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1.
Brief Bioinform ; 24(1)2023 01 19.
Article in English | MEDLINE | ID: mdl-36567252

ABSTRACT

Numerous experimental studies have indicated that alteration and dysregulation in mircroRNAs (miRNAs) are associated with serious diseases. Identifying disease-related miRNAs is therefore an essential and challenging task in bioinformatics research. Computational methods are an efficient and economical alternative to conventional biomedical studies and can reveal underlying miRNA-disease associations for subsequent experimental confirmation with reasonable confidence. Despite the success of existing computational approaches, most of them only rely on the known miRNA-disease associations to predict associations without adding other data to increase the prediction accuracy, and they are affected by issues of data sparsity. In this paper, we present MRRN, a model that combines matrix reconstruction with node reliability to predict probable miRNA-disease associations. In MRRN, the most reliable neighbors of miRNA and disease are used to update the original miRNA-disease association matrix, which significantly reduces data sparsity. Unknown miRNA-disease associations are reconstructed by aggregating the most reliable first-order neighbors to increase prediction accuracy by representing the local and global structure of the heterogeneous network. Five-fold cross-validation of MRRN produced an area under the curve (AUC) of 0.9355 and area under the precision-recall curve (AUPR) of 0.2646, values that were greater than those produced by comparable models. Two different types of case studies using three diseases were conducted to demonstrate the accuracy of MRRN, and all top 30 predicted miRNAs were verified.


Subject(s)
MicroRNAs , Humans , MicroRNAs/genetics , Genetic Predisposition to Disease , Reproducibility of Results , Algorithms , Computational Biology/methods
2.
Small ; : e2403056, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38726792

ABSTRACT

Energy conversion and transfer of enzyme-catalyzed reactions at molecular level are an interesting and challenging scientific topic that helps understanding biological processes in nature. In this study, it is demonstrated that enzyme-catalyzed reactions can enhance diffusion of surrounding molecules and thus accelerate cargo transport within 1D micro/nanochannels. Specifically, urease is immobilized on the inner walls of silica micro/nano-tubes to construct bio-catalytically active micro/nanochannels. The catalytic reaction inside the channels drives a variety of cargoes, including small dye molecules, polymers, and rigid nanoparticles (e.g., quantum dots, QDs), to pass through these micro/nanochannels much faster than they will by free diffusion. The enhanced diffusion of molecular species inside the channels is validated by direct observation of the Brownian motion of tracer particles, and further confirmed by significantly enhanced Raman intensity of reporter molecules. Finite element and Brownian dynamics simulations provide a theoretical understanding of these experimental observations. Furthermore, the effect of the channels' size on the diffusion enhancement is examined. The acceleration effect of the cargo transport through these enzymatically active micro/nanochannels can be turned on or off via chemical activators or inhibitors. This study provides valuable insights on the design of biomimetic channels capable of controlled and efficient transmembrane transport.

3.
Angew Chem Int Ed Engl ; 63(16): e202401209, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38400604

ABSTRACT

Self-propelled micro/nanomotors (MNMs) have shown great application potential in biomedicine, sensing, environmental remediation, etc. In the past decade, various strategies or technologies have been used to prepare and functionalize MNMs. However, the current preparation strategies of the MNMs were mainly following the pre-designed methods based on specific tasks to introduce expected functional parts on the various micro/nanocarriers, which lacks a universal platform and common features, making it difficult to apply to different application scenarios. Here, we have developed a modular assembly strategy based on host-guest chemistry, which enables the on-demand construction of imaging-trackable nanomotors mounted with suitable driving and imaging modules using a universal assembly platform, according to different application scenarios. These assembled nanomotors exhibited enhanced diffusion behavior driven by enzymatic reactions. The loaded imaging functions were used to dynamically trace the swarm motion behavior of assembled nanomotors with corresponding fuel conditions both in vitro and in vivo. The modular assembly strategy endowed with host-guest interaction provides a universal approach to producing multifunctional MNMs in a facile and controllable manner, which paves the way for the future development of MNMs systems with programmable functions.


Subject(s)
Environmental Restoration and Remediation , Nanostructures , Nanotechnology/methods , Nanostructures/chemistry
4.
Acc Chem Res ; 55(1): 98-109, 2022 01 04.
Article in English | MEDLINE | ID: mdl-34931794

ABSTRACT

Active matter refers to the nonequilibrium system composed of interacting units that continually dissipate energy at a single-unit level and transduce it into mechanical force or motion. Such systems are ubiquitous in nature and span most of the biological scales, ranging from cytoskeleton protein polymers at the molecular level to bacterial colonies at the cellular level to swarms of insects, flocks of birds, schools of fish, and even crowds of humans on the organismal scale. The consumption of energy within systems tends to induce the self-organization of active matter as well as the spontaneous emergence of dynamic, complex, and collective states with extraordinary properties, such as adaptability, reconfigurability, taxis, and so on. The research into active matter is expected to deepen the understanding of the underlying mechanisms of how the units in living systems interact with each other and regulate the flow of energy to improve the survival efficiency, which in turn can provide valuable insights into the engineering of artificial active systems with novel and practical collective functionalities.Because of the striking similarity in collective states, a colloidal system is an emerging approach to understanding the guiding principles of the coordinated activities in living systems. Thanks to the capabilities in batch fabrication, size control, and the modulation of interactions (e.g., dipole-dipole interactions, capillary forces, electrostatic interactions, and so on), various complex collective states have been reproduced and programmed in colloidal suspension through the elaborate design of compositions and unit-unit interactions. Among the developed colloidal systems, magnetic colloids energized by alternating magnetic fields demonstrate several unique advantages, including the high-degree-of-freedom and simple modulation of the magnetic field parameters as well as the excellent compatibility of the magnetic field with many application scenarios. Therefore, magnetic active matter not only constitutes a useful platform that leads to a discovery of fascinating emergent collective behaviors but also promises enormous potential in a variety of engineering fields.In this Account, we summarize and highlight the key efforts carried out by our group and others on the investigation of the collective behavior of magnetic active matter in the past 5 years. First, we elucidate the generation mechanisms of the emergent coordinated behaviors, which are classified according to the dominating interactions among agents, that is, the magnetic dipole-dipole interaction, hydrodynamic interaction, and weak interaction. Then we illustrate the construction of magnetic active matter with a higher level of collective effects and functionalities (e.g., reconfigurability, environmental adaptability, 3D swarming, cooperative multifunctionality, and so on) via the synergistic effects between magnetic fields and other fields. Next, potential applications of magnetic active matter are discussed, which mainly focus on the exploration in revolutionizing traditional biomedical fields. Finally, an outlook of future opportunities is presented to promote the development of magnetic active matter, which facilitates a better understanding of living counterparts and the further realization of practical applications.

5.
Int J Hyperthermia ; 40(1): 2256498, 2023.
Article in English | MEDLINE | ID: mdl-37733400

ABSTRACT

PURPOSE: The aim of this study was to develop prognostic scores, including the tumor burden score (TBS) and albumin-bilirubin (ALBI) grade, for evaluating the outcomes of hepatocellular carcinoma (HCC) patients after radiofrequency ablation (RFA). MATERIALS AND METHODS: This retrospective study enrolled treatment-naïve HCC patients with BCLC 0-A who underwent RFA between January 2009 and December 2019. Regular follow-up was conducted after RFA to determine progression-free survival (PFS) and overall survival (OS). The patients were randomly allocated to the training or validation datasets in a 1:1 ratio. Preoperative prognostic scores were developed based on the results of multivariate analysis. The discriminatory ability of the scores was assessed using time-dependent AUC and compared with other models. RESULTS: Serum alpha-fetoprotein (AFP) level and TBS were identified as independent prognostic factors for PFS, while serum AFP, TBS, and ALBI were identified as independent prognostic factors for OS in HCC patients after RFA. The time-dependent AUCs of the AFP-TBS score for the 1-, 3-, and 5-year PFS were 0.651, 0.667, and 0.620, respectively, in the training set, and 0.657, 0.687, and 0.704, respectively, in the validation set. For the 1-, 3-, and 5-year OS, the time-dependent AUCs were 0.680, 0.712, and 0.666, respectively, in the training set, and 0.712, 0.706 and 0.726 in the validation set for the AFP-TBS-ALBI score (ATA). The C-indices and AIC demonstrated that the scores provided better clinical benefits compared to other models. CONCLUSION: The ATA/AT score, derived from clinical and objective laboratory variables, can assist in individually predicting the prognosis of HCC patients undergoing curative RFA.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Radiofrequency Ablation , Humans , Albumins , alpha-Fetoproteins , Bilirubin , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/surgery , Liver Neoplasms/diagnosis , Liver Neoplasms/surgery , Prognosis , Retrospective Studies , Tumor Burden
6.
Small ; 18(37): e2202272, 2022 09.
Article in English | MEDLINE | ID: mdl-35983631

ABSTRACT

Micromachines with high environmental adaptability have the potential to deliver targeted drugs in complex biological networks, such as digestive, neural, and vascular networks. However, the low processing efficiency and single processing material of current 4D printing methods often limit the development and application of shape-morphing micromachines (SMMs). Here, two 4D printing strategies are proposed to fabricate SMMs with pH-responsive hydrogels for complex micro-networks traversing. On the one hand, the 3D vortex light single exposure technique can rapidly fabricate a tubular SMM with controllable size and geometry within 0.1 s. On the other hand, the asymmetric multimaterial direct laser writing (DLW) method is used to fabricate SMMs with designable 3D structures composed of hydrogel and platinum nanoparticles (Pt NPs). Based on the presence of ferroferric oxide (Fe3 O4 ) and Pt NPs in the SMMs, efficient magnetic, bubble, and hybrid propulsion modes are achieved. Finally, it is demonstrated that the spatial shape conversion capabilities of these SMMs can be used for narrow micronetworks traversing, which will find potential applications in targeted cargo delivery in microcapillaries.


Subject(s)
Metal Nanoparticles , Drug Delivery Systems , Hydrogels/chemistry , Platinum , Printing, Three-Dimensional
7.
Mol Cell Proteomics ; 14(4): 1093-103, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25605460

ABSTRACT

Tuberculosis is a global infectious disease caused by Mycobacterium tuberculosis (Mtb). Although novel Mtb biomarkers from both the pathogen and host have been studied, more breakthroughs are still needed to meet different clinic requirements. In an effort to identify Mtb antigens, chaperone-peptide complexes were purified from TB infected lungs using free-solution isoelectric focusing combined with high resolution LTQ Orbitrap Velos mass spectrometry. Antigen specific cellular immune responses in vitro were then examined. Those efforts led to the identification of six Mtb peptides only identified in Tuberculosis lung samples and that were not found in the control samples. Additionally, antigen-specific IFN-γ secretion, T-cell proliferation, cytokine expression, and a cytotoxic assay were also evaluated. Among the peptides isolated, we identified a 34 amino acid peptide named PKAp belonging to a serine/threonine-protein kinase, as being able to generate Mtb-specific cellular immune responses as noted by elevated antigen-specific cytokine secretion levels, increased CD8(+) T-cell proliferation and a strong cytotoxic lymphocyte (CTL) response. Moreover, the immune stimulating abilities of PKAp were further validated in vivo, with target peptide immunized mice showing an increased cellular IFN-γ in both the lungs and spleen without causing immunopathogenesis. In conclusion, we identified novel functional Mtb antigens directly from the granulomatous lesions of Tuberculosis patients, inducing not only significant antigen-specific IFN-γ secretion but also a marked cytotoxic lymphocyte functional response. These findings indicated that PKAp has potential as a novel antigen biomarker for vaccine development.


Subject(s)
Antigens, Bacterial/immunology , Granuloma/immunology , Mycobacterium tuberculosis/immunology , Tuberculosis/immunology , Adult , Amino Acid Sequence , Animals , Cell Proliferation , Epitopes, T-Lymphocyte/immunology , Female , Fluorescence , Granuloma/microbiology , HSP70 Heat-Shock Proteins/metabolism , Histocompatibility Antigens Class I/immunology , Humans , Immunization , Interferon-gamma/metabolism , Isoelectric Focusing , Lung/metabolism , Male , Mass Spectrometry , Membrane Glycoproteins/metabolism , Mice, Inbred C57BL , Middle Aged , Molecular Sequence Data , Peptides/chemistry , Peptides/metabolism , T-Lymphocytes, Cytotoxic/immunology , Tuberculosis/microbiology
8.
Environ Sci Technol ; 50(20): 11424-11432, 2016 Oct 18.
Article in English | MEDLINE | ID: mdl-27668311

ABSTRACT

In this study, a reliable and steady PCDD/F generation system was utilized to investigate the performance of catalysts, in which 130 congeners of tetra- to octapolychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) vapors were studied under simulated flue gas with/without O3. TiO2 and carbon nanotubes (CNTs) supported vanadium oxides (VOX/TiO2-CNTs) modified with MnOX and CuOX, which were reported to be beneficial to the decomposition of model molecules, were found to have a negative effect on the removal of real PCDD/Fs in the simulated flue gas without O3. Moreover, the addition of MnOX presented different effects depending on whether CuOX existed in catalysts or not, which was also contrary to its effects on the degradation of model molecules. In an O3-containing atmosphere, low chlorination level PCDD/Fs congeners were removed well over VOX-MnOX/TiO2-CNTs, while high chlorination level PCDD/Fs congeners were removed well over VOX-CuOX/TiO2-CNTs. Fortunately, all PCDD/Fs congeners decomposed well over VOX-MnOX-CuOX/TiO2-CNTs. Finally, the effects of tetra- to octachlorination level for the adsorption and degradation behaviors of PCDD/Fs congeners were also investigated.

9.
Am J Respir Cell Mol Biol ; 51(4): 575-85, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24805943

ABSTRACT

Cell-mediated immunity is indispensable for host protection against tuberculosis (TB). Growth factor receptor bound protein 2-associated binder (Gab) 2, a scaffolding adaptor protein, negatively regulates signaling pathways critical for T cell-mediated immunity. We sought to investigate the clinical significance and immunological role of Gab2 in Mycobacterium tuberculosis infection. We evaluated Gab2 protein and messenger RNA (mRNA) expression in human patients with pulmonary TB and determined the correlation of the mRNA expression pattern with antigen-specific IFN-γ secretion. Subsequently, we carried out M. tuberculosis infection in Gab2-deficient and wild-type control mice to explore the immunological role of Gab2 by examining bacterial load, histological changes, cytokine secretion, and gene expression of immune-associated transcription factors. mRNA levels of Gab2 and its correlated family member, Gab1, were markedly decreased in untreated patients with pulmonary TB compared with healthy control subjects. Importantly, this decreased Gab2 expression to normal levels after bacterial load in the patient's sputum became undetectable under the standard anti-TB treatment, which negatively correlated with the level of M. tuberculosis antigen-specific IFN-γ secretion. In the M. tuberculosis infection mouse model, infected Gab2-deficient mice exhibited decreased bacterial load and milder lung pathological damage compared with infected wild-type mice, accompanied by decreased production of IL-2, IL-6, and granulocyte/macrophage colony-stimulating factor proinflammatory cytokines, and an increased T-cell-specific T-box transcription factor/GATA binding protein 3 expression ratio. Overall, our study indicates that down-regulation of Gab2 relates to a protective function during M. tuberculosis infection, revealing a potential negative regulatory role for Gab2 in immunity to TB.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Immunity, Cellular , Lung/metabolism , Mycobacterium tuberculosis/immunology , Phosphoproteins/metabolism , Tuberculosis, Pulmonary/metabolism , Adaptor Proteins, Signal Transducing/genetics , Animals , Bacterial Load , Case-Control Studies , Disease Models, Animal , GATA3 Transcription Factor/metabolism , Host-Pathogen Interactions , Humans , Inflammation Mediators/metabolism , Lung/immunology , Lung/pathology , Lung/virology , Mice , Mice, Knockout , Mycobacterium tuberculosis/pathogenicity , Phosphoproteins/deficiency , Phosphoproteins/genetics , RNA, Messenger/metabolism , TCF Transcription Factors/metabolism , Time Factors , Tuberculosis, Pulmonary/genetics , Tuberculosis, Pulmonary/immunology , Tuberculosis, Pulmonary/pathology , Tuberculosis, Pulmonary/prevention & control , Tuberculosis, Pulmonary/virology
10.
Nanomaterials (Basel) ; 13(10)2023 May 21.
Article in English | MEDLINE | ID: mdl-37242103

ABSTRACT

Colloidal microswarms have attracted increasing attention in the last decade due to their unique capabilities in various complex tasks. Thousands or even millions of tiny active agents are gathered with distinctive features and emerging behaviors, demonstrating fascinating equilibrium and non-equilibrium collective states. In recent studies, with the development of materials design, remote control strategies, and the understanding of pair interactions between building blocks, microswarms have shown advantages in manipulation and targeted delivery tasks with high adaptability and on-demand pattern transformation. This review focuses on the recent progress in active micro/nanoparticles (MNPs) in colloidal microswarms under the input of an external field, including the response of MNPs to external fields, MNP-MNP interactions, and MNP-environment interactions. A fundamental understanding of how building blocks behave in a collective system provides the foundation for designing microswarm systems with autonomy and intelligence, aiming for practical application in diverse environments. It is envisioned that colloidal microswarms will significantly impact active delivery and manipulation applications on small scales.

11.
IEEE Trans Cybern ; 53(12): 7699-7711, 2023 Dec.
Article in English | MEDLINE | ID: mdl-36070281

ABSTRACT

Soft magnetic miniature robots (SMMRs) have potential biomedical applications due to their flexible size and mobility to access confined environments. However, navigating the robot to a goal site with precise control performance and high repeatability in unstructured environments, especially in flow rate conditions, still remains a challenge. In this study, drawing inspiration from the control requirements of drug delivery and release to the goal lesion site in the presence of dynamic biofluids, we propose a flow rate rejection control strategy based on a deep reinforcement learning (DRL) framework to actuate an SMMR to achieve goal-reaching and hovering in fluidic tubes. To this end, an SMMR is first fabricated, which can be operated by an external magnetic field to realize its desired functionalities. Subsequently, a simulator is constructed based on neural networks to map the relationship between the applied magnetic field and robot locomotion states. With minimal prior knowledge about the environment and dynamics, a gated recurrent unit (GRU)-based DRL algorithm is formulated by considering the designed history state-action and estimated flow rates. In addition, the randomization technique is applied during training to distill the general control policy for the physical SMMR. The results of numerical simulations and experiments are illustrated to demonstrate the robustness and efficacy of the presented control framework. Finally, in-depth analyses and discussions indicate the potentiality of DRL for soft magnetic robots in biomedical applications.

12.
ACS Nano ; 17(5): 5095-5107, 2023 03 14.
Article in English | MEDLINE | ID: mdl-36861648

ABSTRACT

In nature, there exist a variety of transport proteins on cell membranes capable of actively moving cargos across biological membranes, which plays a vital role in the living activities of cells. Emulating such biological pumps in artificial systems may bring in-depth insights on the principles and functions of cell behaviors. However, it poses great challenges due to difficulty in the sophisticated construction of active channels at the cellular scale. Here, we report the development of bionic micropumps for active transmembrane transportation of molecular cargos across living cells that is realized by enzyme-powered microrobotic jets. By immobilizing urease onto the surface of a silica-based microtube, the prepared microjet is capable of catalyzing the decomposition of urea in surrounding environments and generating microfluidic flow through the inside channel for self-propulsion, which is verified by both numerical simulation and experimental results. Therefore, once naturally endocytosed by the cell, the microjet enables the diffusion and, more importantly, active transportation of molecular substances between the extracellular and intracellular ends with the assistance of generated microflow, thus serving as an artificial biomimetic micropump. Furthermore, by constructing enzymatic micropumps on cancer cell membranes, enhanced delivery of anticancer doxorubicin into cells as well as improved killing efficacy are achieved, which demonstrates the effectiveness of the active transmembrane drug transport strategy in cancer treatment. This work not only extends the applications of micro/nanomachines in biomedical fields but also provides a promising platform for future cell biology research at cellular and subcellular scales.


Subject(s)
Microfluidics , Pharmaceutical Preparations , Biological Transport , Microfluidics/methods , Cell Membrane/metabolism , Diffusion
13.
Adv Sci (Weinh) ; 10(23): e2301292, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37316967

ABSTRACT

Printing or patterning particle-based liquid metal (LM) ink is a good strategy to overcome poor wettability of LM for its circuits' preparation in flexible and printed electronics. Subsequently, a crucial step is to recover conductivity of LM circuits consisting of insulating LM micro/nano-particles. However, most widely used mechanical sintering methods based on hard contact such as pressing, may not be able to contact the LM patterns' whole surface conformally, leading to insufficient sintering in some areas. Hard contact may also break delicate shapes of the printed patterns. Hereby, an ultrasonic-assisted sintering strategy that can not only preserve original morphology of the LM circuits but also sinter circuits on various substrates of complex surface topography is proposed. The influencing factors of the ultrasonic sintering are investigated empirically and interpreted with theoretical understanding by simulation. LM circuits encapsulated inside soft elastomer are successfully sintered, proving feasibility in constructing stretchable or flexible electronics. By using water as energy transmission medium, remote sintering without any direct contact with substrate is achieved, which greatly protect LM circuits from mechanical damage. In virtue of such remote and non-contact manipulation manner, the ultrasonic sintering strategy would greatly advance the fabrication and application scenarios of LM electronics.

14.
Sci Adv ; 9(19): eadf9278, 2023 05 12.
Article in English | MEDLINE | ID: mdl-37172097

ABSTRACT

The recent rise of swarming microrobotics offers great promise in the revolution of minimally invasive embolization procedure for treating aneurysm. However, targeted embolization treatment of aneurysm using microrobots has significant challenges in the delivery capability and filling controllability. Here, we develop an interventional catheterization-integrated swarming microrobotic platform for aneurysm on-demand embolization in physiological blood flow. A pH-responsive self-healing hydrogel doped with magnetic and imaging agents is developed as the embolic microgels, which enables long-term self-adhesion under biological condition in a controllable manner. The embolization strategy is initiated by catheter-assisted deployment of swarming microgels, followed by the application of external magnetic field for targeted aggregation of microrobots into aneurysm sac under the real-time guidance of ultrasound and fluoroscopy imaging. Mild acidic stimulus is applied to trigger the welding of microgels with satisfactory bio-/hemocompatibility and physical stability and realize complete embolization. Our work presents a promising connection between the design and control of microrobotic swarms toward practical applications in dynamic environments.


Subject(s)
Aneurysm , Embolization, Therapeutic , Microgels , Humans , Resin Cements , Hemodynamics , Aneurysm/therapy , Embolization, Therapeutic/methods
15.
Sci Rep ; 13(1): 16537, 2023 10 02.
Article in English | MEDLINE | ID: mdl-37783734

ABSTRACT

Endometrial cancer, one of the common gynecological malignancies, is affected by several influencing factors. This study established a unique patient-derived orthotopic xenograft (PDOX) nude mouse model for the study of influencing factors in ER positive endometrial cancer. The aim of this study was to demonstrate that a high-fat diet can affect the growth of ER positive endometrial cancer PDOX model tumors. The tumor tissues were expanded by subcutaneous transplantation in nude mice, and then the subcutaneous tumor tissues were orthotopically implanted into the nude mouse uterus to establish the PDOX model. After modeling, they were divided into high-fat diet group and normal diet group for 8 weeks of feeding, which showed that high-fat diet significantly promoted tumor growth (P < 0.001) and increased the protein expression level of ERα in tumor tissues. This study demonstrates that PDOX models of endometrial cancer can embody the role of dietary influences on tumor growth and that this model has the potential for preclinical studies of cancer promoting factors.


Subject(s)
Endometrial Neoplasms , Sarcoma , Female , Humans , Mice , Animals , Mice, Nude , Heterografts , Diet, High-Fat/adverse effects , Xenograft Model Antitumor Assays , Disease Models, Animal , Sarcoma/pathology
16.
Nat Commun ; 14(1): 6276, 2023 Oct 07.
Article in English | MEDLINE | ID: mdl-37805612

ABSTRACT

Magnetic liquid metal (LM) soft robots attract considerable attentions because of distinctive immiscibility, deformability and maneuverability. However, conventional LM composites relying on alloying between LM and metallic magnetic powders suffer from diminished magnetism over time and potential safety risk upon leakage of metallic components. Herein, we report a strategy to composite inert and biocompatible iron oxide (Fe3O4) magnetic nanoparticles into eutectic gallium indium LM via reactive wetting mechanism. To address the intrinsic interfacial non-wettability between Fe3O4 and LM, a silver intermediate layer was introduced to fuse with indium component into AgxIny intermetallic compounds, facilitating the anchoring of Fe3O4 nanoparticles inside LM with improved magnetic stability. Subsequently, a miniature soft robot was constructed to perform various controllable deformation and locomotion behaviors under actuation of external magnetic field. Finally, practical feasibility of applying LM soft robot in an ex vivo porcine stomach was validated under in-situ monitoring by endoscope and X-ray imaging.

17.
Sci Adv ; 9(50): eadj0883, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-38100592

ABSTRACT

The magnetic microrobots promise benefits in minimally invasive cell-based therapy. However, they generally suffer from an inevitable compromise between their magnetic responsiveness and biomedical functions. Herein, we report a modularized microrobot consisting of magnetic actuation (MA) and cell scaffold (CS) modules. The MA module with strong magnetism and pH-responsive deformability and the CS module with cell loading-release capabilities were fabricated by three-dimensional printing technique. Subsequently, assembly of modules was performed by designing a shaft-hole structure and customizing their relative dimensions, which enabled magnetic navigation in complex environments, while not deteriorating the cellular functionalities. On-demand disassembly at targeted lesion was then realized to facilitate CS module delivery and retrieval of the MA module. Furthermore, the feasibility of proposed system was validated in an in vivo rabbit bile duct. Therefore, this work presents a modular design-based strategy that enables uncompromised fabrication of multifunctional microrobots and stimulates their development for future cell-based therapy.


Subject(s)
Cell- and Tissue-Based Therapy , Drug Delivery Systems , Animals , Rabbits , Drug Delivery Systems/methods , Printing, Three-Dimensional
18.
Sci Adv ; 9(10): eade8622, 2023 03 10.
Article in English | MEDLINE | ID: mdl-36888700

ABSTRACT

Electrical stimulation is a promising method to modulate gastrointestinal disorders. However, conventional stimulators need invasive implantation and removal surgeries associated with risks of infection and secondary injuries. Here, we report a battery-free and deformable electronic esophageal stent for wireless stimulation of the lower esophageal sphincter in a noninvasive fashion. The stent consists of an elastic receiver antenna infilled with liquid metal (eutectic gallium-indium), a superelastic nitinol stent skeleton, and a stretchable pulse generator that jointly enables 150% axial elongation and 50% radial compression for transoral delivery through the narrow esophagus. The compliant stent adaptive to the dynamic environment of the esophagus can wirelessly harvest energy through deep tissue. Continuous electrical stimulations delivered by the stent in vivo using pig models significantly increase the pressure of the lower esophageal sphincter. The electronic stent provides a noninvasive platform for bioelectronic therapies in the gastrointestinal tract without the need for open surgery.


Subject(s)
Esophageal Sphincter, Lower , Gastrointestinal Tract , Animals , Swine , Stents , Pressure , Electric Stimulation
19.
ACS Nano ; 16(1): 604-616, 2022 Jan 25.
Article in English | MEDLINE | ID: mdl-34985859

ABSTRACT

Untethered small-scale robots offer great promise for medical applications in complex biological environments. However, challenges remain in the control and medical imaging of a robot for targeted delivery inside a living body, especially in flowing conditions (e.g., blood vessels). In this work, we report a strategy to autonomously navigate a miniature helical robot in dynamic blood flow under ultrasound Doppler imaging guidance. A magnetic torque and force-hybrid control approach is implemented, enabling the actuation of a millimeter-scale helical robot against blood flow under a rotating magnetic field with a controllable field gradient. Experimental results demonstrate that the robot (length 7.30 mm; diameter 2.15 mm) exhibits controlled navigation in vascular environments, including upstream and downstream navigation in flowing and pulsatile flowing blood with flow rates up to 24 mL/min (mean flow velocity: 14.15 mm/s). During navigation, the rotating robot-induced Doppler signals enable real-time localization and tracking in flowing and pulsatile flowing blood environments. Moreover, the robot can be selectively navigated along different paths by actively controlling the robot's orientation. We apply this autonomous strategy for localizing thrombus and accelerating thrombolysis rate. Compared with conventional tissue plasminogen activator (tPA) thrombolysis, the robot-enhanced shear stress and tPA convection near the clot-blood interface increase the unblocking and thrombolysis efficiency up to 4.8- and 3.5-fold, respectively. Such a medical imaging-guided navigation strategy provides simultaneous robot navigation and localization in complex dynamic biological environments, providing an intelligent approach toward real-time targeted delivery and diagnostic applications in vivo.


Subject(s)
Robotics , Tissue Plasminogen Activator , Magnetics , Magnetic Fields , Thrombolytic Therapy
20.
ACS Nano ; 16(11): 19025-19037, 2022 11 22.
Article in English | MEDLINE | ID: mdl-36367748

ABSTRACT

The rapidly transformed morphology of natural swarms enables fast response to environmental changes. Artificial microswarms can reconfigure their swarm patterns like natural swarms, which have drawn extensive attention due to their active adaptability in complex environments. However, as a prerequisite for biomedical applications of microswarms in confined environments, achieving on-demand control of pattern transformation rates remains a challenge. In this work, we report a strategy for optimizing pattern transformation rates of colloidal microswarms by coordinating the inner interactions. The influences of magnetic field parameters on pattern transformation rates are theoretically and experimentally studied, which elucidates the mechanism for optimal transformation rate control. The feasibility of the strategy is then validated in viscous Newtonian fluids and non-Newtonian biofluids. Moreover, the strategy is further validated in dynamic flow environments, exhibiting a promising future for practical applications in targeted delivery tasks with an optimal pattern transformation manner.


Subject(s)
Magnetic Fields , Magnetics , Viscosity
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