in Yorkshire domestic swine (n = 9). The heart was paced at 100 and 140 bpm and the results were compared to right atrial pacing. An inverse finite element computational framework based on an animal-specific geometry of the LV and measurements was developed to investigate the effects of mechanical dyssynchrony on LV function and its correlation with regional coronary perfusion.</p><p><strong>Results: </strong>Cardiac dyssynchrony induced significant decrease in LV pressure, volume, dP/dt<sub>(min)</sub>, stroke volume, ejection fraction, and regional longitudinal and circumferential strain. With mechanical dyssynchrony, passive flow decreased by 70% in the left anterior descending artery (LAD) and 67% in the left circumflex (LCX). An animal-specific inverse finite element computational model predicted that in mechanical dyssynchrony, global and regional LV contractility in the septum and LV free wall (LVFW), and myocardial work done in the septum and LVFW decreased.</p><p><strong>Conclusion: </strong>The computational model predicted reduction in global and regional contractility, and regional myocardial work done in the septum and LVFW with mechanical dyssynchrony are positively correlated with the corresponding decrease in experimentally measured regulated coronary flow in the LAD and LCX. These findings demonstrate that this interrelated mechanism between LV function and coronary flow in mechanical dyssynchrony may affect cardiac resynchronization therapy responder rate.</p>","PeriodicalId":12444,"journal":{"name":"Frontiers in Bioengineering and Biotechnology","volume":"13 ","pages":"1630854"},"PeriodicalIF":4.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185283","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}