INTERSTITIAL FLUID FLOW BEHAVIOR IN OSTEON WALL UNDER NON-AXISYMMETRIC LOADING: A FINITE ELEMENT STUDY

Physiological loads are non-axisymmetric and can lead to interstitial bone fluid flow, particularly in osteon. According to research, interstitial bone fluid flow plays a key role in bone mechanotransduction. To evaluate the poroelastic responses of a non-axisymmetric loaded osteon, this paper presents a finite element osteon model that is bulit by using the Comsol Multiphysics software. Obtained results show that under the same loading amplitude, the generated pressure and velocity amplitudes in the axial compression loading case are the largest, followed by that in the compressive bending loading, and smallest in the bending case. Moreover, the induced pressure and velocity amplitudes in axial compression loading exhibit an axial symmetrical distribution and axial centrosymmetric distribution in the compressive bending. In the bend loading case, the pressure amplitude presents an antisymmetric distribution, but the velocity amplitude is axially symmetrically distributed. Therefore, the distributions of pressure and velocity are definitely affected by load types, which lead to different bone fluid stimuli in mechanotransduction.

In Vivo Mesenchymal Stem Cell Proliferation in Response to Dynamic Fluid Flow Stimulation

Osteoporosis is a debilitating disease characterized as decreased bone mass and structural deterioration of bone tissue. Osteoporotic bone tissue turns itself into altered structure, which leads to weaker bones that are more susceptible for fractures. While often happening in elderly, long-term bed-rest patients, e.g. spinal cord injury, and astronauts who participate in long-duration spaceflights, osteoporosis has been considered as a major public health thread and causes great medical cost impacts to the society. Mechanobiology and novel stimulation on regulating bone health have long been recognized. Loading induced bone fluid flow, as a critical mechanotransductive promoter, has been demonstrated to regulate cellular signaling, osteogenesis, and bone adaptation [4]. As one of the factors that mediate bone fluid flow, intromedullary pressure (ImP) creates a pressure gradient that further influence the magnitude of mechanotransductory signals [5]. As for a potential translational development of ImP, our group has recently introduced a novel, non-invasive dynamic hydraulic stimulation (DHS) on bone structural enhancement. Its promising effects on inhibition of disuse bone loss has been shown with 2 Hz loading through a 4-week hindlimb suspension rat study followed by microCT analysis. At the cellular level, mesenchymal stem cells (MSCs) are defined by their self-renewal ability and that to potentially differentiate into the cells that form tissues such as bone [1]. To further elucidate the cellular effects of DHS and its potential mechanism on bone quality enhancement, the objective of this study was to measure MSC quantification in response to the in vivo mechanical signals driven by DHS.

Induced Intramedullary Pressure by Dynamic Hydraulic Stimulation and Its Potential in Attenuation of Bone Loss

Bone loss is a critical health problem of astronauts in long-term space missions. A growing number of evidence has pointed out bone fluid flow as a critical regulator in mechanotransductive signaling and bone adaptation. Intramedullary pressure (ImP) is a key mediator for bone fluid flow initiation and it influences the osteogenic signals within the skeleton. The potential ImP-induced bone fluid flow then triggers bone adaptation [1]. Previous in vivo study has demonstrated that ImP induced by oscillatory electrical stimulations can effectively mitigate disuse osteopenia in a frequency-dependent manner in a disuse rat model [2, 3]. In order to develop the translational potentials of ImP, a non-invasive intervention with direct fluid flow coupling is necessary to develop new treatments for microgravity-induced osteopenia/osteoporosis.

Local and Distant Intramedullary Pressure and Bone Strain by Dynamic Hydraulic Stimulation

Osteoporosis gives rise to fragile bones that have higher fracture risks due to diminished bone mass and altered bone microarchitecture [1]. Mechanical loading mediated bone adaptation has demonstrated promising potentials as a non-pharmacological alteration for both osteogenic response and attenuation of osteopenia [2]. Intramedullary pressure (ImP) has been proposed as a key factor for fluid flow initiation and mechanotransductive signal inductions in bone. It is also suggested that integration of strain signals over time allows low-level mechanical strain in the skeleton to trigger osteogenic activities. The potential bone fluid flow induced by strain and ImP mediates adaptive responses in the skeleton [3]. Previous in vivo studies using oscillatory electrical stimulations showed that dynamic muscle contractions can generate ImP and bone strain to mitigate disuse osteopenia in a frequency-dependent manner. To apply ImP alteration as a means for bone fluid flow regulation, it may be necessary to develop a new method that could couple external loading with internal bone fluid flow. In order to further study the direct effect of ImP on bone adaptation, it was hypothesized that external dynamic hydraulic stimulation (DHS) can generate ImP with minimal strain in a frequency-dependent manner. The aim of this study was to evaluate the immediate effects on local and distant ImP and bone strain induced by a novel, non-invasive dynamic external pressure stimulus in response to a range of loading frequencies.

The Effects of Loading Rate and Duration on Mitigation of Osteopenia by Dynamic Muscle Stimulation

Musculoskeletal adaptations to aging and disuse environment have significant physiological effects on skeletal health, i.e., osteopenia and bone loss. Osteoporosis often occurs together with muscle loss. Such musculoskeletal complications cause severe physiologic changes and have been proposed the synergistic effects of muscle function and bone adaptation. The role of mechanobiology in the skeletal tissue may be closely related to load-induced transductive signals, e.g., bone fluid flow, which is proposed to be a critical mediator of bone and muscle adaptation. The skeletal muscle may serve as a muscle pump that may mediate bone mechanotransduction via modulation of intramedullary pressure. Muscular stimulation (MS) is proposed to be used to simultaneously treat both muscle and bone loss. Indeed, our recent data have demonstrated that high frequency, short duration stimulation can inhibit bone loss and muscle atrophy. Although 10 min dynamic loading can effectively attenuate bone loss, it cannot totally recover disuse osteopenia. The optimal parameters required for such treatment are unclear. Studies have separately investigated the optimal signal parameters for bone or muscle. Insertion of recovery periods during high frequency stimulations to extend the loading cycles have shown potential to reduce muscle atrophy by minimizing fatigue and mimicking physiologic contractions, and demonstrated enhancement of bone remodeling. The overall hypothesis for this study is that dynamic MS can enhance anabolic activity in bone, and inhibit bone loss in a functional disuse condition. Combined high frequency and sufficient loading cycle may be able to completely mitigate bone loss induced by disuse osteopenia.

Inhibition of Bone Loss and Muscle Atrophy by Dynamic Muscle Contractions With Rest Periods in a Functional Disuse Mouse Model

Osteoporosis, induced by aging and long-term disuse, often occurs together with muscle loss. Musculoskeletal disuse causes severe physiologic changes and it has been proposed the synergistic effects of muscle function and bone adaptation. Bone fluid flow has been shown to be induced during mechanical loading, and is proposed to be a critical mediator of bone adaptation. The skeletal muscle may serve as a muscle pump that may mediate bone mechanotransduction via modulation of intramedullary pressure. Thus, muscular stimulation is proposed to be used to simultaneously treat both muscle and bone loss, but the optimal parameters required for such treatment is unclear. Studies have separately investigated the optimal signal parameters for bone or muscle. Insertion of recovery periods during high frequency stimulations have shown potential to reduce muscle atrophy by minimizing fatigue and mimicking physiologic contractions, and demonstrated enhancement of bone remodeling. Our preliminary research has indicated that dynamic muscle contractions within an optimal frequency range can significantly recover disuse induced bone loss. However, the optimal rest periods required to prevent muscle fatigue during stimulations are not clear. The overall objective of this study was to evaluate optimized dynamic muscle stimulations at relatively high frequency, e.g., 20 Hz, and to test the role of varying the rest duration on muscle mass and bone morphology in a functional hind limb disuse mouse model.

Bone Formation and Inhibition of Bone Loss by Dynamic Muscle Stimulation With Altered Interstitial Fluid Pressure

Tissue-level mechanisms and functions, including bone strain and muscle, are the potential key players in bone physiology and adaptation [1,2,3]. However, the mechanisms are not yet fully understood. Exercise such as muscle contraction appears to increase blood flow to the skeletal tissues, i.e., bone and muscle. These evidences imply that bone fluid flow induced by muscle dynamics may be an important role in regulating fluid flow through coupling of muscle and bone via microvascular system.