To fuse or not to fuse: The elderly patient with lumbar stenosis and low-grade spondylolisthesis. Systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: The optimum surgical intervention for elderly patients with lumbar spinal stenosis (LSS) and low-grade degenerative-spondylolisthesis (LGDS) has been extensively debated. We conducted a systematic review and meta-analysis of randomised-controlled-trials (RCTs) comparing the effectiveness of decompression-alone against the gold-standard approach of decompression-with-fusion (D + F) in elderly patients with LSS and LGDS. METHODS: A systematic literature search was performed on published databases from inception to October-2021. English-language RCTs of elderly patients (mean age over-65) with LSS and LGDS, who had undergone DA or D + F were included. The quality and weight of evidence was assessed, and a meta-analysis performed. RESULTS: Six RCTs (n = 531; mean age: 66.2 years; 57.8% female) were included. There was no difference in visual-analogue-scale (VAS) scores of back-pain (BP) or leg-pain (LP) at mean follow-up of 27.4 months between both DA and D + F groups (BP: mean-difference (MD)0.24, 95%CI: -0.38-0.85; LP MD:0.39, 95%CI: -0.34-1.11). No difference in disability, measured by Oswestry-Disability-Index scores, was found between both groups (MD:0.50, 95%CI: -3.31-4.31). However, patients in DA group had less hospital complications and fewer adverse events (total-surgical-complications OR:0.57, 95%CI: 0.36-0.90), despite a higher rate of worsening DS (OR:3.49, 95%CI: 1.05-11.65). No difference in BP or LP was found in subgroup-analysis of open-laminectomy compared to posterolateral-fusion (PLF) (BP: MD: -0.24, 95%CI: -1.80-1.32; LP MD:0.80, 95%CI: -0.95-2.55). CONCLUSIONS: DA is not inferior to D + F in elderly patients with LSS and LGDS. DA carries a lower risk of hospital complications and fewer adverse events, however, surgeons should weigh these findings with the increased risk of DS progressing post-operatively.

How to spot the recurring lumbar disc? Risk factors for recurrent lumbar disc herniation (rLDH) in adult patients with lumbar disc prolapse: a systematic review and meta-analysis.

Despite a fast-growing evidence-base examining the relationship of certain clinical and radiological factors such as smoking, BMI and herniation-type with rLDH, there remains much debate around which factors are clinically important. We conducted a systematic review and meta-analysis to identify risk factors for recurrent lumbar disc herniation (rLDH) in adults after primary discectomy. A systematic literature search was carried out using Ovid-Medline, EMBASE, Cochrane library and Web of Science databases from inception to 23rd June-2022. Observational studies of adult patients with radiologically-confirmed rLDH after ≥3 months of the initial surgery were included, and their quality assessed using the Quality-In-Prognostic-Studies (QUIPS) appraisal tool. Meta-analyses of univariate and multivariate data and a sensitivity-analysis for rLDH post-microdiscectomy were performed. Twelve studies (n=4497, mean age:47.3; 34.5% female) were included, and 11 studies (n=4235) meta-analysed. The mean follow-up was 38.4 months. Mean recurrence rate was 13.1% and mean time-to-recurrence was 24.1 months (range: 6-90 months). Clinically, older age (OR:1.04, 95%CI:1.00-1.08, n=1014), diabetes mellitus (OR:3.82, 95%CI:1.58-9.26, n=2330) and smoking (OR:1.80, 95%CI:1.03- 3.14, n=3425) increased likelihood of recurrence. Radiologically, Modic-change type-2 (OR:7.93, 95%CI:5.70-11.05, n=1706) and disc extrusion (OR:12.23, 95%CI:8.60-17.38, n=1706) increased likelihood of recurrence. The evidence did not support an association between rLDH and sex; BMI; occupational labour/driving; alcohol-consumption; Pfirmann- grade, or herniation-level. Older patients, smokers, patients with diabetes, those with type-2 Modic-changes or disc extrusion are more likely to experience rLDH. Higher quality studies with robust adjustment of confounders are required to determine the clinical bearing of all other potential risk factors for rLDH.

Association between different methods of assessing blood pressure variability and incident cardiovascular disease, cardiovascular mortality and all-cause mortality: a systematic review.

BACKGROUND: Blood pressure variability (BPV) is a possible risk factor for adverse cardiovascular outcomes and mortality. There is uncertainty as to whether BPV is related to differences in populations studied, measurement methods or both. We systematically reviewed the evidence for different methods to assess blood pressure variability (BPV) and their association with future cardiovascular events, cardiovascular mortality and all-cause mortality. METHODS: Literature databases were searched to June 2019. Observational studies were eligible if they measured short-term BPV, defined as variability in blood pressure measurements acquired either over a 24-hour period or several days. Data were extracted on method of BPV and reported association (or not) on future cardiovascular events, cardiovascular mortality and all-cause mortality. Methodological quality was assessed using the CASP observational study tool and data narratively synthesised. RESULTS: Sixty-one studies including 3,333,801 individuals were eligible. BPV has been assessed by various methods including ambulatory and home-based BP monitors assessing 24-hour, "day-by-day" and "week-to-week" variability. There was moderate quality evidence of an association between BPV and cardiovascular events (43 studies analysed) or all-cause mortality (26 studies analysed) irrespective of the measurement method in the short- to longer-term. There was moderate quality evidence reporting inconsistent findings on the potential association between cardiovascular mortality, irrespective of methods of BPV assessment (17 studies analysed). CONCLUSION: An association between BPV, cardiovascular mortality and cardiovascular events and/or all-cause mortality were reported by the majority of studies irrespective of method of measurement. Direct comparisons between studies and reporting of pooled effect sizes were not possible.

Gadopentatic acid affects in vitro proliferation and doxorubicin response in human breast adenocarcinoma cells.

Contrasting agents (CAs) that are administered to patients during magnetic resonance imaging to facilitate tumor identification are generally considered harmless. However, gadolinium (Gd) based contrast agents can be retained in the body, inflicting specific cell line cytotoxicity. We investigate the effect of Gadopentatic acid (Gd-DTPA) on human breast adenocarcinoma MCF-7 cells. These cells exhibit a toggle switch response: exposure to 0.1 and 1 mM concentrations of Gd-DTPA enhances proliferation, which is hindered at a higher 10 mM concentration. Proliferation is enhanced when cells transition to 3D morphologies in post confluent conditions. The proliferation dependence on the concentration of CA is absent for Hs 578T and MDA-MB-231 triple negative cell lines. MCF-7 cells reveal a double toggle switch related to the expression of VEGF, which goes through high-low-high downregulation when cells are exposed to 0.1, 1, and 10 mM Gd-DTPA, respectively. Finally, doxorubicin drug response is assessed, which also reveals a double toggle switch behavior, where drug cytotoxicity exhibits a nonlinear dependence on the CA concentration. A toggle switch in cell characteristics that are exposed to 1 mM of Gd-DTPA amplifies the importance of this threshold, affecting several cell behaviors if surpassed. This work emphasizes the important effects that CAs can have on cells, specifically Gd-DTPA on MCF-7 cells, and the implications for cell growth and drug response during clinical and synthetic biology procedures.

Evaluating the effects of simulation training on stroke thrombolysis: a systematic review and meta-analysis.

BACKGROUND: Ischaemic strokes are medical emergencies, and reperfusion treatment, most commonly intravenous thrombolysis, is time-critical. Thrombolysis administration relies on well-organised pathways of care with highly skilled and efficient clinicians. Simulation training is a widespread teaching modality, but results from studies on the impact of this intervention have yet to be synthesised. This systematic review and meta-analysis aimed to synthesise the evidence and provide a recommendation regarding the effects of simulation training for healthcare professionals on door-to-needle time in the emergency thrombolysis of patients with ischaemic stroke. METHODS: Seven electronic databases were systematically searched (last updated 12th July 2023) for eligible full-text articles and conference abstracts. Results were screened for relevance by two independent reviewers. The primary outcome was door-to-needle time for recombinant tissue plasminogen activator administration in emergency patients with ischaemic stroke. The secondary outcomes were learner-centred, improvements in knowledge and communication, self-perceived usefulness of training, and feeling 'safe' in thrombolysis-related decision-making. Data were extracted, risk of study bias assessed, and analysis was performed using RevMan™ software (Web version 5.6.0, The Cochrane Collaboration). The quality of the evidence was assessed using the Medical Education Research Study Quality Instrument. RESULTS: Eleven studies were included in the meta-analysis and nineteen in the qualitative synthesis (n = 20,189 total patients). There were statistically significant effects of simulation training in reducing door-to-needle time; mean difference of 15 min [95% confidence intervals (CI) 8 to 21 min]; in improving healthcare professionals' acute stroke care knowledge; risk ratio (RR) 0.42 (95% CI 0.30 to 0.60); and in feeling 'safe' in thrombolysis-related decision-making; RR 0.46 (95% CI 0.36 to 0.59). Furthermore, simulation training improved healthcare professionals' communication and was self-perceived as useful training. CONCLUSION: This meta-analysis showed that simulation training improves door-to-needle times for the delivery of thrombolysis in ischaemic stroke. However, results should be interpreted with caution due to the heterogeneity of the included studies.

Mechanical Actuation of Organoids in Synthetic Microenvironments.

Organoids are a powerful model system to explore the role of mechanical forces in sculpting emergent tissue cytoarchitecture. The modulation of the mechanical microenvironment is most readily performed using synthetic extracellular matrices (ECM); however, such materials provide passive, rather than active force modulation. Actuation technologies enable the active tuning of mechanical forces in both time and magnitude. Using such instruments, our group has shown that extrinsically imposed stretching on human neural tube organoids (hNTOs) enhanced patterning of the floor plate domain. Here, we provide a detailed protocol on the implementation of mechanical actuation of organoids embedded in synthetic 3D microenvironments, with additional details on methods to characterize organoid fate and behavior. Our protocol is easy to reproduce and is expected to be broadly applicable to investigate the role of active mechanics with in vitro model systems.

Force-mediated recruitment and reprogramming of healthy endothelial cells drive vascular lesion growth.

Force-driven cellular interactions are crucial for cancer cell invasion but remain underexplored in vascular abnormalities. Cerebral cavernous malformations (CCM), a vascular abnormality characterized by leaky vessels, involves CCM mutant cells recruiting wild-type endothelial cells to form and expand mosaic lesions. The mechanisms behind this recruitment remain poorly understood. Here, we use an in-vitro model of angiogenic invasion with traction force microscopy to reveal that hyper-angiogenic Ccm2-silenced endothelial cells enhance angiogenic invasion of neighboring wild-type cells through force and extracellular matrix-guided mechanisms. We demonstrate that mechanically hyperactive CCM2-silenced tips guide wild-type cells by transmitting pulling forces and by creating paths in the matrix, in a ROCKs-dependent manner. This is associated with reinforcement of ß1 integrin and actin cytoskeleton in wild-type cells. Further, wild-type cells are reprogrammed into stalk cells and activate matrisome and DNA replication programs, thereby initiating proliferation. Our findings reveal how CCM2 mutants hijack wild-type cell functions to fuel lesion growth, providing insight into the etiology of vascular malformations. By integrating biophysical and molecular techniques, we offer tools for studying cell mechanics in tissue heterogeneity and disease progression.

[Sex differences in stroke mortality in Thailand : A National cohort study]. / Différences sexuelles dans la mortalité par accident vasculaire cérébral en Thaïlande : une étude de cohorte nationale.

BACKGROUND: Over half of the growing global stroke-mortality burden is accounted for by the East-Asian-subcontinent alone. Sex differences in stroke-mortality in the Asian population is yet to be assessed in the literature. We aimed to assess the sex-differences in mortality following stroke in a large cohort of Thai-patients. METHOD: All stroke admissions between 2004-2015 were included from the Thailand public-health-insurance-database. The association between sex and mortality was assessed in-hospital, at 1 month, 1 year and 5 years, using multivariable Cox-regressions, separately for ischaemic-stroke (IS), haemorrhagic-stroke (HS) and stroke-of-undetermined-type(SUT), adjusting for confounders. RESULTS: 608,890 patients were included: 370,527 patients with IS(60.9%), 173,236 with HS(28.5%) and 65,127 with SUT(10.6%). Women were older than men in all three groups and had higher prevalence of comorbidities. Adjusted hazard-ratios(HRs) of mortality showed women had higher mortality post-IS compared to men (in-hospital: HR: 1.20; 95% CI: 1.17-1.23; 1 month: HR: 1.17; 95% CI: 1.15-1.20; 1 year: HR: 1.10; 95% CI: 1.09-1.12 and 5 years: HR: 1.02; 95% CI: 1.01-1.03). Women also had higher mortality after HS (in-hospital: HR: 1.02; 95% CI: 1.00-1.04; 1 month: HR: 1.08; 95% CI: 1.06-1.10; 1 year: HR: 1.04; 95% CI: 1.03-1.06 and 5 years: HR: 1.09; 95% CI: 1.08-1.11), and SUT (in-hospital: HR: 1.04; 95% CI: 1.03-1.06; 1 month: HR: 1.20; 95% CI: 1.14-1.27; 1 year: HR: 1.14; 95% CI: 1.09-1.18 and 5 years: HR: 1.06; 95% CI: 1.03-1.10). CONCLUSIONS: Compared to men, women were older at time of stroke-diagnosis and had higher burden of stroke risk-factors. Women also had higher mortality after stroke regardless of stroke-type or duration since stroke-onset. Post-IS, excess stroke-mortality in women was greatest during the in-hospital period, whereas excess stroke-mortality increased with time in women who had HS. No clear relationship was found between duration since stroke-onset and mortality in patients who had SUT.

Targeted mechanical stimulation via magnetic nanoparticles guides in vitro tissue development.

Tissues take shape through a series of morphogenetic movements guided by local cell-scale mechanical forces. Current in vitro approaches to recapitulate tissue mechanics rely on uncontrolled self-organization or on the imposition of extrinsic and homogenous forces using matrix or instrument-driven stimulation, thereby failing to recapitulate highly localized and spatially varying forces. Here we develop a method for targeted mechanical stimulation of organoids using embedded magnetic nanoparticles. We show that magnetic clusters within organoids can be produced by sequential aggregation of magnetically labeled and non-labeled human pluripotent stem cells. These clusters impose local mechanical forces on the surrounding cells in response to applied magnetic fields. We show that precise, spatially defined actuation provides short-term mechanical tissue perturbations as well as long-term cytoskeleton remodeling in these organoids, which we term "magnetoids". We demonstrate that targeted magnetic nanoparticle-driven actuation guides asymmetric tissue growth and proliferation, leading to enhanced patterning in human neural magnetoids. This approach, enabled by nanoparticle technology, allows for precise and locally controllable mechanical actuation in human neural tube organoids, and could be widely applicable to interrogate the role of local mechanotransduction in developmental and disease model systems.

Neuroepithelial organoid patterning is mediated by a neighborhood watch mechanism.

During epithelial tissue patterning, morphogens operate across multiple length scales to instruct cell identities. However, how cell fate changes are coordinated over these scales to establish spatial organization remains poorly understood. Here, we use human neural tube organoids as models of epithelial patterning and develop an in silico approach to define conditions permissive to patterning. By systematically varying morphogen position, diffusivity, and fate-inducing concentration levels, we show that cells follow a "neighborhood watch" (NW) mechanism that is deterministically dictated by initial morphogen source positions, reflecting scale-invariant in vitro phenotypes. We define how the frequency and local bias of morphogen sources stabilize pattern orientation. The model predicts enhanced patterning through floor plate inhibition, and receptor-ligand interaction analysis of single-cell RNA sequencing (scRNA-seq) data identifies wingless-related integration site (WNT) and bone morphogenic protein (BMP) as inhibition modulators, which we validate in vitro. These results suggest that developing neuroepithelia employ NW-based mechanisms to organize morphogen sources, define cellular identity, and establish patterns.

Large-scale perfused tissues via synthetic 3D soft microfluidics.

The vascularization of engineered tissues and organoids has remained a major unresolved challenge in regenerative medicine. While multiple approaches have been developed to vascularize in vitro tissues, it has thus far not been possible to generate sufficiently dense networks of small-scale vessels to perfuse large de novo tissues. Here, we achieve the perfusion of multi-mm3 tissue constructs by generating networks of synthetic capillary-scale 3D vessels. Our 3D soft microfluidic strategy is uniquely enabled by a 3D-printable 2-photon-polymerizable hydrogel formulation, which allows for precise microvessel printing at scales below the diffusion limit of living tissues. We demonstrate that these large-scale engineered tissues are viable, proliferative and exhibit complex morphogenesis during long-term in-vitro culture, while avoiding hypoxia and necrosis. We show by scRNAseq and immunohistochemistry that neural differentiation is significantly accelerated in perfused neural constructs. Additionally, we illustrate the versatility of this platform by demonstrating long-term perfusion of developing neural and liver tissue. This fully synthetic vascularization platform opens the door to the generation of human tissue models at unprecedented scale and complexity.

Gender differences in mortality of hospitalised stroke patients. Systematic review and meta-analysis.

OBJECTIVE: Gender differences in mortality after stroke remains unclear in the current literature. We therefore aimed to systematically review the gender differences in mortality up to five years after ischaemic (IS) or haemorrhagic stroke (HS) to address this evidence gap. METHODS: The literature was systematically searched using Ovid EMBASE, Ovid Medline, and Web of Science databases, from inception-November 2021. The quality of evidence was appraised using the CASP Cohort-study checklist. Unadjusted and adjusted odds and hazard ratios were meta-analysed, separately for IS and HS and a subgroup analysis of age-stratified mortality data was conducted. RESULTS: Forty-one studies were included (n = 8,128,700; mean-age 68.5 yrs; 47.1% female). 37 studies were included in meta-analysis (n = 8, 8008, 110). Compared to men, women who had an IS had lower mortality risk in-hospital (0.94; 95%CI 0.91-0.97), at one-month (0.87; 95%CI 0.77-0.98), 12-months (0.94; 95%CI 0.91-0.98) and five-years (0.93 95%CI 0.90-0.96). The subgroup analysis showed that this gender difference in mortality was present in women ≥ 70 years up to one-month post-IS (in-hospital: 0.94; 95%CI 0.91-0.97; one-month: 0.87; 95% CI 0.77-0.98), however, in women < 70 years this difference was no longer present. Nevertheless, analysis of crude data showed women were at higher risk of mortality in-hospital, at 12-months and five-years (in-hospital: 1.05; 95%CI 1.03-1.07, 12-months: 1.10; 95%CI 1.06-1.14, five-years: 1.06; 95%CI 1.02-1.10). After HS, women had higher mortality risk in-hospital (1.03; 95%CI 1.01-1.04) however, no gender differences were found post-discharge. CONCLUSION: The gender differences in post-stroke mortality differ by stroke type, age group and follow-up. Crude stroke mortality in women is higher than in men and this appears to be driven by pre-existing comorbidities. In adjusted models, women have a lower mortality risk following IS, independent of duration of follow-up. After HS, women had higher mortality in hospital however, no gender differences after hospital discharge were found.

Engineering neurovascular organoids with 3D printed microfluidic chips.

The generation of tissue and organs requires close interaction with vasculature from the earliest moments of embryonic development. Tissue-specific organoids derived from pluripotent stem cells allow for the in vitro recapitulation of elements of embryonic development. However, they are not intrinsically vascularized, which poses a major challenge for their sustained growth, and for understanding the role of vasculature in fate specification and morphogenesis. Current organoid vascularization strategies do not recapitulate the temporal synchronization and spatial orientation needed to ensure in vivo-like early co-development. Here, we developed a human pluripotent stem cell (hPSC)-based approach to generate organoids which interact with vascular cells in a spatially determined manner. The spatial interaction between organoid and vasculature is enabled by the use of a custom designed 3D printed microfluidic chip which allows for a sequential and developmentally matched co-culture system. We show that on-chip hPSC-derived pericytes and endothelial cells sprout and self-assemble into organized vascular networks, and use cerebral organoids as a model system to explore interactions with this de novo generated vasculature. Upon co-development, vascular cells physically interact with the cerebral organoid and form an integrated neurovascular organoid on chip. This 3D printing-based platform is designed to be compatible with any organoid system and is an easy and highly cost-effective way to vascularize organoids. The use of this platform, readily performed in any lab, could open new avenues for understanding and manipulating the co-development of tissue-specific organoids with vasculature.

Actuation enhances patterning in human neural tube organoids.

Tissues achieve their complex spatial organization through an interplay between gene regulatory networks, cell-cell communication, and physical interactions mediated by mechanical forces. Current strategies to generate in-vitro tissues have largely failed to implement such active, dynamically coordinated mechanical manipulations, relying instead on extracellular matrices which respond to, rather than impose mechanical forces. Here, we develop devices that enable the actuation of organoids. We show that active mechanical forces increase growth and lead to enhanced patterning in an organoid model of the neural tube derived from single human pluripotent stem cells (hPSC). Using a combination of single-cell transcriptomics and immunohistochemistry, we demonstrate that organoid mechanoregulation due to actuation operates in a temporally restricted competence window, and that organoid response to stretch is mediated extracellularly by matrix stiffness and intracellularly by cytoskeleton contractility and planar cell polarity. Exerting active mechanical forces on organoids using the approaches developed here is widely applicable and should enable the generation of more reproducible, programmable organoid shape, identity and patterns, opening avenues for the use of these tools in regenerative medicine and disease modelling applications.

Nanoparticles as Versatile Tools for Mechanotransduction in Tissues and Organoids.

Organoids are 3D multicellular constructs that rely on self-organized cell differentiation, patterning and morphogenesis to recapitulate key features of the form and function of tissues and organs of interest. Dynamic changes in these systems are orchestrated by biochemical and mechanical microenvironments, which can be engineered and manipulated to probe their role in developmental and disease mechanisms. In particular, the in vitro investigation of mechanical cues has been the focus of recent research, where mechanical manipulations imparting local as well as large-scale mechanical stresses aim to mimic in vivo tissue deformations which occur through proliferation, folding, invagination, and elongation. However, current in vitro approaches largely impose homogeneous mechanical changes via a host matrix and lack the required positional and directional specificity to mimic the diversity of in vivo scenarios. Thus, while organoids exhibit limited aspects of in vivo morphogenetic events, how local forces are coordinated to enable large-scale changes in tissue architecture remains a difficult question to address using current techniques. Nanoparticles, through their efficient internalization by cells and dispersion through extracellular matrices, have the ability to provide local or global, as well as passive or active modulation of mechanical stresses on organoids and tissues. In this review, we explore how nanoparticles can be used to manipulate matrix and tissue mechanics, and highlight their potential as tools for fate regulation through mechanotransduction in multicellular model systems.

3D cellular structures and co-cultures formed through the contactless magnetic manipulation of cells on adherent surfaces.

A magnet array is employed to manipulate diamagnetic cells that are contained in paramagnetic medium to demonstrate for the first time the contactless bioprinting of three-dimensional (3D) cellular structures and co-cultures of breast cancer MCF-7 and endothelial HUVEC at prescribed locations on tissue culture treated well plates. Sequential seeding of different cell lines and the spatial displacement of the magnet array creates co-cultured cellular structures within a well without using physically intrusive well inserts. Both monotypic and co-culture experiments produce morphologically rich 3D cell structures that are otherwise absent in regular monolayer cell cultures. The magnetic contactless bioprinting of cells provides further insight into cell behaviour, invasion strategies and transformations that are useful for potential applications in drug screening, 3D cell culture formation and tissue engineering.

Printing Three-Dimensional Heterogeneities in the Elastic Modulus of an Elastomeric Matrix.

We present a rapid and controllable method to create microscale heterogeneities in the 3D stiffness of a soft material by printing patterns with a ferrofluid ink. An ink droplet moved through a liquid polydimethylsiloxane (PDMS) volume using an externally applied magnetic field sheds clusters of magnetic nanoparticles (MNPs) in its wake. By varying the field spatiotemporally, a well-defined three-dimensional curvilinear feature is printed that contains MNP clusters. Subsequent cross-linking of the PDMS preserves the feature in place after the magnetic field is removed. Since the ferrofluid ink interferes with the cross-linking of PDMS, a 3D print containing ink density variations leads to corresponding spatial deviations in the elastic modulus of the matrix. The modulus is mapped in the experiments with atomic force microscopy. This rapid method to print 3D heterogeneities in soft matter promises the ability to mimic mechanical variations that occur in natural biomaterials.

High gradient magnetic field microstructures for magnetophoretic cell separation.

Microfluidics has advanced magnetic blood fractionation by making integrated miniature devices possible. A ferromagnetic microstructure array that is integrated with a microfluidic channel rearranges an applied magnetic field to create a high gradient magnetic field (HGMF). By leveraging the differential magnetic susceptibilities of cell types contained in a host medium, such as paramagnetic red blood cells (RBCs) and diamagnetic white blood cells (WBCs), the resulting HGMF can be used to continuously separate them without attaching additional labels, such as magnetic beads, to them. We describe the effect of these ferromagnetic microstructure geometries have on the blood separation efficacy by numerically simulating the influence of microstructure height and pitch on the HGMF characteristics and resulting RBC separation. Visualizations of RBC trajectories provide insight into how arrays can be optimized to best separate these cells from a host fluid. Periodic microstructures are shown to moderate the applied field due to magnetic interference between the adjacent teeth of an array. Since continuous microstructures do not similarly weaken the resultant HGMF, they facilitate significantly higher RBC separation. Nevertheless, periodic arrays are more appropriate for relatively deep microchannels since, unlike continuous microstructures, their separation effectiveness is independent of depth. The results are relevant to the design of microfluidic devices that leverage HGMFs to fractionate blood by separating RBCs and WBCs.

Nickel Nanoparticles Entangled in Carbon Nanotubes: Novel Ink for Nanotube Printing.

We report the serendipitous discovery of a rapid and inexpensive method to attach nanoscale magnetic chaperones to carbon nanotubes (CNTs). Nickel nanoparticles (NiNPs) become entangled in CNTs after both are dispersed in kerosene by sonication and form conjugates. An externally applied magnetic field manipulates the resulting CNTs-NiNP ink without NiNP separation, allowing us to print an embedded circuit in an elastomeric matrix and fabricate a strain gage and an oil sensor. The new method to print a circuit in a soft material using an NiNP-CNT ink is more rapid and inexpensive than the complex physical and chemical means typically used to magnetize CNTs.

In Situ 3D Label-Free Contactless Bioprinting of Cells through Diamagnetophoresis.

Using whole blood, we demonstrate the first realization of a novel macroscale, contactless, label-free method to print in situ three-dimensional (3D) cell assemblies of different morphologies and sizes. This novel bioprinting method does not use nozzles that can contaminate the cell suspension, or to which cells can adhere. Instead, we utilize the intrinsic diamagnetic properties of whole blood cells to magnetically manipulate them in situ in a nontoxic paramagnetic medium, creating (a) rectangular bar, (b) three-pointed star, and (c) spheroids of varying sizes. We envision the technique to be transferable to other cell lines, with potential applications in tissue engineering and drug screening.