Asier Muñoz, Annalisa De Paolis, Luis Cardoso, Alessandra Carriero
{"title":"骨的机械变形在骨细胞周围产生纳米级速度的间质液流动。","authors":"Asier Muñoz, Annalisa De Paolis, Luis Cardoso, Alessandra Carriero","doi":"10.3389/fbioe.2025.1639788","DOIUrl":null,"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":4.8000,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463924/pdf/","citationCount":"0","resultStr":"{\"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\":null,\"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\":4.8000,\"publicationDate\":\"2025-09-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463924/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in Bioengineering and Biotechnology\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://doi.org/10.3389/fbioe.2025.1639788\",\"RegionNum\":3,\"RegionCategory\":\"工程技术\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Bioengineering and Biotechnology","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.3389/fbioe.2025.1639788","RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
Mechanical deformations of bone generate interstitial fluid flow at nanoscale velocities around osteocytes.
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.
期刊介绍:
The translation of new discoveries in medicine to clinical routine has never been easy. During the second half of the last century, thanks to the progress in chemistry, biochemistry and pharmacology, we have seen the development and the application of a large number of drugs and devices aimed at the treatment of symptoms, blocking unwanted pathways and, in the case of infectious diseases, fighting the micro-organisms responsible. However, we are facing, today, a dramatic change in the therapeutic approach to pathologies and diseases. Indeed, the challenge of the present and the next decade is to fully restore the physiological status of the diseased organism and to completely regenerate tissue and organs when they are so seriously affected that treatments cannot be limited to the repression of symptoms or to the repair of damage. This is being made possible thanks to the major developments made in basic cell and molecular biology, including stem cell science, growth factor delivery, gene isolation and transfection, the advances in bioengineering and nanotechnology, including development of new biomaterials, biofabrication technologies and use of bioreactors, and the big improvements in diagnostic tools and imaging of cells, tissues and organs.
In today`s world, an enhancement of communication between multidisciplinary experts, together with the promotion of joint projects and close collaborations among scientists, engineers, industry people, regulatory agencies and physicians are absolute requirements for the success of any attempt to develop and clinically apply a new biological therapy or an innovative device involving the collective use of biomaterials, cells and/or bioactive molecules. “Frontiers in Bioengineering and Biotechnology” aspires to be a forum for all people involved in the process by bridging the gap too often existing between a discovery in the basic sciences and its clinical application.