Molecular dynamics simulation of collagen molecular mechanics under different conditions / 医疗卫生装备

Objective To study the mechanical properties of collagen molecules by molecular dynamics simulation,and to determine the relationship between the mechanical properties of the microstructure of cartilage and the macroscopic mechanical properties. Methods Obtaining the collagen molecular model from the protein database and using GROMACS molecular dynamics simulation software,an analog box was built with a size of 24 nm× 3.2 nm × 3.2 nm. The simulation system contained 6 719 water molecules, 20 sodium ions and 20 chloride ions. This solution was equivalent to a saline environment. The uniaxial tensile simulation of collagen molecules was executed under the conditions of different temperature,different tensile rates and different pressures in this environment.Results When the temperature was constant, the tensile rate and the elastic modulus of collagen increased; when the tensile rate was certain, the temperature of the simulation system rose while the modulus of elasticity decreased;under the conditions of certain temperature and tensile rate, the pressure of the system gradually increased,and its modulus of elasticity decreased gradually. Conclusion Through the uniaxial tensile simulation of collagen molecules under different conditions,the mechanical laws of collagen molecules are obtained.There is a certain correlation between the elastic modulus and the tensile strain during the stretching process,and a way of thinking is provided on the study of the correlation of cartilage rate from the microscopic aspect.

Geometric shapes of tissue-engineered cartilage exert effects on mechanical behaviors of a defected area / 中国组织工程研究

BACKGROUND: Uncertainty of repairing articular cartilage defects is highly associated with the mechanical behaviors of the defected area, and the mechanical environment varies with the defect shape, depth and load. OBJECTIVE: To study the mechanical behaviors of articular cartilage defects under physiological load by finite element analysis. METHODS: The axisymmetric model of articular cartilage injury and repair based on transversely isotropy was established using ABAQUS software. The mechanical behaviors of the defect zone repaired with different repair shapes (cylindrical, frustum of a cone, orthorhombic prism, elliptical column) and depths of tissue-engineered cartilage under compressive load were analyzed. RESULTS AND CONCLUSION: The simulation results showed that there were significant differences in the mechanical behaviors of the defect area repaired with tissue-engineered cartilage in different shapes and depths. The stress concentration was the most obvious at the middle-layer defect repair, and the stress distribution was more reasonable at the deep (whole) layer defect repair. Furthermore, the distribution of the stress field and the liquid flow field at the cylinder-shaped tissue-engineered cartilage repair was the closest to the normal cartilage. That is to say, the tissue-engineered cartilage in cylinder or frustum-cone shape is recommended to repair cartilage defect. Importantly, the middle-layer repair is inadvisable.

Numerical analysis on damage evolution of rectangular articular cartilage with micro-defect under compressive load / 医用生物力学

Objective To study the damage propagation and evolution mechanism of cartilage under compressive load. Methods The fiber-reinforced porous elastic model of cartilage with micro-defect was established by using finite element method, and the process of damage evolution under compressive load was simulated and analyzed with parameters. The patterns of stress and strain distributions on cartilage matrix and collagen fiber at different damage extension stage were obtained. Results The strain in surface and the forefront of cartilage damage increased significantly with the increase of compression displacement, and they were obviously in positive correlation; in the process of damage evolution, there was a trend that cartilage extended to the deep and both sides simultaneously; cracks and damage in cartilage extended preferentially along the fiber tangent direction. With the aggravation of cartilage damage, the lateral extension speed was significantly faster than the longitudinal extension speed. Conclusions The process of cartilage damage extension has a close relationship with the distribution of fibers. And the damage in matrix and fiber promote each other. The evolution speed and degree of cartilage vary constantly in different layers and at different stages. These results can provide the qualitative reference for prediction and repair of cartilage damage, as well as the theoretical basis for explaining clinical pathological phenomena of damage degeneration and treatment.

The mechanical and biological responses of osteoblasts under hypergravity / 医用生物力学

Objective To explore the effect of hypergravity on morphology and osteogenesis function of preosteoblast MC3T3-E1 cells. Methods The cultured MC3T3-E1 cells under hypergravity by different loading forces were divided into five groups, including control group, 5 g group, 10 g group, 15 g group and 20 g group. The experimental groups were loaded for 30 min each time in the three successive days, and the control group was synchronously exposed to the same surrounding except for difference in g-value. The morphology of cytoskeletal protein was observed by phalloidin staining, The alkaline phosphatase (ALP) content was examined by ALP activity assay kit, the gene expression of ALP, collagen Ⅰ(ColⅠ), osteocalcin (OC), runt-related transcription factors (Runx2) was measured by real-time quantitative PCR, and the protein expression of ColⅠ and OC was tested by Western blot. Results Under the condition of hypergravity, cell body of osteoblast became thinner, but its surface area increased significantly; with the structure of skeletal arrangement becoming loose, actin microfilament structure reduced so that arrangement of actin-like dispersion orderly lowered. The gene expressions of related indicators of osteogenic differentiation including ALP, ColⅠ, OC, Runx2 loaded by hypergravity were significantly up-regulated, which was the same as ColⅠ protein and OC protein after hypergravity loading. There was only a very minute quantity of small red-orange nodules in the control group, while the cells after hypergravity loading in experimental groups obviously formed various sizes of red-orange nodules. Conclusions Under hypergravity, changes in osteoblast morphology can be triggered by rearrangements of skeletal structure. Furthermore, osteoblast maturation and differentiation can be stimulated effectively by up-regulating differentiation-related gene and protein expressions.

Ratcheting strain and theoretical prediction of articular cartilage under cyclic loading / 医用生物力学

Objective To obtain the ratcheting strain of articular cartilage under different loading conditions, and construct the theoretical model so as to predict the ratcheting strain of cartilage. Methods The fresh articular cartilage obtained from the trochlear of distal femur was used as experimental subject. The ratcheting strain of articular cartilage was tested under cyclic compressive loads by applying the non-contact digital image correlation technique. The theoretical model was constructed to predict the ratcheting strain of articular cartilage with different stress amplitudes and stress rates. The results from predictions were compared with the experimental results. Results The ratcheting strain of cartilage increased rapidly at initial stage and then showed the slower increase with cycles increasing. The ratcheting strain increased with stress amplitude increasing when the stress rate was constant. However, the ratcheting strain decreased with stress rate increasing when the stress amplitude was constant. When the stress rate increased, the ratcheting stain decreased. The prediction results of the established theoretical model were in good agreement with experimental results. Conclusions The ratcheting strain of articular cartilage is proportional to the stress amplitude, and inversely proportional to the stress rate. The established theoretical model can predict the ratcheting strain of articular cartilage and provide guidance for the construction of tissue engineered artificial cartilage.

Ratcheting strain and theoretical prediction of articular cartilage under cyclic loading / 医用生物力学

Objective To obtain the ratcheting strain of articular cartilage under different loading conditions,and construct the theoretical model so as to predict the ratcheting strain of cartilage.Methods The fresh articular cartilage obtained from the trochlear of distal femur was used as experimental subject.The ratcheting strain of articular cartilage was tested under cyclic compressive loads by applying the non-contact digital image correlation technique.The theoretical model was constructed to predict the ratcheting strain of articular cartilage with different stress amplitudes and stress rates.The results from predictions were compared with the experimental results.Results The ratcheting strain of cartilage increased rapidly at initial stage and then showed the slower increase with cycles increasing.The ratcheting strain increased with stress amplitude increasing when the stress rate was constant.However,the ratcheting strain decreased with stress rate increasing when the stress amplitude was constant.When the stress rate increased,the ratcheting stain decreased.The prediction results of the established theoretical model were in good agreement with experimental results.Conclusions The ratcheting strain of articular cartilage is proportional to the stress amplitude,and inversely proportional to the stress rate.The established theoretical model can predict the ratcheting strain of articular cartilage and provide guidance for the construction of tissue engineered artificial cartilage.

Numerical analysis on damage evolution of rectangular articular cartilage with micro-defect under compressive loads / 医用生物力学

Objective To study the damage propagation and evolution mechanism of cartilage under compressive loads.Methods The fiber-reinforced porous elastic model of cartilage with micro-defect was established by using finite element method,and the process of damage evolution under compressive loads was simulated and analyzed with parameters.The patterns of stress and strain distributions on cartilage matrix and collagen fiber at different damage extension stages were obtained.Results The strain in the surface and forefront of cartilage damage increased significantly with the increase of compression displacement,and they were obviously in positive correlation;in the process of damage evolution,there was a trend that cartilage extended to the deep and both sides simultaneously;cracks and damage in cartilage extended preferentially along the fiber tangent direction.With the aggravation of cartilage damage,the lateral extension speed was significantly faster than the longitudinal extension speed.Conclusions The process of cartilage damage extension has a close relationship with the distribution of fibers.The damages in matrix and fiber promote each other.The evolution speed and degree of cartilage vary constantly in different layers and at different stages.These results can provide the qualitative reference for prediction and repair of cartilage damage,as well as the theoretical basis for explaining pathological phenomena of damage degeneration and its clinic treatment.

The mechanical and biological responses of MC3T3-E1 cells under hypergravity / 医用生物力学

Objective To explore the effect of hypergravity on morphology and osteogenesis function of preosteoblast MC3T3-E1 ceils.Methods The cultured MC3T3-E1 cells under hypergravity by different loading forces were divided into five groups,including control group,5 g group,10 g group,15 g group and 20 g group.The experimental groups were loaded for 30 min each time in 3 successive days,and the control group with no g-value was synchronously exposed to the same surrounding.The morphology of cytoskeletal protein was observed by phalIoidin staining,The alkaline phosphatase (ALP) content was examined by ALP activity assay kit,the gene expression of ALP,collagen Ⅰ (Col Ⅰ),osteocalcin (OC),runt-related transcription factors (Runx2) was measured by real-time quantitative PCR,and the protein expression of Col Ⅰ and OC was tested by Western blotting.Results Under the condition of hypergravity,cell body of osteoblast became thinner,but its surface area increased significantly;with the structure of skeletal arrangement becoming loose,actin microfilament structure reduced so that the orderly arrangement of actin-like dispersion lowered.The gene expressions of related indicators of osteogenic differentiation including ALP,Col][,OC,Runx2 were significantly up-regulated,which was the same as Col Ⅰ protein and OC protein after hypergravity loading.A very minute quantity of small red-orange nodules was found in the control group,while the cells in experimental groups after hypergravity loading obviously formed various sizes of red-orange nodules.Conclusions Under hypergravity,changes in osteoblast morphology can be triggered by rearrangements of skeletal structure.Furthermore,osteoblast maturation and differentiation can be stimulated effectively by up-regulating differentiation-related gene and protein expressions.

Ratcheting strain and theoretical prediction of articular cartilage under cyclic loading / 医用生物力学

Objective To obtain the ratcheting strain of articular cartilage under different loading conditions,and construct the theoretical model so as to predict the ratcheting strain of cartilage.Methods The fresh articular cartilage obtained from the trochlear of distal femur was used as experimental subject.The ratcheting strain of articular cartilage was tested under cyclic compressive loads by applying the non-contact digital image correlation technique.The theoretical model was constructed to predict the ratcheting strain of articular cartilage with different stress amplitudes and stress rates.The results from predictions were compared with the experimental results.Results The ratcheting strain of cartilage increased rapidly at initial stage and then showed the slower increase with cycles increasing.The ratcheting strain increased with stress amplitude increasing when the stress rate was constant.However,the ratcheting strain decreased with stress rate increasing when the stress amplitude was constant.When the stress rate increased,the ratcheting stain decreased.The prediction results of the established theoretical model were in good agreement with experimental results.Conclusions The ratcheting strain of articular cartilage is proportional to the stress amplitude,and inversely proportional to the stress rate.The established theoretical model can predict the ratcheting strain of articular cartilage and provide guidance for the construction of tissue engineered artificial cartilage.

Numerical analysis on damage evolution of rectangular articular cartilage with micro-defect under compressive loads / 医用生物力学

Objective To study the damage propagation and evolution mechanism of cartilage under compressive loads.Methods The fiber-reinforced porous elastic model of cartilage with micro-defect was established by using finite element method,and the process of damage evolution under compressive loads was simulated and analyzed with parameters.The patterns of stress and strain distributions on cartilage matrix and collagen fiber at different damage extension stages were obtained.Results The strain in the surface and forefront of cartilage damage increased significantly with the increase of compression displacement,and they were obviously in positive correlation;in the process of damage evolution,there was a trend that cartilage extended to the deep and both sides simultaneously;cracks and damage in cartilage extended preferentially along the fiber tangent direction.With the aggravation of cartilage damage,the lateral extension speed was significantly faster than the longitudinal extension speed.Conclusions The process of cartilage damage extension has a close relationship with the distribution of fibers.The damages in matrix and fiber promote each other.The evolution speed and degree of cartilage vary constantly in different layers and at different stages.These results can provide the qualitative reference for prediction and repair of cartilage damage,as well as the theoretical basis for explaining pathological phenomena of damage degeneration and its clinic treatment.

The mechanical and biological responses of MC3T3-E1 cells under hypergravity / 医用生物力学

Objective To explore the effect of hypergravity on morphology and osteogenesis function of preosteoblast MC3T3-E1 ceils.Methods The cultured MC3T3-E1 cells under hypergravity by different loading forces were divided into five groups,including control group,5 g group,10 g group,15 g group and 20 g group.The experimental groups were loaded for 30 min each time in 3 successive days,and the control group with no g-value was synchronously exposed to the same surrounding.The morphology of cytoskeletal protein was observed by phalIoidin staining,The alkaline phosphatase (ALP) content was examined by ALP activity assay kit,the gene expression of ALP,collagen Ⅰ (Col Ⅰ),osteocalcin (OC),runt-related transcription factors (Runx2) was measured by real-time quantitative PCR,and the protein expression of Col Ⅰ and OC was tested by Western blotting.Results Under the condition of hypergravity,cell body of osteoblast became thinner,but its surface area increased significantly;with the structure of skeletal arrangement becoming loose,actin microfilament structure reduced so that the orderly arrangement of actin-like dispersion lowered.The gene expressions of related indicators of osteogenic differentiation including ALP,Col][,OC,Runx2 were significantly up-regulated,which was the same as Col Ⅰ protein and OC protein after hypergravity loading.A very minute quantity of small red-orange nodules was found in the control group,while the cells in experimental groups after hypergravity loading obviously formed various sizes of red-orange nodules.Conclusions Under hypergravity,changes in osteoblast morphology can be triggered by rearrangements of skeletal structure.Furthermore,osteoblast maturation and differentiation can be stimulated effectively by up-regulating differentiation-related gene and protein expressions.

The mechanobiology responses of osteoblasts under hypergravity / 医用生物力学

In the environment of adaptive mechanics, osteoblasts, which are the main functional cells of bone formation, are one of the main cells in response to the mechanical loading. With the development of technology, more and more astronauts, pilots and other are exposed to the hypergravity environment. In order to better understand the mechanobiology response of osteoblasts under hypergravity, this paper reviews the mechanobiological research progress in morphology, gene expression, cytokine secretion and signal transduction pathways of ostoblasts, so as to thoughts and preparations for mechanobiology research of bone tissues in hypergravity environment.

Biomechanical research progress on minimally invasive surgical repair of pectus excavatum / 医用生物力学

开展漏斗胸微创矫形手术的生物力学研究以及阐述矫形机制对于提高矫形手术水平、开展个性化手术治疗、发展新的矫形手术方法和扩展微创矫形手术的应用范围具有重要意义。漏斗胸微创矫形手术已经成功用于儿童的漏斗胸矫形，但是成人漏斗胸矫形手术的应用还未普及。面对漏斗胸矫形可能会加重脊柱侧弯的风险，医生被迫放弃手术，致使部分漏斗胸合并脊柱侧弯的患者终生不能得到治疗。总结漏斗胸微创矫形手术的生物力学研究进展，包括胸廓模型的三维重建、矫形模型的应用、矫形过程的数值模拟以及数值模拟结果在临床的应用。结合成人漏斗胸矫形数值模拟的特点提出解决方法，并针对漏斗胸的生物力学研究现状提出需要解决的问题，如计算模型需要考虑主要肌肉、椎间盘、前后纵韧带、椎体横凸棘间韧带和棘上韧带，验证数值计算结果的实验研究方法等。

Loading rate-dependent property of different layers for articular cartilage / 医用生物力学

Objective To investigate the loading rate-dependent property of different layers for articular cartilage by unconfined compression testing on articular cartilage at different loading rates. Methods The non-contact digital image correlation (DIC) technique was applied to investigate the mechanical properties of different layers for fresh pig articular cartilage at different loading rates. Results At constant loading rate, the compressive strain of superficial layer and deep layer was the largest, while that of middle layer was in between under the same compressive stress. The Poisson’s ratio increased from superficial layer to deep layer along with cartilage depth increasing. The stress-strain curves of cartilage were different at different loading rates, indicating that the mechanical properties of cartilage were dependent on the loading rate. The elastic modulus of cartilage increased with loading rates increasing, and the compressive strains of different layers decreased under the same compressive stress with loading rates increasing. Conclusions The compressive strain decreased while the Poisson’s ratio increased from superficial layer to deep layer along the cartilage depth. The mechanical properties of different layers for cartilage were dependent on the loading rate. This study can provide the basis for clinical cartilage disease prevention and treatment, and is important for mechanical function evaluation of artificial cartilage as well.

Normal displacement of different layers for articular cartilage under sliding loads / 医用生物力学

Objective To obtain distributions of normal displacement on different layers of articular cartilage under sliding loads and investigate effects of compressive strain, sliding rate and sliding numbers on depth-dependent normal displacement of articular cartilage. Methods The non-contact digital image correlation (DIC) technique was applied to investigate the normal displacement of different layers for fresh pig articular cartilage under sliding loads, respectively. ResultsThe largest normal displacement was found on the superficial layer, while that on the deep layer was the smallest, with the middle layer was in between under sliding loads. The normal displacement for cartilage at different normalized depth increased with compressive strain increasing and the largest increasing amplitude was in the superficial layer. The depth-dependent normal displacement for cartilage decreased with sliding rates increasing. The normal displacement for cartilage kept increasing with different sliding numbers within its sliding time. The most significant increasing amplitude of normal displacement was found between the first and second slide. Conclusions Under sliding loads, the normal displacement of cartilage usually changes along with its depth from surface to deep layer, and compressive strain, sliding rate and sliding numbers all play important roles in such normal displacement distributions on different layers. These results can provide the basis for clinical cartilage disease treatment and cartilage defect repair, and are also important for structure and construction of artificial cartilage as well as in mechanical function evaluation.

Effects of different decellularization methods on biomechanical properties and histological structure of annulus fibrosus in pigtail / 医用生物力学

Objective To investigate effects of different de-cellularization methods on biomechanical properties and histological structure of annulus fibrosus in pigtails and provide experimental evidence for the construction of tissue engineering annulus fibrosus. Methods Sixty Fresh annulus fibrosus were dissected from caudal disks of pigs and randomly assigned to 4 groups with 15 in each group. Triton X-100 group(Group A): annulus fibrosus were treated with hypotonic Tris-HCl buffer for 48 hours and de-cellularized with Triton X-100, DNase Ⅰ and RNase A. SDS group (Group B): annulus fibrosus were subjected to 3 cycles of freeze-thaw and subsequently de-cellularized with SDS, DNaseⅠ and RNase A. Trypsin group (Group C): annulus fibrosus were de-cellularized with Tris buffer containing trypsin, DNase Ⅰ and RNase A. Control group: fresh annulus fibrosus underwent no treatment. After the de-cellularization process was completed, hematoxylin-eosin (HE) staining was carried out to examine the efficacy on cell removal, and the ultrastructure of annulus fibrosus were observed by scanning electron microscopy. The collagen content, glycosaminoglycan (GAG) content and biomechanical parameters in each group were also detected. Results HE staining and scanning electron microscopy showed that no residual cells were found in Group A, B and C. The structure of annulus fibrosus in Group A was not disturbed, while that in Group B and C was damaged severely and slightly, respectively. There was no statistical difference in collagen content among Group A, B and C, as compared to the control group (P>0.05). But the GAG content was significantly more lower in Group A, B and C than in the control group (P0.05), while these parameters of Group B were lower than those in the control group (P<0.05). Conclusions The Triton X-100-treated annulus fibrosus retained the major extracellular matrix composition after cell removal and preserved the major structure and mechanical strength, which is preferable for the construction of tissue engineering annulus fibrosus.

Mechanical properties ofinstantly repaired articular cartilage defects by tissue engineering / 医用生物力学

Objective To investigate the mechanical properties of both artificial cartilage and host cartilage by establishing the in vitro model of tissue engineered cartilage for repairing defects. Methods The agarose gel as an artificial cartilage was implanted in a deep cartilage defect connected with biological adhesive to set up the in vitro model of tissue engineered articular cartilage defects. Under the compression load, the instant mechanical behavior of the repair area was studied using the digital image correlation technology. Results There was no cracking phenomenon occurred at the interface during the compression process. The Strain distributions at middle layer of the repair area were obtained when the cartilage thickness appeared changes with 3.5%, 5.6%, 7.04% and 9.0% by the compression, respectively. When the compressing change increased from 3.5% to 9%, the maximum compressive strain of host cartilage was increased by 75.9%, and the maximum tensile strain of artificial cartilage was increased by 226.99% in the vertical direction of cartilage surface. In the direction parallel with cartilage surface, the maximum tensile strain at the interface was increased by 116.9%, and the increment was far more than that at the host cartilage area and artificial cartilage area. For shear strain at the repair area, the direction of shear strain at the interface changed oppositely with the compression increasing. Conclusions The repair effect of tissue engineered cartilage was uncertain due to the mechanical environment of the repair area. After the tissue engineered cartilage was implanted in the defect, the repair area was under the influence of complex strain states. The strains changed greatly at the interface both with the host cartilage and artificial cartilage as the compression increasing. The strain in the vertical direction of cartilage surface at the interface might change from compressive stain to tensile strain, which was significantly increased in the direction parallel with cartilage surface. The strain direction at the interface could even be changed oppositely, and the shear strain appeared rapidly increase. The complex strain states lead to such great changes in mechanical environment of the defect area, and may cause cracking at the interface, and even further affect the repair process. Therefore, attention should be given to this complex mechanical environment during cartilage defect repair process in clinical treatment.

Test on compressive properties of trabecular bone in proximal femur using digital image correlation technique / 医用生物力学

Objective To improve the method used for traditional compression test to reflect the compressive elastic modulus of trabecular bone in proximal femur more accurately and investigate its biomechanical properties to provide experimental evidences for clinical treatment. Methods The properties of trabecular bone from normal cadaveric proximal femur(45~60 years old) were measured by the micro material mechanics testing system. Results The elastic modulus in the direction of principle compression and principle tension on trabecular bone were (335.26±183.85) MPa and (59.27±23.88) MPa, respectively. The biomechanical properties of trabecular bone in the direction of principle compression were significantly higher than those in its vertical direction.The displacement and strain distribution profiles under the loading were recorded, which showed to be asymmetric. Conclusions It is feasible to test the biomechanical properties of trabecular bone more accurately by the micro material mechanics testing system. The compressive properties of trabecular bone in proximal femur are obviously anisotropic and heterogeneous.

Advances of mechanical conditions in engineering cartilage tissue / 医用生物力学

There are many physical factors affecting the development of cartilage tissue,the mechanical con-dition is the main important one that particularly act.The mechanical conditions used in engineering cartilage tissue,such as compressive and shear force,fluid flow,hydrostatic pressure and tissue deformation or with some of them combined,were reviewed.From the standpoint of bionics,the mechanical environments ap-plied on tissue engineering should work in three aspects:providing adequately mechanical stimuli to the cells seeded in 3-D scaffold;ensuring the efficient mass-transport of the nutrients and waste products in the cells:promoting the development of functionally extracellular matrix in 3-D scaffold.The mechanical environments currently used only represented the part of mechanical conditions of in vive articular cartilage will be reviewed.In our view that rolling depression load may achieve the fit mechanical environment for cultivation of functional cartilage constructs in vitro.

Advances of mechanical conditions in engineering cartilage tissue / 医用生物力学

There are many physical factors affecting the development of cartilage tissue,the mechanical con-dition is the main important one that particularly act.The mechanical conditions used in engineering cartilage tissue,such as compressive and shear force,fluid flow,hydrostatic pressure and tissue deformation or with some of them combined,were reviewed.From the standpoint of bionics,the mechanical environments ap-plied on tissue engineering should work in three aspects:providing adequately mechanical stimuli to the cells seeded in 3-D scaffold;ensuring the efficient mass-transport of the nutrients and waste products in the cells:promoting the development of functionally extracellular matrix in 3-D scaffold.The mechanical environments currently used only represented the part of mechanical conditions of in vive articular cartilage will be reviewed.In our view that rolling depression load may achieve the fit mechanical environment for cultivation of functional cartilage constructs in vitro.