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Eung-Sam Kim,1,2 Eun Hyun Ahn,3,4 Tal Dvir,5,6 Deok-Ho Kim1,4,71Department of Bioengineering, University of Washington, Seattle, WA, USA; 2Department of Biological Sciences, Chonnam National University, Gwangju, Korea; 3Department of Pathology, 4Institute of Stem Cell and Regenerative Medicine, School of Medicine, University of Washington, Seattle, WA, USA; 5Department of Molecular Microbiology and Biotechnology, 6Center for Nanoscience and Nanotechnology, Tel Aviv University, Tel Aviv, Israel; 7Center for Cardiovascular Biology, University of Washington, Seattle, WA, USAThe history of human kind suggests that there has been a correlation between global population growth and major events in science and technology over the last three centuries. Sharp increases in the world’s population have been triggered by the industrial revolution and scientific and technological breakthroughs including: the advent of the railways, discovery of penicillin and deoxyribonucleic acid (DNA), and the invention of the computer.1 Since the 20th century, interdisciplinary areas in the physical and biological sciences have accelerated the progress of biomedical applications. The recent integration of emerging nanotechnology into biology and biomedicine has resulted in a range of innovative nanoengineering efforts for the repair and regeneration of tissues and organs.2 Thus, it is expected that nanoengineering approaches to biomedical applications can contribute to addressing the present issue of personal and global health care and its economic burden for more than 7 billion people.Why are we paying attention to nanoengineering for biomedical applications? The size of most biomolecules ranges from 0.2 nm to 200 nm (Figure 1). Research has focused on control of the interaction and localization of biomolecules even at the single-molecule level using ever-evolving nanotechnology.3 The evidence indicates that cells can respond to nanoscale changes in the dynamic extracellular matrix and vice versa. Biomimetic nanopatterns alone can direct the differentiation of stem cells without involvement of exogenous soluble biochemical factors.4,5 This regulation of cellular behavior by nanotechnology is one of many examples demonstrating the significant applications of nanoengineering in biomedicine. This special issue includes four review papers and seven research articles that provide an insight into current nanoengineering approaches to the repair or regeneration of tissues and organs.

Kitaev chains in quantum dot-superconductor arrays are a promising platform for the realization of topological superconductivity. As recently demonstrated, even a two-site chain can host Majorana zero modes known as "poor man's Majorana". Harnessing the potential of these states for quantum information processing, however, requires increasing their robustness to external perturbations. Here, we form a two-site Kitaev chain using Yu-Shiba-Rusinov states in proximitized quantum dots. By deterministically tuning the hybridization between the quantum dots and the superconductor, we observe poor man's Majorana states with a gap larger than 70 μeV. The sensitivity to charge fluctuations is also greatly reduced compared to Kitaev chains made with non-proximitized dots. The systematic control and improved energy scales of poor man's Majorana states realized with Yu-Shiba-Rusinov states will benefit the realization of longer Kitaev chains, parity qubits, and the demonstration of non-Abelian physics., (© 2024. The Author(s).)

Overcoming the oxygen diffusion limit of approximately 200 µm remains one of the most significant and intractable challenges to be overcome in tissue engineering. The fabrication of hydrogel microtissues and their assembly into larger structures may provide a solution, though these constructs are not without their own drawbacks; namely, these hydrogels are rapidly degraded in vivo, and cells delivered via microtissues are quickly expelled from the area of action. Here, we report the development of an easily customized protocol for creating a protective, biocompatible hydrogel barrier around microtissues. We show that calcium carbonate nanoparticles embedded within an ECM-based microtissue diffuse outwards and, when then exposed to a solution of alginate, can be used to generate a coated layer around the tissue. We further show that this technique can be fine-tuned by adjusting numerous parameters, granting us full control over the thickness of the hydrogel coating layer. The microtissues' protective hydrogel functioned as hypothesized in both in vitro and in vivo testing by preventing the cells inside the tissue from escaping and protecting the microdroplets against external degradation. This technology may provide microtissues with customized properties for use as sources of regenerative therapies.

Introduction: Few autistic adults are able to integrate successfully into the world of work given their difficulties adapting to the social and stressful aspects of work environments. Interpersonal synchrony, when two or more individuals share body movements or sensations, is a powerful force that consolidates human groups while promoting the ability to self-regulate and cooperate with others. The abilities to self-regulate and cooperate are crucial for maintaining a calm and productive work environment. This study protocol outlines research that aims to assess the effects of group interpersonal synchrony on prosociality and work-related stress of young autistic adults in their work environment., Methods and Analysis: This mixed-methods randomized controlled trial will investigate two movement-based group synchronous and non-synchronous intervention conditions. The sample will be composed of young adults enrolled in an innovative Israeli program designed to integrate cognitively-abled 18- to 25-year-old autistic adults into the Israeli army work force. The movement-based intervention sessions will take place in groups of 10-14 participants, once a week for 10 weeks. Questionnaires, behavioral collaborative tasks and semi-structured interviews will be conducted. Quantitative data will be collected for each participant at three points of time: before and after the intervention period, and 17 weeks after the end of the intervention. Qualitative data will be collected after the intervention period in interviews with the participants., Discussion: Little is known about interventions that promote successful integration into social and stressful work environments. The findings are likely to shed new light on the use of group interpersonal synchrony in autistic individuals at work., Trial Registration: NCT05846308., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Dvir et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Artificial Kitaev chains can be used to engineer Majorana bound states (MBSs) in superconductor-semiconductor hybrids 1-4 . In this work, we realize a two-site Kitaev chain in a two-dimensional electron gas by coupling two quantum dots through a region proximitized by a superconductor. We demonstrate systematic control over inter-dot couplings through in-plane rotations of the magnetic field and via electrostatic gating of the proximitized region. This allows us to tune the system to sweet spots in parameter space, where robust correlated zero-bias conductance peaks are observed in tunnelling spectroscopy. To study the extent of hybridization between localized MBSs, we probe the evolution of the energy spectrum with magnetic field and estimate the Majorana polarization, an important metric for Majorana-based qubits 5,6 . The implementation of a Kitaev chain on a scalable and flexible two-dimensional platform provides a realistic path towards more advanced experiments that require manipulation and readout of multiple MBSs., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: Transcatheter edge-to-edge repair (TEER) is a prominent therapeutic option for mitral regurgitation (MR) patients. However, it lacks objective parameters to assess procedural efficacy. This study aims to investigate pulmonary venous (PV) flow as a surrogate for valvular hemodynamics and its associations to clinical outcomes., Methods: Consecutive MR patients who underwent TEER in our center from January 2020 to October 2021 were retrospectively investigated. PV flow parameters were measured before and after TEER, including velocity (cm/s), velocity time integral (VTI) (cm), and systolic/diastolic ratios. Primary outcomes were 1, 6, and 12 months heart failure hospitalizations (HFH) and 1 year all-cause mortality., Results: The cohort consisted of 80 patients. The mean age was 74.76 ± 10.13 years, 26 with primary and 54 with secondary MR. Systolic wave parameters improved significantly after TEER: mean peak velocity increased from 9.94 ± 31.95 to 35.74 ± 15.03 cm/s, and VTI from 3.62 ± 5.99 to 8.33 ± 4.72 cm. Furthermore, systolic to diastolic VTI and peak-velocities ratios showed significant improvement of 0.39 ± 0.63 to 0.81 ± 0.47 and 0.23 ± 0.66 to 0.91 ± 0.43, respectively. Using multivariable analysis, higher post-procedural S VTI was associated with less HFH: 1-month (OR = 0.72, CI [0.52,0.98]), 6-months (OR = 0.8, CI [0.66,0.97]), 1-year (OR = 0.85, CI [0.73,0.99]), as well as reduced 1-year mortality (OR = 0.64 95% CI [0.45,0.91]). Furthermore, compared to patients with SVTI ≥ 3, patients with SVTI < 3 had a higher risk for HFH at: 1-month (OR = 16.59, CI [1.48,186.02]), 6-months (OR = 12.2, CI [1.69,88.07]), and 1-year (OR = 8.61, CI [1.27,58.27]), as well as elevated 1-year mortality (OR = 8.07, 95% CI [1.04,62.28])., Conclusion: PV flow was significantly improved following TEER, and several hemodynamic parameters were associated with HFH and mortality. These results may offer a basis for establishing future procedural goals to ensure better clinical outcomes., Competing Interests: Declaration of interests None., (Copyright © 2024 Hellenic Society of Cardiology. Published by Elsevier Inc. All rights reserved.)

Tissue engineering is considered a promising approach to treating advanced degenerative maculopathies such as nonexudative age-related macular degeneration (AMD), the leading cause of blindness worldwide. The retina consists of several hierarchical tissue layers, each of which is supported by a layer underneath. Each of these layers has a different morphology and requires distinct conditions for proper assembly. In fact, a prerequisite step for the assembly of each of these layers is the organization of the layer underneath. Advanced retinal degeneration includes degeneration of the other retina layers, including the choroid, the retinal pigmented epithelium (RPE), and the photoreceptors. Here, we report a step-by-step fabrication process of a three-layer retina-like structure. The process included the 3D printing of a choroid-like structure in an extracellular matrix (ECM) hydrogel, followed by deposition of the RPE monolayer. After the formation of the blood vessel-RPE interface, the photoreceptor cells were deposited to interact with the RPE layer. At the end of the fabrication process, each layer was characterized for its morphology and expression of specific markers, and the integration of the three-layer retina was evaluated. We envision that such a retina-like structure may be able to attenuate the deterioration of a degenerated retina and improve engraftment and regeneration. This retinal implant may potentially be suitable for a spectrum of macular degenerative diseases for which there are currently no cures and may save millions from complete blindness.

The formation of a topological superconducting phase in a quantum-dot-based Kitaev chain requires nearest neighbor crossed Andreev reflection and elastic cotunneling. Here, we report on a hybrid InSb nanowire in a three-site Kitaev chain geometry-the smallest system with well-defined bulk and edge-where two superconductor-semiconductor hybrids separate three quantum dots. We demonstrate pairwise crossed Andreev reflection and elastic cotunneling between both pairs of neighboring dots and show sequential tunneling processes involving all three quantum dots. These results are the next step toward the realization of topological superconductivity in long Kitaev chain devices with many coupled quantum dots.

Cardiac monitoring after heart surgeries is crucial for health maintenance and detecting postoperative complications early. However, current methods like rigid implants have limitations, as they require performing second complex surgeries for removal, increasing infection and inflammation risks, thus prompting research for improved sensing monitoring technologies. Herein, we introduce a nanosensor platform that is biodegradable, biocompatible, and integrated with multifunctions, suitable for use as implants for cardiac monitoring. The device has two electrochemical biosensors for sensing lactic acid and pH as well as a pressure sensor and a chemiresistor array for detecting volatile organic compounds. Its biocompatibility with myocytes has been tested in vitro, and its biodegradability and sensing function have been proven with ex vivo experiments using a three-dimensional (3D)-printed heart model and 3D-printed cardiac tissue patches. Moreover, an artificial intelligence-based predictive model was designed to fuse sensor data for more precise health assessment, making it a suitable candidate for clinical use. This sensing platform promises impactful applications in the realm of cardiac patient care, laying the foundation for advanced life-saving developments.

Semiconductor nanowires coupled to superconductors can host Andreev bound states with distinct spin and parity, including a spin-zero state with an even number of electrons and a spin-1/2 state with odd-parity. Considering the difference in spin of the even and odd states, spin-filtered measurements can reveal the underlying ground state. To directly measure the spin of single-electron excitations, we probe an Andreev bound state using a spin-polarized quantum dot that acts as a bipolar spin filter, in combination with a non-polarized tunnel junction in a three-terminal circuit. We observe a spin-polarized excitation spectrum of the Andreev bound state, which can be fully spin-polarized, despite strong spin-orbit interaction in the InSb nanowires. Decoupling the hybrid from the normal lead causes a current blockade, by trapping the Andreev bound state in an excited state. Spin-polarized spectroscopy of hybrid nanowire devices, as demonstrated here, is proposed as an experimental tool to support the observation of topological superconductivity., (© 2023. The Author(s).)

The survival and function of tissues depend on appropriate vascularization. Blood vessels of the tissues supply oxygen, and nutrients and remove waste and byproducts. Incorporating blood vessels into engineered tissues is essential for overcoming diffusion limitations, improving tissue function, and thus facilitating the fabrication of thick tissues. Here, we present a modified ECM bioink, with enhanced mechanical properties and endothelial cell-specific adhesion motifs, to serve as a building material for 3D printing of a multiscale blood vessel network. The bioink is composed of natural ECM and alginate conjugated with a laminin adhesion molecule motif (YIGSR). The hybrid hydrogel was characterized for its mechanical properties, biochemical content, and ability to interact with endothelial cells. The pristine and modified hydrogels were mixed with induced pluripotent stem cells derived endothelial cells (iPSCs-ECs) and used to print large blood vessels with capillary beds in between.

Despite advances in biomaterials engineering, a large gap remains between the weak mechanical properties that can be achieved with natural materials and the strength of synthetic materials. Here, a method is presented for reinforcing an engineered cardiac tissue fabricated from differentiated induced pluripotent stem cells (iPSCs) and an extracellular matrix (ECM)-based hydrogel in a manner that is fully biocompatible. The reinforcement occurs as a post-fabrication step, which allows for the use of 3D-printing technology to generate thick, fully cellularized, and vascularized cardiac tissues. After tissue assembly and during the maturation process in a soft hydrogel, a small, tissue-penetrating reinforcer is deployed, leading to a significant increase in the tissue's mechanical properties. The tissue's robustness is demonstrated by injecting the tissue in a simulated minimally invasive procedure and showing that the tissue is functional and undamaged at the nano-, micro-, and macroscales., (© 2023 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

The proximity effect in semiconductor-superconductor nanowires is expected to generate an induced gap in the semiconductor. The magnitude of this induced gap, together with the semiconductor properties like spin-orbit coupling and g-factor, depends on the coupling between the materials. It is predicted that this coupling can be adjusted through the use of electric fields. We study this phenomenon in InSb/Al/Pt hybrids using nonlocal spectroscopy. We show that these hybrids can be tuned such that the semiconductor and superconductor are strongly coupled. In this case, the induced gap is similar to the superconducting gap in the Al/Pt shell and closes only at high magnetic fields. In contrast, the coupling can be suppressed which leads to a strong reduction of the induced gap and critical magnetic field. At the crossover between the strong-coupling and weak-coupling regimes, we observe the closing and reopening of the induced gap in the bulk of a nanowire. Contrary to expectations, it is not accompanied by the formation of zero-bias peaks in the local conductance spectra. As a result, this cannot be attributed conclusively to the anticipated topological phase transition and we discuss possible alternative explanations., (© 2023. The Author(s).)

In myocardial infarction, a blockage in one of the coronary arteries leads to ischemic conditions in the left ventricle of the myocardium and, therefore, to significant death of contractile cardiac cells. This process leads to the formation of scar tissue, which reduces heart functionality. Cardiac tissue engineering is an interdisciplinary technology that treats the injured myocardium and improves its functionality. However, in many cases, mainly when employing injectable hydrogels, the treatment may be partial because it does not fully cover the diseased area and, therefore, may not be effective and even cause conduction disorders. Here, we report a hybrid nanocomposite material composed of gold nanoparticles and an extracellular matrix-based hydrogel. Such a hybrid hydrogel could support cardiac cell growth and promote cardiac tissue assembly. After injection of the hybrid material into the diseased area of the heart, it could be efficiently imaged by magnetic resonance imaging (MRI). Furthermore, as the scar tissue could also be detected by MRI, a distinction between the diseased area and the treatment could be made, providing information about the ability of the hydrogel to cover the scar. We envision that such a nanocomposite hydrogel may improve the accuracy of tissue engineering treatment.

Majorana bound states constitute one of the simplest examples of emergent non-Abelian excitations in condensed matter physics. A toy model proposed by Kitaev shows that such states can arise at the ends of a spinless p-wave superconducting chain 1 . Practical proposals for its realization 2,3 require coupling neighbouring quantum dots (QDs) in a chain through both electron tunnelling and crossed Andreev reflection 4 . Although both processes have been observed in semiconducting nanowires and carbon nanotubes 5-8 , crossed-Andreev interaction was neither easily tunable nor strong enough to induce coherent hybridization of dot states. Here we demonstrate the simultaneous presence of all necessary ingredients for an artificial Kitaev chain: two spin-polarized QDs in an InSb nanowire strongly coupled by both elastic co-tunnelling (ECT) and crossed Andreev reflection (CAR). We fine-tune this system to a sweet spot where a pair of poor man's Majorana states is predicted to appear. At this sweet spot, the transport characteristics satisfy the theoretical predictions for such a system, including pairwise correlation, zero charge and stability against local perturbations. Although the simple system presented here can be scaled to simulate a full Kitaev chain with an emergent topological order, it can also be used imminently to explore relevant physics related to non-Abelian anyons., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Semiconductor quantum dots have proven to be a useful platform for quantum simulation in the solid state. However, implementing a superconducting coupling between quantum dots mediated by a Cooper pair has so far suffered from limited tunability and strong suppression. This has limited applications such as Cooper pair splitting and quantum dot simulation of topological Kitaev chains. In this Letter, we propose how to mediate tunable effective couplings via Andreev bound states in a semiconductor-superconductor nanowire connecting two quantum dots. We show that in this way it is possible to individually control both the coupling mediated by Cooper pairs and by single electrons by changing the properties of the Andreev bound states with easily accessible experimental parameters. In addition, the problem of coupling suppression is greatly mitigated. We also propose how to experimentally extract the coupling strengths from resonant current in a three-terminal junction. Our proposal will enable future experiments that have not been possible so far.

In most naturally occurring superconductors, electrons with opposite spins form Cooper pairs. This includes both conventional s-wave superconductors such as aluminium, as well as high-transition-temperature, d-wave superconductors. Materials with intrinsic p-wave superconductivity, hosting Cooper pairs made of equal-spin electrons, have not been conclusively identified, nor synthesized, despite promising progress 1-3 . Instead, engineered platforms where s-wave superconductors are brought into contact with magnetic materials have shown convincing signatures of equal-spin pairing 4-6 . Here we directly measure equal-spin pairing between spin-polarized quantum dots. This pairing is proximity-induced from an s-wave superconductor into a semiconducting nanowire with strong spin-orbit interaction. We demonstrate such pairing by showing that breaking a Cooper pair can result in two electrons with equal spin polarization. Our results demonstrate controllable detection of singlet and triplet pairing between the quantum dots. Achieving such triplet pairing in a sequence of quantum dots will be required for realizing an artificial Kitaev chain 7-9 ., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

In superconducting quantum circuits, aluminum is one of the most widely used materials. It is currently also the superconductor of choice for the development of topological qubits. However, aluminum-based devices suffer from poor magnetic field compatibility. Herein, this limitation is resolved by showing that adatoms of heavy elements (e.g., platinum) increase the critical field of thin aluminum films by more than a factor of two. Using tunnel junctions, it is shown that the increased field resilience originates from spin-orbit scattering introduced by Pt. This property is exploited in the context of the superconducting proximity effect in semiconductor-superconductor hybrids, where it is shown that InSb nanowires strongly coupled to Al/Pt films can maintain superconductivity up to 7 T. The two-electron charging effect is shown to be robust against the presence of heavy adatoms. Additionally, non-local spectroscopy is used in a three-terminal geometry to probe the bulk of hybrid devices, showing that it remains free of sub-gap states. Finally, it is demonstrated that proximitized semiconductor states maintain their ability to Zeeman-split in an applied magnetic field. Combined with the chemical stability and well-known fabrication routes of aluminum, Al/Pt emerges as the natural successor to Al-based systems and is a compelling alternative to other superconductors, whenever high-field resilience is required., (© 2022 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

Intracellular recording of action potentials is an essential mean for studying disease mechanisms, and for electrophysiological studies, particularly in excitable cells as cardiomyocytes or neurons. Current strategies to obtain intracellular recordings include three-dimensional (3D) nanoelectrodes that can effectively penetrate the cell membrane and achieve high-quality intracellular recordings in a minimally invasive manner, or transient electroporation of the membrane that can yield temporary intracellular access. However, the former strategy requires a complicated and costly fabrication process, and the latter strategy suffers from high dependency on the method of application of electroporation, yielding inconsistent, suboptimal recordings. These factors hinder the high throughput use of these strategies in electrophysiological studies. In this work, we propose an advanced cell-based biosensing platform that relies on electroporation to produce consistent, high-quality intracellular recordings. The suggested universal system can be integrated with any electrode array, and it enables tunable electroporation with controllable pulse parameters, while the recorded potentials can be analyzed in real time to provide instantaneous feedback on the electroporation effectiveness. This integrated system enables the user to perform electroporation, record and assess the obtained signals in a facile manner, to ultimately achieve stable, reliable, intracellular recording. Moreover, the proposed platform relies on microelectrode arrays which are suited for large-scale production, and additional modules that are low-cost. Using this platform, we demonstrate the tuning of electroporation pulse width, pulse number, and amplitude, to achieve effective electroporation and high-quality intracellular recordings. This integrated platform has the potential to enable larger scale, repeatable, convenient, and low-cost electrophysiological studies., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Cell therapy using induced pluripotent stem cell-derived neurons is considered a promising approach to regenerate the injured spinal cord (SC). However, the scar formed at the chronic phase is not a permissive microenvironment for cell or biomaterial engraftment or for tissue assembly. Engineering of a functional human neuronal network is now reported by mimicking the embryonic development of the SC in a 3D dynamic biomaterial-based microenvironment. Throughout the in vitro cultivation stage, the system's components have a synergistic effect, providing appropriate cues for SC neurogenesis. While the initial biomaterial supported efficient cell differentiation in 3D, the cells remodeled it to provide an inductive microenvironment for the assembly of functional SC implants. The engineered tissues are characterized for morphology and function, and their therapeutic potential is investigated, revealing improved structural and functional outcomes after acute and chronic SC injuries. Such technology is envisioned to be translated to the clinic to rewire human injured SC., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)