Disease animal model is an indispensable part of studying the pathogenesis and treatment of diseases.Review of the ethics and welfare is the necessary measure to ensure the quality of scientific research and promote the scientific and rational use of laboratory animals.In the review practice,it is found that most applicants are difficult to accurately understand the items listed in the application form and ethical principles related to items.Therefore,a practical and feasible set of ethical guidelines for animal experiments is necessary.This review focuses on the legal and ethical basis of developing oral disease animal models,and divides the methods of establishing oral disease animal models into physical methods,chemical methods,biological methods,and combined methods.It also elaborates on the ethical and welfare review points of different modeling methods and model evaluation methods.Hopefully,ethical censors and project applicants may get more understanding of ethical review for disease animal models,and ultimately improve the standardization and applicability of animal models.

The cardiovascular system is a mechanical system with the heart as the center and blood vessels as the network.Mechanical forces play a direct and key role in regulating the physiological state and pathological process of the cardiovascular system.Cardiovascular diseases such as coronary heart disease,hypertension and stroke have similar pathological basis,that is,vascular remodeling caused by vascular dysfunction and abnormal damage.Therefore,investigating how mechanical forces produce biological effects that lead to vascular remodeling,and elucidating cardiovascular mechanical signal transduction pathways and mechanical regulation pathways are of great research significance for in-depth understanding of the nature of cardiovascular disease occurrence.In this review,different mechanical forces and key mechanical response molecules are used as clues,and the latest research progress of vascular mechanobiology in 2023 is summarized.These results provide new ideas for further exploring the role of mechanical factors in the pathogenesis of cardiovascular diseases,and providing markers and potential targets for early diagnosis of the disease.

Vascular biomechanics mainly explores how vascular cells perceive mechanical stimuli,how mechanics affects the development of diseases,and the exploitation of various mathematical models to analyze the effects of mechanical factors on diseases.In recent years,researches in the field of vascular biomechanics are developing rapidly,and various research teams have analyzed the mechanical and biological processes of blood vessels from different directions,in order to gain a deeper understanding of the regulatory mechanisms of vascular biomechanical factors affecting the progression of various vascular diseases,and provide a theoretical basis based on the mechanobiology for the prevention and treatment of cardiovascular and cerebrovascular diseases.This article summarizes and discusses the recent research hotspots and emerging trends in the field of vascular mechanobiology based on domestic and foreign expert teams and combined with the work of this research team,thus providing a systematic framework for grasping hotspots and exploring new research directions in the field of vascular mechanobiology.

Objective To study the hemodynamic effects of enhanced external counter pulsation(EECP)on typical coronary artery disease and microcirculation angina.Methods A physiological model of the right dominant coronary artery,including the coronary conduit arteries and coronary microcirculation,was established using lumped parameter models.Pathological conditions,such as one-vessel lesions,three-vessel lesions,and microcirculation angina,were simulated.EECP intervention models were established,and the hemodynamic effects of EECP on pathological models was simulated.Results The simulation results of the coronary physiological model,pathological models,and EECP intervention model established in this study were consistent with experimental data in related literature.EECP improved coronary blood flow in all three pathological conditions.For one-vessel lesions,EECP could not recover the blood flow of left main coronary artery to a normal level after the stenosis rate reached 80%-85%.For three-vessel lesions,EECP treatment could not be used if the stenosis rate in one of the three vessels exceeded 90%.For microcirculation angina,EECP was effective when critical condition myocardial blood flow was>1.03 mL/min·g and coronary flow reserve was>1.64.Conclusions The model of coronary disease under EECP interference established in this study meets expectations,and the obtained simulation data have certain reference values for the clinical application of EECP.

Objective To investigate the hemodynamic effects of enhanced external counterpulsation(EECP)on cerebral arteries with different stenoses.Methods Zero-dimensional/three-dimensional multiscale hemodynamic models of cerebral arteries with different stenoses were constructed.Numerical simulations of the EECP hemodynamics were performed under different counterpulsation modes to quantify several hemodynamic indicators of the cerebral arteries.Among them,the mean time-averaged wall shear stress(TAWSS)downstream of the stenosis was in the range of 4-7 Pa,a low percentage of TAWSS risk area,and high narrow branch flow were considered to inhibit the development of atherosclerosis and create a good hemodynamic environment.Results For cerebral arteries with 50%,60%,70%,and 80%stenosis,the hemodynamic environment was optimal in counterpulsation mode when the moment of cuff deflation was 0.5,0.6,0.7,and 0.7 s within the cardiac cycle.Conclusions For 50%stenotic cerebral arteries,the counterpulsation mode with a deflation moment of 0.5 s should be selected.For 60%stenotic cerebral arteries,the counterpulsation mode with a deflation moment of 0.6 s should be selected.For 70%or 80%stenotic cerebral arteries,the counterpulsation mode with a deflation moment of 0.7 s should be selected.As stenosis of the cerebral arteries increases,the pressure duration should be prolonged.This study provides a theoretical reference for the EECP treatment strategy for patients with ischemic stroke with different stenoses.

Objective To explore the dynamic process of fluid-structure interaction(FSI)between venous blood and valves and the physiological mechanism that guarantees unidirectional blood reflux back to the heart.Methods A three-dimensional(3D)numerical model of the venous system was established using the immersed boundary/finite element method.In the simulation,information from medical images of human lower-extremity veins and the anatomical structure and size of the bovine great saphenous vein were applied.Moreover,a hyperelastic constitutive model was used to describe the incompressible,nonlinear,and hyperelastic mechanical responses of the venous valve under physiological conditions.Results The simulations visualized the process of venous blood transport and the function of venous valves in preventing reflux.The periodic characteristics of venous valve motion and blood flow were reproduced,and important physiological data during the entire cardiac cycle were discussed and quantified,including the pressure,velocity,and flow rate of venous blood;opening area of the venous valve;and stress and strain distributions on the valve surface.Conclusions The 3D FSI model numerically reproduces the physiological dynamic process within veins and potentially provides important references and guidance for revealing the pathological mechanism of venous diseases.

Objective To investigate the effects of force on mechanical stability of FLNa-Ig21/αⅡbβ3-CT complex and the regulation mechanism.Methods The FLNa-Ig21/αⅡbβ3-CT crystal structures were taken from the PDB database.The stability of the complexes in a physiological environment as well as the unfolding path and mechanical stability induced by mechanical forces were analyzed using equilibrium and steered molecular dynamics simulations.Results During the equilibration,the survival rate of most salt bridge and hydrogen bonds was below 0.5,and the interactions between FLNa-Ig21 and αⅡbβ3-CT was relatively weak.During stretching at a constant velocity,the complex could withstand a tensile force of 70-380 pN,and its mechanical strength depended on the force-induced dissociation path.Under a constant force of 0-60 pN,the complexes exhibited a slipping-bond trend,and the force increase facilitated the breakage of the R995-D723 salt bridge and the activation of αⅡbβ3 integrin.Conclusions The force-induced allostery of αⅡbβ3-MP enhanced the complex mechanical strength and delayed FLNa-Ig21 dissociation from αⅡbβ3-CT.After breaking through the 20 pN threshold,force positively regulated the activation of αⅡbβ3 integrin.These results provide insights into the molecular mechanism of αⅡbβ3 activation and the development of related targeted drugs.

Objective To study the compressive mechanical properties and constitutive models of brain tissue at different strain rates.Methods Quasi-static and medium-velocity compression tests were carried out on the white and gray matter of pig brain tissue using an electronic universal testing machine,and stress-strain curves of pig brain tissue at different strain rates were obtained.The Ogden constitutive model was used to fit the test curve,the parameters of the constitutive model were determined,and the simulation was verified using finite element software.Results The brain tissue stress-strain curves showed nonlinear characteristics,with a strong strain rate correlation and sensitivity.When tissues were compressed to 0.6 strain,the stress of white and gray matter increased by 102%and 129%,respectively,at a strain rate of 5×10-4-5×10-2 s-1,and by 50.7%and 54.6%,respectively,at a strain rate of 1-1.5 s-1.At a strain rate of 1.5 s-1,the stress in the white and gray matter increased by 347%and 413%,respectively,compared with that at 5×10-4 s-1 strain rate.The R2 value of the Ogden model was greater than 0.99,and the error between the simulation and experimental results was within 15%,thereby verifying the validity of the model.Conclusions This study is helpful for the prediction of brain tissue deformation and provides an accurate scientific theoretical basis for the establishment of scientific and reasonable human simulation targets as well as the design and improvement of brain-protective equipment.

Objective To predict the tissue-level failure strain of the cortical bone and discuss the effects of different running speeds on the mechanical properties of rat femoral cortical bone.Methods The threshold for cortical bone tissue-level failure strain was assigned,and fracture simulation under three-point bending was performed on a rat femoral finite element model.The predicted load-displacement curves in each simulation were compared and fitted with the experimental data to back-calculate the tissue-level failure strain.Results The cortical bone tissue-level failure strains at different running speeds were statistically different,which indicated that different running speeds had certain impacts on the micromechanical properties of the cortical bone structures.At a running speed of 12 m/min,the cortical bone structure expressed the greatest tissue-level failure strain,and at a running speed of 20 m/min,the cortical bone structure expressed the lowest tissue-level failure strain.Conclusions Based on the changing trends of tissue-level failure strain and in combination with the changes in macro-level failure load and tissue-level elastic modulus of cortical bone structures,the effects of different running speeds on the mechanical properties of cortical bone structures were discussed in this study.The appropriate running speed for improving the mechanical properties of the cortical bone was explored,thereby providing a theoretical basis for improving bone strength through running exercises.

Objective To investigate the influence of different cell structures on the static and dynamic mechanical performance of porous titanium alloy scaffolds,and to provide a theoretical mechanical basis for the application of scaffolds in the repair of mandibular bone defects.Methods Porous titanium alloy scaffolds with diamond,cubic,and cross-sectional cubic cell structures were manufactured using three-dimensional printing technology.Uniaxial compression tests and ratcheting fatigue with compression load tests were conducted to analyze the static and dynamic mechanical performances of scaffolds with different cell structures.Results The elastic moduli of the diamond cell,cross-sectional cubic cell,and cubic cell scaffolds were 1.17,0.566,and 0.322 GPa,respectively,and the yield strengths were 71.8,65.1,and 31.8 MPa,respectively.After reaching the stable stage,the ratcheting strains of the cross-sectional cubic,diamond,and cubic cell scaffolds were 3.3%,4.0%,and 4.5%,respectively.The ratcheting strain increased with increasing average stress,stress amplitude,and peak holding time,and decreased with increasing loading rate.Conclusions The evaluation results of the static mechanical performance showed that the diamond cell scaffold was the best,followed by the cross-sectional cubic cell scaffold and the cubic cell scaffold.The evaluation results of the dynamic mechanical performance showed that the cross-sectional cubic cell scaffold performed the best,followed by the diamond cell scaffold,whereas the cubic cell scaffold performed the worst.The fatigue performance of the scaffold is affected by the loading conditions.These results provide new insights for scaffold construction for the repair of mandibular bone defects and provide an experimental basis for further clinical applications of this scaffold technology.