Physiological Loading-induced Interstitial Fluid Dynamics in Osteon of Osteogenesis Imperfecta Bone

Author(s):  
Nikhil Vivek Shrivas ◽  
Abhishek Kumar Tiwari ◽  
Rakesh Kumar ◽  
Santosh Patil ◽  
Dharmendra Tripathi ◽  
...  

Abstract Osteogenesis Imperfecta (OI), also known as 'brittle bone disease', is a genetic bone disorder. OI bones experience frequent fractures. It is observed physical activity is equally beneficial in reducing OI bone fractures in both children and adults as mechanical stimulation improves bone mass and strength. Loading-induced mechanical strain and interstitial fluid flow stimulates bone remodeling activities. Several studies have characterized strain environment in OI bones, whereas, a very few studies attempted to characterize the interstitial fluid flow. OI significantly affect bone microarchitecture. Thus, the present study anticipates that canalicular fluid flow reduces in OI bone in comparison to healthy bone in response to physiological loading due to altered poromechanical properties. Hence, this work attempts to understand the canalicular fluid distribution in the single osteon model of OI and healthy bones. A poromechanical model of osteon is developed to compute pore-pressure and interstitial fluid flow as a function of gait loading pattern reported for OI and healthy subjects. Fluid distribution patterns are compared at different time-points of stance phase of the gait cycle. It is observed that fluid flow significantly reduces in OI bone. Additionally, flow is more static than dynamic in OI osteon in comparison to healthy subjects. The present work attempts to identify the plausible explanation behind low mechano-transduction capability of OI bone. This work may further be extended in designing better biomechanical strategies to enhance fluid flow in order to improve osteogenic activities in OI bone.

Author(s):  
Nikhil V. Shrivas ◽  
Abhishek Kumar Tiwari ◽  
Rakesh Kumar ◽  
Dharmendra Tripathi ◽  
Vasu Raman Sharma

Osteogenesis Imperfecta (OI) is a genetic bone disorder which is typically characterized by brittle bones with frequent fractures. It is also known as brittle bone disease. Surgical procedure is one of the ways adopted by clinicians for the management of OI. In recent years, it has however become clear that physical activity is equally important for managing OI in both children and adults. Exogenous mechanical stimulation e.g. prophylactic exercises may be useful in improving the bone mass and strength of OI bones as loading-induced mechanical components e.g. normal strain and canalicular fluid flow stimulate remodeling activities. Several studies have characterized the strain environment in OI bones, whereas, very few studies attempted to characterize the canalicular fluid flow. In the present study, we anticipate that canalicular fluid flow reduces in OI bone as compared to healthy bone under physiological loading. This work accordingly computes the canalicular fluid distribution in the single osteon model of OI and control/normal bones subjected to normal physiological loadings. A transversely isotropic poroelastic model of osteon is developed. Loading is applied in accordance with gait cycles reported for OI and healthy bones. Fluid distribution patterns computed for OI and healthy bones are compared at different time-points of stance phase of the gait cycle. A significant reduction in fluid flow is observed in case of OI bone as compared to healthy bone. This clearly indicates that improvements in physical activities or exercises can be designed to enhance the level of canalicular fluid flow to initiate possible osteogenic activities and the bone.


Author(s):  
Qiuyun Wang ◽  
Shaopeng Pei ◽  
X. Lucas Lu ◽  
Liyun Wang ◽  
Qianhong Wu

2018 ◽  
Vol 29 (16) ◽  
pp. 1927-1940 ◽  
Author(s):  
Ran Li ◽  
Jean Carlos Serrano ◽  
Hao Xing ◽  
Tara A. Lee ◽  
Hesham Azizgolshani ◽  
...  

Tumor tissues are characterized by an elevated interstitial fluid flow from the tumor to the surrounding stroma. Macrophages in the tumor microenvironment are key contributors to tumor progression. While it is well established that chemical stimuli within the tumor tissues can alter macrophage behaviors, the effects of mechanical stimuli, especially the flow of interstitial fluid in the tumor microenvironment, on macrophage phenotypes have not been explored. Here, we used three-dimensional biomimetic models to reveal that macrophages can sense and respond to pathophysiological levels of interstitial fluid flow reported in tumors (∼3 µm/s). Specifically, interstitial flow (IF) polarizes macrophages toward an M2-like phenotype via integrin/Src-mediated mechanotransduction pathways involving STAT3/6. Consistent with this flow-induced M2 polarization, macrophages treated with IF migrate faster and have an enhanced ability to promote cancer cell migration. Moreover, IF directs macrophages to migrate against the flow. Since IF emanates from the tumor to the surrounding stromal tissues, our results suggest that IF could not only induce M2 polarization of macrophages but also recruit these M2 macrophages toward the tumor masses, contributing to cancer cell invasion and tumor progression. Collectively, our study reveals that IF could be a critical regulator of tumor immune environment.


2012 ◽  
Vol 12 (3) ◽  
pp. 533-553 ◽  
Author(s):  
Vittorio Sansalone ◽  
Joanna Kaiser ◽  
Salah Naili ◽  
Thibault Lemaire

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