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In developing medical interventions using untethered milli- and microrobots, ensuring safety and effectiveness relies on robust methods for real-time robot detection, tracking, and precise localization within the body. The inherent non-transparency of human tissues significantly challenges these efforts, as traditional imaging systems like fluoroscopy often lack crucial anatomical details, potentially compromising intervention safety and efficacy. To address this technological gap, in this study, we build a virtual reality environment housing an exact digital replica (digital twin) of the operational workspace and a robot avatar. We synchronize the virtual and real workspaces and continuously send the robot position data derived from the image stream into the digital twin with short average delay time around 20–25 ms. This allows the operator to steer the robot by tracking its avatar within the digital twin with near real-time temporal resolution. We demonstrate the feasibility of this approach with millirobots steered in confined phantoms. Our concept demonstration herein can pave the way for not only improved procedural safety by complementing fluoroscopic guidance with virtual reality enhancement, but also provides a platform for incorporating various additional real-time derivative data, e.g., instantaneous robot velocity, intraoperative physiological data obtained from the patient, e.g., blood flow rate, and pre-operative physical simulation models, e.g., periodic body motions, to further refine robot control capacity. [ABSTRACT FROM AUTHOR]

Human pluripotent stem cells (hPSCs) represent an excellent cell source for regenerative medicine and tissue engineering applications. However, there remains a need for robust and scalable differentiation of stem cells into functional adult tissues. In this paper, we sought to address this challenge by developing magnetic microcapsules carrying hPSC spheroids. A co-axial flow-focusing microfluidic device was employed to encapsulate stem cells in core-shell microcapsules that also contained iron oxide magnetic nanoparticles (MNPs). These microcapsules exhibited excellent response to an external magnetic field and could be held at a specific location. As a demonstration of utility, magnetic microcapsules were used for differentiating hPSC spheroids as suspension cultures in a stirred bioreactor. Compared to standard suspension cultures, magnetic microcapsules allowed for more efficient media change and produced improved differentiation outcomes. In the future, magnetic microcapsules may enable better and more scalable differentiation of hPSCs into adult cell types and may offer benefits for cell transplantation. [ABSTRACT FROM AUTHOR]

Biliary stents are used to optimize ductal patency and enable bile flow in the management of obstruction or injury related to biliary tract tumors, strictures, stones, or leaks. Although direct therapeutic applications of biliary stents are less well developed, stents can be used to deliver drugs, radioisotopes, and photodynamic therapy. This report provides an in-depth overview of the clinical indications, and therapeutic utility of biliary stents. Unique considerations for the design of biliary stents are described. The properties and functionalities of materials used for stents such as metal alloys, plastic polymers, or biodegradable materials are described, and opportunities for design of future stents are outlined. Current and potential applications of stents for therapeutic applications for biliary tract diseases are described. Therapeutic biliary stents could be used to minimize inflammation, prevent stricture formation, reduce infections, or provide localized anti-cancer therapy for biliary tract cancers. Stents could be transformed into therapeutic platforms using advanced materials, 3D printing, nanotechnology, and artificial intelligence. Whilst clinical study and validation will be required for adoption, future advances in stent design and materials are expected to expand the use of therapeutic biliary stents for the treatment of biliary tract disorders. [ABSTRACT FROM AUTHOR]

In this study, the effect of volcanic tuff mineral additive in concrete manufacture on the compressive strength of concrete was investigated using the artificial neural network (ANN). Cement mixtures were produced by adding volcanic tuff (VT) in the ratio of 0% (control), 10%, 15%, and 20%. The effect of curing time was investigated by applying 28- and 90-day periods. The main inputs for the ANN model were cement, VT, super-plasticizer (SP), and aggregates with 4 different mesh sizes and outputs were 28- and 90-day compressive strengths. In the comparison of obtained results by artificial neural networks with the experimental data, good agreements have been seen. It was also seen that the optimum volcanic tuff rate was 20% in concrete in terms of compressive strengths. [ABSTRACT FROM AUTHOR]

Manipulating and separating single label-free cells without biomarker conjugation have attracted significant interest in the field of single-cell research, but digital circuitry control and multiplexed individual storage of single label-free cells remain a challenge. Herein, by analogy with the electrical circuitry elements and electronical holes, we develop a pseudo-diamagnetophoresis (PsD) mattertronic approach in the presence of biocompatible ferrofluids for programmable manipulation and local storage of single PsD holes and label-free cells. The PsD holes conduct along linear negative micro-magnetic patterns. Further, eclipse diode patterns similar to the electrical diode can implement directional and selective switching of different PsD holes and label-free cells based on the diode geometry. Different eclipse heights and junction gaps influence the switching efficiency of PsD holes for mattertronic circuitry manipulation and separation. Moreover, single PsD holes are stored at each potential well as in an electrical storage capacitor, preventing multiple occupancies of PsD holes in the array of individual compartments due to magnetic Coulomb-like interaction. This approach may enable the development of large programmable arrays of label-free matters with high throughput, efficiency, and reliability as multiplex cell research platforms. Here, the authors present a pseudo-diamagnetophoresis mattertronic approach for programmable manipulation of label-free cells. Immersed in biocompatible ferrofluids, single cells are moved along linear negative micromagnetic patterns, switched at eclipse diode patterns and stored in potential wells. [ABSTRACT FROM AUTHOR]

Small‐scale magnetic soft‐bodied robots based on biocompatible and biodegradable materials are essential for their potential high‐impact minimally invasive medical applications inside the human body. Therefore, a strategy for fully biodegradable untethered soft millirobots with encoded 3D magnetic anisotropy for their static or dynamic shape programming is presented. Such a robot body is comprised of a porcine extracellular matrix‐derived collagen‐based hydrogel network with embedded superparamagnetic iron oxide nanoparticles (SPIONs). 3D magnetization programming inside the hydrogel body is achieved by directionally self‐assembled SPION chains using an external permanent magnet. As a proof‐of‐concept demonstration, a hydrogel milli‐gripper that can undergo flexible and reversible shape deformations inside glycerol and biologically relevant liquid media is presented. The gripper can perform cargo grabbing, transportation by rolling, and release by controlling magnetic field inputs. These milli‐grippers can be completely degraded by the matrix metalloproteinase‐2 enzyme in physiologically relevant concentrations. Furthermore, biocompatibility tests using human umbilical cord vein endothelial cells with the degradation products of the grippers demonstrate no acute toxicity. The approach offers a facile fabrication strategy for designing biocompatible and biodegradable soft robots using nanocomposite materials with programmable 3D magnetic anisotropy toward future medical applications. [ABSTRACT FROM AUTHOR]

Biohybrid microswimmers exploit the swimming and navigation of a motile microorganism to target and deliver cargo molecules in a wide range of biomedical applications. Medical biohybrid microswimmers suffer from low manufacturing yields, which would significantly limit their potential applications. In the present study, a biohybrid design strategy is reported, where a thin and soft uniform coating layer is noncovalently assembled around a motile microorganism. Chlamydomonas reinhardtii (a single‐cell green alga) is used in the design as a biological model microorganism along with polymer–nanoparticle matrix as the synthetic component, reaching a manufacturing efficiency of ≈90%. Natural biopolymer chitosan is used as a binder to efficiently coat the cell wall of the microalgae with nanoparticles. The soft surface coating does not impair the viability and phototactic ability of the microalgae, and allows further engineering to accommodate biomedical cargo molecules. Furthermore, by conjugating the nanoparticles embedded in the thin coating with chemotherapeutic doxorubicin by a photocleavable linker, on‐demand delivery of drugs to tumor cells is reported as a proof‐of‐concept biomedical demonstration. The high‐throughput strategy can pave the way for the next‐generation generation microrobotic swarms for future medical active cargo delivery tasks. [ABSTRACT FROM AUTHOR]

The structural design parameters of a medical microrobot, such as the morphology and surface chemistry, should aim to minimize any physical interactions with the cells of the immune system. However, the same surface-borne design parameters are also critical for the locomotion performance of the microrobots. Understanding the interplay of such parameters targeting high locomotion performance and low immunogenicity at the same time is of paramount importance yet has so far been overlooked. Here, we investigated the interactions of magnetically steerable double-helical microswimmers with mouse macrophage cell lines and splenocytes, freshly harvested from mouse spleens, by systematically changing their helical morphology. We found that the macrophages and splenocytes can recognize and differentially elicit an immune response to helix turn numbers of the microswimmers that otherwise have the same size, bulk physical properties, and surface chemistries. Our findings suggest that the structural optimization of medical microrobots for the locomotion performance and interactions with the immune cells should be considered simultaneously because they are highly entangled and can demand a substantial design compromise from one another. Furthermore, we show that morphology-dependent interactions between macrophages and microswimmers can further present engineering opportunities for biohybrid microrobot designs. We demonstrate immunobots that can combine the steerable mobility of synthetic microswimmers and the immunoregulatory capability of macrophages for potential targeted immunotherapeutic applications. [ABSTRACT FROM AUTHOR]

Andesite stone is widely used in civil engineering and architectural applications in Turkey. Mining, cutting and polishing of andesite stone leads to the generation of significant amounts of waste material. Andesite contains SiO 2 as the main component. Therefore, andesite may have pozzolanicity and thus may be used as mineral additive in concrete. In this study, the efficiency factor of andesite waste powder as a mineral additive was investigated and compared with F type fly ashes. The efficiency factors of mineral additives were also analyzed according to the curing ages of concrete specimens. Concrete specimens were prepared at various cement dosages to determine the efficiency factors of mineral additives at different replacement levels. The compressive strengths of concrete specimens were tested at 28th and 90th days. The efficiency factors were calculated by determining the variable Feret coefficient for each specimen series. For C40 strength class, the optimum replacement rate of andesite waste powder was determined as 10% at curing ages of 28 and 90 days. [ABSTRACT FROM AUTHOR]

Untethered micron-scale mobile robots can navigate and non-invasively perform specific tasks inside unprecedented and hard-to-reach inner human body sites and inside enclosed organ-on-a-chip microfluidic devices with live cells. They are aimed to operate robustly and safely in complex physiological environments where they will have a transforming impact in bioengineering and healthcare. Research along this line has already demonstrated significant progress, increasing attention, and high promise over the past several years. The first-generation microrobots, which could deliver therapeutics and other cargo to targeted specific body sites, have just been started to be tested inside small animals toward clinical use. Here, we review frontline advances in design, fabrication, and testing of untethered mobile microrobots for bioengineering applications. We convey the most impactful and recent strategies in actuation, mobility, sensing, and other functional capabilities of mobile microrobots, and discuss their potential advantages and drawbacks to operate inside complex, enclosed and physiologically relevant environments. We lastly draw an outlook to provide directions in the veins of more sophisticated designs and applications, considering biodegradability, immunogenicity, mobility, sensing, and possible medical interventions in complex microenvironments. [ABSTRACT FROM AUTHOR]

Untethered robots miniaturized to the length scale of millimeter and below attract growing attention for the prospect of transforming many aspects of health care and bioengineering. As the robot size goes down to the order of a single cell, previously inaccessible body sites would become available for high-resolution in situ and in vivo manipulations. This unprecedented direct access would enable an extensive range of minimally invasive medical operations. Here, we provide a comprehensive review of the current advances in biomedical untethered mobile milli/microrobots. We put a special emphasis on the potential impacts of biomedical microrobots in the near future. Finally, we discuss the existing challenges and emerging concepts associated with designing such a miniaturized robot for operation inside a biological environment for biomedical applications. [ABSTRACT FROM PUBLISHER]

A bone implant should integrate tothe tissue through a bone-likemineralized interface, which requires increased osteoblast activityat the implant–tissue boundary. Modification of the implantsurface with synthetic bioinstructive cues facilitates on-site differentiationof progenitor stem cells to functional mature osteoblasts and resultsin subsequent mineralization. Inspired by the bioactive domains ofthe bone extracellular matrix proteins and the mussel adhesive proteins,we synthesized peptide nanofibers to promote bone-like mineralizationon the implant surface. Nanofibers functionalized with osteoinductivecollagen I derived Asp-Gly-Glu-Ala (DGEA) peptide sequence providean advantage in initial adhesion, spreading, and early commitmentto osteogenic differentiation for mesenchymal stem cells (hMSCs).In this study, we demonstrated that this early osteogenic commitment,however, does not necessarily guarantee a priority for maturationinto functional osteoblasts. Similar to natural biological cascades,early commitment should be further supported with additional signalsto provide a long-term effect on differentiation. Here, we showedthat peptide nanofibers functionalized with Glu-Glu-Glu (EEE) sequenceenhanced mineralization abilities due to osteoinductive propertiesfor late-stage differentiation of hMSCs. Mussel-inspired functionalizationnot only enables robust immobilization on metal surfaces, but alsoimproves bone-like mineralization under physiologically simulatedconditions. The multifunctional osteoinductive peptide nanofiber biointerfacespresented here facilitate osseointegration for long-term clinicalstability. [ABSTRACT FROM AUTHOR]

News portals are a popular destination for web users. News providers are therefore interested in attaining higher visitor rates and promoting greater engagement with their content. One aspect of engagement deals with keeping users on site longer by allowing them to have enhanced click-through experiences. News portals have invested in ways to embed links within news stories but so far these links have been curated by news editors. Given the manual effort involved, the use of such links is limited to a small scale. In this article, we evaluate a system-based approach that detects newsworthy events in a news article and locates other articles related to these events. Our system does not rely on resources like Wikipedia to identify events, and it was designed to be domain independent. A rigorous evaluation, using Amazon's Mechanical Turk, was performed to assess the system-embedded links against the manually-curated ones. Our findings reveal that our system's performance is comparable with that of professional editors, and that users find the automatically generated highlights interesting and the associated articles worthy of reading. Our evaluation also provides quantitative and qualitative insights into the curation of links, from the perspective of users and professional editors. [ABSTRACT FROM AUTHOR]

A solvent-free fabrication of TiO2 and ZnO nanonetworks is demonstrated by using supramolecular nanotemplates with high coating conformity, uniformity, and atomic scale size control. Deposition of TiO2 and ZnO on three-dimensional nanofibrous network template is accomplished. Ultrafine control over nanotube diameter allows robust and systematic evaluation of the electrochemical properties of TiO2 and ZnO nanonetworks in terms of size-function relationship. We observe hypsochromic shift in UV absorbance maxima correlated with decrease in wall thickness of the nanotubes. Photocatalytic activities of anatase TiO2 and hexagonal wurtzite ZnO nanonetworks are found to be dependent on both the wall thickness and total surface area per unit of mass. Wall thickness has effect on photoexcitation properties of both TiO2 and ZnO due to band gap energies and total surface area per unit of mass. The present work is a successful example that concentrates on nanofabrication of intact three-dimensional semiconductor nanonetworks with controlled band gap energies. [ABSTRACT FROM AUTHOR]

A general drawback of supramolecular peptide networks is their weak mechanical properties. In order to overcome a similar challenge, mussels have adapted to a pH-dependent iron complexation strategy for adhesion and curing. This strategy also provides successful stiffening and self-healing properties. The present study is inspired by the mussel curing strategy to establish iron cross-link points in self-assembled peptide networks. The impact of peptide-iron complexation on the morphology and secondary structure of the supramolecular nanofibers is characterized by scanning electron microscopy, circular dichroism and Fourier transform infrared spectroscopy. Mechanical properties of the cross-linked network are probed by small angle oscillatory rheology and nanoindentation by atomic force microscopy. It is shown that iron complexation has no influence on self-assembly and β-sheet-driven elongation of the nanofibers. On the other hand, the organic-inorganic hybrid network of iron cross-linked nanofibers demonstrates strong mechanical properties comparable to that of covalently cross-linked network. Strikingly, iron cross-linking does not inhibit intrinsic reversibility of supramolecular peptide polymers into disassembled building blocks and the self-healing ability upon high shear load. The strategy described here could be extended to improve mechanical properties of a wide range of supramolecular polymer networks. [ABSTRACT FROM AUTHOR]

Amyloid peptides are important components in many degenerativediseases as well as in maintaining cellular metabolism. Their uniquestable structure provides new insights in developing new materials.Designing bioinspired self-assembling peptides is essential to generatenew forms of hierarchical nanostructures. Here we present oppositelycharged amyloid inspired peptides (AIPs), which rapidly self-assembleinto nanofibers at pH 7 upon mixing in water caused by noncovalentinteractions. Mechanical properties of the gels formed by self-assembledAIP nanofibers were analyzed with oscillatory rheology. AIP gels exhibitedstrong mechanical characteristics superior to gels formed by self-assemblyof previously reported synthetic short peptides. Rheological studiesof gels composed of oppositely charged mixed AIP molecules (AIP-1 2) revealed superior mechanical stability compared to individualpeptide networks (AIP-1 and AIP-2) formed by neutralization of netcharges through pH change. Adhesion and elasticity properties of AIPmixed nanofibers and charge neutralized AIP-1, AIP-2 nanofibers wereanalyzed by high resolution force–distance mapping using atomicforce microscopy (AFM). Nanomechanical characterization of self-assembledAIP-1 2, AIP-1, and AIP-2 nanofibers also confirmed macroscopicrheology results, and mechanical stability of AIP mixed nanofiberswas higher compared to individual AIP-1 and AIP-2 nanofibers self-assembledat acidic and basic pH, respectively. Experimental results were supportedwith molecular dynamics simulations by considering potential noncovalentinteractions between the amino acid residues and possible aggregateforms. In addition, HUVEC cells were cultured on AIP mixed nanofibersat pH 7 and biocompatibility and collagen mimetic scaffold propertiesof the nanofibrous system were observed. Encapsulation of a zwitterionicdye (rhodamine B) within AIP nanofiber network was accomplished atphysiological conditions to demonstrate that this network can be utilizedfor inclusion of soluble factors as a scaffold for cell culture studies. [ABSTRACT FROM AUTHOR]

Abstract: Metal-based scaffolds such as stents are the most preferred treatment methods for coronary artery disease. However, impaired endothelialization on the luminal surface of the stents is a major limitation occasionally leading to catastrophic consequences in the long term. Coating the stent surface with relevant bioactive molecules is considered to aid in recovery of endothelium around the wound site. However, this strategy remains challenging due to restrictions in availability of proper bioactive signals that will selectively promote growth of endothelium and the lack of convenience for immobilization of such signaling molecules on the metal surface. In this study, we developed self-assembled peptide nanofibers that mimic the native endothelium extracellular matrix and that are securely immobilized on stainless steel surface through mussel-inspired adhesion mechanism. We synthesized Dopa-conjugated peptide amphiphile and REDV-conjugated peptide amphiphile that are self-assembled at physiological pH. We report that Dopa conjugation enabled nanofiber coating on stainless steel surface, which is the most widely used backbone of the current stents. REDV functionalization provided selective growth of endothelial cells on the stainless steel surface. Our results revealed that adhesion, spreading, viability and proliferation rate of vascular endothelial cells are remarkably enhanced on peptide nanofiber coated stainless steel surface compared to uncoated surface. On the other hand, although vascular smooth muscle cells exhibited comparable adhesion and spreading profile on peptide nanofibers, their viability and proliferation significantly decreased. Our design strategy for surface bio-functionalization created a favorable microenvironment to promote endothelial cell growth on stainless steel surface, thereby providing an efficient platform for bioactive stent development for long term treatment of cardiovascular diseases. [Copyright &y& Elsevier]

Poor retention rate, low targeting accuracy, and spontaneous transformation of stem cells present major clinical barriers to the success of therapies based on stem cell transplantation. To improve the clinical outcome, efforts should focus on the active delivery of stem cells to the target tissue site within a controlled environment, increasing survival, and fate for effective tissue regeneration. Here, a remotely steerable microrobotic cell transporter is presented with a biophysically and biochemically recapitulated stem cell niche for directing stem cells towards a pre‐destined cell lineage. The magnetically actuated double‐helical cell microtransporters of 76 µm length and 20 µm inner cavity diameter are 3D printed where biological and mechanical information regarding the stem cell niche are encoded at the single‐cell level. Cell‐loaded microtransporters are mobilized inside confined microchannels along computer‐controlled trajectories under rotating magnetic fields. The mesenchymal stem cells are shown retaining their differentiation capacities to commit to the osteogenic lineage when stimulated inside the microswimmers in vitro. Such a microrobotic approach has the potential to enable the development of active microcarriers with embedded functionalities for controlled and precisely localized therapeutic cell delivery. [ABSTRACT FROM AUTHOR]

Understanding the toxicity of nanomaterials remains largely limited to acute cellular response, i.e., short-term in vitro cell-death based assays, and analyses of tissue- and organ-level accumulation and clearance patterns in animal models, which have produced very little information about how these materials (from the toxicity point of view) interact with the complex intracellular machinery. In particular, understanding the mechanism of toxicity caused by the gradual accumulation of nanomaterials due to prolonged exposure times is essential yet still continue to be a largely unexplored territory. Herein, we show intracellular accumulation and the associated toxicity of gold nanoparticles (AuNPs) for over two-months in the cultured vascular endothelial cells. We observed that steady exposure of AuNPs at low (non-lethal) dose leads to rapid intracellular accumulation without causing any detectable cell death while resulting in elevated endoplasmic reticulum (ER) stress. Above a certain intracellular AuNP threshold, inhibition of macropinocytosis mechanism ceases further nanoparticle uptake. Interestingly, the intracellular depletion of nanoparticles is irreversible. Once reaching the maximum achievable intracellular dose, a steady depletion is observed, while no cell death is observed at any stage of this overall process. This depletion is important for reducing the ER stress. To our knowledge, this is the first report suggesting active regulation of nanoparticle uptake by cells and the impact of long-term exposure to nanoparticles in vitro. [ABSTRACT FROM AUTHOR]

A supramolecular hydrogel network is held intact through non‐covalent interactions among lowmolecular weight building blocks. The intermolecular interactions among the building blocks are important for stimuli‐responsive modulation and self‐healing properties. On page 2081 Aykutlu Dana, Mustafa O. Guler, and co‐workers show that a mussel‐inspired metal‐ion coordination into the supramolecular polymer network is advantageous for improving mechanical properties as well as retaining the original properties of the network. [ABSTRACT FROM AUTHOR]