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Description
Introduction
Skeletal muscle is a highly organized and heterogeneous tissue composed of multiple cell types and structural components, arranged in a complex hierarchical architecture. This structure is essential for its mechanical strength, contractile function, and ability to regenerate. Skeletal muscles possess a strong capacity for self-repair; however, they are unable to regenerate effectively following substantial tissue loss, which leads to significant functional impairment. While direct injection of cells has been explored as a therapeutic approach, it has shown limited success due to inadequate integration into the host muscle tissue (Salehi et al., 2017). To overcome these challenges, we introduce here various platforms for biofabrication of skeletal muscle tissue with similar heterogeneity, generating a hierarchical functional structure like skeletal muscle (Koeck et al., 2022; Apsite et al., 2020; Sprenger et al., 2024).
Materials and methods
We have shown various fibrous structures for the generation of the anisotropy in combination with 3D bioprinting technology and added living cells to the structure, and analyzed their biological behavior.. Therefore, 1) sub-micron rod-shaped fillers were fabricated using microfabrication and included in the bioink as composite bioinks. 2) electrospun fibrous structures as bilayers were used to engineer self-rolling scaffolds for multicellular tissue generation, and 3) wetspun microfabricated fibers based on collagen and gelatin were used to mimic the muscle tissue interfaces.
Results and discussion
In this work, we demonstrate that injectable, short, and flexible cell carriers can effectively provide contact guidance to cells within the 3D network of hydrogel-based bioinks. Additionally, microfabricated fibers with diameters ranging from 18 to 500 µm successfully align muscle cells, with well-organized internal structures of differentiated myotubes and clearly visible sarcomeric actin. The aligned cells exhibit homogeneous and synchronous contractions, highlighting the potential of these structures to support the formation of large-scale muscle tissue. Enhanced myotube formation and myogenesis, along with improved intracellular organization and functionality, were also observed in response to electrospun scaffolds. These scaffolds are capable of undergoing self-transformation into tubular structures, making them suitable for constructing implants for the treatment of volumetric muscle loss injuries. We anticipated that the studied substrates would promote the formation of organized muscle microtissues.
References
Salehi, S, et al. 2017, “Development of flexible cell loaded ultrathin ribbons for minimally invasive delivery of skeletal muscle cells”, ACS Biomater Sci Eng. 3 (4), 579–589.
Koeck K, et al. 2022, “Processing of Continuous Non-Crosslinked Collagen Fibers for Microtissue Formation at the Tendon-Muscle Interface”, Adv. Funct. Mater. 32, 2112238.
Apsite I, et al. 2020, “4D biofabrication of skeletal muscle microtissues”, Biofabrication, 12, 015016.
Sprenger L, et al. 2024, “Composite alginate dialdehyde-gelatin (ADA-GEL) hydrogel containing short ribbon-shaped fillers for skeletal muscle tissue biofabrication”, ACS Appl. Mater. Interfaces, 16, 34, 44605–44622.
Acknowledgement
This work was supported by DFG (SA 3575/1-1, SA 3575/2-1, and project number 326998133—SFB/TRR225 (subproject B03)).
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