Study On Mass Transfer In The Bone Lacunar-Canalicular System Under Different Gravity Fields

With the vigorous development of the space industry,especially after the completion of China’s"Tiangong"space station,more and more astronauts have been sent on missions to the space station.During rocket launches,the astronaut’s body is subjected to hypergravity of up to 8G or even 10G,while during missions on the space station the body is in microgravity,which is only one millionth of normal gravity,such an abnormal gravity environment is bound to seriously affect the body’s systems,tissues and organs,especially bone tissue.A large part of the reason astronauts cannot walk upright immediately when they return to Earth is the bone loss caused by microgravity,which in turn leads to osteoporosis.The prevailing theory of the cause of microgravity-induced osteoporosis is that it is mediated by genes,hormones and signalling molecules that increase osteoclast bone resorption and decrease osteoblast bone formation,resulting in increased bone loss and osteoporosis.However,we believe that the key factor contributing to osteoporosis in microgravity is the relationship between mass transfer in the bone lacunar-canalicular system（LCS）.The bone tissue is composed of cylindrical osetons with a central Harvesian canal surrounded by mineralised bone plates arranged in concentric circles,with the bone lacunar-canalicular system within and between the plates.The LCS is a relatively closed three-dimensional tubular network structure within the bone unit,responsible for nutrient transport,waste excretion and signalling of bone cells.We therefore hypothesize that the key factor in osteoporosis under microgravity is the lack of mass transfer in the LCS.In order to test this opinion,we first developed an experimental platform for mass transfer in bone,then performed mass transfer experiments on isolated bone samples,and finally performed a finite element numerical simulation study.A novel microgravity simulation apparatus was also invented and designed to generate periodic realistic microgravity environments for experimental studies of mass transfer in bone.The invention of a bioreactor for dynamic perfusion loading under high G centrifugal conditions was first designed,first with a structural design,then with a description of the specific implementation of the invention,and finally with the physical construction of the device according to the specific practicalities of the experiment.A suitable drive module,perfusion module and monitoring module were selected and later assembled and placed into a highspeed centrifuge,which can be used to perform bone transfer experiments and simulate perfusion loading of isolated bone samples under different hypergravity.The mass transfer experiments in the LCS were carried out using isolated bone samples from bovine tibial cortical bone under different gravity fields and different frequencies of pulsation pressure,with sodium fluorescein as a tracer for perfusion loading of the bone samples.A home-made dynamic perfusion loading device provided different frequencies of pulsation pressure and a high-speed centrifuge provided different hypergravity environments.The effectiveness of the dynamic perfusion loading device can be verified by the gross observation of the bone samples after perfusion loading.At normal gravity（1G）,the peak fluorescence intensity of the superficial lacuna was 84.1,while the peak fluorescence intensity of the shallow,middle and deep lacunae were 52.8%,43.8%and 19.7%of the superficial layer,respectively;at hypergravity of 3G,the deep lacunae fluorescence intensity enhancement index(₃/=1.13±0.27,+13%)was the lowest among the osteon;at hypergravity of 8G and 10 G,the deep lacunae fluorescence intensity enhancement index(₈/=5.43±1.68,+443%和₁₀/=7.31±1.12,+631%)was the highest among the osteon where it was located;during high intensity exercise,the superficial,shallow,middle and deep lacunae fluorescence intensity was 169.70±14.90（+200%）,156.32±14.90（+351%）,123.24±25.83（+373%）and 117.00±21.25（+498%）,respectively.The further away from the Haversian canal within the bone unit the lower the content of osteocyte solute molecules,nutrients and signalling molecules etc.Hypergravity facilitates mass transfer in the LCS to deep lacunae,and microgravity may inhibit mass transfer in the LCS.High-frequency pulsation pressure due to high-intensity exercise increased the efficiency of mass transfer in the LCS.The mass transfer in the LCS was numerically simulated using the finite element method.The 3D modelling was first carried out using Solidworks software to create a multi-scale osteon 3D geometric model.This was then imported into COMSOL Multiphysics for numerical finite element simulations.The numerical simulation results are in agreement with the experimental results.The number of particles in the lacunae increased significantly from 1G to 10G the further away from the Havesian canal,with the number of particles in the superficial layer increasing by 38.2%,86.0%in the shallow layer,120.9%in the middle layer and 202.5%in the deep layer;the number of particles in the lacunae decreased significantly at 0G compared to 1G,with the superficial layer decreasing by 92.3%,the shallow layer decreasing by 94.8%,the middle layer decreasing by 97.4%,and 98.8%in the deep layer;under normal gravity,the number of particles increased greatly when doing high intensity exercise compared to rest,with an increase of 205.1%in the superficial layer,190.5%in the shalllow layer,192.0%in the middle layer,and 198.2%in the deep layer.The more distant the lacunae from the Haversian canal within the osteon,the lower the number of particles within the lacunae.Hypergravity facilitates particle transport within the LCS.Microgravity inhibited particle transport within the LCS.High-intensity motion increased the number of particles in the lacunae.A new micro-low gravity simulation instrument comprising:a housing,an oscillating stand,a slider,a crank,a motor,an oscillating rod and a sample holder;the sample holder comprises a ball,a holder and a jaw fixture.The aim is to provide a novel micro-and low-gravity simulation instrument to achieve a true,long duration and full course periodic micro-and low-gravity environment for a wide range of scientific experimental studies.A new micro-hypogravity simulator with a dual axis oscillation feature,where the oscillating rod and oscillating stand can oscillate independently without interfering with each other and with the same centre of oscillation,where the centrifugal force generated during oscillation can cancel（partially）with gravity and where the combined acceleration vector magnitude is less than the acceleration of gravity,allowing the simulation of a real,long time and full process periodic micro-hypogravity environment.In summary,we have verified by the above methods that the variation in gravity field strength has a significant effect on mass transfer in the LCS.Hypergravity promotes mass transfer in the LCS,and microgravity inhibits this mass transfer.High-intensity exercise can also improve mass transfer efficiency.Therefore,the key factor for osteoporosis under microgravity may be the lack of mass transfer in the LCS.