Publications by authors named "Tian Jian Lu"

92 Publications

Evaporation-Induced Diffusion Acceleration in Liquid-Filled Porous Materials.

ACS Omega 2021 Aug 11;6(33):21646-21654. Epub 2021 Aug 11.

The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, P. R. China.

Liquid-filled porous materials exist widely in nature and engineering fields, with the diffusion of substances in them playing an important role in system functions. Although surface evaporation is often inevitable in practical scenarios, the evaporation effects on diffusion behavior in liquid-filled porous materials have not been well explored yet. In this work, we performed noninvasive diffusion imaging experiments to observe the diffusion process of erioglaucine disodium salt dye in a liquid-filled nitrocellulose membrane under a wide range of relative humidities (RHs). We found that evaporation can significantly accelerate the diffusion rate and alter concentration distribution compared with the case without evaporation. We explained the accelerated diffusion phenomenon by the mechanism that evaporation would induce a weak flow in liquid-filled porous materials, which leads to convective diffusion, , evaporation-induced flow and diffusion (EIFD). Based on the EIFD mechanism, we proposed a convective diffusion model to quantitatively predict the diffusion process in liquid-filled porous materials under evaporation and experimentally validated the model. Introducing the dimensionless Peclet ( ) number to measure the relative contribution of the evaporation effect to pure molecular diffusion, we demonstrated that even at a high RH of 95%, where the evaporation effect is usually assumed negligible in common sense, the evaporation-induced diffusion still overwhelms the molecular diffusion. The flow velocity induced by evaporation in liquid-filled porous materials was found to be 0.4-5 μm/s, comparable to flow in many biological and biomedical systems. The present analysis may help to explain the driving mechanism of tissue perfusion and provide quantitative analysis or inspire new control methods of flow and material exchange in numerous cutting-edge technologies, such as paper-based diagnostics, hydrogel-based flexible electronics, evaporation-induced electricity generation, and seawater purification.
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http://dx.doi.org/10.1021/acsomega.1c03052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8388088PMC
August 2021

A new model of myofibroblast-cardiomyocyte interactions and their differences across species.

Biophys J 2021 Sep 17;120(17):3764-3775. Epub 2021 Jul 17.

Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an, P.R. China; Bioinspired Engineering and Biomechanics Center, Xi'an Jiaotong University, Xi'an, P.R. China. Electronic address:

Although coupling between cardiomyocytes and myofibroblasts is well known to affect the physiology and pathophysiology of cardiac tissues across species, relating these observations to humans is challenging because the effect of this coupling varies across species and because the sources of these effects are not known. To identify the sources of cross-species variation, we built upon previous mathematical models of myofibroblast electrophysiology and developed a mechanoelectrical model of cardiomyocyte-myofibroblast interactions as mediated by electrotonic coupling and transforming growth factor-β1. The model, as verified by experimental data from the literature, predicted that both electrotonic coupling and transforming growth factor-β1 interaction between myocytes and myofibroblast prolonged action potential in rat myocytes but shortened action potential in human myocytes. This variance could be explained by differences in the transient outward K current associated with differential Kv4.2 gene expression across species. Results are useful for efforts to extrapolate the results of animal models to the predicted effects in humans and point to potential therapeutic targets for fibrotic cardiomyopathy.
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http://dx.doi.org/10.1016/j.bpj.2021.06.040DOI Listing
September 2021

Anomalous Loss of Stiffness with Increasing Reinforcement in a Photo-Activated Nanocomposite.

Macromol Rapid Commun 2021 Jul 29;42(14):e2100147. Epub 2021 May 29.

The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, P. R. China.

Hydrogels are commonly doped with stiff nanoscale fillers to endow them with the strength and stiffness needed for engineering applications. Although structure-property relations for many polymer matrix nanocomposites are well established, modeling the new generation of hydrogel nanocomposites requires the study of processing-structure-property relationships because subtle differences in chemical kinetics during their synthesis can cause nearly identical hydrogels to have dramatically different mechanical properties. The authors therefore assembled a framework to relate synthesis conditions (including hydrogel and nanofiller mechanical properties and light absorbance) to gelation kinetics and mechanical properties. They validated the model against experiments on a graphene oxide (GO) doped oligo (ethylene glycol) diacrylate (OEGDA), a system in which, in apparent violation of laws from continuum mechanics, doping can reduce rather than increase the stiffness of the resulting hydrogel nanocomposites. Both model and experiment showed a key role light absorbance-dominated gelation kinetics in determining nanocomposite mechanical properties in conjunction with nanofiller reinforcement, with the nanofiller's attenuation of chemical kinetics sometimes outweighing stiffening effects to explain the observed, anomalous loss of stiffness. By bridging the chemical kinetics and mechanics of nanocomposite hydrogels, the authors' modeling framework shows promise for broad applicability to design of hydrogel nanocomposites.
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http://dx.doi.org/10.1002/marc.202100147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298289PMC
July 2021

Janus Vitrification of Droplet via Cold Leidenfrost Phenomenon.

Small 2021 04 11;17(17):e2007325. Epub 2021 Mar 11.

Bioinspired Engineering and Biomechanics Center (BEBC), MOE Key Laboratory of Biomedical Information Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, P. R. China.

Janus particles with asymmetric crystals show great importance in optoelectronics and photocatalysis, but their synthesis usually requires complicated procedures. Here, an unexpected Janus vitrification phenomenon is observed in a droplet caused by the Leidenfrost effect at a cryogenic temperature, which is commonly regarded as symmetric. The Leidenfrost phenomenon levitates the droplet when it comes in contact with liquid nitrogen causing different cooling conditions on the droplet's top and bottom surfaces. It induces asymmetric crystallization in the droplet, forming a Janus vitrified particle with an asymmetric crystallization borderline after cooling, as further evidenced by cryotransmission electron microscopy (cryo-TEM) experiments. Theoretical analysis and experimental study indicate that the position of the asymmetric crystallization borderline is determined by the droplet radius and density, and the observation window of asymmetric crystallization borderline is determined by the chemical concentration. The finding reveals the asymmetric crystallization phenomenon in droplet vitrification for the first time, and provides a new insight for creating Janus particles through the Leidenfrost phenomenon.
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http://dx.doi.org/10.1002/smll.202007325DOI Listing
April 2021

The Plasticity of Nanofibrous Matrix Regulates Fibroblast Activation in Fibrosis.

Adv Healthc Mater 2021 04 29;10(8):e2001856. Epub 2021 Jan 29.

The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, P. R. China.

Natural extracellular matrix (ECM) mostly has a fibrous structure that supports and mechanically interacts with local residing cells to guide their behaviors. The effect of ECM elasticity on cell behaviors has been extensively investigated, while less attention has been paid to the effect of matrix fiber-network plasticity at microscale, although plastic remodeling of fibrous matrix is a common phenomenon in fibrosis. Here, a significant decrease is found in plasticity of native fibrotic tissues, which is associated with an increase in matrix crosslinking. To explore the role of plasticity in fibrosis development, a set of 3D collagen nanofibrous matrix with constant modulus but tunable plasticity is constructed by adjusting the crosslinking degree. Using plasticity-controlled 3D culture models, it is demonstrated that the decrease of matrix plasticity promotes fibroblast activation and spreading. Further, a coarse-grained molecular dynamic model is developed to simulate the cell-matrix interaction at microscale. Combining with molecular experiments, it is revealed that the enhanced fibroblast activation is mediated through cytoskeletal tension and nuclear translocation of Yes-associated protein. Taken together, the results clarify the effects of crosslinking-induced plasticity changes of nanofibrous matrix on the development of fibrotic diseases and highlight plasticity as an important mechanical cue in understanding cell-matrix interactions.
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http://dx.doi.org/10.1002/adhm.202001856DOI Listing
April 2021

Bending Response of 3D-Printed Titanium Alloy Sandwich Panels with Corrugated Channel Cores.

Materials (Basel) 2021 Jan 24;14(3). Epub 2021 Jan 24.

State Key Laboratory of Mechanics and Control of Mechanical Structures, Nanjing University of Aeronautics and Astronautics, Nanjing 210016, China.

Ultralight sandwich constructions with corrugated channel cores (i.e., periodic fluid-through wavy passages) are envisioned to possess multifunctional attributes: simultaneous load-carrying and heat dissipation via active cooling. Titanium alloy (Ti-6Al-4V) corrugated-channel-cored sandwich panels (3CSPs) with thin face sheets and core webs were fabricated via the technique of selective laser melting (SLM) for enhanced shear resistance relative to other fabrication processes such as vacuum brazing. Four-point bending responses of as-fabricated 3CSP specimens, including bending resistance and initial collapse modes, were experimentally measured. The bending characteristics of the 3CSP structure were further explored using a combined approach of analytical modeling and numerical simulation based on the method of finite elements (FE). Both the analytical and numerical predictions were validated against experimental measurements. Collapse mechanism maps of the 3CSP structure were subsequently constructed using the analytical model, with four collapse modes considered (face-sheet yielding, face-sheet buckling, core yielding, and core buckling), which were used to evaluate how its structural geometry affects its collapse initiation mode.
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http://dx.doi.org/10.3390/ma14030556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865806PMC
January 2021

Characterizing poroelasticity of biological tissues by spherical indentation: an improved theory for large relaxation.

J Mech Phys Solids 2020 May 3;138. Epub 2020 Mar 3.

The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Shaanxi, 710049, P.R. China.

Flow of fluids within biological tissues often meets with resistance that causes a rate- and size-dependent material behavior known as poroelasticity. Characterizing poroelasticity can provide insight into a broad range of physiological functions, and is done qualitatively in the clinic by palpation. Indentation has been widely used for characterizing poroelasticity of soft materials, where quantitative interpretation of indentation requires a model of the underlying physics, and such existing models are well established for cases of small strain and modest force relaxation. We showed here that existing models are inadequate for large relaxation, where the force on the indenter at a prescribed depth at long-time scale drops to below half of the initially peak force (, (0)/() > 2). We developed an indentation theory for such cases of large relaxation, based on Biot theory and a generalized Hertz contact model. We demonstrated that our proposed theory is suitable for biological tissues (, spleen, kidney, skin and human cirrhosis liver) with both small and large relaxations. The proposed method would be a powerful tool to characterize poroelastic properties of biological materials for various applications such as pathological study and disease diagnosis.
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http://dx.doi.org/10.1016/j.jmps.2020.103920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595329PMC
May 2020

Spatiotemporally Controlled Photoresponsive Hydrogels: Design and Predictive Modeling from Processing through Application.

Adv Funct Mater 2020 Aug 18;30(32):2000639. Epub 2020 Jun 18.

The Key Laboratory of Biomedical Information Engineering of Ministry of Education School of Life Science and Technology Xi'an Jiaotong University Xi'an 710049 P. R. China.

Photoresponsive hydrogels (PRHs) are soft materials whose mechanical and chemical properties can be tuned spatially and temporally with relative ease. Both photo-crosslinkable and photodegradable hydrogels find utility in a range of biomedical applications that require tissue-like properties or programmable responses. Progress in engineering with PRHs is facilitated by the development of theoretical tools that enable optimization of their photochemistry, polymer matrices, nanofillers, and architecture. This review brings together models and design principles that enable key applications of PRHs in tissue engineering, drug delivery, and soft robotics, and highlights ongoing challenges in both modeling and application.
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http://dx.doi.org/10.1002/adfm.202000639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418561PMC
August 2020

Sound absorption theory for micro-perforated panel with petal-shaped perforations.

J Acoust Soc Am 2020 Jul;148(1):18

State Key Laboratory of Mechanics and Control of Mechanical Structures, Nanjing University of Aeronautics and Astronautics, Nanjing 210016, People's Republic of China.

Micro-perforated panel (MPP) absorbers with circular perforations are used in many noise control applications due to their attractive wide-brand sound absorption performance. Different from a common MPP with circular perforations, a unique type of MPP absorber with petal-shaped perforations is proposed. The sound absorption theory for the MPP with petal-shaped perforations is developed by accurately considering the fluid velocity in the petal-shaped perforation hole. This theory can account for the effect of altered perforation morphology (from circular to petal) on sound absorption. Finite element simulations are performed to validate the proposed theory, with good agreement achieved. The sound absorption of MPP with petal-shaped perforations is compared with that of the traditional MPP with the same porosity. It is demonstrated that the change in hole shape significantly modifies the fluid velocity field and the flow resistivity in/of the hole, and hence the sound absorption of the proposed MPP with petal-shaped perforations can outperform that of the traditional MPP in the considered case. This work proposes a general MPP theory that not only contains the classical Maa's theory for circular MPP, but also accounts for the MPP with petal-shaped perforations.
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http://dx.doi.org/10.1121/10.0001462DOI Listing
July 2020

The acoustic radiation force of a focused ultrasound beam on a suspended eukaryotic cell.

Ultrasonics 2020 Dec 18;108:106205. Epub 2020 Jun 18.

State Key Laboratory of Mechanics and Control of Mechanical Structures, Nanjing University of Aeronautics and Astronautics, Nanjing 210016, PR China; Nanjing Center for Multifunctional Lightweight Materials and Structures (MLMS), Nanjing University of Aeronautics and Astronautics, Nanjing 210016, PR China. Electronic address:

Although ultrasound tools for manipulating and permeabilizing suspended cells have been available for nearly a century, accurate prediction of the distribution of acoustic radiation force (ARF) continues to be a challenge. We therefore developed an analytical model of the acoustic radiation force (ARF) generated by a focused Gaussian ultrasound beam incident on a eukaryotic cell immersed in an ideal fluid. The model had three layers corresponding to the nucleus, cytoplasm, and membrane, of a eukaryotic cell. We derived an exact expression for the ARF in relation to the geometrical and acoustic parameters of the model cell components. The mechanics of the cell membrane and nucleus, the relative width of the Gaussian beam, the size, position and aspect ratio of the cell had significant influence on the ARF. The model provides a theoretical basis for improved acoustic control of cell trapping, cell sorting, cell assembly, and drug delivery.
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http://dx.doi.org/10.1016/j.ultras.2020.106205DOI Listing
December 2020

Vibration of a liquid-filled capillary tube.

J Mech Behav Biomed Mater 2020 06 26;106:103745. Epub 2020 Mar 26.

State Key Laboratory of Mechanics and Control of Mechanical Structures, Nanjing University of Aeronautics and Astronautics, Nanjing, 210016, PR China; State Key Laboratory for Strength and Vibration of Mechanical Structures, School of Aerospace, Xi'an Jiaotong University, Xi'an, 710049, PR China. Electronic address:

Liquid-filled capillary tubes are common structures in nature and engineering fields, which often function via vibration. Although liquid-solid interfacial tension plays important roles in the vibration behavior of the liquid-filled capillary tube, it remains elusive how the interfacial tension influences the natural frequency of capillary tube vibration. To address this, we developed a theory of beam-string structure to analyze the influence of liquid-solid interfacial tension on the vibration of a liquid-filled capillary cantilever. We used glass capillary tubes as a demo and experimentally validated the theory, where the reduced liquid-solid interfacial tension in a capillary tube decreases the natural frequencies of small-order modes. We then performed theoretical analysis and found that the change of elastocapillarity number, slenderness ratio and inner/outer radius ratio of capillary tubes enables: in higher order modes, a nonmonotonic change of natural frequency due to mode transformation between a beam and string; for lower order modes, decrease in the natural frequency to zero (increase from zero) due to mode disappearance (appearance). The developed theory would provide guidelines for high-accuracy design of capillary sensors.
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http://dx.doi.org/10.1016/j.jmbbm.2020.103745DOI Listing
June 2020

Nanoscale integrin cluster dynamics controls cellular mechanosensing via FAKY397 phosphorylation.

Sci Adv 2020 03 4;6(10):eaax1909. Epub 2020 Mar 4.

The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, P.R. China.

Transduction of extracellular matrix mechanics affects cell migration, proliferation, and differentiation. While this mechanotransduction is known to depend on the regulation of focal adhesion kinase phosphorylation on Y397 (FAKpY397), the mechanism remains elusive. To address this, we developed a mathematical model to test the hypothesis that FAKpY397-based mechanosensing arises from the dynamics of nanoscale integrin clustering, stiffness-dependent disassembly of integrin clusters, and FAKY397 phosphorylation within integrin clusters. Modeling results predicted that integrin clustering dynamics governs how cells convert substrate stiffness to FAKpY397, and hence governs how different cell types transduce mechanical signals. Existing experiments on MDCK cells and HT1080 cells, as well as our new experiments on 3T3 fibroblasts, confirmed our predictions and supported our model. Our results suggest a new pathway by which integrin clusters enable cells to calibrate responses to their mechanical microenvironment.
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http://dx.doi.org/10.1126/sciadv.aax1909DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7056303PMC
March 2020

Translation of a Coated Rigid Spherical Inclusion in an Elastic Matrix: Exact Solution, and Implications for Mechanobiology.

J Appl Mech 2019 May 5;86(5):0510021-5100210. Epub 2019 Mar 5.

State Key Laboratory for Strength and Vibration of Mechanical Structures, Xi'an Jiaotong University, Xi'an 710049, China.

The displacement of relatively rigid beads within a relatively compliant, elastic matrix can be used to measure the mechanical properties of the matrix. For example, in mechanobiological studies, magnetic or reflective beads can be displaced with a known external force to estimate the matrix modulus. Although such beads are generally rigid compared to the matrix, the material surrounding the beads typically differs from the matrix in one or two ways. The first case, as is common in mechanobiological experimentation, is the situation in which the bead must be coated with materials such as protein ligands that enable adhesion to the matrix. These layers typically differ in stiffness relative to the matrix material. The second case, common for uncoated beads, is the situation in which the beads disrupt the structure of the hydrogel or polymer, leading to a region of enhanced or reduced stiffness in the neighborhood of the bead. To address both cases, we developed the first analytical solution of the problem of translation of a coated, rigid spherical inclusion displaced within an isotropic elastic matrix by a remotely applied force. The solution is applicable to cases of arbitrary coating stiffness and size of the coating. We conclude by discussing applications of the solution to mechanobiology.
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http://dx.doi.org/10.1115/1.4042575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6871264PMC
May 2019

Microfluidic Printing of Three-Dimensional Graphene Electroactive Microfibrous Scaffolds.

ACS Appl Mater Interfaces 2020 Jan 3;12(2):2049-2058. Epub 2020 Jan 3.

State Key Laboratory of Mechanics and Control of Mechanical Structures , Nanjing University of Aeronautics and Astronautics , Nanjing 210016 , P. R. China.

Graphene materials have attracted special attention because of their electrical conductivity, mechanical properties, and favorable biocompatibility. Although various methods have been developed for fabricating micro/nano conductive fibrous scaffolds, it is still challenging to fabricate the three-dimensional (3D) graphene fibrous scaffolds. Herein, we developed a new method, termed as microfluidic 3D printing technology (M3DP), to fabricate 3D graphene oxide (GO) microfibrous scaffolds with an adjustable fiber length, fiber diameter, and scaffold structure by integrating the microfluidic spinning technology with a programmable 3D printing system. GO microfibrous scaffolds were then transformed into conductive reduced graphene oxide (rGO) microfibrous scaffolds by hydrothermal reduction. Our results demonstrated that the fabricated 3D fibrous graphene scaffolds exhibited tunable structures, maneuverable mechanical properties, and good electrical conductivity and biocompatibility, as reflected by the adhesion and proliferation of SH-SY5Y cells on the graphene microfibrous scaffolds in an obviously oriented manner. The developed M3DP would be a powerful tool for fabricating 3D graphene microfibrous scaffolds for electroactive tissue regeneration and drug-screening applications.
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http://dx.doi.org/10.1021/acsami.9b17948DOI Listing
January 2020

Regulation of Cell Behavior by Hydrostatic Pressure.

Appl Mech Rev 2019 Jul 23;71(4):0408031-4080313. Epub 2019 Jul 23.

The Key Laboratory of Biomedical InformationEngineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.

Hydrostatic pressure (HP) regulates diverse cell behaviors including differentiation, migration, apoptosis, and proliferation. Abnormal HP is associated with pathologies including glaucoma and hypertensive fibrotic remodeling. In this review, recent advances in quantifying and predicting how cells respond to HP across several tissue systems are presented, including tissues of the brain, eye, vasculature and bladder, as well as articular cartilage. Finally, some promising directions on the study of cell behaviors regulated by HP are proposed.
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http://dx.doi.org/10.1115/1.4043947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6808007PMC
July 2019

A mechanoelectrical coupling model of neurons under stretching.

J Mech Behav Biomed Mater 2019 05 5;93:213-221. Epub 2019 Feb 5.

The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, PR China; Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an 710049, PR China. Electronic address:

Neurons are situated in a microenvironment composed of various mechanical cues, where stretching is thought to have a major impact on neurons, resulting in microstructural changes in neural tissue and further leading to abnormal electrophysiological function. In spite of significant experimental efforts, the underlying mechanism remains elusive, more works are needed to provide a detailed description of the process that leads to the observed phenomena. Here, we developed a mechanoelectrical coupling model of central neurons under stretching and specially considered the plastic deformation of neurons. With the model, we showed that the increasing axial strain induces a decreased membrane action potential and a more frequent neuronal firing, which agree well with experimental observations reported in the literature. The simulation results also showed a faster electrophysiological signal conduction. Our model provides a reference for the prediction and regulation of neuronal function under simplified conditions of mechanical loadings.
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http://dx.doi.org/10.1016/j.jmbbm.2019.02.007DOI Listing
May 2019

Modulation of acoustomechanical instability and bifurcation behavior of soft materials.

Sci Rep 2018 Nov 9;8(1):16661. Epub 2018 Nov 9.

State Key Laboratory for Strength and Vibration of Mechanical Structures, Xi'an Jiaotong University, Xi'an, 710049, P. R. China.

We demonstrate acoustically triggered giant deformation of soft materials, and reveal the snap-through instability and bifurcation behavior of soft materials in nonlinear deformation regime in response to combined loading of mechanical and acoustic radiation forces. Our theoretical results suggest that acoustomechanical instability and bifurcation can be readily modulated by varying either the mechanical or acoustic force. This modulation functionality arises from the sensitivity of acoustic wave propagation to nonlinear deformation of soft material, particularly to ratio of initial geometrical size of soft material to acoustic wavelength in the material. The tunable acoustomechanical instability and bifurcation behavior of soft materials enables innovative design of programmable mechanical metamaterials. PACS numbers: 43.35.+d, 43.25.+y, 46.70.De, 61.41.+e.
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http://dx.doi.org/10.1038/s41598-018-34971-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6226430PMC
November 2018

[The Development of Huaxi Intelligent Endoscopic Skill Training and Assessment System].

Sichuan Da Xue Xue Bao Yi Xue Ban 2018 Sep;49(5):776-780

Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.

Objective: To develop a novel objective standardized endoscopic skill training and assessment system based on artificial intelligence technology.

Methods: By designing five basic skill parts of endoscopic operation including vision location, clamping, delivering, shearing and suturing, we achieved objective standardized indexes which gained automatically with image recognition and refined perception.

Results: With Huaxi intelligent endoscopic skill training system, the accurate rates of vision location, clamping, delivering, shearing and suturing were 90%, 95%, 99%, 90%, and 89%, respectively. The response and performance time were 8-10 s, <1 s, <1 s, 1-3 s, and <1 s, respectively.

Conclusion: Huaxi intelligent endoscopic skill training and assessment system has preliminarily possessed the capability to assess the endoscopic skills of surgeons objectively.
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September 2018

Acousto-thermo-mechanical deformation of hydrogels coupled with chemical diffusion.

Proc Math Phys Eng Sci 2018 Sep 12;474(2217):20180293. Epub 2018 Sep 12.

State Key Laboratory for Strength and Vibration of Mechanical Structures, Xi'an Jiaotong University, Xi'an 710049, People's Republic of China.

We develop an acousto-thermo-mechanical theory for nonlinear (large) deformation of temperature-sensitive hydrogels subjected to temperature and ultrasonic inputs, with diffusion mass transport driven by osmotic pressure accounted for. On the basis of the strain energy due to network stretching, the mixing energy of polymers and small molecules, the Cauchy stress of the deformed hydrogel can be obtained. The acoustic radiation stress generated by the ultrasonic inputs is incorporated into the Cauchy stress to give the constitutive equations of the acousto-thermal-mechanical hydrogel. The mixing energy contains an interaction parameter as a function of temperature and polymer concentration so that hydrogel deformation is temperature dependent. By employing the incompressible condition of polymers and molecules, both the temperature and acoustic radiation stress contribute to osmotic pressure, inducing hydrogel swelling (or shrinking). Specifically, for a temperature-sensitive hydrogel layer immersed in solvent, its acoustic-triggered large deformation is comprehensively analysed under different boundary conditions (e.g. free swelling, uniaxial constraint and biaxial constraint).
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http://dx.doi.org/10.1098/rspa.2018.0293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6189592PMC
September 2018

Heterostructured Silk-Nanofiber-Reduced Graphene Oxide Composite Scaffold for SH-SY5Y Cell Alignment and Differentiation.

ACS Appl Mater Interfaces 2018 Nov 3;10(45):39228-39237. Epub 2018 Oct 3.

The Key Laboratory of Biomedical Information Engineering of Ministry of Education , Xi'an Jiaotong University , Xi'an 710049 , P.R. China.

Stem cell therapy is promising for treating traumatic injuries of the central nervous system, where a major challenge is to effectively differentiate neural stem cells into neurons with uniaxial alignment. Recently, controlling stem cell fate by modulating biophysical cues (e.g., stiffness, conductivity, and patterns) has emerged as an attractive approach. Herein, we report a new heterostructure composite scaffold to induce cell-oriented growth and enhance the neuronal differentiation of SH-SY5Y cells. The scaffold is composed of aligned electrospinning silk nanofibers coated on reduced graphene paper with high conductivity and good biocompatibility. Our experimental results demonstrate that the composite scaffold can effectively induce the oriented growth and enhance neuronal differentiation of SH-SY5Y cells. Our study develops a novel scaffold for enhancing the differentiation of SH-SY5Y cells into neurons, which holds great potential in the treatment of neurological diseases and injuries.
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http://dx.doi.org/10.1021/acsami.8b12562DOI Listing
November 2018

The protective effects of acupoint gel embedding on rats with myocardial ischemia-reperfusion injury.

Life Sci 2018 Oct 5;211:51-62. Epub 2018 Sep 5.

MOE Key Laboratory of Biomedical Information Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, PR China; Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an 710049, PR China. Electronic address:

Aims: Prevention and treatment of myocardial ischemia-reperfusion (I/R) injury has for many years been a hot topic in treating ischemic heart disease. As one of the most well-known methods of complementary and alternative medicine, acupuncture has attracted increasing interest in preventing myocardial I/R injury due to its remarkable effectiveness and minimal side effect. However, traditional acupuncture approaches are limited by cumbersome execution, high labor costs and inevitable pain caused by frequent stimulation. Therefore, in this work, we aimed to develop a novel acupoint gel embedding approach and investigated its role in protecting against myocardial I/R injury in rats.

Main Methods: Gels were embedded at bilateral Neiguan (PC6) points of rats and their protective effects against myocardial I/R injury evaluated in terms of changes in histomorphology, myocardial enzymology, antioxidant capacity, anti-inflammatory response, and anti-apoptosis of cells.

Key Findings: We found that the approach of acupoint gel embedding could significantly reduce myocardial infarcted size, repair pathological changes, mitigate oxidative stress damage and inflammatory response, as well as inhibit apoptosis of cardiomyocytes. Such cardioprotective effects were found to be associated with Notch-1/Jagged-1 signaling pathway.

Significance: The proposed approach of acupoint gel embedding has advantages in continuous acupoint stimulation, dosing controls, and no side effects in the course of treatment, as well as in reducing the pain caused by frequent acupuncture. It can form an alternative therapy to not only protect against myocardial I/R injury but also hold great potential in treating other diseases in the future.
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http://dx.doi.org/10.1016/j.lfs.2018.09.010DOI Listing
October 2018

The relationship between thiol-acrylate photopolymerization kinetics and hydrogel mechanics: An improved model incorporating photobleaching and thiol-Michael addition.

J Mech Behav Biomed Mater 2018 12 24;88:160-169. Epub 2018 Aug 24.

The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, PR China; Bioinspired Engineering & Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an 710049, PR China. Electronic address:

Biocompatible hydrogels with defined mechanical properties are critical to tissue engineering and regenerative medicine. Thiol-acrylate photopolymerized hydrogels have attracted special interest for their degradability and cytocompatibility, and for their tunable mechanical properties through controlling factors that affect reaction kinetics (e.g., photopolymerization, stoichiometry, temperature, and solvent choice). In this study, we hypothesized that the mechanical property of these hydrogels can be tuned by photoinitiators via photobleaching and by thiol-Michael addition reactions. To test this hypothesis, a multiscale mathematical model incorporating both photobleaching and thiol-Michael addition reactions was developed and validated. After validating the model, the effects of thiol concentration, light intensity, and pH values on hydrogel mechanics were investigated. Results revealed that hydrogel stiffness (i) was maximized at a light intensity-specific optimal concentration of thiol groups; (ii) increased with decreasing pH when synthesis occurred at low light intensity; and (iii) increased with decreasing light intensity when synthesis occurred at fixed precursor composition. The multiscale model revealed that the latter was due to higher initiation efficiency at lower light intensity. More broadly, the model provides a framework for predicting mechanical properties of hydrogels based upon the controllable kinetics of thiol-acrylate photopolymerization.
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http://dx.doi.org/10.1016/j.jmbbm.2018.08.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6392438PMC
December 2018

3D Spatiotemporal Mechanical Microenvironment: A Hydrogel-Based Platform for Guiding Stem Cell Fate.

Adv Mater 2018 Dec 31;30(49):e1705911. Epub 2018 Jul 31.

The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, P. R. China.

Stem cells hold great promise for widespread biomedical applications, for which stem cell fate needs to be well tailored. Besides biochemical cues, accumulating evidence has demonstrated that spatiotemporal biophysical cues (especially mechanical cues) imposed by cell microenvironments also critically impact on the stem cell fate. As such, various biomaterials, especially hydrogels due to their tunable physicochemical properties and advanced fabrication approaches, are developed to spatiotemporally manipulate biophysical cues in vitro so as to recapitulate the 3D mechanical microenvironment where stem cells reside in vivo. Here, the main mechanical cues that stem cells experience in their native microenvironment are summarized. Then, recent advances in the design of hydrogel materials with spatiotemporally tunable mechanical properties for engineering 3D the spatiotemporal mechanical microenvironment of stem cells are highlighted. These in vitro engineered spatiotemporal mechanical microenvironments are crucial for guiding stem cell fate and their potential biomedical applications are subsequently discussed. Finally, the challenges and future perspectives are presented.
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http://dx.doi.org/10.1002/adma.201705911DOI Listing
December 2018

Biofriendly, Stretchable, and Reusable Hydrogel Electronics as Wearable Force Sensors.

Small 2018 09 30;14(36):e1801711. Epub 2018 Jul 30.

The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, P. R. China.

The ever-growing overlap between stretchable electronic devices and wearable healthcare applications is igniting the discovery of novel biocompatible and skin-like materials for human-friendly stretchable electronics fabrication. Amongst all potential candidates, hydrogels with excellent biocompatibility and mechanical features close to human tissues are constituting a promising troop for realizing healthcare-oriented electronic functionalities. In this work, based on biocompatible and stretchable hydrogels, a simple paradigm to prototype stretchable electronics with an embedded three-dimensional (3D) helical conductive layout is proposed. Thanks to the 3D helical structure, the hydrogel electronics present satisfactory mechanical and electrical robustness under stretch. In addition, reusability of stretchable electronics is realized with the proposed scenario benefiting from the swelling property of hydrogel. Although losing water would induce structure shrinkage of the hydrogel network and further undermine the function of hydrogel in various applications, the worn-out hydrogel electronics can be reused by simply casting it in water. Through such a rehydration procedure, the dehydrated hydrogel can absorb water from the surrounding and then the hydrogel electronics can achieve resilience in mechanical stretchability and electronic functionality. Also, the ability to reflect pressure and strain changes has revealed the hydrogel electronics to be promising for advanced wearable sensing applications.
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http://dx.doi.org/10.1002/smll.201801711DOI Listing
September 2018

Ultrarapid Inductive Rewarming of Vitrified Biomaterials with Thin Metal Forms.

Ann Biomed Eng 2018 Nov 19;46(11):1857-1869. Epub 2018 Jun 19.

Department of Mechanical Engineering, University of Minnesota, 111 Church Street SE, Minneapolis, MN, 55455, USA.

Arteries with 1-mm thick walls can be successfully vitrified by loading cryoprotective agents (CPAs) such as VS55 (8.4 M) or less concentrated DP6 (6 M) and cooling at or beyond their critical cooling rates of 2.5 and 40 °C/min, respectively. Successful warming from this vitrified state, however, can be challenging. For example, convective warming by simple warm-bath immersion achieves 70 °C/min, which is faster than VS55's critical warming rate of 55 °C/min, but remains far below that of DP6 (185 °C/min). Here we present a new method that can dramatically increase the warming rates within either a solution or tissue by inductively warming commercially available metal components placed within solutions or in proximity to tissues with non-invasive radiofrequency fields (360 kHz, 20 kA/m). Directly measured warming rates within solutions exceeded 1000 °C/min with specific absorption rates (W/g) of 100, 450 and 1000 for copper foam, aluminum foil, and nitinol mesh, respectively. As proof of principle, a carotid artery diffusively loaded with VS55 and DP6 CPA was successfully warmed with high viability using aluminum foil, while standard convection failed for the DP6 loaded tissue. Modeling suggests this approach can improve warming in tissues up to 4-mm thick where diffusive loading of CPA may be incomplete. Finally, this technology is not dependent on the size of the system and should therefore scale up where convection cannot.
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http://dx.doi.org/10.1007/s10439-018-2063-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6208886PMC
November 2018

In vitro diagnosis of DNA methylation biomarkers with digital PCR in breast tumors.

Analyst 2018 Jun;143(13):3011-3020

The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.

Liquid biopsy of cancers using DNA methylation biomarkers has received significant interest, where the quantification of multiple biomarkers is generally needed for improving the sensitivity and specificity of cancer diagnosis. However, the inefficiency of the traditional quantitative polymerase chain reaction (qPCR)-based MethyLight assay for detecting the extremely low concentration of methylated DNA fragments in body fluids limits its clinical applications. Here, we developed an ultrasensitive microwell chip digital polymerase chain reaction (dPCR)-based MethyLight assay. Using the synthesized samples, the developed MethyLight assay can achieve 103-104-fold lower limit of detection and 1-16-fold lower limit of quantification than the traditional MethyLight assay. Four hypermethylated alleles (RARβ2, BRCA1, GSTP1 and RASSF1A) related to breast cancer in twenty-three clinical samples were tested using the microwell chip dPCR-based MethyLight assay. The results showed that the dPCR assay achieves ∼2 times enhancement in the cancer detection rate over the traditional quantitative PCR. Furthermore, the dPCR can detect the healthy and benign samples, which are undetectable using the traditional MethyLight assay. In multiple gene analysis, we achieved the highest detection rate of 93.3% (in the "OR" format of RARβ2 and GSTP1). Lastly, the estimated cut-off values in the dPCR assay were: <1, ∼1 to 100 and >100 (copies per μL) referring to the healthy, benign and malignant breast cancers, respectively. Therefore, the developed microwell chip dPCR-based MethyLight assay could provide a powerful tool for cancer biopsy diagnosis and disease monitoring.
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http://dx.doi.org/10.1039/c8an00205cDOI Listing
June 2018

Droplet based vitrification for cell aggregates: Numerical analysis.

J Mech Behav Biomed Mater 2018 06 22;82:383-393. Epub 2018 Mar 22.

Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an 710049, PR China; State Key Laboratory of Mechanical Structure Strength and Vibration, School of Aerospace, Xi'an Jiaotong University, Xi'an 710049, PR China; MOE Key Laboratory of Multifunctional Structures and Materials, Xi'an Jiaotong University, Xi'an 710049, PR China. Electronic address:

Cell aggregates represent the main format of cells existing in vivo and have been widely used as tissue and disease models in vitro. Nevertheless, the preservation of cell aggregates while maintaining their functionalities for off-the-shelf applications is still challenging. Among various preservation methods, droplet-based vitrification exhibits superior advantages for the cryopreservation of cell aggregates; however, the physical mechanisms underlying droplet-based vitrification of cell aggregate using this method remain elusive. To address this issue, we proposed a voronoi model to construct two-dimensional geometric morphologies of cell aggregates and established a coupled physical model to describe the diffusion, heat transfer and crystallization processes during vitrification. Based on these models, we performed a numerical study on the variation and distribution of cryoprotectant (CPA) concentration, temperature and crystallization in cell aggregates during droplet-based vitrification. The results show that although cell membrane is not an obvious barrier in heat transfer, it affects the diffusion of CPA remarkably as a biologic film and thus the following crystallization in cell aggregates. The effective protection of CPA during vitrification occurs during the initial stage of CPA diffusion, thus a longer CPA loading time does not necessarily lead to significant decrease in crystallization, but rather may induce more toxicity to cells.
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http://dx.doi.org/10.1016/j.jmbbm.2018.03.026DOI Listing
June 2018

Engineering the Cell Microenvironment Using Novel Photoresponsive Hydrogels.

ACS Appl Mater Interfaces 2018 Apr 5;10(15):12374-12389. Epub 2018 Apr 5.

Bioinspired Engineering & Biomechanics Center (BEBC) , Xi'an Jiaotong University , Xi'an , Shaanxi 710049 , P. R. China.

In vivo, cells are located in a dynamic, three-dimensional (3D) cell microenvironment, and various biomaterials have been used to engineer 3D cell microenvironments in vitro to study the effects of the cell microenvironment on the regulation of cell fate. However, conventional hydrogels can only mimic the static cell microenvironment without any synchronous regulations. Therefore, novel hydrogels that are capable of responding to specific stimuli (e.g., light, temperature, pH, and magnetic and electrical stimulations) have emerged as versatile platforms to precisely mimic the dynamic native 3D cell microenvironment. Among these novel hydrogels, photoresponsive hydrogels (PRHs) that are capable of changing their physical and chemical properties after exposure to light irradiation enable the dynamic, native cell microenvironment to be mimicked and show great promise in deciphering the unknown mechanisms of the 3D cell microenvironment in regulating the cell fate. Several reviews have already summarized the advances of PRHs and have focused on specific photosensitive chemical groups and photoresponsive elements or on the reaction categories and mechanism of PRHs. However, a holistic view of novel PRHs, which highlights the multiple physical and chemical properties that can be tuned by remote light activation, as well as their applications in engineering a dynamic cell microenvironment for the regulation of cell behaviors in vitro is still missing and is the focus of this review.
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http://dx.doi.org/10.1021/acsami.7b17751DOI Listing
April 2018

Engineering ellipsoidal cap-like hydrogel particles as building blocks or sacrificial templates for three-dimensional cell culture.

Biomater Sci 2018 Mar;6(4):885-892

Non-equilibrium Condensed Matter and Quantum Engineering Laboratory, The Key Laboratory of Ministry of Education, School of Science, Xi'an Jiaotong University, Xi'an 710049, P.R. China.

Hydrogel particles that can be engineered to compartmentally culture cells in a three-dimensional (3D) and high-throughput manner have attracted increasing interest in the biomedical area. However, the ability to generate hydrogel particles with specially designed structures and their potential biomedical applications need to be further explored. This work introduces a method for fabricating hydrogel particles in an ellipsoidal cap-like shape (i.e., ellipsoidal cap-like hydrogel particles) by employing an open-pore anodic aluminum oxide membrane. Hydrogel particles of different sizes are fabricated. The ability to produce ellipsoidal cap-like magnetic hydrogel particles with controlled distribution of magnetic nanoparticles is demonstrated. Encapsulated cells show high viability, indicating the potential for using these hydrogel particles as structure- and remote-controllable building blocks for tissue engineering application. Moreover, the hydrogel particles are also used as sacrificial templates for fabricating ellipsoidal cap-like concave wells, which are further applied for producing size controllable cell aggregates. The results are beneficial for the development of hydrogel particles and their applications in 3D cell culture.
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http://dx.doi.org/10.1039/c7bm01186eDOI Listing
March 2018

Magnetic steering of liquid metal mobiles.

Soft Matter 2018 May;14(17):3236-3245

The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, P. R. China.

Gallium-based liquid metal has captivated exceptionally keen interest in recent years since it remains in the liquid phase at room temperature and thus conforms to the surrounding medium. Meanwhile, such morphing capability can be tuned via altering the oxide layer on the surface of the liquid metal, which further triggers enthusiasm for investigating its locomotion. In this study, we proposed a magnetic actuation scenario for steering liquid metal locomotion in an easily accessible and highly directed manner. The soft mobile composed of liquid metal performed satisfyingly in locomotion and assembly tasks in various circumstances (on a solid surface and in a water environment). Furthermore, promising applications as switches for logic circuits and carriers for cargo transfer, as well as motors for vessel cleaning were also demonstrated, revealing the versatility of such liquid metal mobiles.
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http://dx.doi.org/10.1039/c8sm00056eDOI Listing
May 2018
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