(I-340) Modular Shape-Controllable Engineered Tissues for Muscle Tissue Engineering

Introduction:: Volumetric muscle loss (VML) is characterized by the loss of a significant portion of skeletal muscle due to traumatic injury, leading to irreversibly impaired muscle function and regeneration. Tissue engineering strategies to regenerate traumatically injured muscle are promising but are limited in the ability to customize the tissue geometry to match that of the muscle defect. The objective was to develop lego-inspired custom-shaped muscle units for bioprinting-assisting engineering of custom-shaped muscle units to treat VML.


Materials and Methods:: We developed shape-customizable building blocks by taking advantage of sacrificial molds whose geometries were designed by computer aided design (CAD) and bioprinted using polylactic acid (PLA). The PLA molds were immersed in agarose and then cooled to 4°C to induce agarose solidification. Third, upon solidification, the mold was removed, leaving behind a negative mold. Fourth, to create a high-density scaffold-free muscle lego, a muscle myoblast cell suspension was filled into the mold to allow for cell compaction into the shape of the mold. We could fabricate modular lego units in diverse sizes and geometries, including star, hexagon, donut, and alphabet letters. In vitro characterization of cell survival was performed, along with therapeutic testing in a murine model of VML, in which aspiration-assisted bioprinting was used for precision placement into the ablated muscle.


Results, Conclusions, and Discussions:: We could fabricate modular lego units in diverse sizes and geometries, including star, hexagon, donut, and alphabet letters. The shape of the tissues showed high fidelity to that of the mold. Live/Dead viability analysis and subsequent confocal imaging through the thickness of the scaffold showed cell viability >80%. The rectangular solid-shaped lego was implanted into the tibialis anterior muscle after a 40% muscle ablation. After 3 weeks, histological analysis showed 5 times higher muscle regeneration area, compared to animals with no treatment.


Acknowledgements (Optional): : These data demonstrate that scaffold-free modular muscle units can be geometrically shaped with high viability and then shown to induce muscle regeneration in a murine VML model with the assistance of aspiration bioprinting.


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