Latest developments in engineered skeletal muscle tissues for drug discovery and development

Ostrovidov, Serge; Ramalingam, Murugan; Bae, Hojae; Orive, Gorka; Fujie, Toshinori; Shi, Xuetao; Kaji, Hirokazu

doi:10.1080/17460441.2023.2160438

Cited by 8 publications

(7 citation statements)

References 139 publications

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“…One of the drawbacks to many tissue engineering materials is their long‐term performance. Specifically for in vitro models of skeletal muscle tissues, culture conditions only tend to last for short time periods (<6 weeks) 48–51 . Longer time periods would allow for further differentiation and maturation to explore cell function and phenotype.…”

Section: Resultsmentioning

confidence: 99%

Impact of crystalline domains on long‐term stability and mechanical performance of anisotropic silk fibroin sponges

Aikman,

Rao,

Jia

et al. 2024

J Biomedical Materials Res

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Sponge‐like materials made from regenerated silk fibroin biopolymers are a tunable and advantageous platform for in vitro engineered tissue culture and in vivo tissue regeneration. Anisotropic, three‐dimensional (3D) silk fibroin sponge‐like scaffolds can mimic the architecture of contractile muscle. Herein, we use silk fibroin solution isolated from the cocoons of Bombyx mori silkworms to form aligned sponges via directional ice templating in a custom mold with a slurry of dry ice and ethanol. Hydrated tensile mechanical properties of these aligned sponges were evaluated as a function of silk polymer concentration (3% or 5%), freezing time (50% or 100% ethanol), and post‐lyophilization method for inducing crystallinity (autoclaving, water annealing). Hydrated static tensile tests were used to determine Young's modulus and ultimate tensile strength across sponge formulations at two strain rates to evaluate rate dependence in the calculated parameters. Results aligned with previous reports in the literature for isotropic silk fibroin sponge‐like scaffolds, where the method by which beta‐sheets were formed and level of beta‐sheet content (crystallinity) had the greatest impact on static parameters, while polymer concentration and freezing rate did not significantly impact static mechanical properties. We estimated the crystalline organization using molecular dynamics simulations to show that larger crystalline regions may be responsible for strength at low strain amplitudes and brittleness at high strain amplitudes in the autoclaved sponges. Within the parameters evaluated, extensional Young's modulus is tunable in the range of 600–2800 kPa. Dynamic tensile testing revealed the linear viscoelastic region to be between 0% and 10% strain amplitude and 0.2–2 Hz frequencies. Long‐term stability was evaluated by hysteresis and fatigue tests. Fatigue tests showed minimal change in the storage and loss modulus of 5% silk fibroin sponges for more than 6000 min of continuous mechanical stimulation in the linear regime at 10% strain amplitude and 1 Hz frequency. Furthermore, we confirmed that these mechanical properties hold when decellularized extracellular matrix is added to the sponges and when the mechanical property assessments were performed in cell culture media. We also used nano‐computed tomography (nano‐CT) and simulations to explore pore interconnectivity and tortuosity. Overall, these results highlight the potential of anisotropic, sponge‐like silk fibroin scaffolds for long‐term (>6 weeks) contractile muscle culture with an in vitro bioreactor system that provides routine mechanical stimulation.

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Section: Resultsmentioning

confidence: 99%

Impact of crystalline domains on long‐term stability and mechanical performance of anisotropic silk fibroin sponges

Aikman,

Rao,

Jia

et al. 2024

J Biomedical Materials Res

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“…Due to the ability to reprogram adult cells into less differentiated cells, named induced pluripotent stem cells (iPSCs), ASCs are a very promising cell source of progenitors for dental regeneration. The technology to reprogram cells into iPSCs has progressed well; rather than using direct reprogramming with the insertion of transcription factors via lentivirus into cells, small molecules are now used in culture medium to induce specific signaling and to prevent viral components (Ostrovidov et al, 2023). However, the use of undifferentiated cells (e.g., MSCs, iPSCs) for transplantation has raised several concerns due to potential tumorigenicity, unwanted immune response inducement, and transmission of adventitious agents (Medvedev et al, 2010;Herberts et al, 2011;Lukomska et al, 2019).…”

Section: Conclusion and Perspectivementioning

confidence: 99%

Bioprinting and biomaterials for dental alveolar tissue regeneration

Ostrovidov

Ramalingam

Bae

et al. 2023

Front. Bioeng. Biotechnol.

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Three dimensional (3D) bioprinting is a powerful tool, that was recently applied to tissue engineering. This technique allows the precise deposition of cells encapsulated in supportive bioinks to fabricate complex scaffolds, which are used to repair targeted tissues. Here, we review the recent developments in the application of 3D bioprinting to dental tissue engineering. These tissues, including teeth, periodontal ligament, alveolar bones, and dental pulp, present cell types and mechanical properties with great heterogeneity, which is challenging to reproduce in vitro. After highlighting the different bioprinting methods used in regenerative dentistry, we reviewed the great variety of bioink formulations and their effects on cells, which have been established to support the development of these tissues. We discussed the different advances achieved in the fabrication of each dental tissue to provide an overview of the current state of the methods. We conclude with the remaining challenges and future needs.

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“…Such systems rely on compaction to enable cell-cell contact (which is imperative for myogenic fusion into myotubes) and depend on anchorage to induce tension, which results in cell alignment, priming the construct for differentiation. The development of a uniform tissue in which cells are aligned via tension and guidance by fibrous structures, thereby promoting sustained myotube attachment, is an indispensable aspect of tissue maturation [13]. However, these systems are animal-based and hence cannot be applicable to animal component-free product development.…”

Section: Introductionmentioning

confidence: 99%

Short-Stranded Zein Fibers for Muscle Tissue Engineering in Alginate-Based Composite Hydrogels

Melzener,

Spaans,

Hauck

et al. 2023

Gels

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Cultivated meat is a nascent technology that aims to create an environmentally and animal-friendly alternative to conventional meat. Producing skeletal muscle tissue in an animal-free system allowing for high levels of myofusion and maturation is important for the nutritional and sensorial value of cultivated meat. Alginate is an attractive biomaterial to support muscle formation as it is food-safe, sustainable and cheap and can be crosslinked using non-toxic methods. Although alginate can be functionalized to promote cell attachment, limitations in its mechanical properties, including form, viscosity, and stress relaxation, hinder the cellular capacity for myogenic differentiation and maturation in alginate-based hydrogels. Here, we show that the addition of electrospun short-stranded zein fibers increased hydrogel degradation, resulting in faster compaction, improved cell–gel interaction, and enhanced alignment of bovine muscle precursor cells. We conclude that fiber-hydrogel composites are a promising approach to support optimal formation of 3D constructs, by improving tissue stability and thus prolonging culture duration. Together, this improves muscle-related protein content by facilitating myogenic differentiation and priming muscle organoids for maturation.

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Latest developments in engineered skeletal muscle tissues for drug discovery and development

Cited by 8 publications

References 139 publications

Impact of crystalline domains on long‐term stability and mechanical performance of anisotropic silk fibroin sponges

Impact of crystalline domains on long‐term stability and mechanical performance of anisotropic silk fibroin sponges

Bioprinting and biomaterials for dental alveolar tissue regeneration

Short-Stranded Zein Fibers for Muscle Tissue Engineering in Alginate-Based Composite Hydrogels

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