3D printed nanomaterial-based electronic, biomedical, and bioelectronic devices.

The ability to seamlessly integrate functional materials into three-dimensional (3D) constructs has been of significant interest, as it can enable the creation of multifunctional devices. Such integration can be achieved with a multiscale, multi-material 3D printing strategy. This technology has enabled the creation of unique devices such as personalized tissue regenerative scaffolds, biomedical implants, 3D electronic devices, and bionic constructs which are challenging to realize with conventional manufacturing processes. In particular, the incorporation of nanomaterials into 3D printed devices can endow a wide range of constructs with tailorable mechanical, chemical, and electrical functionalities. This review highlights the advances and unique possibilities in the fabrication of novel electronic, biomedical, and bioelectronic devices that are realized by the synergistic integration of nanomaterials with 3D printing technologies.

Effect of the Polydispersity of a Colloidal Drop on Drying Induced Stress as Measured by the Buckling of a Floating Sheet.

We study the stress developed during the drying of a colloidal drop of silica nanoparticles. In particular, we use the wrinkling instability of a thin floating sheet to measure the net stress applied by the deposit on the substrate and we focus on the effect of the particle polydispersity. In the case of a bidisperse suspension, we show that a small number of large particles substantially decreases the expected stress, which we interpret as the formation of lower hydrodynamic resistance paths in the porous material. As colloidal suspensions are usually polydisperse, we show for different average particle sizes that the stress is effectively dominated by the larger particles of the distribution and not by the average particle size.

3D Printed Programmable Release Capsules.

The development of methods for achieving precise spatiotemporal control over chemical and biomolecular gradients could enable significant advances in areas such as synthetic tissue engineering, biotic-abiotic interfaces, and bionanotechnology. Living organisms guide tissue development through highly orchestrated gradients of biomolecules that direct cell growth, migration, and differentiation. While numerous methods have been developed to manipulate and implement biomolecular gradients, integrating gradients into multiplexed, three-dimensional (3D) matrices remains a critical challenge. Here we present a method to 3D print stimuli-responsive core/shell capsules for programmable release of multiplexed gradients within hydrogel matrices. These capsules are composed of an aqueous core, which can be formulated to maintain the activity of payload biomolecules, and a poly(lactic-co-glycolic) acid (PLGA, an FDA approved polymer) shell. Importantly, the shell can be loaded with plasmonic gold nanorods (AuNRs), which permits selective rupturing of the capsule when irradiated with a laser wavelength specifically determined by the lengths of the nanorods. This precise control over space, time, and selectivity allows for the ability to pattern 2D and 3D multiplexed arrays of enzyme-loaded capsules along with tunable laser-triggered rupture and release of active enzymes into a hydrogel ambient. The advantages of this 3D printing-based method include (1) highly monodisperse capsules, (2) efficient encapsulation of biomolecular payloads, (3) precise spatial patterning of capsule arrays, (4) "on the fly" programmable reconfiguration of gradients, and (5) versatility for incorporation in hierarchical architectures. Indeed, 3D printing of programmable release capsules may represent a powerful new tool to enable spatiotemporal control over biomolecular gradients.

3D Printed Anatomical Nerve Regeneration Pathways.

An imaging-coupled 3D printing methodology for the design, optimization, and fabrication of a customized nerve repair technology for complex injuries is presented. The custom scaffolds are deterministically fabricated via a microextrusion printing principle which enables the simultaneous incorporation of anatomical geometries, biomimetic physical cues, and spatially controlled biochemical gradients in a one-pot 3D manufacturing approach.

Deposition of Quantum Dots in a Capillary Tube.

The ability to assemble nanomaterials, such as quantum dots, enables the creation of functional devices that present unique optical and electronic properties. For instance, light-emitting diodes with exceptional color purity can be printed via the evaporative-driven assembly of quantum dots. Nevertheless, current studies of the colloidal deposition of quantum dots have been limited to the surfaces of a planar substrate. Here, we investigate the evaporation-driven assembly of quantum dots inside a confined cylindrical geometry. Specifically, we observe distinct deposition patterns, such as banding structures along the length of a capillary tube. Such coating behavior can be influenced by the evaporation speed as well as the concentration of quantum dots. Understanding the factors governing the coating process can provide a means to control the assembly of quantum dots inside a capillary tube, ultimately enabling the creation of novel photonic devices.

3D printed quantum dot light-emitting diodes.

Developing the ability to 3D print various classes of materials possessing distinct properties could enable the freeform generation of active electronics in unique functional, interwoven architectures. Achieving seamless integration of diverse materials with 3D printing is a significant challenge that requires overcoming discrepancies in material properties in addition to ensuring that all the materials are compatible with the 3D printing process. To date, 3D printing has been limited to specific plastics, passive conductors, and a few biological materials. Here, we show that diverse classes of materials can be 3D printed and fully integrated into device components with active properties. Specifically, we demonstrate the seamless interweaving of five different materials, including (1) emissive semiconducting inorganic nanoparticles, (2) an elastomeric matrix, (3) organic polymers as charge transport layers, (4) solid and liquid metal leads, and (5) a UV-adhesive transparent substrate layer. As a proof of concept for demonstrating the integrated functionality of these materials, we 3D printed quantum dot-based light-emitting diodes (QD-LEDs) that exhibit pure and tunable color emission properties. By further incorporating the 3D scanning of surface topologies, we demonstrate the ability to conformally print devices onto curvilinear surfaces, such as contact lenses. Finally, we show that novel architectures that are not easily accessed using standard microfabrication techniques can be constructed, by 3D printing a 2 × 2 × 2 cube of encapsulated LEDs, in which every component of the cube and electronics are 3D printed. Overall, these results suggest that 3D printing is more versatile than has been demonstrated to date and is capable of integrating many distinct classes of materials.

3D printed bionic ears.

The ability to three-dimensionally interweave biological tissue with functional electronics could enable the creation of bionic organs possessing enhanced functionalities over their human counterparts. Conventional electronic devices are inherently two-dimensional, preventing seamless multidimensional integration with synthetic biology, as the processes and materials are very different. Here, we present a novel strategy for overcoming these difficulties via additive manufacturing of biological cells with structural and nanoparticle derived electronic elements. As a proof of concept, we generated a bionic ear via 3D printing of a cell-seeded hydrogel matrix in the anatomic geometry of a human ear, along with an intertwined conducting polymer consisting of infused silver nanoparticles. This allowed for in vitro culturing of cartilage tissue around an inductive coil antenna in the ear, which subsequently enables readout of inductively-coupled signals from cochlea-shaped electrodes. The printed ear exhibits enhanced auditory sensing for radio frequency reception, and complementary left and right ears can listen to stereo audio music. Overall, our approach suggests a means to intricately merge biologic and nanoelectronic functionalities via 3D printing.

Fractal patterns in the parameter space of a bistable Duffing oscillator.

We study the dissipative bistable Duffing oscillator with equal energy wells and observe fractal patterns in the parameter space of driving frequency, forcing amplitude, and damping ratio. Our numerical investigation reveals the Hausdorff fractal dimension of the boundaries that separate the oscillator's intrawell and interwell behaviors. Furthermore, we categorize the interwell behaviors as three steady-state types: switching, reverting, and vacillating. While fractal patterns in the phase space are well known and heavily studied, our results point to another research direction about fractal patterns in the parameter space. Another implication of this study is that the vibration of a continuous bistable system modeled using a single-mode approximation also manifests fractal patterns in the parameter space. In addition, our findings can guide the design of next-generation bistable and multistable mechanical metamaterials.

Diffusiophoresis-enhanced particle deposition for additive manufacturing.

The ability to govern particle assembly in an evaporative-driven additive manufacturing (AM) can realize multi-scale features fundamental to creating printed electronics. However, existing techniques remain challenging and often require templates or contaminating solutes. We explore the control of particle deposition in 3D-printed colloids by diffusiophoresis, a previously unexplored mechanism in multi-scale AM. Diffusiophoresis can introduce spontaneous phoretic particle motion by establishing local solute concentration gradients. We show that diffusiophoresis can play a dominant role in complex evaporative-driven particle assembly, enabling a fundamentally new and versatile control of particle deposition in a multi-scale AM process.

Machine learning-enabled feature classification of evaporation-driven multi-scale 3D printing.

The freeform generation of active electronics can impart advanced optical, computational, or sensing capabilities to an otherwise passive construct by overcoming the geometrical and mechanical dichotomies between conventional electronics manufacturing technologies and a broad range of three-dimensional (3D) systems. Previous work has demonstrated the capability to entirely 3D print active electronics such as photodetectors and light-emitting diodes by leveraging an evaporation-driven multi-scale 3D printing approach. However, the evaporative patterning process is highly sensitive to print parameters such as concentration and ink composition. The assembly process is governed by the multiphase interactions between solutes, solvents, and the microenvironment. The process is susceptible to environmental perturbations and instability, which can cause unexpected deviation from targeted print patterns. The ability to print consistently is particularly important for the printing of active electronics, which require the integration of multiple functional layers. Here we demonstrate a synergistic integration of a microfluidics-driven multi-scale 3D printer with a machine learning algorithm that can precisely tune colloidal ink composition and classify complex internal features. Specifically, the microfluidic-driven 3D printer can rapidly modulate ink composition, such as concentration and solvent-to-cosolvent ratio, to explore multi-dimensional parameter space. The integration of the printer with an image-processing algorithm and a support vector machine-guided classification model enables automated, in-situ pattern classification. We envision that such integration will provide valuable insights in understanding the complex evaporative-driven assembly process and ultimately enable an autonomous optimisation of printing parameters that can robustly adapt to unexpected perturbations.

Digitally-embroidered liquid metal electronic textiles for wearable wireless systems.

Electronic textiles capable of sensing, powering, and communication can be used to non-intrusively monitor human health during daily life. However, achieving these functionalities with clothing is challenging because of limitations in the electronic performance, flexibility and robustness of the underlying materials, which must endure repeated mechanical, thermal and chemical stresses during daily use. Here, we demonstrate electronic textile systems with functionalities in near-field powering and communication created by digital embroidery of liquid metal fibers. Owing to the unique electrical and mechanical properties of the liquid metal fibers, these electronic textiles can conform to body surfaces and establish robust wireless connectivity with nearby wearable or implantable devices, even during strenuous exercise. By transferring optimized electromagnetic patterns onto clothing in this way, we demonstrate a washable electronic shirt that can be wirelessly powered by a smartphone and continuously monitor axillary temperature without interfering with daily activities.

Needle-integrated ultrathin bioimpedance microsensor array for early detection of extravasation.

Extravasation is a common complication during intravenous therapy in which infused fluids leak into the surrounding tissues. Timely intervention can prevent severe adverse consequences, but early detection remains an unmet clinical need because existing sensors are not sensitive to leakage occurring in small volumes (< 200 µL) or at deep venipuncture sites. Here, an ultrathin bioimpedance microsensor array that can be integrated on intravenous needles for early and sensitive detection of extravasation is reported. The array comprises eight microelectrodes fabricated on an ultrathin and flexible polyimide substrate as well as functionalized using poly(3,4-ethylenedioxythiophene) and multi-walled carbon nanotubes. Needle integration places the array proximity to venipuncture site, and functional coating significantly reduces interface impedance, both enable the microsensors with high sensitivity to detect early extravasation. In vitro and in vivo experiments demonstrate the capability of the microsensors to differentiate various intravenous solutions from different tissue layers as well as identify saline extravasation with detection limit as low as 20 µL.

A 3D-Printed Self-Learning Three-Linked-Sphere Robot for Autonomous Confined-Space Navigation.

Reinforcement learning control methods can impart robots with the ability to discover effective behavior, reducing their modeling and sensing requirements, and enabling their ability to adapt to environmental changes. However, it remains challenging for a robot to achieve navigation in confined and dynamic environments, which are characteristic of a broad range of biomedical applications, such as endoscopy with ingestible electronics. Herein, a compact, 3D-printed three-linked-sphere robot synergistically integrated with a reinforcement learning algorithm that can perform adaptable, autonomous crawling in a confined channel is demonstrated. The scalable robot consists of three equally sized spheres that are linearly coupled, in which the extension and contraction in specific sequences dictate its navigation. The ability to achieve bidirectional locomotion across frictional surfaces in open and confined spaces without prior knowledge of the environment is also demonstrated. The synergistic integration of a highly scalable robotic apparatus and the model-free reinforcement learning control strategy can enable autonomous navigation in a broad range of dynamic and confined environments. This capability can enable sensing, imaging, and surgical processes in previously inaccessible confined environments in the human body.

Nanomaterial Patterning in 3D Printing.

The synergistic integration of nanomaterials with 3D printing technologies can enable the creation of architecture and devices with an unprecedented level of functional integration. In particular, a multiscale 3D printing approach can seamlessly interweave nanomaterials with diverse classes of materials to impart, program, or modulate a wide range of functional properties in an otherwise passive 3D printed object. However, achieving such multiscale integration is challenging as it requires the ability to pattern, organize, or assemble nanomaterials in a 3D printing process. This review highlights the latest advances in the integration of nanomaterials with 3D printing, achieved by leveraging mechanical, electrical, magnetic, optical, or thermal phenomena. Ultimately, it is envisioned that such approaches can enable the creation of multifunctional constructs and devices that cannot be fabricated with conventional manufacturing approaches.

Ingestible transiently anchoring electronics for microstimulation and conductive signaling.

Ingestible electronic devices enable noninvasive evaluation and diagnosis of pathologies in the gastrointestinal (GI) tract but generally cannot therapeutically interact with the tissue wall. Here, we report the development of an orally administered electrical stimulation device characterized in ex vivo human tissue and in in vivo swine models, which transiently anchored itself to the stomach by autonomously inserting electrically conductive, hooked probes. The probes provided stimulation to the tissue via timed electrical pulses that could be used as a treatment for gastric motility disorders. To demonstrate interaction with stomach muscle tissue, we used the electrical stimulation to induce acute muscular contractions. Pulses conductively signaled the probes' successful anchoring and detachment events to a parenterally placed device. The ability to anchor into and electrically interact with targeted GI tissues controlled by the enteric nervous system introduces opportunities to treat a multitude of associated pathologies.

Corrigendum to "3D printed bionic nanodevices" [Nano Today 11 (2016) 330-350].

[This corrects the article PMC5016035.].

3D-Printed Gastric Resident Electronics.

Long-term implantation of biomedical electronics into the human body enables advanced diagnostic and therapeutic functionalities. However, most long-term resident electronics devices require invasive procedures for implantation as well as a specialized receiver for communication. Here, a gastric resident electronic (GRE) system that leverages the anatomical space offered by the gastric environment to enable residence of an orally delivered platform of such devices within the human body is presented. The GRE is capable of directly interfacing with portable consumer personal electronics through Bluetooth, a widely adopted wireless protocol. In contrast to the passive day-long gastric residence achieved with prior ingestible electronics, advancement in multimaterial prototyping enables the GRE to reside in the hostile gastric environment for a maximum of 36 d and maintain ≈15 d of wireless electronics communications as evidenced by the studies in a porcine model. Indeed, the synergistic integration of reconfigurable gastric-residence structure, drug release modules, and wireless electronics could ultimately enable the next-generation remote diagnostic and automated therapeutic strategies.

Addressing Unmet Clinical Needs with 3D Printing Technologies.

Recent advances in 3D printing have enabled the creation of novel 3D constructs and devices with an unprecedented level of complexity, properties, and functionalities. In contrast to manufacturing techniques developed for mass production, 3D printing encompasses a broad class of fabrication technologies that can enable 1) the creation of highly customized and optimized 3D physical architectures from digital designs; 2) the synergistic integration of properties and functionalities of distinct classes of materials to create novel hybrid devices; and 3) a biocompatible fabrication approach that facilitates the creation and cointegration of biological constructs and systems. This progress report describes how these capabilities can potentially address a myriad of unmet clinical needs. First, the creation of 3D-printed prosthetics to regain lost functionalities by providing structural support for skeletal and tubular organs is highlighted. Second, novel drug delivery strategies aided by 3D-printed devices are described. Third, the advancement of medical research heralded by 3D-printed tissue/organ-on-chips systems is discussed. Fourth, the developments of 3D-printed tissue and organ regeneration are explored. Finally, the potential for seamless integration of engineered organs with active devices by leveraging the versatility of multimaterial 3D printing is envisioned.