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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. 

Thermoset elastomers are widely used high‐performance materials due to their thermal stability, chemical resistance, and mechanical properties. However, established casting and molding techniques limit the overall 3D complexity of parts that can be fabricated. Advanced manufacturing methods such as 3D printing have improved design flexibility and reduced development time but have proved challenging using thermally‐cured thermosets due to their viscosity, slow gelation kinetics, and high surface tension. To address this, freeform reversible embedding (FRE) 3D printing extrudes thermosets such as polydimethylsiloxane (PDMS) elastomer within a carbomer support bath, but due to the liquid‐like state of the prepolymer during extrusion has been limited to hollow structures. Here, FRE printing is significantly improved through rheological modification of PDMS with a thixotropic additive (1.0–10.0 wt.%) that imparts a yield stress (30–120 Pa) to help control filament morphology. Further, print process controls consisting of region‐specific slicing, filament retraction, and nonprint travel moves outside of the print to minimize the interaction of the nozzle with previously printed PDMS are implemented. The combined result is the FRE printing of PDMS in complex 3D parts with high fidelity, establishing a 3D printing methodology that can be used broadly with thermally‐cured thermoset elastomers and related polymers.

 

Thermally cured thermoset polymers such as epoxies are widely used in industry and manufacturing due to their thermal, chemical, and electrical resistance, and mechanical strength and toughness. However, it can be challenging to 3D print thermally cured thermosets without rheological modification because they tend to flow and not hold their shape when extruded due to cure times of minutes to hours. 3D printing inside a support bath addresses this by allowing the liquid polymer to be held in place until the thermoset is fully cured and expands the structures that can be printed as extrusion is not limited to layer‐by‐layer. Here, the use of Freeform Reversible Embedding (FRE) to 3D print off‐the‐shelf thermoset epoxy into lattice structures using nonplanar extrusion is reported. To do this, the authors investigate how extrusion direction in 3D space impacts epoxy filament morphology and fusion at filament intersections. Furthermore, the advantages of this approach are shown by using nonplanar printing to produce lattice geometries that show ≈ four times greater specific modulus compared with lattice structures printed using other materials and printing techniques.

 

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”. 

Despite the impressive performance of recent marine robots, many of their components are non‐biodegradable or even toxic and may negatively impact sensitive ecosystems. To overcome these limitations, biologically‐sourced hydrogels are a candidate material for marine robotics. Recent advances in embedded 3D printing have expanded the design freedom of hydrogel additive manufacturing. However, 3D printing small‐scale hydrogel‐based actuators remains challenging. In this study, Free form reversible embedding of suspended hydrogels (FRESH) printing is applied to fabricate small‐scale biologically‐derived, marine‐sourced hydraulic actuators by printing thin‐wall structures that are water‐tight and pressurizable. Calcium‐alginate hydrogels are used, a sustainable biomaterial sourced from brown seaweed. This process allows actuators to have complex shapes and internal cavities that are difficult to achieve with traditional fabrication techniques. Furthermore, it demonstrates that fabricated components are biodegradable, safely edible, and digestible by marine organisms. Finally, a reversible chelation‐crosslinking mechanism is implemented to dynamically modify alginate actuators' structural stiffness and morphology. This study expands the possible design space for biodegradable marine robots by improving the manufacturability of complex soft devices using biologically‐sourced materials.

 

Soft tissue injuries such as volumetric muscle loss (VML) are often too large to heal normally on their own, resulting in scar formation and functional deficits. Decellularized extracellular matrix (dECM) scaffolds placed into these wounds have shown the ability to modulate the immune response and drive constructive healing. This provides a potential solution for functional tissue regeneration, however, these acellular dECM scaffolds are challenging to fabricate into complex geometries. 3D bioprinting is uniquely positioned to address this, being able to create patient‐specific scaffolds based on clinical 3D imaging data. Here, a process to use freeform reversible embedding of suspended hydrogels (FRESH) 3D bioprinting and computed tomography (CT) imaging to build large volume, patient‐specific dECM patches (≈12 × 8 × 2 cm) for implantation into canine VML wound models is developed. Quantitative analysis shows that these dECM patches are dimensionally accurate and conformally adapt to the surface of complex wounds. Finally, this approach is extended to a human VML injury to demonstrate the fabrication of clinically relevant dECM scaffolds with precise control over fiber alignment and micro‐architecture. Together these advancements represent a step towards an improved, clinically translatable, patient‐specific treatment for soft tissue defects from trauma, tumor resection, and other surgical procedures.