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Developing theranostic devices to detect bleeding and effectively control hemorrhage in the prehospital setting is an unmet medical need. Herein, an all‐in‐one theranostic platform is presented, which is constructed by sandwiching silk fibroin (SF) between two silver nanowire (AgNW) based conductive electrodes to non‐enzymatically diagnose local bleeding and stop the hemorrhage at the wound site. Taking advantage of the hemostatic property of natural SF, the device is composed of a shape‐memory SF sponge, facilitating blood clotting, with ≈82% reduction in hemostatic time in vitro as compared with untreated blood. Furthermore, this sandwiched platform serves as a capacitive sensor that can detect bleeding and differentiate between blood and other body fluids (i.e., serum and water) via capacitance change. In addition, the AgNW electrode endows anti‐infection efficiency against Escherichia coli and Staphylococcus aureus. Also, the device shows excellent biocompatibility and gradually biodegrades in vivo with no major local or systemic inflammatory responses. More importantly, the theranostic platform presents considerable hemostatic efficacy comparable with a commercial hemostat, Dengen, in rat liver bleeding models. The theranostic platform provides an unexplored strategy for the intelligent management of hemorrhage, with the potential to significantly improve patients' well‐being through the integration of diagnostic and therapeutic capabilities. [ABSTRACT FROM AUTHOR]

Exosomes, a form of small extracellular vesicles, play a crucial role in the metastasis of cancers and thus are investigated as potential biomarkers for cancer diagnosis. However, conventional detection methods like immune‐based assay and microRNA analyses are expensive and require tedious pretreatments and lengthy analysis time. Since exosomes related to cancers are reported to exist in tears, a poly(2‐hydroxyethyl methacrylate) contact lens embedded with antibody‐conjugated signaling microchambers (ACSM‐PCL) capable of detecting tear exosomes is reported. The ACSM‐PCL exhibits high optical transparency and mechanical properties, along with extraordinary biocompatibility and good sensitivity to exosomes. A gold nanoparticle colorimetric assay is employed to visualize captured exosomes. The ACSM‐PCL can detect exosomes in the pH range of 6.5–7.4 (similar to the human tear pH) and have a strong recovery yield in bovine serum albumin solutions. In particular, the ACSM‐PCL can detect exosomes in various solutions, including regular buffer, cell culture media from various cell lines, and human tears. Finally, the ACSM‐PCL can differentiate expression of exosome surface proteins hypothesized as cancer biomarkers. With these encouraging results, this ACSM‐PCL is promised to be the next generation smart contact lens as an easy‐to‐use, rapid, noninvasive monitoring platform of cancer pre‐screening and supportive diagnosis. [ABSTRACT FROM AUTHOR]

Wearable piezoresistive sensors are being developed as electronic skins (E‐skin) for broad applications in human physiological monitoring and soft robotics. Tactile sensors with sufficient sensitivities, durability, and large dynamic ranges are required to replicate this critical component of the somatosensory system. Multiple micro/nanostructures, materials, and sensing modalities have been reported to address this need. However, a trade‐off arises between device performance and device complexity. Inspired by the microstructure of the spinosum at the dermo epidermal junction in skin, a low‐cost, scalable, and high‐performance piezoresistive sensor is developed with high sensitivity (0.144 kPa‐1), extensive sensing range (0.1–15 kPa), fast response time (less than 150 ms), and excellent long‐term stability (over 1000 cycles). Furthermore, the piezoresistive functionality of the device is realized via a flexible transparent electrode (FTE) using a highly stable reduced graphene oxide self‐wrapped copper nanowire network. The developed nanowire‐based spinosum microstructured FTEs are amenable to wearable electronics applications. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) have been widely used for regenerative therapy. In most current clinical applications, MSCs are delivered by injection but face significant issues with cell viability and penetration into the target tissue due to a limited migration capacity. Some therapies have attempted to improve MSC stability by their encapsulation within biomaterials; however, these treatments still require an enormous number of cells to achieve therapeutic efficacy due to low efficiency. Additionally, while local injection allows for targeted delivery, injections with conventional syringes are highly invasive. Due to the challenges associated with stem cell delivery, a local and minimally invasive approach with high efficiency and improved cell viability is highly desired. In this study, a detachable hybrid microneedle depot (d‐HMND) for cell delivery is presented. The system consists of an array of microneedles with an outer poly(lactic‐co‐glycolic) acid shell and an internal gelatin methacryloyl (GelMA)‐MSC mixture (GMM). The GMM is characterized and optimized for cell viability and mechanical strength of the d‐HMND required to penetrate mouse skin tissue is also determined. MSC viability and function within the d‐HMND is characterized in vitro and the regenerative efficacy of the d‐HMND is demonstrated in vivo using a mouse skin wound model. [ABSTRACT FROM AUTHOR]

The use of conducting polymers such as poly(3,4‐ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) for the development of soft organic bioelectronic devices, such as organic electrochemical transistors (OECTs), is rapidly increasing. However, directly manipulating conducting polymer thin films on soft substrates remains challenging, which hinders the development of conformable organic bioelectronic devices. A facile transfer‐printing of conducting polymer thin films from conventional rigid substrates to flexible substrates offers an alternative solution. In this work, it is reported that PEDOT:PSS thin films on glass substrates, once mixed with surfactants, can be delaminated with hydrogels and thereafter be transferred to soft substrates without any further treatments. The proposed method allows easy, fast, and reliable transferring of patterned PEDOT:PSS thin films from glass substrates onto various soft substrates, facilitating their application in soft organic bioelectronics. By taking advantage of this method, skin‐attachable tattoo‐OECTs are demonstrated, relevant for conformable, imperceptible, and wearable organic biosensing. [ABSTRACT FROM AUTHOR]

Chronic wounds do not heal in an orderly fashion in part due to the lack of timely release of biological factors essential for healing. Topical administration of various therapeutic factors at different stages is shown to enhance the healing rate of chronic wounds. Developing a wound dressing that can deliver biomolecules with a predetermined spatial and temporal pattern would be beneficial for effective treatment of chronic wounds. Here, an actively controlled wound dressing is fabricated using composite fibers with a core electrical heater covered by a layer of hydrogel containing thermoresponsive drug carriers. The fibers are loaded with different drugs and biological factors and are then assembled using textile processes to create a flexible and wearable wound dressing. These fibers can be individually addressed to enable on-demand release of different drugs with a controlled temporal profile. Here, the effectiveness of the engineered dressing for on-demand release of antibiotics and vascular endothelial growth factor (VEGF) is demonstrated for eliminating bacterial infection and inducing angiogenesis in vitro. The effectiveness of the VEGF release on improving healing rate is also demonstrated in a murine model of diabetic wounds. [ABSTRACT FROM AUTHOR]

Muscle-based biohybrid actuators have generated significant interest as the future of biorobotics but so far they move without having much control over their actuation behavior. Integration of microelectrodes into the backbone of these systems may enable guidance during their motion and allow precise control over these actuators with specific activation patterns. Here, this challenge is addressed by developing aligned carbon nanotube (CNT) forest microelectrode arrays and incorporating them into scaffolds for cell stimulation. Aligned CNTs are successfully embedded into flexible and biocompatible hydrogels exhibiting excellent anisotropic electrical conductivity. Bioactuators are then engineered by culturing cardiomyocytes on the CNT microelectrode-integrated hydrogel constructs. The resulting cardiac tissue shows homogeneous cell organization with improved cell-to-cell coupling and maturation, which is directly related to the contractile force of muscle tissue. This centimeter-scale bioactuator has excellent mechanical integrity, embedded microelectrodes, and is capable of spontaneous actuation behavior. Furthermore, it is demonstrated that a biohybrid machine can be controlled by an external electrical field provided by the integrated CNT microelectrode arrays. In addition, due to the anisotropic electrical conductivity of the electrodes provided by aligned CNTs, significantly different excitation thresholds are observed in different configurations such as the ones with electrical fields applied in directions parallel versus perpendicular to the CNT alignment. [ABSTRACT FROM AUTHOR]

Carbon-based nanomaterials have been considered promising candidates to mimic certain structure and function of native extracellular matrix materials for tissue engineering. Significant progress has been made in fabricating carbon nanoparticle-incorporated cell culture substrates, but only a limited number of studies have been reported on the development of 3D tissue constructs using these nanomaterials. Here, a novel approach to engineer 3D multilayer constructs using layer-by-layer (LbL) assembly of cells separated with self-assembled graphene oxide (GO)-based thin films is presented. The GO-based structures are shown to serve as cell adhesive sheets that effectively facilitate the formation of multilayer cell constructs with interlayer connectivity. By controlling the amount of GO deposited in forming the thin films, the thickness of the multilayer tissue constructs could be tuned with high cell viability. Specifically, this approach could be useful for creating dense and tightly connected cardiac tissues through the co-culture of cardiomyocytes and other cell types. In this work, the fabrication of stand-alone multilayer cardiac tissues with strong spontaneous beating behavior and programmable pumping properties is demonstrated. Therefore, this LbL-based cell construct fabrication approach, utilizing GO thin films formed directly on cell surfaces, has great potential in engineering 3D tissue structures with improved organization, electrophysiological function, and mechanical integrity. [ABSTRACT FROM AUTHOR]

Hydrogels represent a class of materials suitable for numerous biomedical applications such as tissue engineering and drug delivery. Hydrogels are by definition capable of absorbing large amount of fluid, making them adequate for cell seeding and encapsulation as well as for implantation because of their biocompatibility and excellent diffusion properties. They also possess other desirable properties for fundamental research as they have the ability to mimic the basic three-dimensional (3D) biological, chemical, and mechanical properties of native tissues. Furthermore, their biological interactions with cells can be modified through the numerous side groups of the polymeric chains. Thus, the biological, chemical, and mechanical properties, as well as the degradation kinetics of hydrogels can be tailored depending on the application. In addition, their fabrication process can be combined with microtechnologies to enable precise control of cell-scale features such as surface topography and the presence of adhesion motifs on the hydrogel material. This ability to control the microscale structure of hydrogels has been used to engineer tissue models and to study cell behavior mechanisms in vitro. New approaches such as bottom-up and directed assembly of microscale hydrogels (microgels) are currently emerging as powerful methods to enable the fabrication of 3D constructs replicating the microenvironment found in vivo. WIREs Nanomed Nanobiotechnol 2012, 4:235-246. doi: 10.1002/wnan.171 For further resources related to this article, please visit the . [ABSTRACT FROM AUTHOR]

Biodegradable Polymers: A Patch of Detachable Hybrid Microneedle Depot for Localized Delivery of Mesenchymal Stem Cells in Regeneration Therapy (Adv. Funct. Keywords: biodegradable polymer; gelatin methacryloyl hydrogel; mesenchymal stem cell; microneedle; regenerative therapy EN biodegradable polymer gelatin methacryloyl hydrogel mesenchymal stem cell microneedle regenerative therapy 1 1 1 06/06/20 20200604 NES 200604 In article number 2000086, KangJu Lee, Ali Khademhosseini, and co-workers present a novel device for enhancing wound healing, the detachable hybrid microneedle depot. Biodegradable polymer, gelatin methacryloyl hydrogel, mesenchymal stem cell, microneedle, regenerative therapy. [Extracted from the article]

Hydrogel-Enabled Transfer Printing: Hydrogel-Enabled Transfer-Printing of Conducting Polymer Films for Soft Organic Bioelectronics (Adv. Funct. Keywords: hydrogel; OECTs; PEDOT:PSS; transfer-printing; wearable biosensing Hydrogel, OECTs, PEDOT:PSS, transfer-printing, wearable biosensing. [Extracted from the article]

Microphysiological systems, also known as organ‐on‐a‐chip platforms, show promise for the development of new testing methods that can be more accurate than both conventional two‐dimensional (2D) cultures and costly animal studies. The development of more intricate microphysiological systems can help to better mimic the human physiology and highlight the systemic effects of different drugs and materials. Nanomaterials are among a technologically important class of materials used for diagnostic, therapeutic, and monitoring purposes; all of which can be tested using new organ‐on‐a‐chip systems. In addition, the toxicity of nanomaterials which have entered the body from ambient air or diet can have deleterious effects on various body systems. This in turn can be studied in newly developed microphysiological systems. While organ‐on‐a‐chip models can be useful, they cannot pick up secondary and systemic toxicity. Thus, the utilization of multiorgan‐on‐a‐chip systems for advancing nanotechnology will largely be reflected in the future of drug development, toxicology studies, and precision medicine. Various aspects of related studies, current challenges, and future perspectives are discussed in this paper. [ABSTRACT FROM AUTHOR]

Liver-on-a-Chip: A Human Liver-on-a-Chip Platform for Modeling Nonalcoholic Fatty Liver Disease (Adv. Biosys. In article number 1900104, Junmin Lee, Ali Khademhosseini, and co-workers develop a bioengineered liver steatosis model based on the interactions between human hepatocytes and primary human endothelial cells by forming multicellular aggregates to investigate steatosis pathogenesis. The spheroids on a chip platform can be used for monitoring hepatocyte functionality and developing pharmaceutical tools to evaluate new potential drugs. [Extracted from the article]

The liver possesses a unique microenvironment with a complex internal vascular system and cell–cell interactions. Nonalcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease, and although much effort has been dedicated to building models to target NAFLD, most in vitro systems rely on simple models failing to recapitulate complex liver functions. Here, an in vitro system is presented to study NAFLD (steatosis) by coculturing human hepatocellular carcinoma (HepG2) cells and umbilical vein endothelial cells (HUVECs) into spheroids. Analysis of colocalization of HepG2–HUVECs along with the level of steatosis reveals that the NAFLD pathogenesis could be better modeled when 20% of HUVECs are presented in HepG2 spheroids. Spheroids with fat supplements progressed to the steatosis stage on day 2, which could be maintained for more than a week without being harmful for cells. Transferring spheroids onto a chip system with an array of interconnected hexagonal microwells proves helpful for monitoring functionality through increased albumin secretions with HepG2–HUVEC interactions and elevated production of reactive oxygen species for steatotic spheroids. The reversibility of steatosis is demonstrated by simply stopping fat‐based diet or by antisteatotic drug administration, the latter showing a faster return of intracellular lipid levels to the basal level. [ABSTRACT FROM AUTHOR]