From Academia: 3D Printing Organoid, Bioelectronic Implant, Tensegrity Structures

Category: Blog,From Academia
blank blank Oct 09, 2020

From Academia” features recent, relevant, close to commercialization academic publications in the space of healthcare 3D printing, 3D bioprinting, and related emerging technologies. In this issue, we included three articles focusing on 3D printing organoids that can recapitulate macroscale tissue self-organization, personalized bioelectronic neuromuscular implant, and tensegrity structures in soft robotic design.

Email: Rance Tino (tino.rance@gmail.com) if you want to pen an Expert Corner blog for us or want to share relevant academic publications with us.

Recapitulating macro-scale tissue self-organization through organoid bioprinting

– Authored by Jonathan A. Brassard, Mike Nikolaev, Tania Hübscher, Moritz Hofer & Matthias P. Lutolf. Nature Materials, 21 September 2020

Illustration of the BATE concept using spontaneously self-organizing building blocks to create large-scale tissues. b, Representative fluorescent images of cells stained with cell tracker dyes showing the modulation of the resolution (left) and printing of complex geometry (right). Scale bars, 500 µm. c, Representative images of viability of HUVECs after printing with a low (left) and high (right) density, shown by calcein AM (live, green) and ethidium homodimer-1 (dead, red) cell stainings. See also Extended Data Fig. 1e for quantification. Scale bars, 250 µm. d,e, Bright-field images of the cell patterning immediately after printing (d) and after self-organization (e) of hMSC, hISC and HUVEC cells. Scale bars, 500 µm. f,g, Fluorescence confocal images of macroscopic (f) and microscopic (g) tissue architecture. Cells are labelled with DAPI (blue) and F-actin (green) or CD31 (pink). All images are representative of n = 3 biologically independent experiments. Scale bars, 250 µm (f) and 75 µm (g). Copyright. Nature Materials
Illustration of the BATE concept using spontaneously self-organizing building blocks to create large-scale tissues. b, Representative fluorescent images of cells stained with cell tracker dyes showing the modulation of the resolution (left) and printing of complex geometry (right). Scale bars, 500 µm. c, Representative images of viability of HUVECs after printing with a low (left) and high (right) density, shown by calcein AM (live, green) and ethidium homodimer-1 (dead, red) cell stainings. See also Extended Data Fig. 1e for quantification. Scale bars, 250 µm. d,e, Bright-field images of the cell patterning immediately after printing (d) and after self-organization (e) of hMSC, hISC and HUVEC cells. Scale bars, 500 µm. f,g, Fluorescence confocal images of macroscopic (f) and microscopic (g) tissue architecture. Cells are labelled with DAPI (blue) and F-actin (green) or CD31 (pink). All images are representative of n = 3 biologically independent experiments. Scale bars, 250 µm (f) and 75 µm (g). Copyright. Nature Materials

Abstract: 

Bioprinting promises enormous control over the spatial deposition of cells in three dimensions, but current approaches have had limited success at reproducing the intricate micro-architecture, cell-type diversity, and function of native tissues formed through cellular self-organization. We introduce a three-dimensional bioprinting concept that uses organoid-forming stem cells as building blocks that can be deposited directly into extracellular matrices conducive to spontaneous self-organization.

By controlling the geometry and cellular density, we generated centimeter-scale tissues that comprise self-organized features such as lumens, branched vasculature, and tubular intestinal epithelia with in vivo-like crypts and villus domains. Supporting cells were deposited to modulate morphogenesis in space and time, and different epithelial cells were printed sequentially to mimic the organ boundaries present in the gastrointestinal tract. We thus show how biofabrication and organoid technology can be merged to control tissue self-organization from millimeter to centimeter scales, opening new avenues for drug discovery, diagnostics, and regenerative medicine.

Rapid prototyping of soft bioelectronic implants for use as neuromuscular interfaces

– Authored by Dzmitry Afanasenkau, Daria Kalinina, Vsevolod Lyakhovetskii, Christoph Tondera, Oleg Gorsky, Seyyed Moosavi, Natalia Pavlova, Natalia Merkulyeva, Allan V. Kalueff, Ivan R. Minev & Pavel Musienko. Nature Biomedical Engineering. 21 September 2020

a, The integrated platform for hybrid printing combines ink-jet dispensing of low-viscosity conductive inks, extrusion of insulating silicone pastes and in situ surface activation via cold-air plasma. b, Electrode implants printed from platinum microparticles and silicone can be adapted to the anatomy of electrogenic tissues. Insets: (i) cortical surface electrode array with nine contact sites; (ii) spinal surface electrode array with four contact sites; (iii) peripheral nerve monopolar electrode; and (iv) intramuscular shank electrodes with one contact per shank. Scale bars, 4 mm. Copyright. Nature Biomedical Engineering
a, The integrated platform for hybrid printing combines ink-jet dispensing of low-viscosity conductive inks, extrusion of insulating silicone pastes and in situ surface activation via cold-air plasma. b, Electrode implants printed from platinum microparticles and silicone can be adapted to the anatomy of electrogenic tissues. Insets: (i) cortical surface electrode array with nine contact sites; (ii) spinal surface electrode array with four contact sites; (iii) peripheral nerve monopolar electrode; and (iv) intramuscular shank electrodes with one contact per shank. Scale bars, 4 mm. Copyright. Nature Biomedical Engineering

Abstract: 

Neuromuscular interfaces are required to translate bioelectronic technologies for application in clinical medicine. Here, by leveraging the robotically controlled ink-jet deposition of low-viscosity conductive inks, extrusion of insulating silicone pastes and in situ activation of electrode surfaces via cold-air plasma, we show that soft biocompatible materials can be rapidly printed for the on-demand prototyping of customized electrode arrays well adjusted to specific anatomical environments, functions and experimental models. We also show, with the monitoring and activation of neuronal pathways in the brain, spinal cord and neuromuscular system of cats, rats and zebrafish, that the printed bioelectronic interfaces allow for long-term integration and functional stability. This technology might enable personalized bioelectronics for neuroprosthetic applications.

3D-printed programmable tensegrity for soft robotics

– Authored by Hajun Lee, Yeonwoo Jang, Jun Kyu Choe, Suwoo Lee, Hyeonseo Song, Jin Pyo Lee, Nasreena Lone and Jiyun Kim. Science Robotics. 26 August 2020

Fabrication process of the tensegrity structure and mechanical features of its elements. Copyright. Science Robotics
Fabrication process of the tensegrity structure and mechanical features of its elements. Copyright. Science Robotics

Abstract: 

Tensegrity structures provide both structural integrity and flexibility through the combination of stiff struts and a network of flexible tendons. These structures exhibit useful properties: high stiffness-to-mass ratio, controllability, reliability, structural flexibility, and large deployment. The integration of smart materials into tensegrity structures would provide additional functionality and may improve existing properties. However, manufacturing approaches that generate multimaterial parts with intricate three-dimensional (3D) shapes suitable for such tensegrities are rare. Furthermore, the structural complexity of tensegrity systems fabricated through conventional means is generally limited because these systems often require manual assembly.

Here, we report a simple approach to fabricate tensegrity structures made of smart materials using 3D printing combined with sacrificial molding. Tensegrity structures consisting of monolithic tendon networks based on smart materials supported by struts could be realized without an additional post-assembly process using our approach. By printing tensegrity with coordinated soft and stiff elements, we could use design parameters (such as geometry, topology, density, coordination number, and complexity) to program system-level mechanics in a soft structure. Last, we demonstrated a tensegrity robot capable of walking in any direction and several tensegrity actuators by leveraging smart tendons with magnetic functionality and the programmed mechanics of tensegrity structures. The physical realization of complex tensegrity metamaterials with programmable mechanical components can pave the way toward more algorithmic designs of 3D soft machines.

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