Hypergravity stimulates mechanical behavior and micro-architecture of tibia in rats.

INTRODUCTION: The bone tissue is susceptible to hypergravity (+ G) environment. It is necessary to discuss the extent to which specific + G values are beneficial or detrimental to bone tissue. The objective of this study was to characterize the effects of high + G values on mechanical properties, microstructures, and cellular metabolism of bone. MATERIALS AND METHODS: 30 male Wistar rats aged 12 weeks were randomly divided into 5 groups, and bore different + G (namely + 1G, + 4G, + 8G, + 10G and + 12G) environments respectively for 4 weeks, 5 days each week, and 3 minutes each day. The macro-mechanical parameters, microstructure parameters, and mRNA transcription levels of the tibia were determined through the three-point bending method, micro-CT detection, and q-PCR analysis, respectively. RESULTS: As the + G value increases, hypergravity becomes increasingly detrimental to the macro-mechanical performance of rat tibia. Concerning the microstructure of cancellous bone, there appears to be a favorable trend at + 4G, followed by a progressively detrimental trend at higher G values. In addition, the mRNA transcription levels of OPG and RANKL show an initial tendency of enhanced bone absorption at +4G, followed by an increase in bone remodeling capacity as G value increases. CONCLUSION: The higher G values correspond to poorer macro-mechanical properties of the tibia, and a + 4G environment benefits the microstructure of the tibia. At the cellular level, bone resorption is enhanced in the + 4G group, but the bone remodeling capability gradually increases with further increments in G values.

Treadmill exercise promotes bone tissue recovery in rats subjected to high + Gz loads.

INTRODUCTION: High + Gz loads, the gravitational forces experienced by the body in hypergravity environments, can lead to bone loss in pilots and astronauts, posing significant health risks. MATERIALS AND METHODS: To explore the effect of treadmill exercise on bone tissue recovery, a study was conducted on 72 male Wistar rats. These rats were subjected to four weeks of varying levels of periodic high + Gz loads (1G, 8G, 20G) experiments, and were subsequently divided into the treadmill group and the control group. The treadmill group underwent a continuous two-week treadmill experiment, while the control group rested during this period. The mechanical properties, microstructure, and molecular markers of their tibial bone tissue were measured using three-point bending, micro-CT, and PCR. RESULTS: The results showed that treadmill exercise improved the elastic modulus, ultimate deflection, and ultimate load of rat bone tissue. It also increased the number, density, and volume fraction of bone trabeculae, and decreased their separation. Moreover, treadmill exercise enhanced osteogenesis and inhibited osteoclastogenesis. CONCLUSION: This study demonstrates that treadmill exercise can promote the recovery of bone tissue in rats subjected to high + Gz loads, providing a potential countermeasure for bone loss in pilots and astronauts.

[Design and performance study of bone trabecular scaffolds based on triply periodic minimal surface method].

Triply periodic minimal surface (TPMS) is widely used because it can be used to control the shape of porous scaffolds precisely by formula. In this paper, an I-wrapped package (I-WP) type porous scaffolds were constructed. The finite element method was used to study the relationship between the wall thickness and period, the morphology and mechanical properties of the scaffolds, as well as to study the compression and fluid properties. It was found that the porosity of I-WP type scaffolds with different wall thicknesses (0.1 ~ 0.2 mm) and periods (I-WP 1 ~ I-WP 5) ranged from 68.01% ~ 96.48%, and the equivalent elastic modulus ranged from 0.655 ~ 18.602 GPa; the stress distribution of the scaffolds tended to be uniform with the increase of periods and wall thicknesses; the equivalent elastic modulus of the I-WP type scaffolds was basically unchanged after the topology optimization, and the permeability was improved by 52.3%. In conclusion, for the I-WP type scaffolds, the period parameter can be adjusted first, then the wall thickness parameter can be controlled. Topology optimization can be combined to meet the design requirements. The I-WP scaffolds constructed in this paper have good mechanical properties and meet the requirements of repairing human bone tissue, which may provide a new choice for the design of artificial bone trabecular scaffolds.

[Effects of removing superficial layer of cartilage on the surface morphology and mechanical behavior of cartilage].

Superficial cartilage defect is an important factor that causes osteoarthritis. Therefore, it is very important to investigate the influence of superficial cartilage defects on its surface morphology and mechanical properties. In this study, the knee joint cartilage samples of adult pig were prepared, which were treated by enzymolysis with chymotrypsin and physical removal with electric friction pen, respectively. Normal cartilage and surface treated cartilage were divided into five groups: control group (normal cartilage group), chymotrypsin immersion group, chymotrypsin wiping group, removal 10% group with electric friction pen, and removal 20% group with electric friction pen. The surface morphology and structure of five groups of samples were characterized by laser spectrum confocal microscopy and environmental field scanning electron microscopy, and the mechanical properties of each group of samples were evaluated by tensile tests. The results show that the surface arithmetic mean height and fracture strength of the control group were the smallest, and the fracture strain was the largest. The surface arithmetic mean height and fracture strength of the removal 20% group with electric friction pen were the largest, and the fracture strain was the smallest. The surface arithmetic mean height, fracture strength and fracture strain values of the other three groups were all between the above two groups, but the surface arithmetic mean height and fracture strength of the removal 10% group with electric friction pen, the chymotrypsin wiping group and the chymotrypsin soaking group decreased successively, and the fracture strain increased successively. In addition, we carried out a study on the elastic modulus of different groups, and the results showed that the elastic modulus of the control group was the smallest, and the elastic modulus of the removal 20% group with electric friction pen was the largest. The above study revealed that the defect of the superficial area of cartilage changed its surface morphology and structure, and reduced its mechanical properties. The research results are of great significance for the prevention and repair of cartilage injury.

A Numerical Study on Mechanical Effects of Low-Intensity Pulsed Ultrasound on Trabecular Bone and Osteoblasts.

The lack of sufficient mechanical stimulation to the human bone, results in disuse osteoporosis. Low-intensity pulsed ultrasound (LIPUS) promotes fracture healing and the treatment of disuse osteoporosis, but its biomechanical mechanism remains unknown. Simulative research on the mechanical effects of LIPUS on disuse trabecular bone and osteoblasts have been performed. The von Mises stress of disuse trabecular bone and osteoblasts obviously increased under LIPUS irradiation. The average von Mises stress of osteoblasts were two orders of magnitude higher under the irradiation of simulant LIPUS than that without LIPUS irradiation, and the von Mises stress of osteoblasts was positively correlated with the amplitude of sound pressure excitation. The results showed that LIPUS irradiation could obviously improve the mechanical micro-environment of trabecular bone and osteoblasts to alleviate the lack of mechanical stimulation. The results of the research can reveal the biomechanical mechanism of LIPUS in the treatment of disuse osteoporosis to some extent and provide theoretical guidance for clinical treatment of disuse osteoporosis through physical methods.

Mechanistic insights of evaporation-induced actuation in supramolecular crystals.

Water-responsive materials undergo reversible shape changes upon varying humidity levels. These mechanically robust yet flexible structures can exert substantial forces and hold promise as efficient actuators for energy harvesting, adaptive materials and soft robotics. Here we demonstrate that energy transfer during evaporation-induced actuation of nanoporous tripeptide crystals results from the strengthening of water hydrogen bonding that drives the contraction of the pores. The seamless integration of mobile and structurally bound water inside these pores with a supramolecular network that contains readily deformable aromatic domains translates dehydration-induced mechanical stresses through the crystal lattice, suggesting a general mechanism of efficient water-responsive actuation. The observed strengthening of water bonding complements the accepted understanding of capillary-force-induced reversible contraction for this class of materials. These minimalistic peptide crystals are much simpler in composition compared to natural water-responsive materials, and the insights provided here can be applied more generally for the design of high-energy molecular actuators.

Development and characteristics of infrared gradient refractive index chalcogenide glasses by hot pressing.

Compared with ordinary uniform lenses, the length and refractive index distribution of gradient refractive index (GRIN) lenses can effectively correct aberration and chromatic aberration. This advantage makes the miniaturization, integration, and lens lightweight possible. Although the visible GRIN lenses based on silicate glass are widely used, the infrared GRIN lenses based on chalcogenide glass are still elusive. This paper introduces a new method for preparing this kind of lens by hot pressing sintering diffusion of chalcogenide glasses. A series of chalcogenide glasses Ge10As22Se68-xSx (x = 4, 7, 10, 14, 24, 28, 34 mol%) with refractive index range from 2.37 to 2.57 (n@8 µm) and similar glass transition temperature (ΔTg < 10℃) were prepared by melt quenching. The relationship between Raman peaks and the refractive index of glasses was studied. Furthermore, the refractive index profile formed by elemental diffusion was characterized by Raman signals. The results show that the diffusion length reaches more than 290 µm, and larger diffusion distances can be achieved by stacking multiple layers. The obtained GRIN glass maintains good transmittance in the whole atmospheric window of 2 ∼ 12 µm.

Study on mass transfer in the bone lacunar-canalicular system under different gravity fields.

INTRODUCTION: The bone lacunar-canalicular system (LCS) is an important microstructural basis for signaling and material transport in bone tissue, guaranteeing normal physiological processes in tissues. Spaceflight astronauts and elderly osteoporosis are related to its function, so it is necessary to reveal the mass transfer laws in bone microstructure under different gravity fields to provide insight for effective clinical treatment. MATERIALS AND METHODS: Using the natural LCS structure of bovine tibial cortical bone as the object, the mass transfer experiments on cortical bone were conducted by using sodium fluorescein tracer through different frequency pulsating pressure provided by dynamic perfusion loading device and different high G environments provided by high-speed centrifuge to analyze the mass transfer laws under different gravity fields and different pulsating pressures. RESULTS: The fluorescence intensity of lacunae within the osteon was lower the farther away from the Haversian canal. As the gravity field magnitude increased, the fluorescence intensity within each lacuna enhanced, and the more distant the lacunae from the Haversian canal, the greater the fluorescence intensity enhancement. High-frequency pulsating pressure simulated high-intensity exercise in humans can improve mass transfer efficiency in the LCS. CONCLUSION: High-intensity exercise may greatly increase solute molecules, nutrients, and signaling molecules in osteocytes and improve the activity of osteocytes. Hypergravity can enhance the transport of solute molecules, nutrients, and signaling molecules in the LCS, especially promoting mass transfer to deep layer lacunae. Conversely, mass transfer to deep layer lacunae may be inhibited under microgravity, causing bone loss and ultimately leading to osteoporosis.

A Calixarene Assembly Strategy of Combined Anti-Neuroinflammation and Drug Delivery Functions for Traumatic Brain Injury Therapy.

Excessive inflammatory reaction aggravates brain injury and hinders the recovery of neural function in nervous system diseases. Microglia, as the major players of neuroinflammation, control the progress of the disease. There is an urgent need for effective non-invasive therapy to treat neuroinflammation mediated by microglia. However, the lack of specificity of anti-inflammatory agents and insufficient drug dose penetrating into the brain lesion area are the main problems. Here, we evaluated a series of calixarenes and found that among them the self-assembling architecture of amphiphilic sulfonatocalix[8]arene (SC8A12C) had the most potent ability to suppress neuroinflammation in vitro and in vivo. Moreover, SC8A12C assemblies were internalized into microglia through macropinocytosis. In addition, after applying the SC8A12C assemblies to the exposed brain tissue, we observed that SC8A12C assemblies penetrated into the brain parenchyma and eliminated the inflammatory factor storm, thereby restoring neurobiological functions in a mouse model of traumatic brain injury.

[Experimental study of the response of articular cartilage surface roughness to load].

Cartilage surface fibrosis is an early sign of osteoarthritis and cartilage surface damage is closely related to load. The purpose of this study was to study the relationship between cartilage surface roughness and load. By applying impact, compression and fatigue loads on fresh porcine articular cartilage, the rough value of cartilage surface was measured at an interval of 10 min each time and the change rule of roughness before and after loading was obtained. It was found that the load increased the roughness of cartilage surface and the increased value was related to the load size. The time of roughness returning to the initial condition was related to the load type and the load size. The impact load had the greatest influence on the roughness of cartilage surface, followed by the severe fatigue load, compression load and mild fatigue load. This article provides reference data for revealing the pathogenesis of early osteoarthritis and preventing and treating articular cartilage diseases.

[Study on transport of small molecule rhodamine B within different layers of cartilage].

The small molecule nutrients and cell growth factors required for the normal metabolism of chondrocyte mainly transport into the cartilage through free diffusion. However, the specific mass transfer law in the cartilage remains to be studied. In this study, using small molecule rhodamine B as tracer, the mass transfer models of cartilage were built under different pathways including surface pathway, lateral pathway and composite pathway. Sections of cartilage at different mass transfer times were observed by using laser confocal microscopy and the transport law of small molecules within different layers of cartilage was studied. The results showed that rhodamine B diffused into the whole cartilage layer through surface pathway within 2 h. The fluorescence intensity in the whole cartilage layer increased with the increase of mass transfer time. Compared to mass transfer of 2 h, the mean fluorescence intensity in the superficial, middle, and deep layers of cartilage increased by 1.83, 1.95, and 3.64 times, respectively, after 24 h of mass transfer. Under lateral path condition, rhodamine B was transported along the cartilage width, and the molecular transport distance increased with increasing mass transfer time. It is noted that rhodamine B could be transported to 2 mm away from cartilage side after 24 h of mass transfer. The effect of mass transfer under the composite path was better than those under the surface path and the lateral path, and especially the mass transfer in the deep layer of cartilage was improved. This study may provide a reference for the treatment and repair of cartilage injury.

[Development of a culture chamber for mechanical loading of adherent cells with large uniform strain].

Based on the current study of the influence of mechanical factors on cell behavior which relies heavily on experiments in vivo, a culture chamber with a large uniform strain area containing a linear motor-powered, up-to-20-Hz cell stretch loading device was developed to exert mechanical effects on cells. In this paper, using the strain uniformity as the target and the substrate thickness as the variable, the substrate bottom of the conventional incubation chamber is optimized by using finite element technique, and finally a new three-dimensional model of the incubation chamber with "M" type structure in the section is constructed, and the distribution of strain and displacement fields are detected by 3D-DIC to verify the numerical simulation results. The experimental results showed that the new cell culture chamber increased the accuracy and homogeneous area of strain loading by 49.13% to 52.45% compared with that before optimization. In addition, the morphological changes of tongue squamous carcinoma cells under the same strain and different loading times were initially studied using this novel culture chamber. In conclusion, the novel cell culture chamber constructed in this paper combines the advantages of previous techniques to deliver uniform and accurate strains for a wide range of cell mechanobiology studies.

Developmentally regulated activation of defense allows for rapid inhibition of infection in age-related resistance to Phytophthora capsici in cucumber fruit.

BACKGROUND: Age-related resistance (ARR) is a developmentally regulated phenomenon conferring resistance to pathogens or pests. Although ARR has been observed in several host-pathogen systems, the underlying mechanisms are largely uncharacterized. In cucumber, rapidly growing fruit are highly susceptible to Phytophthora capsici but become resistant as they complete exponential growth. We previously demonstrated that ARR is associated with the fruit peel and identified gene expression and metabolomic changes potentially functioning as preformed defenses. RESULTS: Here, we compare the response to infection in fruit at resistant and susceptible ages using microscopy, quantitative bioassays, and weighted gene co-expression analyses. We observed strong transcriptional changes unique to resistant aged fruit 2-4 h post inoculation (hpi). Microscopy and bioassays confirmed this early response, with evidence of pathogen death and infection failure as early as 4 hpi and cessation of pathogen growth by 8-10 hpi. Expression analyses identified candidate genes involved in conferring the rapid response including those encoding transcription factors, hormone signaling pathways, and defenses such as reactive oxygen species metabolism and phenylpropanoid biosynthesis. CONCLUSION: The early pathogen death and rapid defense response in resistant-aged fruit provide insight into potential mechanisms for ARR, implicating both pre-formed biochemical defenses and developmentally regulated capacity for pathogen recognition as key factors shaping age-related resistance.

Depth-dependent ratcheting strains of young and adult articular cartilages by experiments and predictions.

BACKGROUND: Ratcheting strain is produced due to the repeated accumulation of compressive strain in cartilage and may be a precursor to osteoarthritis. The aim of this study was to investigate the ratcheting behaviors of young and adult articular cartilages under cyclic compression by experiments and theoretical predictions. METHODS: A series of uniaxial cyclic compression tests were conducted for young and adult cartilage, and the effects of different loading conditions on their ratcheting behaviors were probed. A theoretical ratcheting model was constructed and applied to predict the ratcheting strains of young and adult cartilages with different loading conditions. RESULTS: Ratcheting strains of young and adult cartilages rapidly increased at the initial stage, followed by a slower increase in subsequent stages. The strain accumulation value and its rate for young cartilage were greater than them for adult cartilage. The ratcheting strains of the two groups of cartilage samples decreased with increasing stress rate, while they increased with increasing stress amplitude. As the stress amplitude increased, the gap between the ratcheting strains of young and adult cartilages increased gradually. The ratcheting strains of young and adult cartilages decreased along the cartilage depth from the surface to the deep layer. The ratcheting strains of different layers increased with the compressive cycle, and the difference among the three layers was noticeable. Additionally, the theoretical predictions agreed with the experimental data. CONCLUSIONS: Overall, the ratcheting behavior of articular cartilage is affected by the degree of articular cartilage maturation.

[Experiments study on mechanical behavior of porcine lumbar intervertebral disc after nucleotomy under compression].

In order to study the mechanical behavior of degeneration and nucleotomy of lumbar intervertebral disc, compression experiments with porcine lumbar intervertebral discs were carried out. The lumbar intervertebral discs with trypsin-treated and nucleus nucleotomy served as the experimental group and the normal discs as the control group. Considering the effects of load magnitude and loading rate, the relationship between stress and strain, instantaneous elastic modulus and creep property of intervertebral disc were obtained. The creep constitutive model was established. The results show that the strain and creep strain of the experimental group increase significantly with the increase of compression load and loading rate, whereas the instantaneous elastic modulus decreases obviously, compared with the control group. It indicates that the effect of load magnitude and loading rate on load-bearing capacity of intervertebral disc after nucleotomy is larger obviously than that of normal disc. The creep behavior of the experimental group can be still predicted by the Kelvin three-parameter solid model. The results will provide theoretical foundation for clinical treatment and postoperative rehabilitation of intervertebral disc disease.

[Analysis of the stress state in articular cartilage defect repairing area].

Based on transversely isotropic theory, a finite element model for three-dimensional solid-liquid coupling defect repair of articular cartilage was established. By studying stress state of host cartilage near the restoration interface, we identified deformation type of cartilage and discussed the cause of restoration interface cracking. The results showed that the host cartilage surface node near the restoration interface underwent compression deformation in the condition of surface layer defect repair. When the middle layer, deep layer or full-thickness defect were repaired, the node underwent tensile deformation. At this point, the radial dimension of cartilage increased, which might cause restoration interface cracking. If elastic modulus of the tissue engineered cartilage (TEC) was lower (0.1 MPa, 0.3 MPa), the host cartilage surface layer and middle layer mainly underwent tensile deformation. While elastic modulus of TEC was higher (0.6 MPa, 0.9 MPa), each layer of host cartilage underwent compression deformation. Therefore, the elastic modulus of TEC could be increased properly for full-thickness defect repair. This article provides a new idea for evaluating the effect of cartilage tissue engineering repair, and has a certain guiding significance for clinical practice.

[Study on the effect of artificial cartilage with different elastic modulus on the mechanical environment of the chondrocyte in defect cartilage repaired area].

A solid-liquid two-phase finite element model of articular cartilage and a microscopic finite element model of chondrocytes were established using the finite element software COMSOL in this study. The purpose of the study is to investigate the mechanics environment and the liquid flow field of the host cartilage chondrocytes in each layer by multi-scale method, under physiological load, with the different elastic modulus of artificial cartilage to repair cartilage defect. The simulation results showed that the uniform elastic modulus of artificial cartilage had different influences on the microenvironment of different layer chondrocytes. With the increase of the elastic modulus of artificial cartilage, the stress of the shallow surface layer and the intermediate layer chondrocytes increased and the stress of deep layer chondrocytes decreased. The flow field direction of the middle layer and the bottom layer of cartilage can also be changed by artificial cartilage implantation, as well as the ways of nourishment supply of the middle layer and underlying chondrocytes change.A barrier to underlying chondrocytes nutrition supply may be caused by this, thus resulting in the uncertainty of the repair results. With cross-scale finite element model simulation analysis of chondrocytes, we can quantitatively evaluate the mechanical environment of chondrocytes in each layer of the host cartilage. It is helpful to assess the clinical effect of cartilage defect reparation more accurately.

Switchable Hydrolase Based on Reversible Formation of Supramolecular Catalytic Site Using a Self-Assembling Peptide.

The reversible regulation of catalytic activity is a feature found in natural enzymes which is not commonly observed in artificial catalytic systems. Here, we fabricate an artificial hydrolase with pH-switchable activity, achieved by introducing a catalytic histidine residue at the terminus of a pH-responsive peptide. The peptide exhibits a conformational transition from random coil to ß-sheet by changing the pH from acidic to alkaline. The ß-sheet self-assembles to form long fibrils with the hydrophobic edge and histidine residues extending in an ordered array as the catalytic microenvironment, which shows significant esterase activity. Catalytic activity can be reversible switched by pH-induced assembly/disassembly of the fibrils into random coils. At higher concentrations, the peptide forms a hydrogel which is also catalytically active and maintains its reversible (de-)activation.

Zinc Oxide Nanoparticles as Adjuvant To Facilitate Doxorubicin Intracellular Accumulation and Visualize pH-Responsive Release for Overcoming Drug Resistance.

Multidrug resistance (MDR) of cancer is a challenge to effective chemotherapeutic interventions. The stimulus-responsive drug delivery system (DDS) based on nanotechnology provides a promising approach to overcome MDR. Through the development of a doxorubicin delivery system based on zinc oxide nanomaterials, we have demonstrated that MDR in breast cancer cell line can be significantly circumvented by a combination of efficient cellular uptake and a pH-triggered rapid drug release due to degradation of nanocarriers in acidic environment. Doxorubicin and zinc oxide nanoparticles, compared with free doxorubicin, effectively enhanced the intracellular drug concentration by simultaneously increasing cell uptake and decreasing cell efflux in MDR cancer cells. The acidic environment-triggered release of drug can be tracked real-time by the doxorubicin fluorescence recovery from its quenched state. Therefore, with the combination of therapeutic potential and the capacity to track release of drug in cancer cells, our system holds great potential in nanomedicine by serving dual roles of overcoming drug resistance and tracking intracellular drug release from the DDS.