The lacunar-canalicular system(LCS)is acknowledged to directly participate in bone tissue remodeling.The fluid flow in the LCS is synergic driven by the pressure gradient and electric field loads due to the electro-me...The lacunar-canalicular system(LCS)is acknowledged to directly participate in bone tissue remodeling.The fluid flow in the LCS is synergic driven by the pressure gradient and electric field loads due to the electro-mechanical properties of bone.In this paper,an idealized annulus Maxwell fluid flow model in bone canaliculus is established,and the analytical solutions of the fluid velocity,the fluid shear stress,and the fluid flow rate are obtained.The results of the fluid flow under pressure gradient driven(PGD),electric field driven(EFD),and pressure-electricity synergic driven(P-ESD)patterns are compared and discussed.The effects of the diameter of canaliculi and osteocyte processes are evaluated.The results show that the P-ESD pattern can combine the regulatory advantages of single PGD and EFD patterns,and the osteocyte process surface can feel a relatively uniform shear stress distribution.As the bone canalicular inner radius increases,the produced shear stress under the PGD or P-ESD pattern increases slightly but changes little under the EFD pattern.The increase in the viscosity makes the flow slow down but does not affect the fluid shear stress(FSS)on the canalicular inner wall and osteocyte process surface.The increase in the high-valent ions does not affect the flow velocity and the flow rate,but the FSS on the canalicular inner wall and osteocyte process surface increases linearly.In this study,the results show that the shear stress sensed by the osteocyte process under the P-ESD pattern can be regulated by changing the pressure gradient and the intensity of electric field,as well as the parameters of the annulus fluid and the canaliculus size,which is helpful for the osteocyte mechanical responses.The established model provides a basis for the study of the mechanisms of electro-mechanical signals stimulating bone tissue(cells)growth.展开更多
Mechanosensors are the most important organelles for osteocytes to perceive the changes of surrounding mechanical environment.To evaluate the biomechanical effectiveness of collagen hillock,cell process and primary...Mechanosensors are the most important organelles for osteocytes to perceive the changes of surrounding mechanical environment.To evaluate the biomechanical effectiveness of collagen hillock,cell process and primary·cilium in lacunar-canalicular system(LCS),we developed pressure-electricity-structure interaction models by using the COMSOL Multiphysics software to characterize the deformation of collagen hillocks-and primary cilium-based mechanosensors in osteocyte under fluid flow and electric field stimulation.And mechanical signals(pore pressure,fluid velocity,stress,deformation)were analyzed in LCS.The effects of changes in the elastic modulus of collagen hillocks,the number and location of cell processes,the length and location of primary cilia on the mechanosensitivity and the overall poroelastic responses of osteocytes were studied.These models predict that the presence of primary cilium and collagen hillocks resulted in significant stress amplifications(one and two orders of magnitude larger than osteocyte body)on the osteocyte.The growth of cell process along the long axis could stimulate osteocyte to a higher level than along the short axis.The Mises stress of the basal body of primary cilia near the top of osteocyte is 8 Pa greater than that near the bottom.However,the presence of collagen hillocks and primary cilium does not affect the mechanical signal of the whole osteocyte body.The established model can be used for studying the mechanism of bone mechanotransduction at the multiscale level.展开更多
Osteocytes,the primary cells in bone,play a crucial role in sensing external load environments and regulating other bone cells.Due to the piezoelectric effect of the mineralized matrix and collagen that make up bone,t...Osteocytes,the primary cells in bone,play a crucial role in sensing external load environments and regulating other bone cells.Due to the piezoelectric effect of the mineralized matrix and collagen that make up bone,the mechanical stimulus received is converted into an electrical stimulus to affect the reconstruction of bone.Despite the importance of osteocyte,many studies have focused on the mechanical loading and fluid flow of it,there is still a gap in the study of the piezoelectric effects of various mechanosensors on the microscale.In this paper,we developed a finite element model of osteocytes that incorporates the piezoelectric bone matrix.This model is comprehensive,comprising the osteocyte cell body enclosed by lacuna,osteocyte processes enclosed by canaliculi,and the interposed charged ionic fluid.Additionally,it features mechanosensors such as collagen hillocks and primary cilia.In our study,we subjected the piezoelectric bone matrix model to triaxial displacement,subsequently assessing the electrical signal variations across different mechanosensors within the osteocyte.The observed disparities in mechanical perception by various mechanosensors were primarily attributable to greater liquid velocity changes in the polarization direction as opposed to other directions.Collagen hillocks showed insensitivity to piezoelectric signals,serving predominantly to mechanically transmit signals through solid-to-solid contact.In contrast,processes and primary cilia were highly responsive to piezoelectric signals.Interestingly,the processes oriented in the direction of the electric field demonstrated a differential piezoelectric signal perception compared to those in other directions.Primary cilia were especially sensitive to fluid flow pressure changes,which were influenced both by loading rates and external piezoelectric effects.Overall,our findings illuminate the complexity of mechanical perception within osteocytes in a piezoelectric environment.This adds a new dimension to our understanding and suggests avenues for future research in bone reconstruction and cellular mechanical behavioral transmission.展开更多
The superficial zone(SFZ)of articular cartilage is an important interface that isolates deeper zones from the microenvironment of the articular cavity and is directly exposed to various biological and mechanical stimu...The superficial zone(SFZ)of articular cartilage is an important interface that isolates deeper zones from the microenvironment of the articular cavity and is directly exposed to various biological and mechanical stimuli.The SFZ is not only a crucial structure for maintaining the normal physiological function of articular cartilage but also the earliest site of osteoarthritis(OA)cartilage degeneration and a major site of cartilage progenitor cells,suggesting that the SFZ might represent a key target for the early diagnosis and treatment of OA.However,to date,SFZ research has not received sufficient attention,accounting for only about 0.58%of cartilage tissue research.The structure,biological composition,function,and related mechanisms of the SFZ in the physiological and pathological processes of articular cartilage remain unclear.This article reviews the key role of the SFZ in articular cartilage physiology and pathology and focuses on the characteristics of SFZ in articular cartilage degeneration and regeneration in OA,aiming to provide researchers with a systematic understanding of the current research status of the SFZ of articular cartilage,hoping that scholars will give more attention to the SFZ of articular cartilage in the future.展开更多
Abnormal biomechanics plays a central role in the development of knee osteoarthritis(KOA).Low-intensity laser therapy(LILT)is considered an applicable method for the treatment of osteoarthritis.Current research on LIL...Abnormal biomechanics plays a central role in the development of knee osteoarthritis(KOA).Low-intensity laser therapy(LILT)is considered an applicable method for the treatment of osteoarthritis.Current research on LILT for the treatment of KOA has focused on the regeneration of articular cartilage.Its biomechanical changes in periarticular tissues have been less well studied,and its role in improving abnormal joint biomechanics is unclear.This study aimed to investigate the role of LILT in improving the biomechanical properties of muscle and cartilage in KOA joints to alleviate cartilage degradation.In this study,a semiconductor laser with a wavelength of 808 nm was used to perform laser interventions in a KOA rat model 3 days per week for 6 weeks.The results of muscle stretch tests showed that LILT could significantly reduce the modulus of elasticity of KOA soleus muscle.Hematoxylin and eosin staining showed that LILT significantly increased the cross-sectional area of the soleus muscle fibers.This suggests that LILT alleviated KOA-induced soleus muscle atrophy and restored the mechanical properties of the muscle tissue.The results of compressive elastic modulus and electrical impedance characterization of cartilage showed that laser intervention significantly increased the elastic modulus and resistivity of cartilage.Results from safranin o-fast green staining and immunohistochemistry showed that LILT significantly increased the synthesis of type II collagen in the cartilage matrix.This may be one of the potential mechanisms by which LILT improves the mechanical properties of cartilage.In addition,immunohistochemistry also showed that LILT reduced the expression of matrix metallo-proteinase-13 in cartilage and effectively inhibited the degradation of the cartilage matrix in KOA.In conclusion,the present study demonstrated that LILT alleviated the abnormal biomechanics of KOA joint tissues by improving the mechanical properties of joint muscles and cartilage,thereby slowing down the degradation of KOA cartilage.展开更多
Cartilage has limited self-repair ability due to its avascular,alymphatic and aneural features.The combination of three-dimensional(3D)printing and tissue engineering provides an up-and-coming approach to address this...Cartilage has limited self-repair ability due to its avascular,alymphatic and aneural features.The combination of three-dimensional(3D)printing and tissue engineering provides an up-and-coming approach to address this issue.Here,we designed and fabricated a tri-layered(superficial layer(SL),middle layer(ML)and deep layer(DL))stratified scaffold,inspired by the architecture of collagen fibers in native cartilage tissue.The scaffold was composed of 3D printed depth-dependent gradient poly(e-caprolactone)(PCL)impregnated with methacrylated alginate(ALMA),and its morphological analysis and mechanical properties were tested.To prove the feasibility of the composite scaffolds for cartilage regeneration,the viability,proliferation,collagen deposition and chondrogenic differentiation of embedded rat bone marrow mesenchymal stem cells(BMSCs)in the scaffolds were assessed by Live/dead assay,CCK-8,DNA content,cell morphology,immunofluorescence and real-time reverse transcription polymerase chain reaction.BMSCs-loaded gradient PCL/ALMA scaffolds showed excellent cell survival,cell proliferation,cell morphology,collagen II deposition and hopeful chondrogenic differentiation compared with three individual-layer scaffolds.Hence,our study demonstrates the potential use of the gradient PCL/ALMA construct for enhanced cartilage tissue engineering.展开更多
基金supported by the National Natural Science Foundation of China(Nos.11972242 and 11632013)the China Postdoctoral Science Foundation(No.2020M680913)。
文摘The lacunar-canalicular system(LCS)is acknowledged to directly participate in bone tissue remodeling.The fluid flow in the LCS is synergic driven by the pressure gradient and electric field loads due to the electro-mechanical properties of bone.In this paper,an idealized annulus Maxwell fluid flow model in bone canaliculus is established,and the analytical solutions of the fluid velocity,the fluid shear stress,and the fluid flow rate are obtained.The results of the fluid flow under pressure gradient driven(PGD),electric field driven(EFD),and pressure-electricity synergic driven(P-ESD)patterns are compared and discussed.The effects of the diameter of canaliculi and osteocyte processes are evaluated.The results show that the P-ESD pattern can combine the regulatory advantages of single PGD and EFD patterns,and the osteocyte process surface can feel a relatively uniform shear stress distribution.As the bone canalicular inner radius increases,the produced shear stress under the PGD or P-ESD pattern increases slightly but changes little under the EFD pattern.The increase in the viscosity makes the flow slow down but does not affect the fluid shear stress(FSS)on the canalicular inner wall and osteocyte process surface.The increase in the high-valent ions does not affect the flow velocity and the flow rate,but the FSS on the canalicular inner wall and osteocyte process surface increases linearly.In this study,the results show that the shear stress sensed by the osteocyte process under the P-ESD pattern can be regulated by changing the pressure gradient and the intensity of electric field,as well as the parameters of the annulus fluid and the canaliculus size,which is helpful for the osteocyte mechanical responses.The established model provides a basis for the study of the mechanisms of electro-mechanical signals stimulating bone tissue(cells)growth.
基金supported by the National Natural Science Foundation of China(Grant Nos.11972242,11632013,11702183)China Postdoctoral Science Foundation(Grant No.2020M680913).
文摘Mechanosensors are the most important organelles for osteocytes to perceive the changes of surrounding mechanical environment.To evaluate the biomechanical effectiveness of collagen hillock,cell process and primary·cilium in lacunar-canalicular system(LCS),we developed pressure-electricity-structure interaction models by using the COMSOL Multiphysics software to characterize the deformation of collagen hillocks-and primary cilium-based mechanosensors in osteocyte under fluid flow and electric field stimulation.And mechanical signals(pore pressure,fluid velocity,stress,deformation)were analyzed in LCS.The effects of changes in the elastic modulus of collagen hillocks,the number and location of cell processes,the length and location of primary cilia on the mechanosensitivity and the overall poroelastic responses of osteocytes were studied.These models predict that the presence of primary cilium and collagen hillocks resulted in significant stress amplifications(one and two orders of magnitude larger than osteocyte body)on the osteocyte.The growth of cell process along the long axis could stimulate osteocyte to a higher level than along the short axis.The Mises stress of the basal body of primary cilia near the top of osteocyte is 8 Pa greater than that near the bottom.However,the presence of collagen hillocks and primary cilium does not affect the mechanical signal of the whole osteocyte body.The established model can be used for studying the mechanism of bone mechanotransduction at the multiscale level.
基金This work was supported by the National Natural Science Foundation of China(Grant Nos.11972242 and 12272250)China Postdoctoral Science Foundation(Grant No.2020M680913)Shanxi Scholarship Council of China and Shanxi Postgraduate Innovation Project.
基金This work was supported by the National Natural Science Foundation of China(Grant Nos.11972242 and 12272250)China Postdoctoral Science Foundation(Grant No.2020M680913)+1 种基金Shanxi Scholarship Council of China and Shanxi Posigraduate Innovation ProjectShanxi Huajin Orthopaedic Public Foundation.
基金supported by the National Natural Science Foundation of China(Grant Nos.12272250,12372310,and 82172503)China Postdoctoral Science Foundation(Grant No.2020M680913)+1 种基金Shanxi Scholarship Council of China(Grant No.2022081)Shanxi Province Graduate Education Innovation Program(Grant Nos.2022Y278 and 2023-125).
文摘Osteocytes,the primary cells in bone,play a crucial role in sensing external load environments and regulating other bone cells.Due to the piezoelectric effect of the mineralized matrix and collagen that make up bone,the mechanical stimulus received is converted into an electrical stimulus to affect the reconstruction of bone.Despite the importance of osteocyte,many studies have focused on the mechanical loading and fluid flow of it,there is still a gap in the study of the piezoelectric effects of various mechanosensors on the microscale.In this paper,we developed a finite element model of osteocytes that incorporates the piezoelectric bone matrix.This model is comprehensive,comprising the osteocyte cell body enclosed by lacuna,osteocyte processes enclosed by canaliculi,and the interposed charged ionic fluid.Additionally,it features mechanosensors such as collagen hillocks and primary cilia.In our study,we subjected the piezoelectric bone matrix model to triaxial displacement,subsequently assessing the electrical signal variations across different mechanosensors within the osteocyte.The observed disparities in mechanical perception by various mechanosensors were primarily attributable to greater liquid velocity changes in the polarization direction as opposed to other directions.Collagen hillocks showed insensitivity to piezoelectric signals,serving predominantly to mechanically transmit signals through solid-to-solid contact.In contrast,processes and primary cilia were highly responsive to piezoelectric signals.Interestingly,the processes oriented in the direction of the electric field demonstrated a differential piezoelectric signal perception compared to those in other directions.Primary cilia were especially sensitive to fluid flow pressure changes,which were influenced both by loading rates and external piezoelectric effects.Overall,our findings illuminate the complexity of mechanical perception within osteocytes in a piezoelectric environment.This adds a new dimension to our understanding and suggests avenues for future research in bone reconstruction and cellular mechanical behavioral transmission.
基金This manuscript was supported by funds from the Regional Innovation Joint Fund of the National Natural Science Foundation of China(Integrated Project)(No.U23A6009)Regional Innovation Joint Fund of the National Natural Science Foundation of China(Key Project)(No.U21A20353)+2 种基金Natural Science Foundation of Shanxi Province(No.20210302123285)Key R&D Program Projects of Shanxi Province(No.202202040201012)Hainan Provincial Medical and Health Research Program(No.21A200349).
文摘The superficial zone(SFZ)of articular cartilage is an important interface that isolates deeper zones from the microenvironment of the articular cavity and is directly exposed to various biological and mechanical stimuli.The SFZ is not only a crucial structure for maintaining the normal physiological function of articular cartilage but also the earliest site of osteoarthritis(OA)cartilage degeneration and a major site of cartilage progenitor cells,suggesting that the SFZ might represent a key target for the early diagnosis and treatment of OA.However,to date,SFZ research has not received sufficient attention,accounting for only about 0.58%of cartilage tissue research.The structure,biological composition,function,and related mechanisms of the SFZ in the physiological and pathological processes of articular cartilage remain unclear.This article reviews the key role of the SFZ in articular cartilage physiology and pathology and focuses on the characteristics of SFZ in articular cartilage degeneration and regeneration in OA,aiming to provide researchers with a systematic understanding of the current research status of the SFZ of articular cartilage,hoping that scholars will give more attention to the SFZ of articular cartilage in the future.
基金supported by the Regional Joint Key Funding Program of the National Natural Science Foundation of China(Grant No.U21A20353)the National Natural Science Foundation of China(Grant Nos.12272250,11972242 and 82172503)+2 种基金China Postdoctoral Science Foundation(Grant No.2020M680913)Shanxi Province Returned Overseas Foundation(Grant No.2022-081)the Shanxi Province Basic Research Program(Grant No.202203021212254).
文摘Abnormal biomechanics plays a central role in the development of knee osteoarthritis(KOA).Low-intensity laser therapy(LILT)is considered an applicable method for the treatment of osteoarthritis.Current research on LILT for the treatment of KOA has focused on the regeneration of articular cartilage.Its biomechanical changes in periarticular tissues have been less well studied,and its role in improving abnormal joint biomechanics is unclear.This study aimed to investigate the role of LILT in improving the biomechanical properties of muscle and cartilage in KOA joints to alleviate cartilage degradation.In this study,a semiconductor laser with a wavelength of 808 nm was used to perform laser interventions in a KOA rat model 3 days per week for 6 weeks.The results of muscle stretch tests showed that LILT could significantly reduce the modulus of elasticity of KOA soleus muscle.Hematoxylin and eosin staining showed that LILT significantly increased the cross-sectional area of the soleus muscle fibers.This suggests that LILT alleviated KOA-induced soleus muscle atrophy and restored the mechanical properties of the muscle tissue.The results of compressive elastic modulus and electrical impedance characterization of cartilage showed that laser intervention significantly increased the elastic modulus and resistivity of cartilage.Results from safranin o-fast green staining and immunohistochemistry showed that LILT significantly increased the synthesis of type II collagen in the cartilage matrix.This may be one of the potential mechanisms by which LILT improves the mechanical properties of cartilage.In addition,immunohistochemistry also showed that LILT reduced the expression of matrix metallo-proteinase-13 in cartilage and effectively inhibited the degradation of the cartilage matrix in KOA.In conclusion,the present study demonstrated that LILT alleviated the abnormal biomechanics of KOA joint tissues by improving the mechanical properties of joint muscles and cartilage,thereby slowing down the degradation of KOA cartilage.
基金This study was supported by the National Natural Science Foundation of China(Nos 51975400,61703298,61501316,51505324)National Key Research and Development Program(2019YFB1310200)+1 种基金Shanxi Provincial Key Research and Development Project(201803D421050)Beijing Natural Science Foundation(7202190).
文摘Cartilage has limited self-repair ability due to its avascular,alymphatic and aneural features.The combination of three-dimensional(3D)printing and tissue engineering provides an up-and-coming approach to address this issue.Here,we designed and fabricated a tri-layered(superficial layer(SL),middle layer(ML)and deep layer(DL))stratified scaffold,inspired by the architecture of collagen fibers in native cartilage tissue.The scaffold was composed of 3D printed depth-dependent gradient poly(e-caprolactone)(PCL)impregnated with methacrylated alginate(ALMA),and its morphological analysis and mechanical properties were tested.To prove the feasibility of the composite scaffolds for cartilage regeneration,the viability,proliferation,collagen deposition and chondrogenic differentiation of embedded rat bone marrow mesenchymal stem cells(BMSCs)in the scaffolds were assessed by Live/dead assay,CCK-8,DNA content,cell morphology,immunofluorescence and real-time reverse transcription polymerase chain reaction.BMSCs-loaded gradient PCL/ALMA scaffolds showed excellent cell survival,cell proliferation,cell morphology,collagen II deposition and hopeful chondrogenic differentiation compared with three individual-layer scaffolds.Hence,our study demonstrates the potential use of the gradient PCL/ALMA construct for enhanced cartilage tissue engineering.
