Intracellular detection and communication of a wireless chip in cell.

The rapid growth and development of technology has had significant implications for healthcare, personalized medicine, and our understanding of biology. In this work, we leverage the miniaturization of electronics to realize the first demonstration of wireless detection and communication of an electronic device inside a cell. This is a significant forward step towards a vision of non-invasive, intracellular wireless platforms for single-cell analyses. We demonstrate that a 25 [Formula: see text]m wireless radio frequency identification (RFID) device can not only be taken up by a mammalian cell but can also be detected and specifically identified externally while located intracellularly. The S-parameters and power delivery efficiency of the electronic communication system is quantified before and after immersion in a biological environment; the results show distinct electrical responses for different RFID tags, allowing for classification of cells by examining the electrical output noninvasively. This versatile platform can be adapted for realization of a broad modality of sensors and actuators. This work precedes and facilitates the development of long-term intracellular real-time measurement systems for personalized medicine and furthering our understanding of intrinsic biological behaviors. It helps provide an advanced technique to better assess the long-term evolution of cellular physiology as a result of drug and disease stimuli in a way that is not feasible using current methods.

A self-sustainable wearable multi-modular E-textile bioenergy microgrid system.

Despite the fast development of various energy harvesting and storage devices, their judicious integration into efficient, autonomous, and sustainable wearable systems has not been widely explored. Here, we introduce the concept and design principles of e-textile microgrids by demonstrating a multi-module bioenergy microgrid system. Unlike earlier hybrid wearable systems, the presented e-textile microgrid relies solely on human activity to work synergistically, harvesting biochemical and biomechanical energy using sweat-based biofuel cells and triboelectric generators, and regulating the harvested energy via supercapacitors for high-power output. Through energy budgeting, the e-textile system can efficiently power liquid crystal displays continuously or a sweat sensor-electrochromic display system in pulsed sessions, with half the booting time and triple the runtime in a 10-min exercise session. Implementing "compatible form factors, commensurate performance, and complementary functionality" design principles, the flexible, textile-based bioenergy microgrid offers attractive prospects for the design and operation of efficient, sustainable, and autonomous wearable systems.

Engineering human hematopoietic environments through ossicle and bioreactor technologies exploitation.

The bone marrow microenvironment contains cellular niches that maintain the pool of hematopoietic stem and progenitor cells and support hematopoietic maturation. Malignant hematopoietic cells also co-opt normal cellular interactions to promote their own growth and evade therapy. In vivo systems used to study human hematopoiesis have been developed through transplantation into immunodeficient mouse models. However, incomplete cross-compatibility between the murine stroma and transplanted human hematopoietic cells limits the rate of engraftment and the study of relevant interactions. To supplement in vivo xenotransplantation models, complementary strategies have recently been developed, including the use of three-dimensional human bone marrow organoids in vivo, generated from bone marrow stromal cells seeded onto osteo-inductive scaffolds, as well as the use of ex vivo bioreactor models. These topics were the focus of the Spring 2020 International Society for Experimental Hematology New Investigator webinar. We review here the latest advances in generating humanized hematopoietic organoids and how they allow for the study of novel microenvironmental interactions.

Controlled packing and single-droplet resolution of 3D-printed functional synthetic tissues.

3D-printing networks of droplets connected by interface bilayers are a powerful platform to build synthetic tissues in which functionality relies on precisely ordered structures. However, the structural precision and consistency in assembling these structures is currently limited, which restricts intricate designs and the complexity of functions performed by synthetic tissues. Here, we report that the equilibrium contact angle (θDIB) between a pair of droplets is a key parameter that dictates the tessellation and precise positioning of hundreds of picolitre-sized droplets within 3D-printed, multi-layer networks. When θDIB approximates the geometrically-derived critical angle (θc) of 35.3°, the resulting networks of droplets arrange in regular hexagonal close-packed (hcp) lattices with the least fraction of defects. With this improved control over droplet packing, we can 3D-print functional synthetic tissues with single-droplet-wide conductive pathways. Our new insights into 3D droplet packing permit the fabrication of complex synthetic tissues, where precisely positioned compartments perform coordinated tasks.

Locally coupled electromechanical interfaces based on cytoadhesion-inspired hybrids to identify muscular excitation-contraction signatures.

Coupling myoelectric and mechanical signals during voluntary muscle contraction is paramount in human-machine interactions. Spatiotemporal differences in the two signals intrinsically arise from the muscular excitation-contraction process; however, current methods fail to deliver local electromechanical coupling of the process. Here we present the locally coupled electromechanical interface based on a quadra-layered ionotronic hybrid (named as CoupOn) that mimics the transmembrane cytoadhesion architecture. CoupOn simultaneously monitors mechanical strains with a gauge factor of ~34 and surface electromyogram with a signal-to-noise ratio of 32.2 dB. The resolved excitation-contraction signatures of forearm flexor muscles can recognize flexions of different fingers, hand grips of varying strength, and nervous and metabolic muscle fatigue. The orthogonal correlation of hand grip strength with speed is further exploited to manipulate robotic hands for recapitulating corresponding gesture dynamics. It can be envisioned that such locally coupled electromechanical interfaces would endow cyber-human interactions with unprecedented robustness and dexterity.

The emerging science of electrosynbionics.

Dramatic changes in electricity generation, use and storage are needed to keep pace with increasing demand while reducing carbon dioxide emissions. There is great potential for application of bioengineering in this area. We have the tools to re-engineer biological molecules and systems, and a significant amount of research and development is being carried out on technologies such as biophotovoltaics, biocapacitors, biofuel cells and biobatteries. However, there does not seem to be a satisfactory overarching term to describe this area, and I propose a new word-'electrosynbionics'. This is to be defined as: the creation of engineered devices that use components derived from or inspired by biology to perform a useful electrical function. Here, the phrase 'electrical function' is taken to mean the generation, use and storage of electricity, where the primary charge carriers may be either electrons or ions. 'Electrosynbionics' is distinct from 'bioelectronics', which normally relates to applications in sensing, computing or electroceuticals. Electrosynbionic devices have the potential to solve challenges in electricity generation, use and storage by exploiting or mimicking some of the desirable attributes of biological systems, including high efficiency, benign operating conditions and intricate molecular structures.

Biofunctional Silk Kirigami With Engineered Properties.

The fabrication of multifunctional materials that interface with living environments is a problem of great interest. A variety of structural design concepts have been integrated with functional materials to form biodevices and surfaces for health monitoring. In particular, approaches based on kirigami-inspired cuts can engineer flexibility in materials through the creation of patterned defects. Here, the fabrication of a biodegradable and biofunctional "silk kirigami" material is demonstrated. Mechanically flexible, free-standing, optically transparent, large-area biomaterial sheets with precisely defined and computationally designed microscale cuts can be formed using a single-step photolithographic process. Using modeling techniques, it is shown how cuts can generate remarkable "self-shielding" leading to engineered elastic behavior and deformation. As composites with conducting polymers, flexible, intrinsically electroactive sheets can be formed. Importantly, the silk kirigami sheets are biocompatible, can serve as substrates for cell culture, and be proteolytically resorbed. The unique properties of silk kirigami suggest a host of applications as transient, "green", functional biointerfaces, and flexible bioelectronics.

Enzyme Immobilization in Wall-Coated Flow Microreactors.

Flow microreactors are emergent engineering tools for the development of continuous biocatalytic transformations. Exploiting enzymes in continuous mode requires their retention for multiple rounds of conversions. To achieve this goal, immobilizing the enzymes on microchannel walls is a promising approach. However, protein immobilization within closed structures is difficult. Here, we describe a methodology based on the confluent design of enzyme and microreactor; fusion to the silica-binding module Zbasic2 is used to engineer enzymes for high-affinity-oriented attachment to the plain wall surface of glass microchannels. As a practical case, the methodology is described using a sucrose phosphorylase; the assayed reaction is synthesis of α-D-glucose 1-phosphate (αGlc 1-P) from sucrose and phosphate using the immobilized enzyme microreactor. Procedures of enzyme immobilization, reactor characterization, and operation are described. The methodology is applicable for any other enzymes fused to Zbasic2 and silica (glass)-based microfluidic reactors.

Recent Advances in Enabling Technologies in 3D Printing for Precision Medicine.

Advances in areas such as data analytics, genomics, and imaging have revealed individual patient complexities and exposed the inherent limitations of generic therapies for patient treatment. These observations have also fueled the development of precision medicine approaches, where therapies are tailored for the individual rather than the broad patient population. 3D printing is a field that intersects with precision medicine through the design of precision implants with patient-directed shapes, structures, and materials or for the development of patient-specific in vitro models that can be used for screening precision therapeutics. Toward their success, advances in 3D printing and biofabrication technologies are needed with enhanced resolution, complexity, reproducibility, and speed and that encompass a broad range of cells and materials. The overall goal of this progress report is to highlight recent advances in 3D printing technologies that are helping to enable advances important in precision medicine.

Integrated additive design and manufacturing approach for the bioengineering of bone scaffolds for favorable mechanical and biological properties.

Additive manufacturing (AM) presents the possibility of personalized bone scaffolds with unprecedented structural and functional designs. In contrast to earlier conventional design concepts, e.g. raster-angle, a workflow was established to produce scaffolds with triply periodic minimal surface (TPMS) architecture. A core challenge is the realization of such structures using melt-extrusion based 3D printing. This study presents methods for generation of scaffold design files, finite element (FE) analysis of scaffold Young's moduli, AM of scaffolds with polycaprolactone (PCL), and a customized in vitro assay to evaluate cell migration. The reliability of FE analysis when using computer-aided designed models as input may be impeded by anomalies introduced during 3D printing. Using micro-computed tomography reconstructions of printed scaffolds as an input for numerical simulation in comparison to experimentally obtained scaffold Young's moduli showed a moderate trend (R 2 = 0.62). Interestingly, in a preliminary cell migration assay, adipose-derived mesenchymal stromal cells (AdMSC) migrated furthest on PCL scaffolds with Diamond, followed by Gyroid and Schwarz P architectures. A similar trend, but with an accelerated AdMSC migration rate, was observed for PCL scaffolds surface coated with calcium-phosphate-based apatite. We elaborate on the importance of start-to-finish integration of all steps of AM, i.e. design, engineering and manufacturing. Using such a workflow, specific biological and mechanical functionality, e.g. improved regeneration via enhanced cell migration and higher structural integrity, may be realized for scaffolds intended as temporary guiding structures for endogenous tissue regeneration.

Emerging role of cardiac computed tomography in heart failure.

Despite medical advancements, the prognosis of patients with heart failure remains poor. While echocardiography and cardiac magnetic resonance imaging remain at the forefront of diagnosing and monitoring patients with heart failure, cardiac computed tomography (CT) has largely been considered to have a limited role. With the advancements in scanner design, technology, and computer processing power, cardiac CT is now emerging as a valuable adjunct to clinicians managing patients with heart failure. In the current manuscript, we review the current applications of cardiac CT to patients with heart failure and also the emerging areas of research where its clinical utility is likely to extend into the realm of treatment, procedural planning, and advanced heart failure therapy implementation.

Perovskite nickelates as bio-electronic interfaces.

Functional interfaces between electronics and biological matter are essential to diverse fields including health sciences and bio-engineering. Here, we report the discovery of spontaneous (no external energy input) hydrogen transfer from biological glucose reactions into SmNiO3, an archetypal perovskite quantum material. The enzymatic oxidation of glucose is monitored down to ~5 × 10-16 M concentration via hydrogen transfer to the nickelate lattice. The hydrogen atoms donate electrons to the Ni d orbital and induce electron localization through strong electron correlations. By enzyme specific modification, spontaneous transfer of hydrogen from the neurotransmitter dopamine can be monitored in physiological media. We then directly interface an acute mouse brain slice onto the nickelate devices and demonstrate measurement of neurotransmitter release upon electrical stimulation of the striatum region. These results open up avenues for use of emergent physics present in quantum materials in trace detection and conveyance of bio-matter, bio-chemical sciences, and brain-machine interfaces.

Biomimetic cardiovascular platforms for in vitro disease modeling and therapeutic validation.

Bioengineered tissues have become increasingly more sophisticated owing to recent advancements in the fields of biomaterials, microfabrication, microfluidics, genetic engineering, and stem cell and developmental biology. In the coming years, the ability to engineer artificial constructs that accurately mimic the compositional, architectural, and functional properties of human tissues, will profoundly impact the therapeutic and diagnostic aspects of the healthcare industry. In this regard, bioengineered cardiac tissues are of particular importance due to the extremely limited ability of the myocardium to self-regenerate, as well as the remarkably high mortality associated with cardiovascular diseases worldwide. As novel microphysiological systems make the transition from bench to bedside, their implementation in high throughput drug screening, personalized diagnostics, disease modeling, and targeted therapy validation will bring forth a paradigm shift in the clinical management of cardiovascular diseases. Here, we will review the current state of the art in experimental in vitro platforms for next generation diagnostics and therapy validation. We will describe recent advancements in the development of smart biomaterials, biofabrication techniques, and stem cell engineering, aimed at recapitulating cardiovascular function at the tissue- and organ levels. In addition, integrative and multidisciplinary approaches to engineer biomimetic cardiovascular constructs with unprecedented human and clinical relevance will be discussed. We will comment on the implementation of these platforms in high throughput drug screening, in vitro disease modeling and therapy validation. Lastly, future perspectives will be provided on how these biomimetic platforms will aid in the transition towards patient centered diagnostics, and the development of personalized targeted therapeutics.

Cell Patterning Method on a Clinically Ubiquitous Culture Dish Using Acoustic Pressure Generated From Resonance Vibration of a Disk-Shaped Ultrasonic Transducer.

Cell patterning methods have been previously reported for cell culture. However, these methods use inclusions or devices that are not used in general cell culture and that might affect cell functionality. Here, we report a cell patterning method that can be conducted on a general cell culture dish without any inclusions by employing a resonance vibration of a disk-shaped ultrasonic transducer located under the dish. A resonance vibration with a single nodal circle patterned C2C12 myoblasts into a circular shape on the dish with 10-min exposure of the vibration with maximum peak-peak amplitude of 10 µm[Formula: see text]. Furthermore, the relationship between the amplitude distribution of the transducer and the cell density in the patterned sample could be expressed as a linear function, and there was a clear threshold of amplitude for cell adhesion. To evaluate the cell function of the patterned cells, we conducted proliferation and protein assays at 120-h culture after patterning. Our results showed that the cell proliferation rate did not decrease and the expression of cellular proteins was unchanged. Thus, we conclude, this method can successfully pattern cells in the clinically ubiquitous culture dish, while maintaining cell functionality.

Engineered microenvironments and microdevices for modeling the pathophysiology of type 1 diabetes.

The pathophysiology of type 1 diabetes is a complex process involving tightly controlled microenvironments, a number of highly specific immune cell - islet cell interactions, and the eventual breaking of immune tolerance leading to beta cell death. Modeling this process can provide researchers with powerful insights into how and when to best provide treatment, but has proven difficult to accurately model due to its complex nature and differences between animal models and humans. Much progress has been made in determining the genetic, molecular, and cellular mechanisms of type 1 diabetes, yet translating that knowledge to clinical treatments remains challenging. Thus, there exists a capabilities gap between understanding the disease pathophysiology and engineering effective clinical treatment strategies. Biomimetic modeling of human type 1 diabetes is a valuable tool to study and manipulate islet function and can be employed to address immunological aspects of type 1 diabetes. This article will review recent advances in this field, and will suggest ways to synergize systems to model and observe the pathophysiology of autoimmune diabetes with bioengineered therapeutic strategies.

Emerging Technology and Applications of 3D Printing in the Medical Field.

3D printing technology evolved in the 1980s, but has made great strides in the last decade from both a cost and accessibility standpoint. While most printers are employed for commercial uses, medical 3D printing is a growing application which serves to aid physicians in the diagnosis, therapeutic planning, and potentially the treatment of patients with complex diseases. In this article we will delineate the types of printers available to the consumer, the various materials which can be utilized, and potential applications of 3D models in the healthcare field.

Solid-State Fermentation as an Economic Production Method of Lipases.

Solid-state fermentation (SSF) has been largely employed during the last three decades to produce different biomolecules of industrial interest, particularly enzymes. Through the use of agroindustrial wastes as SSF substrates, an economic process of lipases production can be achieved. In this chapter we describe a comprehensive SSF method for producing an economical preparation of Rhizomucor miehei lipase, employing sugarcane bagasse and used vegetal oil as substrates. To demonstrate the usefulness of the lipase produced by this method, we utilized directly the dried fermented solid, as a heterogeneous biocatalyst for the ethanolysis of different fats and oils. Final ethyl ester conversions (>90%, 24 h) were similar with those obtained using a commercial immobilized Rhizomucor miehei lipase at our best conditions. In this work we demonstrated that SSF is an easy and economical method for the production of lipases that can be used directly as heterogeneous biocatalysts for biodiesel production, employing low-cost feedstocks.

Engineered Airway Models to Study Liquid Plug Splitting at Bifurcations: Effects of Orientation and Airway Size.

Delivery of biological fluids, such as surfactant solutions, into lungs is a major strategy to treat respiratory disorders including respiratory distress syndrome that is caused by insufficient or dysfunctional natural lung surfactant. The instilled solution forms liquid plugs in lung airways. The plugs propagate downstream in airways by inspired air or ventilation, continuously split at airway bifurcations to smaller daughter plugs, simultaneously lose mass from their trailing menisci, and eventually rupture. A uniform distribution of the instilled biofluid in lung airways is expected to increase the treatments success. The uniformity of distribution of instilled liquid in the lungs greatly depends on the splitting of liquid plugs between daughter airways, especially in the first few generations from which airways of different lobes of lungs emerge. To mechanistically understand this process, we developed a bioengineering approach to computationally design three-dimensional bifurcating airway models using morphometric data of human lungs, fabricate physical models, and examine dynamics of liquid plug splitting. We found that orientation of bifurcating airways has a major effect on the splitting of liquid plugs between daughter airways. Changing the relative gravitational orientation of daughter tubes with respect to the horizontal plane caused a more asymmetric splitting of liquid plugs. Increasing the propagation speed of plugs partially counteracted this effect. Using airway models of smaller dimensions reduced the asymmetry of plug splitting. This work provides a step toward developing delivery strategies for uniform distribution of therapeutic fluids in the lungs.

Silkworm silk-based materials and devices generated using bio-nanotechnology.

Silks are natural fibrous protein polymers that are spun by silkworms and spiders. Among silk variants, there has been increasing interest devoted to the silkworm silk of B. mori, due to its availability in large quantities along with its unique material properties. Silk fibroin can be extracted from the cocoons of the B. mori silkworm and combined synergistically with other biomaterials to form biopolymer composites. With the development of recombinant DNA technology, silks can also be rationally designed and synthesized via genetic control. Silk proteins can be processed in aqueous environments into various material formats including films, sponges, electrospun mats and hydrogels. The versatility and sustainability of silk-based materials provides an impressive toolbox for tailoring materials to meet specific applications via eco-friendly approaches. Historically, silkworm silk has been used by the textile industry for thousands of years due to its excellent physical properties, such as lightweight, high mechanical strength, flexibility, and luster. Recently, due to these properties, along with its biocompatibility, biodegradability and non-immunogenicity, silkworm silk has become a candidate for biomedical utility. Further, the FDA has approved silk medical devices for sutures and as a support structure during reconstructive surgery. With increasing needs for implantable and degradable devices, silkworm silk has attracted interest for electronics, photonics for implantable yet degradable medical devices, along with a broader range of utility in different device applications. This Tutorial review summarizes and highlights recent advances in the use of silk-based materials in bio-nanotechnology, with a focus on the fabrication and functionalization methods for in vitro and in vivo applications in the field of tissue engineering, degradable devices and controlled release systems.