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Our ability to produce human-scale biomanufactured organs is limited by inadequate vascularization and perfusion. For arbitrarily complex geometries, designing and printing vasculature capable of adequate perfusion poses a major hurdle. We introduce a model-driven design platform that demonstrates rapid synthetic vascular model generation alongside multifidelity computational fluid dynamics simulations and three-dimensional bioprinting. Key algorithmic advances accelerate vascular generation 230-fold and enable application to arbitrarily complex shapes. We demonstrate that organ-scale vascular network models can be generated and used to computationally vascularize >200 engineered and anatomic models. Synthetic vascular perfusion improves cell viability in fabricated living-tissue constructs. This platform enables the rapid, scalable vascular model generation and fluid physics analysis for biomanufactured tissues that are necessary for future scale-up and production. 

The recent popularity of soft robots for marine applications has established a need for the reliable fabrication of actuators that enable locomotion, articulation, and grasping in aquatic environments. These actuators should also reduce the negative impact on sensitive ecosystems by using biodegradable materials such as organic hydrogels. Freeform Reversible Embedding of Suspended Hydrogels (FRESH) printing can be used for additive manufacturing of small-scale biologically derived, marine-sourced hydraulic actuators by printing thin-wall structures out of sustainably sourced calcium-alginate hydrogels. However, controlling larger alginate robots with complex geometries and multiple actuation mechanisms remains challenging due to the reduced strength of such soft structures. For tethered hydrogel hydraulic robots, a direct interface with fluid lines is necessary for actuation, but the drag forces associated with tethered lines can quickly overcome the actuation force of distal and extremity structures. To overcome this challenge, in this study, we identify printing parameters and interface geometries to allow the working fluid to be channeled to distal components of FRESH-printed alginate robots and demonstrate a proof-of-concept biodegradable robotic arm for small object manipulation and grasping in marine environments. 

Abstract We present a new computational framework of neuron growth based on the phase field method and develop an open-source software package called “NeuronGrowth_IGAcollocation”. Neurons consist of a cell body, dendrites, and axons. Axons and dendrites are long processes extending from the cell body and enabling information transfer to and from other neurons. There is high variation in neuron morphology based on their location and function, thus increasing the complexity in mathematical modeling of neuron growth. In this paper, we propose a novel phase field model with isogeometric collocation to simulate different stages of neuron growth by considering the effect of tubulin. The stages modeled include lamellipodia formation, initial neurite outgrowth, axon differentiation, and dendrite formation considering the effect of intracellular transport of tubulin on neurite outgrowth. Through comparison with experimental observations, we can demonstrate qualitatively and quantitatively similar reproduction of neuron morphologies at different stages of growth and allow extension towards the formation of neurite networks. 

Hydrogels are candidate building blocks in a wide range of biomaterial applications including soft and biohybrid robotics, microfluidics, and tissue engineering. Recent advances in embedded 3D printing have broadened the design space accessible with hydrogel additive manufacturing. Specifically, the Freeform Reversible Embedding of Suspended Hydrogels (FRESH) technique has enabled the fabrication of complex 3D structures using extremely soft hydrogels, e.g., alginate and collagen, by assembling hydrogels within a fugitive support bath. However, the low structural rigidity of FRESH printed hydrogels limits their applications, especially those that require operation in nonaqueous environments. In this study, we demonstrated long-fiber embedded hydrogel 3D printing using a multihead printing platform consisting of a custom-built fiber extruder and an open-source FRESH bioprinter with high embedding fidelity. Using this process, fibers were embedded in 3D printed hydrogel components to achieve significant structural reinforcement (e.g., tensile modulus improved from 56.78 ± 8.76 to 382.55 ± 25.29 kPa and tensile strength improved from 9.44 ± 2.28 to 45.05 ± 5.53 kPa). In addition, we demonstrated the versatility of this technique by using fibers of a wide range of sizes and material types and implementing different 2D and 3D embedding patterns, such as embedding a conical helix using electrochemically aligned collagen fiber via nonplanar printing. Moreover, the technique was implemented using low-cost material and is compatible with open-source software and hardware, which facilitates its adoption and modification for new research applications. 

Stimuli-responsive hydrogels are candidate building blocks for soft robotic applications due to many of their unique properties, including tunable mechanical properties and biocompatibility. Over the past decade, there has been significant progress in developing soft and biohybrid actuators using naturally occurring and synthetic hydrogels to address the increasing demands for machines capable of interacting with fragile biological systems. Recent advancements in three-dimensional (3D) printing technology, either as a standalone manufacturing process or integrated with traditional fabrication techniques, have enabled the development of hydrogel-based actuators with on-demand geometry and actuation modalities. This mini-review surveys existing research efforts to inspire the development of novel fabrication techniques using hydrogel building blocks and identify potential future directions. In this article, existing 3D fabrication techniques for hydrogel actuators are first examined. Next, existing actuation mechanisms, including pneumatic, hydraulic, ionic, dehydration-rehydration, and cell-powered actuation, are reviewed with their benefits and limitations discussed. Subsequently, the applications of hydrogel-based actuators, including compliant handling of fragile items, micro-swimmers, wearable devices, and origami structures, are described. Finally, challenges in fabricating functional actuators using existing techniques are discussed. 

The ability to engineer complex multicellular systems has enormous potential to inform our understanding of biological processes and disease and alter the drug development process. Engineering living systems to emulate natural processes or to incorporate new functions relies on a detailed understanding of the biochemical, mechanical, and other cues between cells and between cells and their environment that result in the coordinated action of multicellular systems. On April 3–6, 2022, experts in the field met at the Keystone symposium “Engineering Multicellular Living Systems” to discuss recent advances in understanding how cells cooperate within a multicellular system, as well as recent efforts to engineer systems like organ-on-a-chip models, biological robots, and organoids. Given the similarities and common themes, this meeting was held in conjunction with the symposium “Organoids as Tools for Fundamental Discovery and Translation”.