3D Dynamic System Research Articles

Holographic RG flows in a 3D gauged supergravity at finite temperature

In this paper, we consider finite-temperature holographic renormalization group (RG) flows in D=3 N=(2,0) gauged truncated supergravity coupled to a sigma model with a hyperbolic target space. In the context of the holographic duality, fixed points (CFTs) at finite temperature are described by anti–de Sitter (AdS) black holes. We come from the gravity equations of motion to a 3D autonomous dynamical system, which critical points can be related to fixed points of dual field theories. Near-horizon black hole solutions correspond to infinite points of this system. We use Poincaré transformations to project the system on R3 into the 3D unit cylinder such that the infinite points are mapped onto the boundary of the cylinder. We explore numerically the space of solutions. We show that the exact RG flow at zero temperature is the separatrix for asymptotically AdS black hole solutions if the potential has one extremum, while for the potential with three extrema the separatrices are RG flows between AdS fixed points. We find near-horizon analytical solutions for asymptotically AdS black holes using the dynamical equations. We also present a method for constructing full analytical solutions. Published by the American Physical Society 2024

A Comparative Evaluation of Real-Time Guided Dynamic Navigation and Conventional Techniques for Post Space Preparation During Post Endodontic Management: An In Vitro Study.

The three-dimensional (3D) dynamic navigation system (DNS; Navident, ClaroNav Technology, Toronto, ON) is a revolutionary technique in endodontics that offers superior precision and efficiency compared to existing techniques for post space preparation. The aim is to evaluate and contrast the efficacy and efficiency of the DNS with conventional post space preparation techniques. This assessment considers severalparameters, notably canal deviation (global coronal and apical deviation and angular deflection), duration of the procedure, and total volumetric loss of instrumented root canal and volumetric loss of instrumented root canal above 4 mm from the apex. Freshly extracted maxillary central incisors were chosen for this study. A total sample size of 60 (n) was included. The extracted teeth samples were divided into two groups: 3D DNS (group I; n = 30)and conventional techniques (group II; n = 30). The samples were taken, and 50% of the crown structure was reduced for post space preparation to ensure standardization between thetwo groups. The samples were root canal-treated and mounted in a 3D-printed maxillary cast. Preoperative micro-computed tomography (micro-CT) and cone-beam computed tomography (CBCT) were taken for both groups.For group I, post space preparation was conducted with the DNS, which provided comprehensive guidance. The procedure was stopped when post space preparation was 4 mm short of the apex, as indicated in the system display. For group II, post space preparation was done without the guidance of DNS. Time taken for the procedure was assessed using a timer; canal deviation was evaluated using CBCT analysis, and volumetric loss was estimated using micro-CT analysis. The dynamic navigation group achieves significantly more precise outcomes in post space preparation than the conventional technique. The DNS group has significantly lesser global coronal and apical deviation and angular deflection compared to the conventional group (p < 0.05). The DNS group has reduced the volumetric loss of instrumented root canals compared to the conventional group (p < 0.05). Furthermore, the DNS group requires significantlyless time than the conventional method, with a mean difference of about 10.567 minutes (p < 0.05). Implementing dynamic navigation improves precision in post space preparation, with a notable reduction in canal deviation and volumetric loss and a decrease in procedure time compared to the conventional method.

Research on three-dimensional dynamic design and decision system of airport

Abstract Due to the lack of elevation information, the traditional airport design system based on the AutoCAD 2D platform is often unable to make a comprehensive and objective analysis and judgment when the designer evaluates the advantages and disadvantages of the design scheme. Therefore, this paper focuses on the development of airport 3D dynamic design and decision systems based on the Cesium framework. Firstly, based on the 3D geographic information platform, a multi-type 3D digital map loading and display module will be developed to realize the combination of 3D geographic information and the airfield model. Then, according to the 3D model data and the characteristics of the platform development, the method of calculating the earth volume of clearance processing, the evaluation algorithm of airport clearance obstacle limit surface, the optimization analysis method of tower position, and the analysis method of navigation station and flight track visibility are constructed.

Small extracellular vesicles-derived from 3d cultured human nasal mucosal mesenchymal stem cells during differentiation to dopaminergic progenitors promote neural damage repair via miR-494–3p after manganese exposed mice

Manganese (Mn) exposure is a common environmental risk factor for Parkinson's disease (PD), with pathogenic mechanisms associated with dopaminergic neuron damage and neuroinflammation. Mesenchymal stem cells (MSCs)-derived small extracellular vesicles (sEVs) have emerged as a novel therapeutic approach for neural damage repair. The functional sEVs released from MSCs when they are induced into dopaminergic progenitors may have a better repair effect on neural injury. Therefore, we collected sEVs obtained from primary human nasal mucosal mesenchymal stem cells (hnmMSC-sEVs) or cells in the process of dopaminergic progenitor cell differentiation (da-hnmMSC-sEVs), which were cultured in a 3D dynamic system, and observed their repair effects and mechanisms of Mn-induced neural damage by intranasal administration of sEVs. In Mn-exposed mice, sEVs could reach the site of brain injury after intranasal administration, da-hnmMSC enhanced the repair effects of sEVs in neural damage and behavioral competence, as evidenced by restoration of motor dysfunction, enhanced neurogenesis, decreased microglia activation, up-regulation of anti-inflammatory factors, and down-regulation of pro-inflammatory factors. The transcriptomics of hnmMSC-sEVs and da-hnmMSC-sEVs revealed that miRNAs, especially miR-494–3p in sEVs were involved in neuroprotective and anti-inflammatory effects. Overexpression of miR-494–3p in sEVs inhibited Mn-induced inflammation and neural injury, and its repair mechanism might be related to the down-regulation of CMPK2 and NLRP3 in vitro experiments. Thus, intranasal delivery of da-hnmMSC-sEVs is an effective strategy for the treatment of neural injury repair.

Investigation of Thermo-Electrical Instabilities in a Semiconductor as 2D Dynamical Systems

A semiconducting sample placed in cryogenic media with applied electric field generates low frequency oscillations of electric current and sample temperature and known to be thermo-electrical instabilities. Although observation of current oscillations on oscilloscope is possible, change of sample temperature cannot be detected experimentally. Description of the phenomenon through mathematical equations helps to understand relationship of the two variables as well as their connection to deep trap behavior that are involved in supporting the instability. Mathematical model for thermo-electrical instabilities in an n type semiconductor based on the two deep trap level model with non-degenerate electron statistics has been introduced in order to investigate the unique relationship between the change in time of both electric current flowing through a semiconductor sample and the sample temperature. The 3D dynamical system of nonlinear inhomogeneous ordinary differential equations has been investigated as component 2D dynamical systems (n,T), (n,n&amp;lt;sub&amp;gt;t&amp;lt;/sub&amp;gt;) and (n&amp;lt;sub&amp;gt;t&amp;lt;/sub&amp;gt;,T) for local behavior at isolated equilibrium and at points on individual trajectories, where n, n&amp;lt;sub&amp;gt;t&amp;lt;/sub&amp;gt; and T are free electron concentration at conduction band, electron concentration at deep traps and temperature of a semiconductor sample accordingly. Each of the planar systems is expressed in canonical form and investigated as a Cauchy problem with a set of appropriate initial values. This paper presents investigation results of phase trajectories of the planar systems depending on a single parameter – the temperature of cooling media T&amp;lt;sub&amp;gt;0&amp;lt;/sub&amp;gt;. Based on obtained calculation results of time sequences of the three variables n, n&amp;lt;sub&amp;gt;t&amp;lt;/sub&amp;gt; and T, phase differences among these variables have been determined for different values of T&amp;lt;sub&amp;gt;0&amp;lt;/sub&amp;gt;. It has been established that the change in sample temperature lags behind change in current and this lag increases with T&amp;lt;sub&amp;gt;0&amp;lt;/sub&amp;gt;. Clearly defined correlations among systems (n,T), (n,n&amp;lt;sub&amp;gt;t&amp;lt;/sub&amp;gt;) and (n&amp;lt;sub&amp;gt;t&amp;lt;/sub&amp;gt;,T) are seen, being the result of balance between field aided and thermal ionization mechanisms for charge carrier generation and recombination processes. Thermal and field assisted generation mechanisms compete with one another in achieving steady non equilibrium state in the system depending on temperature of cooling media T&amp;lt;sub&amp;gt;0&amp;lt;/sub&amp;gt;.

Abstract B041: Modeling the malignant transformation of fallopian tube epithelium driven by extracellular vesicles cargos in an organ-on-chip microphysiological system

Abstract Epithelial ovarian cancer (EOC) remains the leading cause of death from gynecological malignancy and the fifth leading cause of all cancer-related deaths among American women. The most common and lethal subtype, high-grade serous ovarian cancer (HGSOC) tends to originate from the fallopian tube. Precursor lesions of HGSOC such as secretory cell expansion (SCE), the loss of PAX2, PTEN, p53 mutation and serous tubal intraepithelial carcinoma (STIC) are often found at the fallopian tube epithelium (FTE). However, the mechanism of how neoplastic lesions disseminate in FTE and eventually colonize the ovary is unclear. We are interested in understanding if ovarian cancer initiation in the FTE is mediated by extracellular vesicles (EVs), which are nanosized biovesicles secreted by all living cells. EVs serve as vehicles for nucleic acids, proteins, and lipids. Cancer cells commonly secrete more EVs than healthy cells and shift their EV cargos to promote tumorigenesis. The alteration of molecular content of tumor-derived EV can potentially indicate disease states and serve as a new class of cancer biomarkers. Hence, our hypothesis is that EV cargos secreted by tumor cells contain factors promoting preneoplastic lesions in the FTE. Our goal is to interrogate the role of EVs in the initiation of ovarian cancer in the FTE at the early stage, for which there is no adequate in vitro model. We created a microfluidic model using a 3D dynamic culture system termed PREDICT-MOS to enable the direct interaction of hFTE with EVs and the long-term culture of the fallopian tube explant. We are interested to 1) test the role of EVs to drive preneoplastic transformation of hFTE progenitor cells and 2) to test whether tumor derived-EVs shift EV proteins cargos secreted by hFTE. The hFTE cultured on PREDICT-MOS is directly exposed to OVCAR3-derived EVs and embedded for transcriptomic profiling utilizing GeoMx Digital Spatial Profiler to identify differentially expressed genes in both ciliated and secretory cells within the epithelium. In parallel, we are characterizing the hFTE EV protein content with or without OVCAR3 EV treatment to detect the alteration in hFTE cargos using mass spectrometry proteomics. Our preliminary transcriptomic data from 8 patient fallopian tube samples demonstrates the deregulation of pathways associated with inflammation (TNF and NF-kappa B signaling), immune suppression (PD-1 checkpoint signaling) and epithelium morphogenesis. In addition, we have identified 295 proteins as the results of the first proteomic characterization of hFTE-derived EV proteins, which can serve as a “baseline” to evaluate whether the fallopian tube shifts its sEV cargo during ovarian cancer carcinogenesis. Further validation of transcriptomic findings on translational level using immunohistochemistry and identification of OVCAR3 EV protein cargos that induce the transcriptomic changes are needed to establish the role of EVs in the initiation of HGSOC in the fallopian tube. This project is supported by the Ovarian Cancer Research Fund Alliance Program Grant. Citation Format: Didi Zha, Jared Sipes, Sagar Rayamajhi, Leonidas E. Bantis, Angela Russo, Harsh Pathak, Andrew K. Godwin, Joanna E. Burdette. Modeling the malignant transformation of fallopian tube epithelium driven by extracellular vesicles cargos in an organ-on-chip microphysiological system [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr B041.

A novel four-wing chaotic system with multiple equilibriums: Dynamical analysis, multistability, circuit simulation and pseudo random number generator (PRNG) based on the voice encryption

Recently, there has been tremendous interest worldwide in the possibility of using chaos in communication systems. Many different chaos-based secure communication schemes have been proposed up until now. However, systems with strong chaoticity are more suitable for chaos-based secure communication. From the viewpoint of Lyapunov exponents, a chaotic system with a larger positive Lyapunov exponent is said to be more complex. This paper constructing a multistable chaotic system that can produce coexisting attractors is an attractive field of research due to its theoretical and practical usefulness. An innovative 3D dynamical system is presented in this research. It can display various coexisting attractors for the same values of parameters. The new system is more suitable for chaos-based applications than recently reported systems since it exhibits strong multistable chaotic behavior, as proved by its large positive Lyapunov exponent. Furthermore, the accuracy of the numerical calculation and the system's physical implementations are confirmed by analog circuit simulation. Finally, implementing the proposed voice encryption is done using a four-wing chaotic system based on the PRNG.

A Hybrid Algorithms Based on the Aizawa Attractor and Rabbit-Lightweight Cipher for Image Encryption

Social media and networks rely heavily on images. Those images should be distributed in a private manner. Image encryption is therefore one of the most crucial components of cyber security. In the present study, an effective image encryption technique is developed that combines the Rabbit Algorithm, a simple algorithm, with the Attractor of Aizawa, a chaotic map. The lightweight encryption algorithm (Rabbit Algorithm), which is a 3D dynamic system, is made more secure by the Attractor of Aizawa. The process separates color images into blocks by first dividing them into bands of red, green, and blue (RGB). The presented approach generates multiple keys, or sequences, based on the initial parameters and conditions, which are then utilized for encrypting each one of the blocks. The peak signal-to-noise ratio (PSNR), Mean Squared Error (MSE), and structural similarity index measure (SSIM) tests are among performance tests that are used to assess the effectiveness of the approach. With the help of National Institute of Standards and Technology (NIST), the produced keys have been checked for randomness. Additionally, research is being done into how long decryption and encryption take. The encryption approach is particularly secure because of the chaotic attractor's unpredictability. The correlation coefficient, Shannon entropy, and a histogram are used to analyse the encryption technique's performance. The findings demonstrate that the suggested encryption approach dependably operates since it makes use of a mechanism to strengthen security against the attack of known or selected plain-text. The outcomes also demonstrated that both decoding and encoding using the suggested encoding approach require less time. For instance, images 3's decoding time is 0.002000, whereas images 3's encoding time is 0.001200.

Approximate Closed-Form Solutions for a Class of 3D Dynamical Systems Involving a Hamilton–Poisson Part

The goal of this paper is to build some approximate closed-form solutions for a class of dynamical systems involving a Hamilton–Poisson part. The chaotic behaviors are neglected. These solutions are obtained by means of a new version of the optimal parametric iteration method (OPIM), namely, the modified optimal parametric iteration method (mOPIM). The effect of the physical parameters is investigated. The Hamilton–Poisson part of the dynamical systems is reduced to a second-order nonlinear differential equation, which is analytically solved by the mOPIM procedure. A comparison between the approximate analytical solution obtained with mOPIM, the analytical solution obtained with the iterative method, and the corresponding numerical solution is presented. The mOPIM technique has more advantages, such as the convergence control (in the sense that the residual functions are smaller than 1), the efficiency, the writing of the solutions in an effective form, and the nonexistence of small parameters. The accuracy of the analytical and corresponding numerical results is illustrated by graphical and tabular representations. The same procedure could be successfully applied to more dynamical systems.

Mesenchymal stem cells paracrine proteins from three-dimensional dynamic culture system promoted wound healing in third-degree burn models.

Recovery of skin function remains a significant clinical challenge for deep burns owing to the severe scar formation and poor appendage regeneration, and stem cell therapy has shown great potential for injured tissue regeneration. Here, a cell-free therapy system for deep burn skin was explored using mesenchymal stem cell paracrine proteins (MSC-PP) and polyethylene glycol (PEG) temperature-sensitive hydrogels. A three-dimensional (3D) dynamic culture system for MSCs' large-scale expansion was established using a porous gelatin microcarrier crosslinked with hyaluronic acid (PGM-HA), and the purified MSC-PP from culture supernatant was characterized by mass spectrometric analysis. The results showed the 3D dynamic culture system regulated MSCs cell cycle, reduced apoptosis, and decreased lactic acid content, and the MSC-PP produced in 3D group can promote cell proliferation, migration, and adhesion. The MSC-PP + PEG system maintained stable release in 28 days of observation in vitro. The in vivo therapeutic efficacy was investigated in the rabbit's third-degree burn model, and saline, PEG, MSC-PP, and MSC-PP + PEG treatments groups were set. The in vivo results showed that the MSC-PP + PEG group significantly improved wound healing, inhibited scar formation, and facilitated skin appendage regeneration. In conclusion, the MSC-PP + PEG sustained-release system provides a potentially effective treatment for deep burn skin healing.

Study on Structure Design and Motion Characteristics of Pneumatic Flexible Wrist with Braking Function

A flexible pneumatic wrist with spatial position maintenance function is developed in this paper to settle the matter of insufficient flexibility of the robot wrist and self-braking technology. The wrist is made up of four artificial muscles and a pneumatic spherical brake in parallel, with 2 degrees of freedom. The wrist can realize multidirectional bending and adjust the wrist damping and braking in real time as required to achieve position maintenance. The theoretical model of the wrist bending angle is built based on torque balance. The variation of wrist bending angle and motion trajectory with air pressure is acquired through experiments. Simultaneously, the validity of the bending angle theoretical model is verified experimentally. A normally open pneumatic spherical brake is developed, and the mathematical model of braking torque is built and experimentally validated. Using a 3D dynamic capture system to compare the dynamic characteristics of the wrist under different excitation signals and different damping conditions. The experimental results reveal that the wrist has good flexibility and can achieve the functions of human hand pitch and yaw. The bending angle is 20.72° at 0.34 MPa. The pneumatic spherical brake has the function of spatial multidirection braking, and the braking force is adjustable. The maximum braking torque can reach 1.4 N m at 0.35 MPa.

A Cadaver-based Comparison of Sleeve-guided Implant-drill and Dynamic Navigation Osteotomy and Root-end Resections

IntroductionThis study compared the accuracy and efficiency of fully guided static and dynamic computer-assisted surgical navigation techniques for osteotomy and root-end resection (RER). MethodsFifty roots from cadaver heads were divided into two groups: fully guided static computer-assisted endodontic microsurgery (FG sCAEMS) and dynamic computer-assisted endodontic microsurgery (dCAEMS) (all, n = 25). Cone-beam computed tomography scans were taken pre and postoperatively. The osteotomy and RER were planned virtually in the preoperative cone-beam computed tomography scan and guided using 3D-printed surgical guides in the FG sCAEMS and 3D-dynamic navigation system in the dCAEMS. The 2D and 3D deviations and angular deflection were calculated. The osteotomy volume, resected root length, and resection angle were measured. The osteotomy and RER time and the number of procedural mishaps were recorded. ResultsFG sCAEMS was as accurate as dCAEMS, with no difference in the 2D and 3D deviation values or angular deflection (P > .05). The osteotomy and RER time were shortened using FG sCAEMS (P < .05). The FG sCAEMS showed a greater number of incomplete RERs than dCAEMS. Osteotomy volume, RER angle, and root length resected were similar in both groups (P > .05). FG sCAEMS and dCAEMS were feasible for osteotomy and RER. ConclusionsWithin the limitations of this cadaver-based study, FG sCAEMS was as accurate as dCAEMS. Both FG sCAEMS and dCAEMS were time-efficient for osteotomy and RER.

Development of a Pneumatic-Driven Fiber-Shaped Robot Scaffold for Use as a Complex 3D Dynamic Culture System

Cells can sense and respond to different kinds of continuous mechanical strain in the human body. Mechanical stimulation needs to be included within the in vitro culture system to better mimic the existing complexity of in vivo biological systems. Existing commercial dynamic culture systems are generally two-dimensional (2D) which fail to mimic the three-dimensional (3D) native microenvironment. In this study, a pneumatically driven fiber robot has been developed as a platform for 3D dynamic cell culture. The fiber robot can generate tunable contractions upon stimulation. The surface of the fiber robot is formed by a braiding structure, which provides promising surface contact and adequate space for cell culture. An in-house dynamic stimulation using the fiber robot was set up to maintain NIH3T3 cells in a controlled environment. The biocompatibility of the developed dynamic culture systems was analyzed using LIVE/DEAD™ and alamarBlue™ assays. The results showed that the dynamic culture system was able to support cell proliferation with minimal cytotoxicity similar to static cultures. However, we observed a decrease in cell viability in the case of a high strain rate in dynamic cultures. Differences in cell arrangement and proliferation were observed between braided sleeves made of different materials (nylon and ultra-high molecular weight polyethylene). In summary, a simple and cost-effective 3D dynamic culture system has been proposed, which can be easily implemented to study complex biological phenomena in vitro.

On the Bifurcations of a 3D Symmetric Dynamical System

The paper studies the bifurcations that occur in the T-system, a 3D dynamical system symmetric in respect to the Oz axis. Results concerning some local bifurcations (pitchfork and Hopf bifurcation) are presented and our attention is focused on a special bifurcation, when the system has infinitely many equilibrium points. It is shown that, at the bifurcation limit, the phase space is foliated by infinitely many invariant surfaces, each of them containing two equilibrium points (an attractor and a saddle). For values of the bifurcation parameter close to the bifurcation limit, the study of the system’s dynamics is done according to the singular perturbation theory. The dynamics is characterized by mixed mode oscillations (also called fast-slow oscillations or oscillations-relaxations) and a finite number of equilibrium points. The specific features of the bifurcation are highlighted and explained. The influence of the pitchfork and Hopf bifurcations on the fast-slow dynamics is also pointed out.

Unique osteogenic profile of bone marrow stem cells stimulated in perfusion bioreactor is Rho-ROCK-mediated contractility dependent.

The fate determination of bone marrow mesenchymal stem/stromal cells (BMSC) is tightly regulated by mechanical cues, including fluid shear stress. Knowledge of mechanobiology in 2D culture has allowed researchers in bone tissue engineering to develop 3D dynamic culture systems with the potential for clinical translation in which the fate and growth of BMSC are mechanically controlled. However, due to the complexity of 3D dynamic cell culture compared to the 2D counterpart, the mechanisms of cell regulation in the dynamic environment remain relatively undescribed. In the present study, we analyzed the cytoskeletal modulation and osteogenic profiles of BMSC under fluid stimuli in a 3D culture condition using a perfusion bioreactor. BMSC subjected to fluid shear stress (mean 1.56 mPa) showed increased actomyosin contractility, accompanied by the upregulation of mechanoreceptors, focal adhesions, and Rho GTPase-mediated signaling molecules. Osteogenic gene expression profiling revealed that fluid shear stress promoted the expression of osteogenic markers differently from chemically induced osteogenesis. Osteogenic marker mRNA expression, type 1 collagen formation, ALP activity, and mineralization were promoted in the dynamic condition, even in the absence of chemical supplementation. The inhibition of cell contractility under flow by Rhosin chloride, Y27632, MLCK inhibitor peptide-18, or Blebbistatin revealed that actomyosin contractility was required for maintaining the proliferative status and mechanically induced osteogenic differentiation in the dynamic culture. The study highlights the cytoskeletal response and unique osteogenic profile of BMSC in this type of dynamic cell culture, stepping toward the clinical translation of mechanically stimulated BMCS for bone regeneration.

The differentiation of human induced pluripotent stem cells into hematopoietic stem cells on 3D bone scaffold in a dynamic culture system

Hematopoietic stem cell transplantation is used for cell-based therapy for many hematological disorders. However, difficulty in finding proper donors has limited this source of stem cells. For clinical application, the generation of these cells from induced pluripotent stem cells (iPSs) is a fascinating and endless source. One of the experimental methods to generate HSCs from iPSs is the mimicking of the hematopoietic niche. In the current study, as the first phase of differentiation, embryoid bodies were formed from iPSs. They were then cultured in different dynamic conditions in order to determine the appropriate settings for their differentiation into HSCs. The dynamic culture was composed of DBM Scaffold with or without growth factor. After ten days, the specific HSC markers (CD34, CD133, CD31 and CD45) were assessed using flow-cytometry. Our findings demonstrated that the dynamic conditions were significantly suitable than static ones. In addition, in 3D scaffold and dynamic system the expression of CXCR4, as a homing marker, was increased. These results suggest that the 3D culture bioreactor with DBM scaffold could provide a new approach for differentiation of iPSs into HSCs. Moreover, this system could provide maximum mimicry of bone marrow niche.

The Hollow Porous Sphere Cell Carrier for the Dynamic Three-Dimensional Cell Culture.

Large-scale mammalian cell culture is essential in cell therapy, vaccine production, and the manufacturing of therapeutic protein drugs. Due to the adherent growth characteristic of most mammalian cell types, the combination of cell carrier and bioreactor is a common choice in large-scale mammalian cell culture. Current cell carriers developed by polymer crosslinking, lithography, or emulsion drops are unable to obtain a structure with uniformed porous structure and porous interior design, which results in an inhomogeneous culture condition for cells and therefore cannot ensure an optimal dynamic culture condition for cell proliferation, matrix production, and cell differentiation. In addition, the fluidic shear stress (a standard mechanical stimulation in bioreactor culture) and inner-carrier velocity (to ensure nutrient transport and waste exchange), which influence cell viability and growth, are not well-controlled/analyzed due to an irregular porous structure with these traditionally synthesized cell carriers. To solve these problems, we designed four types of hollow porous spheres (HPS, 1.0 cm diameter) with different porous structures. To investigate the impacts of porous structure on surface shear stress and inner velocity, computational fluid dynamics (CFD) simulations were conducted to analyze the liquid flow behavior in HPSs, based on which an optimal structure with minimal surface shear stress and best inner velocity was obtained and fabricated using fused deposition modeling three-dimensional (3D) printing technology. Inspired by the industrial large-scale culture system, a novel 3D dynamic culture system was then established using HPSs to seed the cells, which were then placed in a mini bioreactor on a tube roller. CFD analysis showed that under 0.1 m/s water flow, the shear stress at most surface areas from four HPSs was lower than 20 dynes/cm2, which suggests that the HPSs should provide protection against physical stress to the cells living on the scaffold surface. A dynamic cell seeding was developed and refined using the 3D culture system, which increased the 32% seeding efficiency of MC3T3 cells compared to the traditional static cell seeding method. The cell proliferation analysis demonstrated that HPSs could speed up cell growth in dynamic cell culture. The HPS with a honeycomb-like structure showed the highest inner pore velocity (CFD analysis) and achieved the fastest cell proliferation and the highest cell viability. Overall, our study, for the first time, developed a 3D printed HPS cell culture device with a uniformed porous structure, which can effectively facilitate cell adhesion and proliferation in the dynamic cultural environment, thereby could be considered an ideal carrier candidate.

Advanced 3D dynamic culture system with transforming growth factor-β3 enhances production of potent extracellular vesicles with modified protein cargoes via upregulation of TGF-β signaling

IntroductionMesenchymal stromal cells (MSCs) release extracellular vesicles (MSC-EVs) containing various cargoes. Although MSC-EVs show significant therapeutic effects, the low production of EVs in MSCs hinders MSC-EV-mediated therapeutic development. ObjectivesHere, we developed an advanced three-dimensional (a3D) dynamic culture technique with exogenous transforming growth factor beta-3 (TGF-β3) treatment (T-a3D) to produce potent MSC-EVs. MethodsOur system enabled preparation of a highly concentrated EV-containing medium for efficient EV isolation and purification with higher yield and efficacy. ResultsMSC spheroids in T-a3D system (T-a3D spheroids) showed high expression of CD9 and TGF-β3, which was dependent on TGF-β signaling. Treatment with EVs produced under T-a3D conditions (T-a3D-EVs) led to significantly improved migration of dermal fibroblasts and wound closure in an excisional wound model. The relative total efficacy (relative yield of single-batch EVs (10–11-fold) × relative regeneration effect of EVs (2–3-fold)) of T-a3D-EVs was approximately up to 33-fold higher than that of 2D-EVs. Importantly the quantitative proteomic analyses of the T-a3D spheroids and T-a3D-EVs supported the improved EV production as well as the therapeutic potency of T-a3D-EVs. ConclusionTGF-β signalling differentially regulated by fluid shear stress produced in our system and exogenous TGF-β3 addition was confirmed to play an important role in the enhanced production of EVs with modified protein cargoes. We suggest that the T-a3D system leads to the efficient production of MSC-EVs with high potential in therapies and clinical development.

The Wearable Lower Limb Rehabilitation Exoskeleton Kinematic Analysis and Simulation.

In recent years, due to the increase in the incidence of traffic accidents, the number of people with limb injuries has also increased. At the same time, among the aging population, neurological diseases or cardiovascular and cerebrovascular diseases have caused many people to have limb hemiplegia. It has been clinically proven that the use of rehabilitation equipment can help patients with limb injuries to restore limb motor function. This paper takes wearable lower limb rehabilitation exoskeleton as the research object, and its main contents are mechanical structure design, kinematics analysis, gait planning, virtual prototype simulation, and experimental verification and analysis. Based on the physiological characteristics of human body and the principle of comfortable and reliable wearing, this paper designs wearable exoskeleton for lower limb rehabilitation. Firstly, the physiological structure characteristics and movement mechanism of human lower limbs were studied and analyzed. By referring to the rotation range and height and size of each joint of human lower limbs, the overall scheme of wearable lower limb rehabilitation exoskeleton was designed and the degree of freedom was allocated. At the same time, Solidworks was used to establish a three-dimensional model. On the basis of a 3D model, a kinematics model was established, and the forward kinematics solution was obtained by using homogeneous coordinate transformation. Since the inverse kinematics solution was relatively complicated, the inverse kinematics solution was conducted in this paper according to the geometric relations of the joints of the lower limbs. Kinematics analysis of the exoskeleton structure of wearable lower limb rehabilitation was carried out to lay a theoretical foundation for gait planning. The off-line gait planning was carried out by using the method based on ZMP stability criterion, and the gait planning was divided into five stages: squat, start, middle step, stop and rise, and the motion trajectory of the center of mass and ankle joint was planned. Based on the inverse kinematics formula, the function of the change of joint angle with time in walking process is derived. The virtual prototype is established in ADAMS, and the simulation of virtual prototype is carried out by using the function of gait planning's joint angle and time. The correctness of structural design and gait planning was verified by measuring the trajectories of the centroid and ankle joints in each gait stage and the functional relationship between the rotation angle of each joint and time. Then, using a 3D dynamic capture system to capture the human lower limb motion trajectory of each joint, each joint trajectory data output, using the MATLAB software to output data, gets the joint trajectory change over time function curve and is used to verify feasibility and applicability of human gait planning. Through the research and analysis of the joints of the lower limbs of the human body, it can be concluded that the hip joint and the knee joint have 3 degrees of freedom, respectively, and the knee joint has 1 degree of freedom.

A vertex-centred finite volume method for the 3D multi-term time and space fractional Bloch–Torrey equation with fractional Laplacian

We investigate the suitability of a fractional Laplacian in the construction of a three-dimensional (3D) multi-term time–space fractional Bloch–Torrey equation. Instead of using the Riesz fractional derivative as in most previous research, we consider the fractional Laplacian in space and multi-term Caputo fractional derivative in time. A vertex-centred finite volume method is firstly derived to discretise this 3D fractional dynamic system in combination with the matrix transfer technique and the weighted and shifted Grünwald–Letnikov formula. Since computing the fractional power of the matrix representation m(−Δ) of the Laplacian operator results in a highly dense matrix, we use matrix function approximations developed in a Krylov subspace framework and exploit the sparsity of m(−Δ) to reduce the computational overhead. Then the Lanczos method is employed to approximate vector products of matrix functions. A preconditioner is applied to accelerate the convergence process, which shows excellent performance and reduces the memory considerably. In particular, we introduce block matrix functions to deal with the coupled system. Furthermore, the analytical solution of the two-term time–space fractional diffusion equation is derived and expressed by the multinomial Mittag-Leffler function. The feasibility and effectiveness of the proposed numerical techniques are verified by some numerical examples. Compared with two-dimensional fractional models or single-term time fractional dynamic systems, this multi-term time–space fractional model provides more flexibility for the characterisation of anomalous diffusion in biological tissues.