Biomedical Tools Research Articles

A Review of Endogenous and Exogenous Contrast Agents Used in Photoacoustic Tomography with Different Sensing Configurations.

Optical-based sensing approaches have long been an indispensable way to detect molecules in biological tissues for various biomedical research and applications. The advancement in optical microscopy is one of the main drivers for discoveries and innovations in both life science and biomedical imaging. However, the shallow imaging depth due to the use of ballistic photons fundamentally limits optical imaging approaches’ translational potential to a clinical setting. Photoacoustic (PA) tomography (PAT) is a rapidly growing hybrid imaging modality that is capable of acoustically detecting optical contrast. PAT uniquely enjoys high-resolution deep-tissue imaging owing to the utilization of diffused photons. The exploration of endogenous contrast agents and the development of exogenous contrast agents further improve the molecular specificity for PAT. PAT’s versatile design and non-invasive nature have proven its great potential as a biomedical imaging tool for a multitude of biomedical applications. In this review, representative endogenous and exogenous PA contrast agents will be introduced alongside common PAT system configurations, including the latest advances of all-optical acoustic sensing techniques.

Constitutive Modeling of multi-stimuli-responsive shape memory polymers with multi-functional capabilities

Nowadays, shape memory polymers (SMPs)-based devices are required to be much smarter to produce large shape memory recovery and recovery force with lower working temperatures in order to enable multi-functionality in them. They could play a vital role in the advancement of multi-functional soft robot manipulators, biomedical tools and wearable devices where the working temperatures is a key challenge and must be around the body temperature, or in sustainable smart systems with low energy consumption. The aim of this paper is to introduce thermo-electro-magneto-responsive fibrous SMPs (TEMFSMPs) as a new class of SMPs with highly enhanced shape recovery and recovery force and reduced working temperature. A three-dimensional constitutive model is developed to simulate thermo-electro-magneto-visco-hyperelastic behaviors of SMPs under large deformation for the first time. Constitutive relations are derived by adopting an electro-magneto-visco-hyperelasticity theory and implementing it in a thermo-mechanical cycle of SMPs. To improve the strength of thermo-electro-magneto-responsive SMPs, a bunch of fibers is also embedded into the SMP matrix. Then, the proposed model for thermo-electro-magneto-responsive fibrous shape memory polymers (TEMFSMPs) under uniaxial tension and complex loading regimes such as simultaneous torsion and extension are solved semi-analytically. In addition, the thermo-mechanical response through the proposed model is validated via available SMP experimental tests. Numerical results reveal that electro-magnetic features can significantly enhance shape memory recovery and recovery force of TEMFSMPs and lower their working temperatures. It is found that the electro-magnetic field, the orientation, and stiffness of fibers can effectively be set to tune the shape memory effect and bio-applicability of TEMFSMPs with highly enhanced stress/strain recovery and reduced working temperature.

The PrEPARE Pretoria Project: protocol for a cluster-randomized factorial-design trial to prevent HIV with PrEP among adolescent girls and young women in Tshwane, South Africa

BackgroundDespite increased prevention efforts, HIV remains the leading cause of death among adolescent girls and young women in South Africa. Although research indicates important determinants of HIV acquisition at the individual and interpersonal levels, structural-level stigma and discrimination continue to be critical barriers to reaching and retaining this key population for HIV prevention and sexual and reproductive health services. Innovative and multilevel interventions are needed that can address the intersectional structural and gender issues that young women face, including stigma, alcohol and drug use, gender-based violence, and other risk factors when seeking health services. Oral pre-exposure prophylaxis (PrEP) taken daily has been found to be an effective biomedical HIV prevention tool. Testing a comprehensive gender-focused biobehavioral HIV prevention intervention that is inclusive of social ecological determinants, such as stigma and discrimination reduction in clinics, is critical for reducing HIV among adolescent girls and young women.MethodsThis project involves both a Community Collaborative Board and a Youth Advisory Board in helping to adapt the Young Women’s Health CoOp intervention and the Health Policy Project (HPP) Stigma and Discrimination (S&D) reduction training curriculum to the setting and population. This study uses a two-by-two factorial design with stratified randomization of 12 clinics, each with distinct catchment areas. The Young Women’s Health CoOp addresses substance use, sexual risk, violence prevention and sexual negotiation, condom demonstration, and problem solving with the following additions: knowledge of PrEP, the importance of PrEP adherence, and sexual and reproductive health. Adolescent girls and young women will be assessed with behavioral and biological measures at baseline, 3-, 6- and 9-month follow-up. The S&D reduction training is provided for all staff in the clinics randomized to this condition. Clinic staff will be surveyed at baseline, 4- and 8-month follow-up. We will recruit 900 AGYW from communities in the 12 clinic catchment areas.DiscussionThe study findings, if efficacious across the outcomes, will be incorporated into the gender-focused HIV prevention intervention toolkit and disseminated to inform multilevel prevention approaches.Trial registrationClinicalTrials.gov. Identifier: NCT04048551 (Recruiting). Registered: August 7, 2019 (Retrospectively registered).

Recognition of nucleolin through interaction with RNA G-quadruplex

The development of novel biomarkers for early-stage diagnosis of prostate cancer (PCa) has attracted the attention of researchers in the last decade. Nucleolin (NCL) has emerged as a possible biomarker of PCa due to its high expression levels in the surface of PCa cells and affinity towards parallel G4s since it contains four RNA-binding domains (RBDs). Herein, we developed a novel strategy based on a microfluidic platform for the detection of NCL in biological samples, such as human plasma. The RNA G4 (rG4) sequence found in human precursor microRNA 92b (pre-miR-92b) was used as a molecular recognition probe since it forms a single dominant parallel rG4 conformation in the presence of 0.1 mM K+ as confirmed by NMR spectroscopy. The additional stability of the rG4 structure was provided by the acridine orange derivative ligand C8, which stabilizes the pre-miR-92b rG4 structure, as denoted by an increase in more than 30 °C of its melting temperature. FRET-melting assay revealed a remarkable synergistic effect of NCL RBD1,2 and C8 on the stabilization of the pre-miR-92b rG4. The binding of pre-miR-92b to NCL RBD1,2 was determined by in silico studies, which revealed a binding pocket formed by a 12-residue linker between RBD1 and RBD2. Both, pre-miR-92b rG4 and pre-miR-92b rG4/C8 complex demonstrated high affinity towards NCL RBD1,2, as proved by fluorimetric titrations (KD range between 10-12 and 10-9 M). The stability and nuclease resistance of pre-miR-92b rG4 and pre-miR-92b rG4/C8 complex were evaluated as molecular recognition probes to capture and detect NCL. Finally, the microfluidic platform detects NCL in complex biological samples, such as human plasma. Overall, this work demonstrates the usefulness of the microfluidic platform based on the pre-miR-92b to detect NCL and the possibility to be used as a valuable biomedical tool in PCa diagnosis.

Neuroimaging PheWAS (Phenome-Wide Association Study): A Free Cloud-Computing Platform for Big-Data, Brain-Wide Imaging Association Studies.

Large-scale, case-control genome-wide association studies (GWASs) have revealed genetic variations associated with diverse neurological and psychiatric disorders. Recent advances in neuroimaging and genomic databases of large healthy and diseased cohorts have empowered studies to characterize effects of the discovered genetic factors on brain structure and function, implicating neural pathways and genetic mechanisms in the underlying biology. However, the unprecedented scale and complexity of the imaging and genomic data requires new advanced biomedical data science tools to manage, process and analyze the data. In this work, we introduce Neuroimaging PheWAS (phenome-wide association study): a web-based system for searching over a wide variety of brain-wide imaging phenotypes to discover true system-level gene-brain relationships using a unified genotype-to-phenotype strategy. This design features a user-friendly graphical user interface (GUI) for anonymous data uploading, study definition and management, and interactive result visualizations as well as a cloud-based computational infrastructure and multiple state-of-art methods for statistical association analysis and multiple comparison correction. We demonstrated the potential of Neuroimaging PheWAS with a case study analyzing the influences of the apolipoprotein E (APOE) gene on various brain morphological properties across the brain in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. Benchmark tests were performed to evaluate the system's performance using data from UK Biobank. The Neuroimaging PheWAS system is freely available. It simplifies the execution of PheWAS on neuroimaging data and provides an opportunity for imaging genetics studies to elucidate routes at play for specific genetic variants on diseases in the context of detailed imaging phenotypic data.

Initiation of HIV pre-exposure prophylaxis in adolescents and young adults: Barriers and opportunities

Adolescents and young adults (AYA) ages 13 to 24 years comprise a quarter of the new HIV diagnoses in the United States. Lack of access to HIV-preventive biomedical tools such as pre-exposure prophylaxis (PrEP) reduces opportunities to prevent HIV infection in this population. Initiating PrEP in AYA significantly reduces the negative health outcomes of HIV, but many providers are still reluctant to initiate PrEP in their AYA patients based on perceived threats and barriers. This review aims to highlight the barriers and opportunities for initiating PrEP services in AYA and provides recommendations for PrEP services in this population. Ten scholarly articles rated levels IIA through IIIB were identified using the Johns Hopkins Evidence-Based Practice ratings. These included quasi-experimental and nonexperimental publications. Both quantitative and qualitative data contributed to identifying perceived barriers, opportunities, and recommendations for increased PrEP access and prescription in AYA. Pre-exposure prophylaxis is a vital component of a robust HIV prevention program. Themes that emerged hindering optimal PrEP utilization in AYA included provider-related barriers (e.g., knowledge deficit, lack of familiarity with PrEP guidelines, and protocols), patient-related barriers (e.g., lack of awareness, confidentiality issue, and HIV stigma), and structure-related barriers (e.g., lack of AYA-friendly clinics and insurance coverage). Providers in any setting should be able identify at-risk AYA and prescribe PrEP accordingly. Nurse practitioners should make PrEP accessible to AYA by addressing the barriers to PrEP utilization, prescribing, and continuity of care. Nurse practitioner curriculum, training, and continuing education should include PrEP for AYA.

The current landscape of pre-exposure prophylaxis service delivery models for HIV prevention: a scoping review

BackgroundStrengthening HIV prevention is imperative given the continued high HIV incidence worldwide. The introduction of oral PrEP as a new biomedical HIV prevention tool can be a potential game changer because of its high clinical efficacy and the feasibility of its provision to different key populations. Documenting the existing experience with PrEP service delivery in a variety of real-world settings will inform how its uptake and usage can be maximised.MethodsWe conducted a scoping review using the five-step framework provided by Arksey and O’Malley. We systematically searched the existing peer-reviewed international and grey literature describing the implementation of real-world PrEP service delivery models reporting on four key components: the target population of PrEP services, the setting where PrEP was delivered, PrEP providers’ professionalisation and PrEP delivery channels. We restricted our search to English language articles. No geographical or time restrictions were set.ResultsThis review included 33 articles for charting and analysing of the results. The identified service delivery models showed that PrEP services mainly targeted people at high risk of HIV acquisition, with some models targeting specific key populations, mainly men who have sex with men. PrEP was often delivered centralised and in a clinical or hospital setting. Yet also community-based as well as home-based PrEP delivery models were reported. Providers of PrEP were mainly clinically trained health professionals, but in some rare cases community workers and lay providers also delivered PrEP. In general, in-person visits were used to deliver PrEP. More innovative digital options using mHealth and telemedicine approaches to deliver specific parts of PrEP services are currently being applied in a minority of the service delivery models in mainly high-resource settings.ConclusionsA range of possible combinations was found between all four components of PrEP service delivery models. This reflects differentiation of care according to different contextual settings. More research is needed on how integration of services in these contexts could be expanded and optimised to respond to key populations with unmet HIV prevention needs in different settings.

Sexual Subcultures and HIV Prevention Methods: An Assessment of Condom Use, PrEP, and TasP Among Gay, Bisexual, and Other Men Who Have Sex with Men Using a Social and Sexual Networking Smartphone Application.

Despite being grouped together in epidemiological risk categories, gay, bisexual, and other men who have sex with men (GBM) are not a homogenous group. In addition to traditional segmentation along race, ethnicity, and socioeconomic status, many GBM also identify with sexual subcultural communities. Previous research has shown differences across a variety of health outcomes between these sexual subcultural communities. The purpose of this study was to determine whether HIV prevention practices among GBM differed according to sexual subcultural community. The study was conducted in collaboration with a popular social and sexual networking smartphone application company. A total of 23,577GBM responded to the survey. A latent class analysis identified 6 distinct classes related to sexual subcultural community identification. We found significant differences across sociodemographic characteristics, HIV prevention practices, and condomless anal sex in the past 6months related to sexual subculture identification. Findings suggest that sexual subcultural identity is related to decision-making around HIV prevention among GBM. Differences in HIV prevention strategies are likely a function of group norms, unique shared experiences among GBM identifying with a particular sexual subculture community, and sociodemographic characteristics associated with these groups. As such, sexual subculture identity should be considered in developing interventions and social marketing campaigns to increase uptake of biomedical HIV prevention tools among GBM. Identifying group norms and shared experiences related to HIV prevention practices among sexual subcultures is necessary to understand the role these identities play in lives of GBM, especially as it relates to their sexual health and well-being.

Emission-tunable probes using terbium(III)-doped self-activated luminescent hydroxyapatite for in vitro bioimaging

Lanthanide ion (Ln3+)-doped nanoscale hydroxyapatites (nHAp) with tunable luminescence have attracted increasing attention due to their potential applications as useful biomedical tools (e.g., imaging and clinical therapy). In this study, we reported that doping Terbium (III) ions (Tb3+) in self-activated luminescent nHAp via a facile hydrothermal reaction, using trisodium citrate (Cit3−), generates unique emission-tunable probes known as Cit/Tb-nHAp. The morphology, crystal phase, and luminescence properties of these Cit/Tb-nHAp probes are studied in detail. Moreover, the results demonstrate that the luminescence of self-activated nHAp originates from the carbon dots trapped within the nHAp crystals, in which partial energy transfer occurs from carbon dots (CDs) to Tb3+. The color tunability is successfully achieved by regulating the addition of Cit3−. Biocompatibility study indicates that when co-cultured with C6 glioma cells in vitro for 3 days, ≤800 ppm Cit/Tb-nHAp is not cytotoxic for C6 glioma cells. We also present in vitro data showing efficient cytoplasmic localization of transferrin conjugated Cit/Tb-nHAp into C6 glioma cells by fluorescence cell imaging. We have successfully engineered Cit/Tb-nHAp, a promising biocompatible agent for future in vitro and in vivo fluorescence bioimaging.

Using informatics to guide public health policy during the COVID-19 pandemic in the USA.

BackgroundCurrent and future pandemics will require informatics solutions to assess the risks, resources and policies to guide better public health decision-making.MethodsCross-sectional study of all COVID-19 cases and deaths in the USA on a population- and resource-adjusted basis (as of 24 April 2020) by applying biomedical informatics and data visualization tools to several public and federal government datasets, including analysis of the impact of statewide stay-at-home orders.ResultsThere were 2753.2 cases and 158.0 deaths per million residents, respectively, in the USA with variable distributions throughout divisions, regions and states. Forty-two states and Washington, DC, (84.3%) had statewide stay-at-home orders, with the remaining states having population-adjusted characteristics in the highest risk quartile.ConclusionsEffective national preparedness requires clearly understanding states’ ability to predict, manage and balance public health needs through all stages of a pandemic. This will require leveraging data quickly, correctly and responsibly into sound public health policies.

Microgripper captures single cells

Sampling diseased tissue, which can contain many types of cells, calls for precise biomedical tools. Current methods for manipulating single cells, like laser microdissection, require complicated s...

Point-of-care and Near Real-time Testing for Antiretroviral Adherence Monitoring to HIV Treatment and Prevention.

In this report, we review the need for point-of-care (POC) or near real-time testing for antiretrovirals, progress in the field, evidence for guiding implementation of these tests globally, and future directions in objective antiretroviral therapy (ART) or pre-exposure prophylaxis (PrEP) adherence monitoring. Two cornerstones to end the HIV/AIDS pandemic are ART, which provides individual clinical benefits and eliminates forward transmission, and PrEP, which prevents HIV acquisition with high effectiveness. Maximizing the individual and public health benefits of these powerful biomedical tools requires high and sustained antiretroviral adherence. Routine monitoring of medication adherence in individuals receiving ART and PrEP may be an important component in interpreting outcomes and supporting optimal adherence. Existing practices and subjective metrics for adherence monitoring are often inaccurate or unreliable and, therefore, are generally ineffective for improving adherence. Laboratory measures of antiretroviral concentrations using liquid chromatography tandem mass spectrometry have been utilized in research settings to assess medication adherence, although these are too costly and resource-intensive for routine use. Newer, less costly technologies such as antibody-based methods can provide objective drug-level measurement and may allow for POC or near-patient adherence monitoring in clinical settings. When coupled with timely and targeted counseling, POC drug-level measures can support adherence clinic-based interventions to ART or PrEP in near real time.

Graphene, other carbon nanomaterials and the immune system: toward nanoimmunity-by-design

Carbon-based materials (CBMs), such as graphene, nanodiamonds, carbon fibers, and carbon dots, have attracted a great deal scientific attention due to their potential as biomedical tools. Following exposure, particularly intravenous injection, these nanomaterials can be recognized by immune cells. Such interactions could be modulated by the different physicochemical properties of the materials (e.g. structure, size, and chemical functions), by either stimulating or suppressing the immune response. However, a harmonized cutting-edge approach for the classification of these materials based not only on their physicochemical parameters but also their immune properties has been missing. The European Commission-funded G-IMMUNOMICS and CARBO-IMmap projects aimed to fill this gap, developing a functional pipeline for the qualitative and quantitative immune characterization of graphene, graphene-related materials (GRMs), and other CBMs. The goal was to open breakthrough perspectives for the definition of the immune profiles of these materials. Here, we summarize our methodological approach, key results, and the necessary multidisciplinary expertise ranging across various fields, from material chemistry to engineering, immunology, toxicology, and systems biology. G-IMMUNOMICS, as a partnering project of the Graphene Flagship, the largest scientific research initiative on graphene worldwide, also complemented the studies performed in the Flagship on health and environmental impact of GRMs. Finally, we present the nanoimmunity-by-design concept, developed within the projects, which can be readily applied to other 2D materials. Overall, the G-IMMUNOMICS and CARBO-IMmap projects have provided new insights on the immune impact of GRMs and CBMs, thus laying the foundation for their safe use and future translation in medicine.

A new strategy of using dielectric barrier discharge plasma in tubular geometry for surface coating and extension to biomedical application.

There has always been a quest for nanotechnology to develop inexpensive coating methods with the capability of depositing biocompatible nanomaterials on biomedical and surgical tools. In this mini-report, a plasma-based innovative idea of coating a solid surface with antibacterial/antimicrobial nanosilver is floated and experimentally realized. The desired antibacterial nanosilver was obtained from laser ablation and directly entrained in an outflowing plasma jet, excited in the flow of argon at 10 l min-1 using 20 kV/20 kHz. Under these conditions, the jet can protrude 15 mm deeply into ambient air. The quality of the surface coating can be described by sparsely distributed particles or densely agglomerated clusters, controlled by the plasma length and the surface separation. Apart from the coating, plasma interaction leads to the sterilization of the exposed surface. The idea is essentially important to extend and upscale for coating biomedical and surgical devices in a flexible open processing environment.

Fragmentation of Proteins in the Corona of Gold Nanoparticles As Observed in Live Cell Surface-Enhanced Raman Scattering

Surface-enhanced Raman scattering (SERS) can provide information on the structure, composition, and interaction of molecules in the proximity of gold nanoparticles, thereby enabling studies of adsorbed biomolecules in vivo. Here, the processing of the protein corona and the corresponding protein-nanoparticle interactions in live J774 cells incubated with gold nanoparticles was characterized by SERS. Samples of isolated cytoplasm, devoid of active processing, of the same cell line were used as references. The occurrence of the most important SERS signals was compared in both types of samples. The comparison of signal abundances, supported by multivariate assessment, suggests a decreased nanoparticle-peptide backbone interaction and an increased contribution of denatured proteins in endolysosomal compartments, indicating an interaction of protein fragments with the gold nanoparticles in the endolysosome of the living cells. To study the protein fragmentation in a model and to confirm the assignment of specific spectral signatures in the live cell spectra, SERS data were collected from a solution of bovine serum albumin (BSA) digested by trypsin as an enzymatic model and from solutions of intact BSA and trypsin. The spectra from the enzymatic model confirm the strong interaction of protein fragments with the gold nanoparticles in the endolysosomal compartments. By proteomic analysis, using combined sodium dodecyl sulfate-polyacrylamide gel electrophoresis and high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry of the extracted hard corona, we directly identified protein fragments, some originating from the culture medium. The results illustrate the use of appropriate models for the validation of SERS spectra and have potential implications for further developments of SERS as an in vivo analytical and biomedical tool.

Chrysin loaded lipid-core nanocapsules ameliorates neurobehavioral alterations induced by β-amyloid1-42 in aged female mice

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by a clinically and progressive loss of cognitive function, neuropsychiatric and behavioral disorders. Some studies showed that chrysin has antioxidant and anti-inflammatory properties. However, your bioavailability is relatively low. Therefore, the present study was designed to investigate the effects of chrysin loaded lipid-core nanocapsules (LNCs) on neurochemical and behavioral changes in a model of AD induced by β-amyloid1–42 (Aβ1−42) peptide in aged female mice. For this purpose, aged female mice received free chrysin (FC) (5 mg/kg, per oral, p.o.) or chrysin loaded LNCs (C1-LNC and C5-LNC) (1 or 5 mg/kg, p.o.) for 14 days after Aβ1–42 administration (400 pmol, i.c.v.). Aβ1–42 induced significant impairments on memory and learning (morris water maze task, object recognition and step-down-type passive avoidance), also caused oxidative stress, reduced the levels of brain-derived neurotrophic factor (BDNF), increased neuroinflammation in prefrontal cortex and hippocampus of aged animals. Thus, C1-LNC and C5-LNC displayed significant effect against Aβ₁−₄2, via attenuation of oxidative stress and neuroinflammation, modulation of neurochemical and behavioral changes in a model of AD. These results point to chrysin loaded LNCs (mainly C5-LNC) can be a promising biomedical tool and a new therapeutic approach for treatment and prevention of AD.

Efficient and Accurate Extracting of Unstructured EHRs on Cancer Therapy Responses for the Development of RECIST Natural Language Processing Tools: Part I, the Corpus

PURPOSEElectronic health records (EHRs) are created primarily for nonresearch purposes; thus, the amounts of data are enormous, and the data are crude, heterogeneous, incomplete, and largely unstructured, presenting challenges to effective analyses for timely, reliable results. Particularly, research dealing with clinical notes relevant to patient care and outcome is seldom conducted, due to the complexity of data extraction and accurate annotation in the past. RECIST is a set of widely accepted research criteria to evaluate tumor response in patients undergoing antineoplastic therapy. The aim for this study was to identify textual sources for RECIST information in EHRs and to develop a corpus of pharmacotherapy and response entities for development of natural language processing tools.METHODSWe focused on pharmacotherapies and patient responses, using 55,120 medical notes (n = 72 types) in Mayo Clinic’s EHRs from 622 randomly selected patients who signed authorization for research. Using the Multidocument Annotation Environment tool, we applied and evaluated predefined keywords, and time interval and note-type filters for identifying RECIST information and established a gold standard data set for patient outcome research.RESULTSKey words reduced clinical notes to 37,406, and using four note types within 12 months postdiagnosis further reduced the number of notes to 5,005 that were manually annotated, which covered 97.9% of all cases (n = 609 of 622). The resulting data set of 609 cases (n = 503 for training and n = 106 for validation purpose), contains 736 fully annotated, deidentified clinical notes, with pharmacotherapies and four response end points: complete response, partial response, stable disease, and progressive disease. This resource is readily expandable to specific drugs, regimens, and most solid tumors.CONCLUSIONWe have established a gold standard data set to accommodate development of biomedical informatics tools in accelerating research into antineoplastic therapeutic response.

Phononic-Crystal-Enabled Dynamic Manipulation of Microparticles and Cells in an Acoustofluidic Channel

Contactless manipulation of particles and cells using acoustic forces that can be adjusted in real time is now important in $e.g.$ biomedical sensors, imaging devices, and diagnostic tools. Dynamic manipulation typically requires huge phased arrays with complex electrical control, or a moving source with an inflexible displacement platform, but here the authors develop a method using an acoustic field modulated by a phononic crystal plate (PCP) in an acoustofluidic channel. PCP resonance-based dynamic manipulation via a single source, by switching the frequency, has the advantages of being simple, disposable, scalable, and combinable with a microfluidic chip.

Tuning energy dissipation in damage tolerant bio-inspired interfaces

Tuning interfacial behavior is very desirable in many engineering applications, including adhesive bonds in composite materials, advanced biomedical tools, and metamaterials. Recent experimental work has shown that modifying the sub-surface region of an interface is a viable strategy to control the structural response. The effect of buried cylindrical hollow channels, mimicking the base plate of the Amphibalanus (=Balanus) amphitrite, was assessed on a model material system comprising adhesively bonded 3D printed polyamide substrates in the Double Cantilever Beam (DCB) configuration. Beneficial crack-trapping effect and remarkable enhancement of the total work of separation were reported. The present work supplements our experimental study with an extensive series of finite element analyses (FEA) of crack growth using interface elements. The simulations were able to mimic the serrated behavior observed in experimental load-displacement responses, which was due to snap-through interfacial cracking, i.e., a sudden and almost instantaneous growth of apparently stable cracks. Since we expect that specific geometrical properties of the channels play an essential role in the mechanical behavior of the joint, a parametric investigation was herein carried out to ascertain their effect on the work of fracture. The results show that the channels aspect ratio and pitch play a fundamental role and may allow to tailor the dissipated energy needed to sever the interface. Ancillary experimental tests, carried out on 3D printed DCBs adhesive joints, support the results of the finite element simulations and allow us to pinpoint the effect of channel geometry on the mechanisms of crack growth.

Innovations in 3-Dimensional Tissue Models of Human Brain Physiology and Diseases.

3-dimensional (3D) laboratory tissue cultures have emerged as an alternative to traditional 2-dimensional (2D) culture systems that do not recapitulate native cell behavior. The discrepancy between in vivo and in vitro tissue-cell-molecular responses impedes understanding of human physiology in general and creates roadblocks for the discovery of therapeutic solutions. Two parallel approaches have emerged for the design of 3D culture systems. The first is biomedical engineering methodology, including bioengineered materials, bioprinting, microfluidics and bioreactors, used alone or in combination, to mimic the microenvironments of native tissues. The second approach is organoid technology, in which stem cells are exposed to chemical and/or biological cues to activate differentiation programs that are reminiscent of human (prenatal) development. This review article describes recent technological advances in engineering 3D cultures that more closely resemble the human brain. The contributions of in vitro 3D tissue culture systems to new insights in neurophysiology, neurological diseases and regenerative medicine are highlighted. Perspectives on designing improved tissue models of the human brain are offered, focusing on an integrative approach merging biomedical engineering tools with organoid biology.