生物力学建模与应用——贺冯元桢先生百岁诞辰

近代生物力学自以冯元桢先生为代表的科学家们创立以来,将工程学的系统思想和演绎方法运用到对生命组织特性和行为的定量描述和预测中,为人们进一步理解生命活动、推动人类健康科学的发展提出了至关重要的新思路和新方法。

Biomimetic delivery of signals for bone tissue engineering

Bone tissue engineering is an exciting approach to directly repair bone defects or engineer bone tissue for transplantation.Biomaterials play a pivotal role in providing a template and extracellular environment to support regenerative cells and promote tissue regeneration. A variety of signaling cues have been identified to regulate cellular activity, tissue development, and the healing process. Numerous studies and trials have shown the promise of tissue engineering, but successful translations of bone tissue engineering research into clinical applications have been limited, due in part to a lack of optimal delivery systems for these signals. Biomedical engineers are therefore highly motivated to develop biomimetic drug delivery systems, which benefit from mimicking signaling molecule release or presentation by the native extracellular matrix during development or the natural healing process. Engineered biomimetic drug delivery systems aim to provide control over the location, timing, and release kinetics of the signal molecules according to the drug's physiochemical properties and specific biological mechanisms. This article reviews biomimetic strategies in signaling delivery for bone tissue engineering, with a focus on delivery systems rather than specific molecules. Both fundamental considerations and specific design strategies are discussed with examples of recent research progress, demonstrating the significance and potential of biomimetic delivery systems for bone tissue engineering.

A new method for computing the uniaxial modulus of articular cartilages using modified inhomogeneous triphasic model

It is well known that subtle changes in structure and tissue composition of articular cartilage can lead to its degeneration. The present paper puts forward a modified layered inhomogeneous triphasic model with four parameters based on the inhomogeneous triphasic model proposed by Narmoneva et al. Incorporating a piecewise fitting optimization criterion, the new model was used to obtain the uniaxial modulus Ha, and predict swelling pattern for the articular cartilage based on ultrasound-measured swelling strain data. The results show that the new method can be used to provide more accurate estimation on the uniaxial modulus than the inhomogeneous triphasic model with three parameters and the homogeneous mode, and predict effectively the swell- ing strains of highly nonuniform distribution of degenerated articular cartilages. This study can provide supplementary information for exploring mechanical and material properties of the cartilage, and thus be helpful for the diagnosis of osteoarthritis-related diseases.

Numerical simulation of pulsatile non-Newtonian flow in the carotid artery bifurcation

Both clinical and post mortem studies indicate that, in humans, the carotid sinus of the carotid artery bifurcation is one of the favored sites for the genesis and development of atherosclerotic lesions. Hemodynamic factors have been suggested to be important in atherogenesis. To understand the correlation between atherogenesis and fluid dynamics in the carotid sinus, the blood flow in artery was simulated numerically. In those studies, the property of blood was treated as an incompressible, Newtonian fluid. In fact, however, the blood is a complicated non-Newtonian fluid with shear thinning and viscoelastic properties, especially when the shear rate is low. A variety of non-Newtonian models have been applied in the numerical studies. Among them, the Casson equation was widely used. However, the Casson equation agrees well only when the shear rate is less than 10 s-1. The flow field of the carotid bifurcation usually covers a wide range of shear rate. We therefore believe that it may not be sufficient to describe the property of blood only using the Casson equation in the whole flow field of the carotid bifurcation. In the present study, three different blood constitutive models, namely, the Newtonian, the Casson and the hybrid fluid constitutive models were used in the flow simulation of the human carotid bifurcation. The results were compared among the three models. The results showed that the Newtonian model and the hybrid model had verysimilar distributions of the axial velocity, secondary flow and wall shear stress, but the Casson model resulted in significant differences in these distributions from the other two models. This study suggests that it is not appropriate to only use the Casson equation to simulate the whole flow field of the carotid bifurcation, and on the other hand, Newtonian fluid is a good approximation to blood for flow simulations in the carotid artery bifurcation.

A Hybrid Biofuel and Triboelectric Nanogenerator for Bioenergy Harvesting

Various types of energy exist everywhere around us,and these energies can be harvested from multiple sources to power micro-/nanoelectronic system and even personal electronic products.In this work,we proposed a hybrid energy-harvesting system(HEHS)for potential in vivo applications.The HEHS consisted of a triboelectric nanogenerator and a glucose fuel cell for simultaneously harvesting biomechanical energy and biochemical energy in simulated body fluid.These two energy-harvesting units can work individually as a single power source or work simultaneously as an integrated system.This design strengthened the flexibility of harvesting multiple energies and enhanced corresponding electric output.Compared with any individual device,the integrated HEHS outputs a superimposed current and has a faster charging rate.Using the harvested energy,HEHS can power a calculator or a green light-emitting diode pattern.Considering the widely existed biomechanical energy and glucose molecules in the body,the developed HEHS can be a promising candidate for building in vivo self-powered healthcare monitoring system.

Age- and direction-related adaptations of lumbar vertebral trabecular bone with respect to apparent stiffness and tissue level stress distribution

The objective of this study was to study the age-related adaptation of lumbar vertebral trabecular bone at the apparent level, as well as the tissue level in three orthogonal directions. Ninety trabecular specimens were obtained from six normal L4 vertebral bodies of six male cadavers in two age groups, three aged 62 years and three aged 69 years, and were scanned using a high-resolution micro-computed tomography （micro-CT） system, then converted to micro- finite element models to do micro-finite element analyses. The relationship between apparent stiffness and bone volume fraction, and the tissue level yon Mises stress distribution for each trabecular specimen when compressed separately in the longitudinal direction, medial-lateral and anterior-posterior directions （transverse directions） were derived and compared between two age groups. The results showed that at the apparent level, trabecular bones from 69-year group had stiffer bone structure relative to their volume fractions in all three directions, and in both age groups, changes in bone volume fraction could explain more variations in apparent stiffness in the longitudinal direction than the transverse directions; at the tissue level, aging had little effect on the tissue von Mises stress distributions for the compressions in all the three directions. The novelty of the present study was that it provided quantitative assessments on the age and direction- related adaptation of Chinese male lumbar vertebral trabecular bone from two different levels： stiffness at the apparent level and stress distribution at the tissue level. It may help to understand the failure mechanisms and fracture risks of vertebral body associated with aging and direction for the prevention of fracture risks in elder individuals.

Microfluidic chips for the endothelial biomechanics and mechanobiology of the vascular system

Endothelial cells arranged on the vessel lumen are constantly stimulated by blood flow,blood pressure and pressureinduced cyclic stretch.These stimuli are sensed through mechanical sensory structures and converted into a series of functional responses through mechanotransduction pathways.The process will eventually affect vascular health.Therefore,there has been an urgent need to establish in vitro endothelial biomechanics and mechanobiology of models,which reproduce three-dimensional structure vascular system.In recent years,the rapid development in microfluidic technology makes it possible to replicate the key structural and functionally biomechanical characteristics of vessels.Here,we summarized the progress of microfluidic chips used for the investigation of endothelial biomechanics and mechanobiology of the vascular system.Firstly,we elucidated the contribution of shear stress and circumferential stress,to vascular physiology.Then,we reviewed some applications using microfluidic technology in angiogenesis and vasculogenesis,endothelial permeability and mechanotransduction,as well as the blood-brain barrier under these physical forces.Finally,we discussed the future obstacles in terms of the development and application of microfluidic vascular chips.

Biomechanics and mechanobiology of the bone matrix

The bone matrix plays an indispensable role in the human body,and its unique biomechanical and mechanobiological properties have received much attention.The bone matrix has unique mechanical anisotropy and exhibits both strong toughness and high strength.These mechanical properties are closely associated with human life activities and correspond to the function of bone in the human body.None of the mechanical properties exhibited by the bone matrix is independent of its composition and structure.Studies on the biomechanics of the bone matrix can provide a reference for the preparation of more applicable bone substitute implants,bone biomimetic materials and scaffolds for bone tissue repair in humans,as well as for biomimetic applications in other fields.In providing mechanical support to the human body,bone is constantly exposed to mechanical stimuli.Through the study of the mechanobiology of the bone matrix,the response mechanism of the bone matrix to its surrounding mechanical environment can be elucidated and used for the health maintenance of bone tissue and defect regeneration.This paper summarizes the biomechanical properties of the bone matrix and their biological significance,discusses the compositional and structural basis by which the bone matrix is capable of exhibiting these mechanical properties,and studies the effects of mechanical stimuli,especially fluid shear stress,on the components of the bone matrix,cells and their interactions.The problems that occur with regard to the biomechanics and mechanobiology of the bone matrix and the corresponding challenges that may need to be faced in the future are also described.

Tissue level microstructure and mechanical properties of the femoral head in the proximal femur of fracture patients

This study aims to investigate the regional variations of trabecular morphological parameters and mechanical parameters of the femoral head,as well as to determine the relationship between trabecular morphological and mechanical parameters.Seven femoral heads from patients with fractured proximal femur were scanned using a micro-CT system.Each femoral head was divided into 12 sub-regions according to the trabecular orientation.One 125 mm^3 trabecular cubic model was reconstructed from each sub-region.A total of 81 trabecular models were reconstructed,except three destroyed sub-regions from two femoral heads during the surgery.Trabecular morphological parameters,i.e.trabecular separation（Tb.Sp）,trabecular thickness（Tb.Th）,specific bone surface（BS/B V）,bone volume fraction（BV/TV）,structural model index（SMI）,and degree of anisotropy（DA） were measured.Micro-finite element analyses were performed for each cube to obtain the apparent Young＇s modulus and tissue level von Mises stress distribution under 1%compressive strain along three orthogonal directions,respectively.Results revealed significant regional variations in the morphological parameters（P〈0.05）.Young＇s moduli along the trabecular orientation were significantly higher than those along the other two directions.In general,trabecular mechanical properties in the medial region were lower than those in the lateral region.Trabecular mechanical parameters along the trabecular orientation were significantly correlated with BS/BV,BV/TV,Tb.Th,and DA.In this study,regional variations of microstructural features and mechanical properties in the femoral head of patients with proximal femur fracture were thoroughly investigated at the tissue level.The results of this study will help to elucidate the mechanism of femoral head fracture for reducing fracture risk and developing treatment strategies for the elderly.

Image-based nonlinear finite element analysis for the assessment of bone strength

Introduction As a major component of musculoskeletal system,bones support body weight,facilitate body motion,protect internal organs,and also play critical roles in mineral homeostasis.Osteoporosis,one of the most common bone diseases,is a result of imbalance in bone metabolism that causes low bone mass and micro-architectural deterioration.The inferior quality of osteoporotic bone leads to a consequent increase in bone fragility and susceptibility to fracture.It is known that osteoporotic fractures occur most frequently in trabeculae-rich skeletal sites such as spine,hip,distal radius,and ankle.With the great increase in the number of senile population,

Numerical simulation on the adaptation of forms in trabecular bone to mechanical disuse and basic multi-cellular unit activation threshold at menopause

The objective of this paper is to identify the effects of mechanical disuse and basic multi-cellular unit （BMU） activation threshold on the form of trabecular bone during menopause. A bone adaptation model with mechanical- biological factors at BMU level was integrated with finite element analysis to simulate the changes of trabecular bone structure during menopause. Mechanical disuse and changes in the BMU activation threshold were applied to the model for the period from 4 years before to 4 years after menopause. The changes in bone volume fraction, trabecular thickness and fractal dimension of the trabecular structures were used to quantify the changes of trabecular bone in three different cases associated with mechanical disuse and BMU activation threshold. It was found that the changes in the simulated bone volume fraction were highly correlated and consistent with clinical data, and that the trabecular thickness reduced signi-ficantly during menopause and was highly linearly correlated with the bone volume fraction, and that the change trend of fractal dimension of the simulated trabecular structure was in correspondence with clinical observations. The numerical simulation in this paper may help to better understand the relationship between the bone morphology and the mecha-nical, as well as biological environment; and can provide a quantitative computational model and methodology for the numerical simulation of the bone structural morphological changes caused by the mechanical environment, and/or the biological environment.

Mechano-Sensing by Endothelial Primary Cilium

Introduction Primary cilium is a non-motile microstructure,protruding from cell surface of most mammalian cells.It was previously thought to be vestigial.However,recent studies indicate that it may serve as one of the most vital mechanosensors for many types of cells such as epithelial and endothelial cells and osteocytes.Protruding from the apical membrane,the primary cilium can directly sense subtle variation of mechanical forces exerted on the cell and then transduce the mechanical cues into biochemical signals into the cell,although the mechanism remain elusive.Vascular endothelial cells(ECs)lining the inner wall of our blood vessels are continuously exposed to the blood flow.In order to maintain proper functions for the cardiovascular system,ECs should have a variety of mechano-sensors and transducers to sense the blood flow change and adjust the vessel size and transport across the vessel wall accordingly.Among more than a dozen recognized EC mechano-sensors,the primary cilium has drawn more and more attention recently.Primary cilium on endothelial cells is essential for the homeostasis of vessels.It is reported to be prevalent in areas of disturbed flow where atherosclerosis and intracranial aneurysm usually occur.Deficiencies of primary cilia may promote atherosclerosis,endothelial-to-mesenchymal transition(EndoMT)and loss of direction orientation,to name a few.Therefore understanding why the primary cilia are necessary to maintain the homeostasis of blood vessels and how will help us develop better treatment strategies for the common cardiovascular diseases.Dimension and structure of primary cilium Primary cilium is reported to be shorter than 8 in length and about 0.2 in diameter.The length of primary cilium varies in different cell types and under different conditions.The major structural components of the primary cilium include basal body,ciliary axoneme(consisting of nine doublet microtubules),ciliary membrane,transition zone,basal feet,and striated rootlets.Each part of the primary cilium is essential and has specific function.Current methods investigating the EC primary cilium as a mechano-sensor:Immunostaining and imaging techniques have been used to investigate the molecular mechanisms by which EC primary cilium serves as a mechano-sensor and transducer.It has been found that various proteins locate on the primary cilium,working together to maintain the function of primary cilium.Some proteins function as ion-channels,mediating Ca2+entry into the primary cilium.Some are involved in the cascade signal pathway.Others are related to the assembly and maintenance of primary cilium.Briefly,the flow induces the deflection of the EC primary cilium,which triggers calcium increase via opening of the PC2 cation channel that is responsible for calcium ion influx.This PC2 cation channel is localized to the primary cilium and is assumed to be stretch-activated.The resulting change in the intracellular calcium concentration then regulates numerous molecular activities inside the cell that contribute to vessel homeostasis.In addition to triggering calcium release,another mechanism has also been found in blood-pressure maintenance in the vasculature,where the vessel diameter is regulated by endothelial primary cilia through adjusting nitric oxide production.So far,little is known about the mechanical mechanism behind this deflection-triggered o-pening of signaling pathways.For example,what is the flow induced bending behavior and force distribution? What is the threshold value of stretch/defection for activating a corresponding signaling pathway? These all remain to be answered.In combination of image data and experiments,several computational models have been established to answer these questions.However,the current models are not able to include the complex structure of primary cilium and the model predictions are limited.Future studies With the development of super high resolution optical microscopy,more detailed images for the structural(molecular)components of EC primary cilia will be revealed,especially when the ECs are alive and the forces are known.Combining these experimental observations with more sophisticated mathematical models will elucidate the mechano-sensing mechanism of EC primary cilia,as the force and stress distribution on cilium along with other mechanical properties are still beyond the capability of experimental approaches due to the scales of the quantities involved.By using numerical approaches,much more detailed dynamic information can be obtained.

Bilayer nicorandil-loaded small-diameter vascular grafts improve endothelial cell function via PI3K/AKT/eNOS pathway

For the surgical treatment of cardiovascular disease(CVD),there is a clear and unmet need in developing small-diameter(diameter<6 mm)vascular grafts.In our previous work,sulfated silk fibroin(SF)was successfully fabricated as a potential candidate for preparing vascular grafts due to the great cytocompatibility and hemocompatibility.However,vascular graft with single layer is difficult to adapt to the complex internal environment.In this work,polycaprolactone(PCL)and sulfated SF were used to fabricate bilayer vascular graft(BLVG)to mimic the structure of natural blood vessels.To enhance the biological activity of BLVG,nicorandil(NIC),an FDA-approved drug with multi-bioactivity,was loaded in the BLVG to fabricate NIC-loaded BLVG.The morphology,chemical composition and mechanical properties of NIC-loaded BLVG were assessed.The results showed that the bilayer structure of NIC-loaded BLVG endowed the graft with a biphasic drug release behavior.The in vitro studies indicated that NIC-loaded BLVG could significantly increase the proliferation,migration and antioxidation capability of endothelial cells(ECs).Moreover,we found that the potential biological mechanism was the activation of PI3K/AKT/eNOS signaling pathway.Overall,the results effectively demonstrated that NIC-loaded BLVG had a promising in vitro performance as a functional small-diameter vascular graft.

Mechano-Sensing and shear stress-shielding by endothelial primary cilia:structure,composition,and function

Primary cilium is an antenna-like and non-motile structure protruding from the apical surface of most mammalian cells including endothelial cells lining the inner side of all the blood vessels in our body.Although it has been over a century since primary cilia were discovered,the investigation about their mechano-sensing and other roles in maintaining normal functions of cardiovascular system has just started in recent years.This focused review aims to give an update about the current literature for the role of endothelial primary cilia in blood flow mechanosensing and shear stress-shielding.To do this,we first summarized the characteristic features of endothelial primary cilia in terms of structure,dimension,molecular composition,and mechanical properties(e.g.,bending rigidity),which are the dominant factors for their functions in mechano-sensing and transduction,as well as vascular protection from the blood flow-induced wall shear stress.We also described the experimental techniques and mathematical models for determining the dimension and mechanical properties of the primary cilium.Then we reviewed the molecular mechanisms underlying mechano-sensing and transduction by endothelial primary cilia and the mathematical model prediction for their roles in redistribution and reduction of wall shear stresses.Finally,we briefly discussed the common cardiovascular diseases,e.g.,atherosclerosis,hypertension,and aneurysm,due to defects and malfunction of endothelial primary cilia and suggested potential targets for therapeutic treatments.

Correction to:A Hybrid Biofuel and Triboelectric Nanogenerator for Bioenergy Harvesting

In the original publication,the authors’contribution is missing in the acknowledgment section.The correct acknowledgement is provided in this correction.Also,in Fig.4,the second(c)after figure(d)should be read as(e).In Fig.5(i),the Y-axis label“Current(μA)”should be read as“Voltage”.

Optimal Siting of Electric Vehicle Charging Stations Based on Voronoi Diagram and FAHP Method

The electric vehicle charging station should be allocated based on traffic density, geographical distribution and other factors, and Voronoi diagram is adopted to set the service area of charging station. In combination with the actual situation of site selection of electric vehicle charging station, the comprehensive benefits index system is established. There are numerous factors influencing the site selection, among which there are uncertainty and fuzziness. The comprehensive evaluation method based on the fuzzy analysis and Analytical Hierarchy Process (AHP) is used to evaluate the comprehensive benefits in the site selection of electric vehicle charging stations, with the consultation of experts. This paper contributes to the best selection of comprehensive benefits and provides the reference for the decision-making of building the electric vehicle charging station. Actual examples show that the method proposed is effective.

Impact of Electric Vehicle Charging on Power Load Based on TOU Price

Large-scale electric vehicle charging has a significant impact on power grid load, disorderly charging will increase power grid peak load. This article proposes an orderly charging mechanism based on TOU price. To build an orderly charging model by researching TOU price and user price reaction model. This article research the impact of electric vehicle charging on grid load by orderly charging model. With this model the grid’s peak and valley characteristics, the utilization of charging equipment, the economics of grid operation can all be improved.

Comparison among Chargers of Electric Vehicle Based on Different Control Strategies

The charger of electric vehicle is a power electronic device which consists of rectifying devices and DC-DC converters. This nonlinear diode rectifier circuit has low power factor and high harmonic content. In order to improve power factor and reduce the harmonic distortion rate of the AC side current, single-phase non-controlled rectifier charger needs to install the active power factor correction device. A piece of power system analysis software which is called PSCAD is used in modeling of an EV charger which contains Boost-APFC. By means of simulation and analysis, differences of APFC characteristics between the hysteresis current control mode and average current control mode which has an influence on the power grid are compared. The consequence of simulation shows that the two control strategies achieve power factor correction and harmonic reduction requirements;Boost type power conversion circuit employs the average current control mode is better, which has following features: relatively faster settling time of the output voltage, relatively smaller overshoot, lower current harmonic distortion rate on AC side, lower switching frequency and better control effect.

Impact Analysis of Off-board Charger to Power Quality

In this paper, we tested the entire charging process of a single off-board charger in one charging station in Beijing. Among the testing data, we chose the typical power quality parameters and compared them with national standard. Then we drew conclusions as follows: 1) Electric vehicle battery is the capacitive load. It can export reactive power when charging. 2) In the charging process of the off-board charger, indicators of voltage deviation, frequency deviation, power factor, and voltage distortion rate are qualified. 3) Off-board charger produces odd harmonics in the charging process, and with increasing harmonic order, harmonic content reduces. There is a certain amount of high-order harmonic in off-board charger, mainly distributing around 6650 kHz. 4) Generated harmonics of the actual device, the harmonic is mainly reflected in the current, voltage, only a small distortion.

Effect of mechanical stresses on degradation behavior of high-purity magnesium in bone environments

High-purity(HP)magnesium(Mg)has emerged as a promising biomaterial for supporting functional bone tissue.Our previous study found that mechanical stresses and the surrounding fibrotic tissue(subcuta-neous)both play crucial roles in the degradation of HP Mg.However,due to challenges in the degradation and regeneration process in vivo,it remains unclear how stress affects HP Mg degradation in bone en-vironments,limiting its further application.In this study,novel loading devices were designed and the effects of tensile and compressive stresses on HP Mg degradation in vivo and in vitro bone environments were quantitatively analyzed.In addition,bone osteointegration around HP Mg was explored preliminar-ily.Tensile stress increases the degradation rate of HP Mg in vivo and in vitro.HP Mg degradation in vivo is more sensitive to stress factors than in vitro,but the sensitivity decreases with corrosion time.The volume loss rate of HP Mg is multilinear with the applied stress and degradation time.The volume of bone tissue surrounding HP Mg is larger in the no-stress group compared to the stressed groups,which is more pronounced with increasing implantation time.These results provide valuable insights for optimiz-ing the design of HP Mg-based implants considering load conditions.This will help to achieve a balance between the degradation rate of the implant and the regeneration rate of the surrounding bone.