Pub Date : 2025-07-28DOI: 10.1016/j.mbm.2025.100145
Gurneet S. Sangha , Lauren V. Smith , Marzyeh Kheradmand , Kashif M. Munir , Nimisha Rangachar , Callie M. Weber , Zohreh Safari , Stephen C. Rogers , Allan Doctor , Alisa Morss Clyne
Nitric oxide (NO) is a key signaling molecule in maintaining cardiovascular health. While endothelial cells were initially thought to exclusively contain endothelial nitric oxide synthase (eNOS), an enzyme that produces NO, recent evidence suggests that red blood cells (RBC) also contain functional eNOS that impacts cardiovascular function. However, the mechanisms driving RBC eNOS activation are not well understood. Like endothelial cells, RBC are mechanosensitive via the stretch-activated piezo1 Ca2+ channel. Therefore, we investigated how piezo1 stimulation induced RBC and endothelial eNOS phosphorylation. We further examined how this mechanism is affected during diabetes, a condition known to impair vascular NO bioavailability. Our results reveal that piezo1 stimulation activated RBC eNOS via protein kinase C (PKC) and endothelial eNOS partially via protein kinase B (Akt). Surprisingly, piezo1-stimulation increased eNOS phosphorylation at the Ser1177 activation site nearly 20-fold in RBC from diabetic patients compared to 5.5-fold in RBC from non-diabetic patients. These findings highlight important differences in eNOS activation between RBC and endothelial cells and suggest potential biomolecular markers for targeting vascular NO bioavailability in health and disease.
{"title":"Piezo1 activates nitric oxide synthase in red blood cells via protein kinase C with increased activity in diabetes","authors":"Gurneet S. Sangha , Lauren V. Smith , Marzyeh Kheradmand , Kashif M. Munir , Nimisha Rangachar , Callie M. Weber , Zohreh Safari , Stephen C. Rogers , Allan Doctor , Alisa Morss Clyne","doi":"10.1016/j.mbm.2025.100145","DOIUrl":"10.1016/j.mbm.2025.100145","url":null,"abstract":"<div><div>Nitric oxide (NO) is a key signaling molecule in maintaining cardiovascular health. While endothelial cells were initially thought to exclusively contain endothelial nitric oxide synthase (eNOS), an enzyme that produces NO, recent evidence suggests that red blood cells (RBC) also contain functional eNOS that impacts cardiovascular function. However, the mechanisms driving RBC eNOS activation are not well understood. Like endothelial cells, RBC are mechanosensitive via the stretch-activated piezo1 Ca<sup>2+</sup> channel. Therefore, we investigated how piezo1 stimulation induced RBC and endothelial eNOS phosphorylation. We further examined how this mechanism is affected during diabetes, a condition known to impair vascular NO bioavailability. Our results reveal that piezo1 stimulation activated RBC eNOS via protein kinase C (PKC) and endothelial eNOS partially via protein kinase B (Akt). Surprisingly, piezo1-stimulation increased eNOS phosphorylation at the Ser1177 activation site nearly 20-fold in RBC from diabetic patients compared to 5.5-fold in RBC from non-diabetic patients. These findings highlight important differences in eNOS activation between RBC and endothelial cells and suggest potential biomolecular markers for targeting vascular NO bioavailability in health and disease.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"3 3","pages":"Article 100145"},"PeriodicalIF":0.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144771986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-28DOI: 10.1016/j.mbm.2025.100144
Alanna Krug , Gabrielle Inserra , Rhonda Drewes , Amanda Krajnik , Joseph A. Brazzo III , Thomas Mousso , Su Chin Heo , Yongho Bae
Scaffold-free three-dimensional (3D) cellular spheroid cultures better replicate the in vivo cellular microenvironments of complex tissues than traditional two-dimensional (2D) cell cultures, as they promote more intricate cell-cell and cell-extracellular matrix (ECM) interactions. In the context of cardiovascular research, 3D spheroids have emerged as valuable models for studying angiogenesis, modeling the cardiac microenvironment, and advancing drug development and cardiac tissue repair. Given that cardiovascular disease remains the leading cause of morbidity worldwide, exploring 3D spheroids as in vitro models in cardiovascular research holds potential for advancing the field. Despite their promise, the experimental potential of 3D spheroids in cardiovascular disease and biology has yet to be realized. Therefore, this review discusses the advantages and limitations of 3D spheroid models for studying angiogenesis and cardiovascular pathobiology, their applications in cardiac drug development and tissue repair, and how these models can advance cardiovascular research.
{"title":"Three-dimensional spheroid models for cardiovascular biology and pathology","authors":"Alanna Krug , Gabrielle Inserra , Rhonda Drewes , Amanda Krajnik , Joseph A. Brazzo III , Thomas Mousso , Su Chin Heo , Yongho Bae","doi":"10.1016/j.mbm.2025.100144","DOIUrl":"10.1016/j.mbm.2025.100144","url":null,"abstract":"<div><div>Scaffold-free three-dimensional (3D) cellular spheroid cultures better replicate the <em>in vivo</em> cellular microenvironments of complex tissues than traditional two-dimensional (2D) cell cultures, as they promote more intricate cell-cell and cell-extracellular matrix (ECM) interactions. In the context of cardiovascular research, 3D spheroids have emerged as valuable models for studying angiogenesis, modeling the cardiac microenvironment, and advancing drug development and cardiac tissue repair. Given that cardiovascular disease remains the leading cause of morbidity worldwide, exploring 3D spheroids as <em>in vitro</em> models in cardiovascular research holds potential for advancing the field. Despite their promise, the experimental potential of 3D spheroids in cardiovascular disease and biology has yet to be realized. Therefore, this review discusses the advantages and limitations of 3D spheroid models for studying angiogenesis and cardiovascular pathobiology, their applications in cardiac drug development and tissue repair, and how these models can advance cardiovascular research.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"3 3","pages":"Article 100144"},"PeriodicalIF":0.0,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144535580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-09DOI: 10.1016/j.mbm.2025.100137
Ruobing Liu , Yaru Huang , Maogang Jiang , Fei Xu , Qilin Pei , Jiajun Ma , Youru Li , Siqi Shen , Bo Zhang , Xiangyang Guo , Jing Cai , Wenwen Wang
Blood metabolomes have been linked to osteoporosis, yet the precise causal relationship with osteopenia, its preventable early stage, remains unclear. This study aimed to uncover the genetic causality between blood metabolomes and osteopenia, pinpointing potential targets for mechanomedicine. Utilizing genome-wide association study summary statistics, we analyzed 1091 metabolites and 309 metabolite ratios from 8299 individuals, correlating them with total body bone mineral density (BMD) from 56,284 individuals in the IEU GWAS database and osteopenia data from 408,961 European populations. Through two-sample Mendelian randomization, we investigated the association between blood metabolomes and skeletal characteristics. We then conducted summary-data-based Mendelian randomization (MR) analysis and colocalization analyses to identify causal genes related to skeletal phenotypes, predicting therapeutic targets for osteopenia. Expression of potential targets in osteocytes under fluid shear stress (FSS) stimulation was tested using qRT-PCR to explore mechanical sensitivity and bone health mechanisms. Our findings revealed five metabolites affecting total body BMD and osteopenia, with biliverdin emerging as a potential protective factor against osteopenia (OR = 0.93, 95 %CI = 0.88–0.98, P = 0.009). Additionally, three genes—LRRC14, SLC22A16, and TNFRSF1A—were identified as potential therapeutic targets for osteopenia. Notably, LRRC14 and TNFRSF1A are also associated with other musculoskeletal diseases. In vitro experiments showed that FSS significantly increased LRRC14 expression in osteocytes, suggesting its potential as a mechanosensitive factor. This study identifies candidate blood metabolites and mechanomedicine targets for osteopenia, offering a scientific basis for new diagnostic and treatment strategies and deepening our understanding of bone mechanics response characteristics.
血液代谢组与骨质疏松症有关，但与骨质减少的确切因果关系，其可预防的早期阶段，仍不清楚。本研究旨在揭示血液代谢组与骨质减少之间的遗传因果关系，确定机械医学的潜在靶点。利用全基因组关联研究汇总统计，我们分析了8299名个体的1091种代谢物和309种代谢物比率，并将它们与IEU GWAS数据库中56,284名个体的总体骨密度（BMD）和408,961名欧洲人群的骨质减少数据进行了关联。通过双样本孟德尔随机化，我们研究了血液代谢组与骨骼特征之间的关系。然后，我们进行了基于汇总数据的孟德尔随机化（MR）分析和共定位分析，以确定与骨骼表型相关的致病基因，预测骨质减少的治疗靶点。利用qRT-PCR技术检测了在流体剪切应力（FSS）刺激下骨细胞中潜在靶点的表达，以探索机械敏感性和骨健康机制。我们的研究结果显示，有5种代谢物影响全身骨密度和骨质减少，其中胆绿素是预防骨质减少的潜在保护因子（OR = 0.93, 95% CI = 0.88-0.98, P = 0.009）。此外，三个基因lrrc14、SLC22A16和tnfrsf1a被确定为骨质减少的潜在治疗靶点。值得注意的是，LRRC14和TNFRSF1A也与其他肌肉骨骼疾病相关。体外实验表明，FSS显著增加了LRRC14在骨细胞中的表达，提示其可能是一种机械敏感因子。本研究确定了骨减少的候选血液代谢物和机械药物靶点，为新的诊断和治疗策略提供了科学依据，加深了我们对骨力学反应特征的理解。
{"title":"Causal association analysis between blood metabolomes and osteopenia and therapeutic target prediction for mechanomedicine","authors":"Ruobing Liu , Yaru Huang , Maogang Jiang , Fei Xu , Qilin Pei , Jiajun Ma , Youru Li , Siqi Shen , Bo Zhang , Xiangyang Guo , Jing Cai , Wenwen Wang","doi":"10.1016/j.mbm.2025.100137","DOIUrl":"10.1016/j.mbm.2025.100137","url":null,"abstract":"<div><div>Blood metabolomes have been linked to osteoporosis, yet the precise causal relationship with osteopenia, its preventable early stage, remains unclear. This study aimed to uncover the genetic causality between blood metabolomes and osteopenia, pinpointing potential targets for mechanomedicine. Utilizing genome-wide association study summary statistics, we analyzed 1091 metabolites and 309 metabolite ratios from 8299 individuals, correlating them with total body bone mineral density (BMD) from 56,284 individuals in the IEU GWAS database and osteopenia data from 408,961 European populations. Through two-sample Mendelian randomization, we investigated the association between blood metabolomes and skeletal characteristics. We then conducted summary-data-based Mendelian randomization (MR) analysis and colocalization analyses to identify causal genes related to skeletal phenotypes, predicting therapeutic targets for osteopenia. Expression of potential targets in osteocytes under fluid shear stress (FSS) stimulation was tested using qRT-PCR to explore mechanical sensitivity and bone health mechanisms. Our findings revealed five metabolites affecting total body BMD and osteopenia, with biliverdin emerging as a potential protective factor against osteopenia (OR = 0.93, 95 %CI = 0.88–0.98, <em>P</em> = 0.009). Additionally, three genes—LRRC14, SLC22A16, and TNFRSF1A—were identified as potential therapeutic targets for osteopenia. Notably, LRRC14 and TNFRSF1A are also associated with other musculoskeletal diseases. In vitro experiments showed that FSS significantly increased LRRC14 expression in osteocytes, suggesting its potential as a mechanosensitive factor. This study identifies candidate blood metabolites and mechanomedicine targets for osteopenia, offering a scientific basis for new diagnostic and treatment strategies and deepening our understanding of bone mechanics response characteristics.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"3 3","pages":"Article 100137"},"PeriodicalIF":0.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144296837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Understanding the regulatory mechanisms of intestinal organoid morphogenesis remains a fundamental challenge in organoid biology. Emerging evidence highlights mechanical bistability as a critical regulator, mediated by dynamic lumen-actomyosin feedback. The recently developed 3D vertex model demonstrates that crypt curvature modulates actomyosin localization via mechanosensitive pathways, creating two stable morphological states—bulged or budded—depending on mechanical history. This model advances beyond static vertex models by incorporating epithelial thickness variations and lumen pressure effects, explaining previously unresolved phenomena like irreversible crypt budding and snap-through transitions. The findings establish a new framework for understanding mechanical decision-making in epithelial tissues, with implications for organoid engineering and developmental biology.
{"title":"Beyond biochemical patterning: How mechanical bistability governs robust organoid morphogenesis","authors":"Qigan Gao, Yuehua Yang, Haoxiang Yang, Hongyuan Jiang","doi":"10.1016/j.mbm.2025.100134","DOIUrl":"10.1016/j.mbm.2025.100134","url":null,"abstract":"<div><div>Understanding the regulatory mechanisms of intestinal organoid morphogenesis remains a fundamental challenge in organoid biology. Emerging evidence highlights mechanical bistability as a critical regulator, mediated by dynamic lumen-actomyosin feedback. The recently developed 3D vertex model demonstrates that crypt curvature modulates actomyosin localization via mechanosensitive pathways, creating two stable morphological states—bulged or budded—depending on mechanical history. This model advances beyond static vertex models by incorporating epithelial thickness variations and lumen pressure effects, explaining previously unresolved phenomena like irreversible crypt budding and snap-through transitions. The findings establish a new framework for understanding mechanical decision-making in epithelial tissues, with implications for organoid engineering and developmental biology.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"3 2","pages":"Article 100134"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144184941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-05-29DOI: 10.1016/j.mbm.2025.100136
Yibo Feng , Bingchen Che , Yonggang Liu , Cangmin Zhang , Jiameng Niu , Jiangcun Yang , Guangyin Jing , Dan Sun , Xiaobo Gong , Ce Zhang
Early diagnosis of diabetes is crucial, as diabetes, particularly type 2, can eventually lead to irreversible changes and complications. Conventional techniques, such as the Fasting Plasma Glucose (FPG) Test and Hemoglobin A1c (HbA1c) Test, measure blood glucose levels, which fluctuate over time and are insensitive to early stages. In this study, we focus on measuring the mechanical properties of red blood cells, as their irreversible changes can indicate early pathological impacts of diabetes. We developed a microfluidic chip with a symmetrical hyperbolic structure. By periodically altering the state of the valve membrane, we generate a reciprocating shear flow field that repeatedly acts on groups of RBCs. We then quantify the morphological parameters of the RBCs, establishing a correlation between the reciprocating shear flow field and the morphological changes of the cells. Using the developed microfluidic chip, we investigated the resistance of blood cells from 20 healthy volunteers to mechanical stimuli. The results indicated a significant correlation between the deformability of red blood cells and age, while no such correlation was found among individuals of the same gender. This study highlights the potential of utilizing the mechanical properties of red blood cells as an early diagnostic tool for diabetes. Furthermore, given the ease of integration of microfluidic chips, they present a promising high-throughput diagnostic solution for large-scale clinical screening.
{"title":"Early diabetes screening via red blood cell mechanics using microfluidic chip integration","authors":"Yibo Feng , Bingchen Che , Yonggang Liu , Cangmin Zhang , Jiameng Niu , Jiangcun Yang , Guangyin Jing , Dan Sun , Xiaobo Gong , Ce Zhang","doi":"10.1016/j.mbm.2025.100136","DOIUrl":"10.1016/j.mbm.2025.100136","url":null,"abstract":"<div><div>Early diagnosis of diabetes is crucial, as diabetes, particularly type 2, can eventually lead to irreversible changes and complications. Conventional techniques, such as the Fasting Plasma Glucose (FPG) Test and Hemoglobin A1c (HbA1c) Test, measure blood glucose levels, which fluctuate over time and are insensitive to early stages. In this study, we focus on measuring the mechanical properties of red blood cells, as their irreversible changes can indicate early pathological impacts of diabetes. We developed a microfluidic chip with a symmetrical hyperbolic structure. By periodically altering the state of the valve membrane, we generate a reciprocating shear flow field that repeatedly acts on groups of RBCs. We then quantify the morphological parameters of the RBCs, establishing a correlation between the reciprocating shear flow field and the morphological changes of the cells. Using the developed microfluidic chip, we investigated the resistance of blood cells from 20 healthy volunteers to mechanical stimuli. The results indicated a significant correlation between the deformability of red blood cells and age, while no such correlation was found among individuals of the same gender. This study highlights the potential of utilizing the mechanical properties of red blood cells as an early diagnostic tool for diabetes. Furthermore, given the ease of integration of microfluidic chips, they present a promising high-throughput diagnostic solution for large-scale clinical screening.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"3 3","pages":"Article 100136"},"PeriodicalIF":0.0,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144242828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-05-21DOI: 10.1016/j.mbm.2025.100135
Chenyang Ji, Junwei Chen, Fuxiang Wei
The nuclear envelope (NE) is a dynamic, mechanosensitive structure that functions as a protective barrier for the genome and serves as a checkpoint responding to external stimuli. It plays a critical role in maintaining genomic stability and regulating cell fate. This review synthesizes recent research highlighting the role of NE as a mechanical checkpoint in ensuring accurate chromosome segregation, regulating cell cycle progression, and contributing to cancer development. Chromosome mis-segregation during cell division is a major driver of aneuploidy, a condition closely associated with genomic instability and cellular transformation. The role of NE in chromatin organization and gene expression regulation is also discussed, underscoring its importance in cell differentiation and identity.
{"title":"Mechanosensitive nuclear checkpoint: nuclear envelope as a sensor of chromosomal instability and driver of cell fate","authors":"Chenyang Ji, Junwei Chen, Fuxiang Wei","doi":"10.1016/j.mbm.2025.100135","DOIUrl":"10.1016/j.mbm.2025.100135","url":null,"abstract":"<div><div>The nuclear envelope (NE) is a dynamic, mechanosensitive structure that functions as a protective barrier for the genome and serves as a checkpoint responding to external stimuli. It plays a critical role in maintaining genomic stability and regulating cell fate. This review synthesizes recent research highlighting the role of NE as a mechanical checkpoint in ensuring accurate chromosome segregation, regulating cell cycle progression, and contributing to cancer development. Chromosome mis-segregation during cell division is a major driver of aneuploidy, a condition closely associated with genomic instability and cellular transformation. The role of NE in chromatin organization and gene expression regulation is also discussed, underscoring its importance in cell differentiation and identity.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"3 2","pages":"Article 100135"},"PeriodicalIF":0.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144168768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-05-15DOI: 10.1016/j.mbm.2025.100133
Kaiyang Wang , Shuhui Ren , Yunfang Jia , Xiaobing Yan , Lizhen Wang , Yubo Fan
The modern medical field faces two critical challenges: the dramatic increase in data complexity and the explosive growth in data size. Especially in current research, medical diagnostic, and data processing devices relying on traditional computer architecture are increasingly showing limitations when faced with dynamic temporal and spatial processing requirements, as well as high-dimensional data processing tasks. Neuromorphic devices provide a new way for biomedical data processing due to their low energy consumption and high dynamic information processing capabilities. This paper aims to reveal the advantages of neuromorphic devices in biomedical applications. First, this review emphasizes the urgent need of biomedical engineering for diversify clinical diagnostic techniques. Secondly, the feasibility of the application in biomedical engineering is demonstrated by reviewing the historical development of neuromorphic devices from basic modeling to multimodal signal processing. In addition, this paper demonstrates the great potential of neuromorphic chips for application in the fields of biosensing technology, medical image processing and generation, rehabilitation medical engineering, and brain-computer interfaces. Finally, this review provides the pathways for constructing standardized experimental protocols using biocompatible technologies, personalized treatment strategies, and systematic clinical validation. In summary, neuromorphic devices will drive technological innovation in the biomedical field and make significant contributions to life health.
{"title":"Neuromorphic chips for biomedical engineering","authors":"Kaiyang Wang , Shuhui Ren , Yunfang Jia , Xiaobing Yan , Lizhen Wang , Yubo Fan","doi":"10.1016/j.mbm.2025.100133","DOIUrl":"10.1016/j.mbm.2025.100133","url":null,"abstract":"<div><div>The modern medical field faces two critical challenges: the dramatic increase in data complexity and the explosive growth in data size. Especially in current research, medical diagnostic, and data processing devices relying on traditional computer architecture are increasingly showing limitations when faced with dynamic temporal and spatial processing requirements, as well as high-dimensional data processing tasks. Neuromorphic devices provide a new way for biomedical data processing due to their low energy consumption and high dynamic information processing capabilities. This paper aims to reveal the advantages of neuromorphic devices in biomedical applications. First, this review emphasizes the urgent need of biomedical engineering for diversify clinical diagnostic techniques. Secondly, the feasibility of the application in biomedical engineering is demonstrated by reviewing the historical development of neuromorphic devices from basic modeling to multimodal signal processing. In addition, this paper demonstrates the great potential of neuromorphic chips for application in the fields of biosensing technology, medical image processing and generation, rehabilitation medical engineering, and brain-computer interfaces. Finally, this review provides the pathways for constructing standardized experimental protocols using biocompatible technologies, personalized treatment strategies, and systematic clinical validation. In summary, neuromorphic devices will drive technological innovation in the biomedical field and make significant contributions to life health.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"3 3","pages":"Article 100133"},"PeriodicalIF":0.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-05-13DOI: 10.1016/j.mbm.2025.100132
Timothy Hung , Kaitlyn S. Broz , Remy E. Walk , Simon Y. Tang
Individuals with type 2 diabetes (T2D) are prone to fracture at numerous skeletal sites despite presenting with a higher bone mineral density (BMD). The accumulation of Advanced Glycation End-products (AGEs) in the bone tissues of patients with T2D could be contributing to this paradox of increased skeletal fragility with higher BMD. AGEs can also impair bone cell homeostasis via the receptor for AGEs (RAGE). To investigate the effects of diabetes, AGE accumulation, and RAGE signaling on mouse cortical bone, we utilized male and female leptin receptor-deficient (db/db) diabetic mice from three age groups ranging from 3 to 12 months of age, which were crossed with mice carrying constitutively active alleles for a RAGE nullifying point mutation (RAGE−/−). The morphological, mechanical and material outcomes of bone were measured using microCT, three-point bending, and AGE assays. We observed significant impairments dependent on age and sex to the bone matrix and whole-bone mechanical behavior due to diabetes, with some impairments alleviated by the deletion of RAGE. In older female diabetic mice, the removal of RAGE signaling prevented the deficits in bone mechanics, morphology, and tissue mineral density (TMD). Male diabetic mice without RAGE signaling exhibited improved material properties compared to wild type controls. The study demonstrated that bone impairments associated with T2D can be prevented with RAGE deletion, and T2D complications may be partially reversible with the therapeutic inhibition of RAGE signaling.
{"title":"The sex-specific effects of RAGE signaling and type 2 diabetes on mouse cortical bone mechanics, structure, and material properties","authors":"Timothy Hung , Kaitlyn S. Broz , Remy E. Walk , Simon Y. Tang","doi":"10.1016/j.mbm.2025.100132","DOIUrl":"10.1016/j.mbm.2025.100132","url":null,"abstract":"<div><div>Individuals with type 2 diabetes (T2D) are prone to fracture at numerous skeletal sites despite presenting with a higher bone mineral density (BMD). The accumulation of Advanced Glycation End-products (AGEs) in the bone tissues of patients with T2D could be contributing to this paradox of increased skeletal fragility with higher BMD. AGEs can also impair bone cell homeostasis via the receptor for AGEs (RAGE). To investigate the effects of diabetes, AGE accumulation, and RAGE signaling on mouse cortical bone, we utilized male and female leptin receptor-deficient (db/db) diabetic mice from three age groups ranging from 3 to 12 months of age, which were crossed with mice carrying constitutively active alleles for a RAGE nullifying point mutation (RAGE<sup>−/−</sup>). The morphological, mechanical and material outcomes of bone were measured using microCT, three-point bending, and AGE assays. We observed significant impairments dependent on age and sex to the bone matrix and whole-bone mechanical behavior due to diabetes, with some impairments alleviated by the deletion of RAGE. In older female diabetic mice, the removal of RAGE signaling prevented the deficits in bone mechanics, morphology, and tissue mineral density (TMD). Male diabetic mice without RAGE signaling exhibited improved material properties compared to wild type controls. The study demonstrated that bone impairments associated with T2D can be prevented with RAGE deletion, and T2D complications may be partially reversible with the therapeutic inhibition of RAGE signaling.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"3 3","pages":"Article 100132"},"PeriodicalIF":0.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-24DOI: 10.1016/j.mbm.2025.100131
Xinman Chen , Chenyang Ji , Xi Liu , Ning Wang , Fuxiang Wei , Junwei Chen
Endogenous forces generated by living cells are essential for biological processes and physiological functions of cells and tissues. Over the last several decades, numerous methods for detecting traction forces have been developed. Here we review these methods and discuss their respective strengths and limitations. Being able to reliably quantify tractions in living cells and tissues are critical in understanding how forces drive and regulate cell and tissue functions in physiology and diseases.
{"title":"Three-dimensional traction technology and its application in mechanomedicine","authors":"Xinman Chen , Chenyang Ji , Xi Liu , Ning Wang , Fuxiang Wei , Junwei Chen","doi":"10.1016/j.mbm.2025.100131","DOIUrl":"10.1016/j.mbm.2025.100131","url":null,"abstract":"<div><div>Endogenous forces generated by living cells are essential for biological processes and physiological functions of cells and tissues. Over the last several decades, numerous methods for detecting traction forces have been developed. Here we review these methods and discuss their respective strengths and limitations. Being able to reliably quantify tractions in living cells and tissues are critical in understanding how forces drive and regulate cell and tissue functions in physiology and diseases.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"3 3","pages":"Article 100131"},"PeriodicalIF":0.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-30DOI: 10.1016/j.mbm.2025.100130
Shubo Wang , Tiankuo Chu , Murtaza Wasi , Rosa M. Guerra , Xu Yuan , Liyun Wang
The management of skeletal-related events (SREs), particularly the prevention of pathological fractures, is crucial for cancer patients. Current clinical assessment of fracture risk is mostly based on medical images, but incorporating sequential images in the assessment remains challenging. This study addressed this issue by leveraging a comprehensive dataset consisting of 260 longitudinal micro-computed tomography (μCT) scans acquired in normal and breast cancer bearing mice. A machine learning (ML) model based on a spatial–temporal neural network was built to forecast bone structures from previous μCT scans, which were found to have an overall similarity coefficient (Dice) of 0.814 with ground truths. Despite the predicted lesion volumes (18.5 % ± 15.3 %) being underestimated by ∼21 % than the ground truths’ (22.1 % ± 14.8 %), the time course of the lesion growth was better represented in the predicted images than the preceding scans (10.8 % ± 6.5 %). Under virtual biomechanical testing using finite element analysis (FEA), the predicted bone structures recapitulated the loading carrying behaviors of the ground truth structures with a positive correlation (y = 0.863x) and a high coefficient of determination (R2 = 0.955). Interestingly, the compliances of the predicted and ground truth structures demonstrated nearly identical linear relationships with the lesion volumes. In summary, we have demonstrated that bone deterioration could be proficiently predicted using machine learning in our preclinical dataset, suggesting the importance of large longitudinal clinical imaging datasets in fracture risk assessment for cancer bone metastasis.
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