In nature, various types of animals will form self-organised large-scale structures. Through designing wireless actuation methods, microrobots can emulate natural swarm behaviours, which have drawn ...extensive attention due to their great potential in biomedical applications. However, as the prerequisite for their in-vivo applications, whether microrobotic swarms can take effect in bio-fluids with complex components has yet to be fully investigated. In this work, we first categorise magnetic active swarms into three types, and individually investigate the generation and navigation behaviours of two types of the swarms in bio-fluids. The influences of viscosities, ionic strengths and mesh-like structures are studied. A strategy is then proposed to select the optimised swarms in different fluidic environments based on their physical properties, and the results are further validated in various bio-fluids. Moreover, we also realise the swarm generation and navigation in bovine eyeballs, which also validates the proposed prediction in the ex-vivo environment.
Biofilm eradication from medical implants is of fundamental importance, and the treatment of biofilm‐associated pathogen infections on inaccessible biliary stents remains challenging. Magnetically ...driven microrobots with controlled motility, accessibility to the tiny lumen, and swarm enhancement effects can physically disrupt the deleterious biostructures while not developing drug resistance. Magnetic urchin‐like capsule robots (MUCRs) loaded with magnetic liquid metal droplets (MLMDs, antibacterial agents) are designed using natural sunflower pollen, and the therapeutic effect of swarming MUCR@MLMDs is explored for eradicating complex mixtures of bacterial biofilm within biliary stents collected from patients. The external magnetic field triggers the emergence of the microswarm and induces MLMDs to transform their shape into spheroids and rods with sharp edges. The inherent natural microspikes of MUCRs and the obtained sharp edges of MLMDs actively rupture the dense biological matrix and multiple species of embedded bacterial cells by exerting mechanical force, finally achieving synergistic biofilm eradication. The microswarm is precisely and rapidly deployed into the biliary stent via endoscopy in 10 min. Notably, fluoroscopy imaging is used to track and navigate the locomotion of microswarm in biliary stents in real‐time. The microswarm has great potential for treating bacterial biofilm infections associated with medical implants.
A proposed magnetic microswarm, consisting of urchin‐like MUCR@MLMD, with controlled motility on a curved surface, restricted space accessibility, and swarm enhancement effects is expected to be of great value in treating bacterial biofilm infections associated with medical implants in situ. Moreover, a fluoroscopy‐imaging‐guided microswarm with rapid endoscopic delivery is demonstrated for biofilm eradication deep inside the body with high time efficiency.
Microrobotic delivery possesses a promising perspective for precision medicine and has attracted much attention recently. However, its automation remains challenging, especially with complex ...environmental conditions, such as obstacles and obstructed optical feedback. In this article, we propose an automated control approach for a new type of magnetic microrobot, i.e., the multifunctional magnetic spore (Mag-Spore), which has good potential for targeted delivery. By the surface functionalization of the spore with Fe 3 O 4 nanoparticles and carbon quantum dots (QDs), it can be remotely actuated and tracked by an electromagnetic coil system and the fluorescence microscopy, respectively. Our control approach uses fluorescence imaging for vision feedback, which enhances the recognition and tracking of Mag-Spores, obstacles, and cells. Then, information of the obstacles, targeted cells, and Mag-Spores for planning and control is identified by image processing, and an optimal path planner with obstacle-avoidance capability is designed based on the particle swarm optimization (PSO) algorithm. To make the Mag-Spore follow the planed path accurately, a robust model predictive trajectory-tracking controller is synthesized. Simulations are conducted to validate the proposed control approach and tune the control parameters. Experiments demonstrate the effective targeted delivery of the Mag-Spore by using the proposed automated control method under the guidance of fluorescence imaging. Note to Practitioners-This article was motivated by the recent wide interest of precise targeted delivery using biohybrid magnetic microrobots. Driven by external magnetic fields, microrobots accomplish the targeted delivery tasks. In practical applications, obstacles and obstructed optical feedback often exist that make the delivery task challenging. The Mag-Spore presented here has a hollow structure, so that the cargo-carrying capability is maximized and supported by the proposed automated control techniques, and the delivery precision and efficiency are promised in multiple-obstacle scenarios. In addition, the control method has the robustness to model uncertainties and external disturbances that should be considered and well solved in applications. Fluorescence imaging, a common way for observing biomaterials, is compatible with the proposed control scheme and the developed software so that the recognition and tracking of the Mag-Spore and other biomaterials are improved. Moreover, the self-established plug-and-play (PnP) electromagnetic magnetic coil system has the feature of easy installation and configuration on fluorescence microscopes. Simulations and experiments validate the effectiveness of our method in fluorescence-guided targeted delivery using magnetic microrobots.
Endoscopic submucosal dissection (ESD) is the current standard treatment for early-stage esophageal neoplasms. However, the postoperative esophageal stricture after extensive mucosal dissection ...remains a severe challenge with limited effective treatments available. In this study, we introduced a chitosan/gelatin (ChGel) sponge encapsulating the adipose mesenchymal stem cells (ADMSCs)-derived exosomes (ChGel
) for the prevention of esophageal stenosis after ESD in a porcine model.
Pigs were randomly assigned into (1) ChGel
treatment group, (2) ChGel
group, and (3) the controls. Exosome treatments were applied immediately on the day after ESD as well as on day 7. Exosome components crucial for wound healing were investigated by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and small RNA sequencing. ChGel
treatment significantly reduced mucosal contraction on day 21, with less fiber accumulation and inflammatory infiltration, and enhanced angiogenesis when compared with the control and ChGel
groups. The anti-fibrotic effects following MSC-Exo treatment were further found to be associated with the anti-inflammatory M2 polarization of the resident macrophages, especially within the M2b subset characterized by the reduced TGFβ1 secretion, which sufficiently inhibited inflammation and prevented the activation of myofibroblast with less collagen production at the early stage after ESD. Moreover, the abundant expression of exosomal MFGE8 was identified to be involved in the transition of the M2b-macrophage subset through the activation of MFGE8/STAT3/Arg1 axis.
Our study demonstrates that exosomal MFGE8 significantly promotes the polarization of the M2b-macrophage subset, consequently reducing collagen deposition. These findings suggest a promising potential for MSC-Exo therapy in preventing the development of esophageal stricture after near-circumferential ESD.
Ferromagnetic particles (FMPs) have attracted a large amount of attention for tumor treatment in recent decades in the form of magnetic hyperthermia and thermoablation therapies. Previous research ...has commonly focused on the improvement of the specific loss power and the increase in the particle concentration to enhance the heating temperature during hyperthermia. Instead of magnetic hyperthermia with passive particles, here a feasible approach of using reconfigurable swarms of ferromagnetic colloidal particles is reported to realize enhanced local hyperthermia. The concentration of the particle swarm can be tuned up to 500% of the original particle concentration via reversible pattern transformation, i.e., shrinking and swelling. The FMP swarms with a controllable pattern size show their potential for directed energy delivery and offer a new strategy for realizing a highly localized heating effect using a low dose of the active FMPs.
A reconfigurable ferromagnetic colloidal swarm is developed for enhanced local hyperthermia. The simulation and experimental results indicate that the local heating effects and the spatial resolution of the hyperthermia process can be significantly improved by using a microrobotic swarm.
To evaluate the midterm clinical and angiographic outcomes after pipeline embolization device (PED) placement for treatment of intracranial aneurysms.
This prospective nonrandomized multicenter study ...was approved by the review boards of all involved centers; informed consent was obtained. Patients (143 patients, 178 aneurysms) with unruptured saccular or fusiform aneurysms or recurrent aneurysms after previous treatment were included and observed angiographically for up to 18 months and clinically for up to 3 years. Study endpoints included complete aneurysm occlusion; neurologic complications within 30 days and up to 3 years; clinical outcome of cranial nerve palsy after PED placement; angiographic evidence of occlusion or stenosis of parent artery and that of occlusion of covered side branches at 6, 12, and 18 months; and clinical and computed tomographic evidence of perforator infarction.
There were five (3.5%) cases of periprocedural death or major stroke (modified Rankin Scale mRS > 3) (95% confidence interval CI: 1.3%, 8.4%), including two posttreatment delayed ruptures, two intracerebral hemorrhages, and one thromboembolism. Five (3.5%) patients had minor neurologic complications within 30 days (mRS = 1) (95% CI: 1.3%, 8.4%), including transient ischemic attack (n = 2), small cerebral infarction (n = 2), and cranial nerve palsy (n = 1). Beyond 30 days, there was one fatal intracerebral hemorrhage and one transient ischemic attack. Ten of 13 patients (95% CI: 46%, 93.8%) completely recovered from symptoms of cranial nerve palsy within a median of 3.5 months. Angiographic results at 18 months revealed a complete aneurysm occlusion rate of 84% (49 of 58; 95% CI: 72.1%, 92.2%), with no cases of parent artery occlusion, parent artery stenosis (<50%) in three patients, and occlusion of a covered side branch in two cases (posterior communicating arteries). Perforator infarction did not occur.
PED placement is a reasonably safe and effective treatment for intracranial aneurysms. The treatment is promising for aneurysms of unfavorable morphologic features, such as wide neck, large size, fusiform morphology, incorporation of side branches, and posttreatment recanalization, and should be considered a first choice for treating unruptured aneurysms and recurrent aneurysms after previous treatments.
http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120422/-/DC1.
Remote, noninvasive, and reversible control over the nanoscale presentation of bioactive ligands, such as Arg-Gly-Asp (RGD) peptide, is highly desirable for temporally regulating cellular functions ...in vivo. Herein, we present a novel strategy for physically uncaging RGD using a magnetic field that allows safe and deep tissue penetration. We developed a heterodimeric nanoswitch consisting of a magnetic nanocage (MNC) coupled to an underlying RGD-coated gold nanoparticle (AuNP) via a long flexible linker. Magnetically controlled movement of MNC relative to AuNP allowed reversible uncaging and caging of RGD that modulate physical accessibility of RGD for integrin binding, thereby regulating stem cell adhesion, both in vitro and in vivo. Reversible RGD uncaging by the magnetic nanoswitch allowed temporal regulation of stem cell adhesion, differentiation, and mechanosensing. This physical and reversible RGD uncaging utilizing heterodimeric magnetic nanoswitch is unprecedented and holds promise in the remote control of cellular behaviors in vivo.
Glioblastoma (GBM) is an aggressive primary malignant brain tumour with a dismal prognosis, despite the improvement from the new establishment of post-operative treatment protocol of concomitant ...chemoradiotherapy (CCRT) plus adjuvant chemotherapy. This study aimed to evaluate the health-related quality of life (HRQoL) in post-operative GBM patients treated with CCRT plus adjuvant chemotherapy with subjective standardised questionnaires at various time points.
Patients with newly diagnosed GBM who were treated at our centre with post-operative CCRT plus adjuvant chemotherapy were included. Their HRQoL scales were measured with the European Organisation for Research and Treatment of Cancer (EORTC) CLC30 and BN20 questionnaires. Assessments were made before the beginning of post-operative CCRT, and at 0 (within 2 weeks), 3 and 6 months after the end of CCRT. A mixed-level linear model was used to analyse the change in each HRQoL scale over time.
21 patients were recruited with a median overall survival of 27 months (range:4–55 months). There was no significant change in the global health status over time. An improvement in insomnia and an aggravation in communication deficit were found with statistical significance and clinical meaningfulness. Greater improvement in insomnia was associated with methylated MGMT gene promoter in the tumour while worse aggravation in communication deficit was associated with older age (≥65).
The global health status did not worsen during post-operative CCRT plus adjuvant chemotherapy, while the severity of insomnia lessened and communication deficit worsened. This may provide insight for clinicians to formulate treatment plan for patients with GBM.
Primary acquired nasolacrimal duct obstruction (PANDO) is the commonest cause of obstructive tearing and can lead to infections including dacryocystitis, cellulitis and postoperative endophthalmitis. ...External or endoscopic dacryocystorhinostomy (DCR) is the current standard treatment of PANDO. However, DCR is technically challenging, invasive, and not without risks, especially epistaxis and recurrent obstruction. We designed and constructed a magnetic micro-driller system for nasolacrimal duct (NLD) recanalization as a minimally invasive alternative to conventional treatment. The drilling microrobot consists of a 3D printed helical tip and a permanent magnet. A magnetic actuation system with three electromagnets is developed to well accommodate the human anatomy and generate three-dimensional dynamic magnetic fields along the NLD. To navigate the microrobot safely inside the NLD, the micro-driller is integrated with a guidewire and a feed drive system to control its motion. Furthermore, a force sensor is installed on the proximal end of the guidewire to report the force signal, through which the state of the micro-driller can be detected and the control input can be decided. Our results show that the guide-wired microrobot can navigate through the NLD phantom and remove the blockage automatically. The proposed strategy provides a microrobot-assisted endoluminal solution for NLD recanalization with improved safety by introducing the magnetic manipulation and force control method.
Coalescence and splitting of liquid marbles (LMs) are critical for the mixture of precise amount precursors and removal of the wastes in the microliter range. Here, the coalescence and splitting of ...LMs are realized by a simple gravity‐driven impact method and the two processes are systematically investigated to obtain the optimal parameters. The formation, coalescence, and splitting of LMs can be realized on‐demand with a designed channel box. By selecting the functional channels on the device, gravity‐based fusion and splitting of LMs are performed to mix medium/drugs and remove spent culture medium in a precise manner, thus ensuring that the microenvironment of the cells is maintained under optimal conditions. The LM‐based 3D stem cell spheroids are demonstrated to possess an approximately threefold of cell viability compared with the conventional spheroid obtained from nonadhesive plates. Delivery of the cell spheroid to a hydrophilic surface results in the in situ respreading of cells and gradual formation of typical 2D cell morphology, which offers the possibility for such spheroid‐based stem cell delivery in regenerative medicine.
An integrated device for the formation, coalescence, and splitting of liquid marbles is developed with automation. The proposed strategy shows its potential in in vitro cell spheroid production with high cell viability.
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