Spinal cord injury (SCI) is a devastating event that frequently becomes a chronic condition. The consequences of neurological damage are multifaceted, with no effective clinical treatments. The majority of rodent studies have been conducted on acute and subacute SCI, while chronic SCI remains an unmet need. Strategies for treatment aim to achieve functional independence, optimize residual function, and minimize complications associated with chronic SCI. It is unlikely that there will be one single therapy for chronic SCI, which suggests that combinatorial strategies, such as scaffold-supported cellular transplantation with or without neuromodulation, may be required for effective functional improvement. In this review, we focus on one specific strategy, transplantation of scaffold-supported human stem/progenitor cells (NSPCs) in rodent models, with or without neuromodulation therapies, in particular electrical stimulation (ES), that will further elucidate the therapeutic potential in the treatment of chronic SCI.

Complex fibrous microarchitectures are common in biology, with fiber orientation playing a key role in the structure–function relationships that govern tissue behavior. Directional imaging modalities, such as diffusion tensor magnetic resonance imaging (DTMRI), can be used to derive a 3D vector map of fiber orientation. Incorporating this alignment information into engineered tissues remains a challenging and evolving area of research, with direct incorporation of directional imaging data into engineered tissue structures yet to be achieved. Here we describe an algorithmic framework, entitled Nonplanar, Architecture-Aligned Toolpathing for In Vitro 3D bioprinting (NAATIV3), which processes DTMRI data to map tissue fibers, reduce them to a representative subset, remove conflicting fibers, select a printable sequence, and output a G-code file. DTMRI data from a human left ventricle was used to 3D print fibered models with high accuracy. It is anticipated that NAATIV3 is generalizable beyond the cardiac application demonstrated here. Directional imaging data from a variety of organs, disease states, and developmental timepoints may be processible by NAATIV3, enabling the creation of models for understanding development, physiology, and pathophysiology. Furthermore, the NAATIV3 framework could be extended to bioengineered food manufacturing, plant engineering, and beyond. Complex, fibrous architectures are essential to the function of engineered tissues, but precisely replicating anatomical fiber structures remains difficult. Meghan Griffin, Spencer Bertram, and colleagues present NAATIV3, a framework that leverages medical imaging data for anatomically-accurate 3D bioprinting.

The transplantation of regionally specific spinal neural progenitor cells (sNPCs) has shown promise for functional restoration after spinal cord injury (SCI) by forming connections with host neural circuits. Here, 3D-printed organoid scaffolds for transplantation using clinically relevant human induced pluripotent stem cell-derived regionally specific sNPCs is developed. Scaffolds with microscale channels are printed, and sNPCs are subsequently printed within these channels. The scaffolds direct axonal projections along the channels and guide the cells to simulate in vivo-like conditions, leading to more effective cell maturation and the development of neuronal networks crucial for restoring function after SCI. The scaffolds, with organoids assembled along their lengths, are transplanted into the transected spinal cords of rats. This significantly promotes the functional recovery of the rats. At 12 weeks post-transplantation, the majority of the cells in the scaffolds differentiate into neurons and integrate into the host spinal cord tissue. These results demonstrate their potential to create a relay system along the spinal cord and form synapses in both the rostral and caudal directions relative to the scaffold. It is envisioned that combining sNPCs, organoid assembly, and 3D printing strategies can ultimately lead to a transformative treatment approach for SCI.

Human tissues are primarily composed of collagen and elastin fiber networks that exhibit directional mechanical properties that are not replicable by conventional tissue simulants manufactured via casting. Here, we 3D print tissue simulants that incorporate anisotropic mechanical properties through the manipulation of infill voxel shape and dimensions. A mathematical model for predicting the anisotropy of single- and multimaterial structures with orthogonal infill patterns is developed. We apply this methodology to generate conformal printing toolpaths for replicating the structure and directional mechanics observed in native tissue within 3D printed tissue simulants. Further, a method to embed fluid-filled capsules within the infill structure of these tissue simulants to mimic blood is also presented. The improvements in simulation quality when using 3D printed anisotropic tissue simulants over conventional tissue simulants are demonstrated via a comparative acceptability study. These advances open avenues for the manufacture of next-generation tissue simulants with high mechanical fidelity for enhanced medical simulation and training.

Devising an approach to deterministically position organisms can impact various fields such as bioimaging, cybernetics, cryopreservation, and organism-integrated devices. This requires continuously assessing the locations of randomly distributed organisms to collect and transfer them to target spaces without harm. Here, an aspiration-assisted adaptive printing system is developed that tracks, harvests, and relocates living and moving organisms on target spaces via a pick-and-place mechanism that continuously adapts to updated visual and spatial information about the organisms and target spaces. These adaptive printing strategies successfully positioned a single static organism, multiple organisms in droplets, and a single moving organism on target spaces. Their capabilities are exemplified by printing vitrification-ready organisms in cryoprotectant droplets, sorting live organisms from dead ones, positioning organisms on curved surfaces, organizing organism-powered displays, and integrating organisms with materials and devices in customizable shapes. These printing strategies can ultimately lead to autonomous biomanufacturing methods to evaluate and assemble organisms for a variety of single and multi-organism-based applications.

The ability to construct multiplexed micro-systems for fluid regulation could substantially impact multiple fields, including chemistry, biology, biomedicine, tissue engineering, and soft robotics, among others. 3D printing is gaining traction as a compelling approach to fabricating microfluidic devices by providing unique capabilities, such as 1) rapid design iteration and prototyping, 2) the potential for automated manufacturing and alignment, 3) the incorporation of numerous classes of materials within a single platform, and 4) the integration of 3D microstructures with prefabricated devices, sensing arrays, and nonplanar substrates. However, to widely deploy 3D printed microfluidics at research and commercial scales, critical issues related to printing factors, device integration strategies, and incorporation of multiple functionalities require further development and optimization. In this review, we summarize important figures of merit of 3D printed microfluidics and inspect recent progress in the field, including ink properties, structural resolutions, and hierarchical levels of integration with functional platforms. Particularly, we highlight advances in microfluidic devices printed with thermosetting elastomers, printing methodologies with enhanced degrees of automation and resolution, and the direct printing of microfluidics on various 3D surfaces. The substantial progress in the performance and multifunctionality of 3D printed microfluidics suggests a rapidly approaching era in which these versatile devices could be untethered from microfabrication facilities and created on demand by users in arbitrary settings with minimal prior training.

Abstract Photodetectors that are intimately interfaced with human skin and measure real‐time optical irradiance are appealing in the medical profiling of photosensitive diseases. Developing compliant devices for this purpose requires the fabrication of photodetectors with ultraviolet (UV)‐enhanced broadband photoresponse and high mechanical flexibility, to ensure precise irradiance measurements across the spectral band critical to dermatological health when directly applied onto curved skin surfaces. Here, a fully 3D printed flexible UV‐visible photodetector array is reported that incorporates a hybrid organic‐inorganic material system and is integrated with a custom‐built portable console to continuously monitor broadband irradiance in‐situ. The active materials are formulated by doping polymeric photoactive materials with zinc oxide nanoparticles in order to improve the UV photoresponse and trigger a photomultiplication (PM) effect. The ability of a stand‐alone skin‐interfaced light intensity monitoring system to detect natural irradiance within the wavelength range of 310–650 nm for nearly 24 h is demonstrated.

OLED arrays were fully 3D-printed under ambient conditions to produce a flexible information display technology.

Bionic-engineered tissues have been proposed for testing the performance of cardiovascular medical devices and predicting clinical outcomes ex vivo. Progress has been made in the development of compliant electronics that are capable of monitoring treatment parameters and being coupled to engineered tissues; however, the scale of most engineered tissues is too small to accommodate the size of clinical-grade medical devices. Here, we show substantial progress toward bionic tissues for evaluating cardiac ablation tools by generating a centimeter-scale human cardiac disk and coupling it to a hydrogel-based soft-pressure sensor. The cardiac tissue with contiguous electromechanical function was made possible by our recently established method to 3D bioprint human pluripotent stem cells in an extracellular matrix-based bioink that allows for in situ cell expansion prior to cardiac differentiation. The pressure sensor described here utilized electrical impedance tomography to enable the real-time spatiotemporal mapping of pressure distribution. A cryoablation tip catheter was applied to the composite bionic tissues with varied pressure. We found a close correlation between the cell response to ablation and the applied pressure. Under some conditions, cardiomyocytes could survive in the ablated region with more rounded morphology compared to the unablated controls, and connectivity was disrupted. This is the first known functional characterization of living human cardiomyocytes following an ablation procedure that suggests several mechanisms by which arrhythmia might redevelop following an ablation. Thus, bionic-engineered testbeds of this type can be indicators of tissue health and function and provide unique insight into human cell responses to ablative interventions.

Three-dimensional (3D) bioprinting strategies use computer-aided processes to enable automated simultaneous spatial patterning of cells and/or biomaterials. These technologies are suitable for a broad range of biomedical applications owing to their capability to produce structurally sophisticated and functionally relevant tissue constructs. Extrusion-based 3D bioprinting strategies were among the first modalities developed and are now arguably the most widely used for producing 3D tissue constructs. These technologies have rapidly evolved over the past two decades, providing a powerful tool set for the biofabrication of tissues that can facilitate translational efforts in the field. In this Primer, we describe the methodology of 3D extrusion bioprinting, focusing on the selection of hardware, software and bioinks. We expand upon recent advances in 3D extrusion bioprinting by illustrating the key variations that promote its biofabrication abilities. Finally, we provide an outlook on possible future refinements of the technology. 3D extrusion bioprinting methods can be used to produce tissue constructs in vitro and in situ and are arguably the most commonly used bioprinting strategies. In this Primer, Zhang and colleagues describe the variants of 3D extrusion bioprinting methods and their specific applications, considerations for the formulation of bioinks and strategies for assessing print quality. The authors conclude by looking to recent and upcoming developments in 4D printing and artificial intelligence-assisted dynamic printing strategies.

Droplet vitrification has emerged as a promising ice-free cryopreservation approach to provide a supply chain for off-the-shelf cell products in cell therapy and regenerative medicine applications. Translation of this approach requires the use of low concentration (i.e., low toxicity) permeable cryoprotectant agents (CPA) and high post cryopreservation viability (>90%), thereby demanding fast cooling and warming rates. Unfortunately, with traditional approaches using convective heat transfer, the droplet volumes that can be successfully vitrified and rewarmed are impractically small (i.e., 180 picoliter) for <2.5 m permeable CPA. Herein, a novel approach to achieve 90-95% viability in micro-liter size droplets with 2 m permeable CPA, is presented. Droplets with plasmonic gold nanorods (GNRs) are printed onto a cryogenic copper substrate for improved cooling rates via conduction, while plasmonic laser heating yields >400-fold improvement in warming rates over traditional convective approach. High viability cryopreservation is then demonstrated in a model cell line (human dermal fibroblasts) and an important regenerative medicine cell line (human umbilical cord blood stem cells). This approach opens a new paradigm for cryopreservation and rewarming of dramatically larger volume droplets at lower CPA concentration for cell therapy and other regenerative medicine applications.

The emerging capability to 3D print a diverse palette of functional inks will enable the mass democratization of patient-specific wearable devices and smart biomedical implants for applications such as health monitoring and regenerative biomedicines. These personalized wearables could be fabricated via ex situ printing, which involves first printing a design on a planar substrate and then deploying it to the target surface. However, this can result in a geometrically and dynamically mismatched interface between printed materials and target surfaces. In situ printing provides a potential remedy by directly printing 3D constructs on the target surfaces. This new manufacturing procedure requires the assistance of artificial intelligence (AI) to sense, adapt and predict the state of the printing environment, such as a dynamically morphing organ. In this Review, we discuss electronic and biological inks for in situ 3D printing, AI-empowered 3D-printing approaches with open-loop, closed-loop and predictive control, and recent developments in surgical robotics and AI that could be integrated in future 3D-printing approaches. We anticipate that this convergence of AI, 3D printing, functional materials and personalized biomedical devices will lead to a compelling future for smart manufacturing. Artificial intelligence can be used to facilitate the 3D printing of functional materials and devices directly on target surfaces, such as human bodies. This Review surveys ex situ and in situ artificial-intelligence-assisted 3D printing of multifunctional materials and its combination with surgical robots to enable autonomous medical care and smart biomanufacturing.

This roadmap includes the perspectives and visions of leading researchers in the key areas of flexible and printable electronics. The covered topics are broadly organized by the device technologies (sections 1–9), fabrication techniques (sections 10–12), and design and modeling approaches (sections 13 and 14) essential to the future development of new applications leveraging flexible electronics (FE). The interdisciplinary nature of this field involves everything from fundamental scientific discoveries to engineering challenges; from design and synthesis of new materials via novel device design to modelling and digital manufacturing of integrated systems. As such, this roadmap aims to serve as a resource on the current status and future challenges in the areas covered by the roadmap and to highlight the breadth and wide-ranging opportunities made available by FE technologies.

The use of atmospheric pressure low temperature plasmas (APPs) for decontamination is seeing renewed interest. A particularly challenging application is the treatment of biofilms (surface-attached bacterial communities) which are less susceptible to anti-microbial treatment [1] . Plasma treatment is a possible technique for both deactivation and regulation of biofilms. The demarcation between deactivation and regulation will be determined by the identity and magnitude of plasma produced reactants onto the surface. One possible method of toggling between deactivation and regulation of the biofilm is whether the plasma source is direct or remote. In the direct configuration, the plasma is in contact with the ECM (extracellular matrix) of the biofilm, which delivers charged and short lived species. In the remote configuration, the effluent to the ECM is largely long lived species.

This data set includes the supporting data for the Science Advances article, 3D Printed Self-Supporting Elastomeric Structures for Multifunctional Microfluidics (DOI: 10.1126/sciadv.abc9846).

The ability to directly print compliant biomedical devices on live human organs could benefit patient monitoring and wound treatment, which requires the 3D printer to adapt to the various deformations of the biological surface. We developed an in situ 3D printing system that estimates the motion and deformation of the target surface to adapt the toolpath in real time. With this printing system, a hydrogel-based sensor was printed on a porcine lung under respiration-induced deformation. The sensor was compliant to the tissue surface and provided continuous spatial mapping of deformation via electrical impedance tomography. This adaptive 3D printing approach may enhance robot-assisted medical treatments with additive manufacturing capabilities, enabling autonomous and direct printing of wearable electronics and biological materials on and inside the human body.