Design Considerations for Muscle‐Actuated Biohybrid Devices

Akiyama, Yoshitake; Park, Sung‐Jin; Takayama, Shuichi

doi:10.1002/9783527818341.ch11

Cited by 5 publications

(3 citation statements)

References 164 publications

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“…Despite all of these advances, scalability still represents a big challenge and a bottleneck that hampers the translation of 3D muscle cell cultures into practical fields such as skeletal muscle tissue engineering (SMTE) and biohybrid soft robotics. , Making 3D tissues with macroscopic dimensions (cm range) remains a difficult task to achieve from the standpoint of oxygen and nutrient supply. , This becomes critically limited in avascular constructs thicker than 150 μm, with a cellular density resembling the one found in vivo (∼10 9 cells/cm 3 ). , Currently, the best solution to improve mass transport into scaffolds is the use of perfusion devices. , Perfusion devices specifically developed for skeletal muscle cells usually consist of a porous scaffold seeded with myoblasts, which is sealed in a perfusion chamber. The latter is then connected, through an inlet and an outlet, to a fluidic circuit controlled by a peristaltic pump .…”

Section: Introductionmentioning

confidence: 99%

“…26,27 This becomes critically limited in avascular constructs thicker than 150 μm, with a cellular density resembling the one found in vivo (∼10 9 cells/cm 3 ). 28,29 Currently, the best solution to improve mass transport into scaffolds is the use of perfusion devices. 30,31 Perfusion devices specifically developed for skeletal muscle cells usually consist of a porous scaffold seeded with myoblasts, which is sealed in a perfusion chamber.…”

Section: Introductionmentioning

confidence: 99%

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Soft Perfusable Device to Culture Skeletal Muscle 3D Constructs in Air

Iberite,

Piazzoni,

Guarnera

et al. 2023

ACS Appl. Bio Mater.

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Devices for in vitro culture of three-dimensional (3D) skeletal muscle tissues have multiple applications, including tissue engineering and muscle-powered biorobotics. In both cases, it is crucial to recreate a biomimetic environment by using tailored scaffolds at multiple length scales and to administer prodifferentiative biophysical stimuli (e.g., mechanical loading). On the contrary, there is an increasing need to develop flexible biohybrid robotic devices capable of maintaining their functionality beyond laboratory settings. In this study, we describe a stretchable and perfusable device to sustain cell culture and maintenance in a 3D scaffold. The device mimics the structure of a muscle connected to two tendons: Tendon–Muscle–Tendon (TMT). The TMT device is composed of a soft (E ∼ 6 kPa) porous (pore diameter: ∼650 μm) polyurethane scaffold, encased within a compliant silicone membrane to prevent medium evaporation. Two tendon-like hollow channels interface the scaffold with a fluidic circuit and a stretching device. We report an optimized protocol to sustain C2C12 adhesion by coating the scaffold with polydopamine and fibronectin. Then, we show the procedure for the soft scaffold inclusion in the TMT device, demonstrating the device’s ability to bear multiple cycles of elongations, simulating a protocol for cell mechanical stimulation. By using computational fluid dynamic simulations, we show that a flow rate of 0.62 mL/min ensures a wall shear stress value safe for cells (<2 Pa) and 50% of scaffold coverage by an optimal fluid velocity. Finally, we demonstrate the effectiveness of the TMT device to sustain cell viability under perfusion for 24 h outside of the CO2 incubator. We believe that the proposed TMT device can be considered an interesting platform to combine several biophysical stimuli, aimed at boosting skeletal muscle tissue differentiation in vitro, opening chances for the development of muscle-powered biohybrid soft robots with long-term operability in real-world environments.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Soft Perfusable Device to Culture Skeletal Muscle 3D Constructs in Air

Iberite,

Piazzoni,

Guarnera

et al. 2023

ACS Appl. Bio Mater.

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show abstract

“…Animal muscular systems have evolved by natural selection over several billion years. Compared to state-of-the-art artificial actuators, natural muscle has several distinguishing and desirable advantages, such as its high-energy conversion efficiency, its independency from electrical or fossil fuel energy supplies, its softness and flexibility, and its capability for self-repair [3]. Many muscle-actuated devices have been reported in the past decade such as pumping devices [4,5], manipulators [6,7], crawling robots [8][9][10], and swimming robots [11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

An Electrical Stimulation Culture System for Daily Maintenance-Free Muscle Tissue Production

et al. 2021

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Low-labor production of tissue-engineered muscles (TEMs) is one of the key technologies to realize the practical use of muscle-actuated devices. This study developed and then demonstrated the daily maintenance-free culture system equipped with both electrical stimulation and medium replacement functions. To avoid ethical issues, immortal myoblast cells C2C12 were used. The system consisting of gel culture molds, a medium replacement unit, and an electrical stimulation unit could produce 12 TEMs at one time. The contractile forces of the TEMs were measured with a newly developed microforce measurement system. Even the TEMs cultured without electrical stimulation generated forces of almost 2 mN and were shortened by 10% in tetanic contractions. Regarding the contractile forces, electrical stimulation by a single pulse at 1 Hz was most effective, and the contractile forces in tetanus were over 2.5 mN. On the other hand, continuous pulses decreased the contractile forces of TEMs. HE-stained cross-sections showed that myoblast cells proliferated and fused into myotubes mainly in the peripheral regions, and fewer cells existed in the internal region. This must be due to insufficient supplies of oxygen and nutrients inside the TEMs. By increasing the supplies, one TEM might be able to generate a force up to around 10 mN. The tetanic forces of the TEMs produced by the system were strong enough to actuate microstructures like previously reported crawling robots. This daily maintenance-free culture system which could stably produce TEMs strong enough to be utilized for microrobots should contribute to the advancement of biohybrid devices.

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Bioinks and Bioprinting Strategies for Skeletal Muscle Tissue Engineering

et al. 2022

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Skeletal muscles play important roles in critical body functions and their injury or disease can lead to limitation of mobility and loss of independence. Current treatments result in variable functional recovery, while reconstructive surgery, as the gold-standard approach, is limited due to donor shortage, donor-site morbidity, and limited functional recovery. Skeletal muscle tissue engineering (SMTE) has generated enthusiasm as an alternative solution for treatment of injured tissue and serves as a functional disease model. Recently, bioprinting has emerged as a promising tool for recapitulating the complex and highly organized architecture of skeletal muscles at clinically relevant sizes. Here, skeletal muscle physiology, muscle regeneration following injury, and current treatments following muscle loss are discussed, and then bioprinting strategies implemented for SMTE are critically reviewed. Subsequently, recent advancements that have led to improvement of bioprinting strategies to construct large muscle structures, boost myogenesis in vitro and in vivo, and enhance tissue integration are discussed. Bioinks for muscle bioprinting, as an essential part of any bioprinting strategy, are discussed, and their benefits, limitations, and areas to be improved are highlighted. Finally, the directions the field should expand to make bioprinting strategies more translational and overcome the clinical unmet needs are discussed.

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Design Considerations for Muscle‐Actuated Biohybrid Devices

Cited by 5 publications

References 164 publications

Soft Perfusable Device to Culture Skeletal Muscle 3D Constructs in Air

Soft Perfusable Device to Culture Skeletal Muscle 3D Constructs in Air

An Electrical Stimulation Culture System for Daily Maintenance-Free Muscle Tissue Production

Bioinks and Bioprinting Strategies for Skeletal Muscle Tissue Engineering

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