通过聚丙烯酰胺辅助同轴三维生物打印技术制造筋膜样骨骼肌生物致动器

Judith Fuentes, Rafael Mestre, Maria Guix, Ibtissam Ghailan, Noela Ruiz-Gonzalez, Tania Patino, Samuel Sanchez
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摘要

三维生物打印技术的进步为开发模仿原生组织结构和功能的生物工程肌肉模型提供了新的可能性。骨骼肌组织与人工元素的结合促进了生物医学领域和生物混合致动器开发领域的各种创新解决方案。然而,目前的生物工程方法并不能完全再现骨骼肌复杂的束状分层组织,由于支架内部区域缺乏氧气和营养物质供应,肌肉成熟过程受到影响。在此,我们探索了同轴三维生物打印技术作为克服这一挑战的策略,创造出厚度可控的单个/非融合细丝,呈现出类似束状的组织结构。传统的三维生物打印是通过单个注射器注入含有细胞的生物墨水,与之相比,我们的Pluronic辅助同轴三维生物打印系统(PACA-3D)可在挤出过程中对生物墨水进行物理限制,从而有效地获得具有可控形状的纤细且独立的打印纤维。使用 PACA-3D 制作骨骼肌致动器可改善细胞分化,与传统三维生物打印技术制作的生物致动器相比,可获得更强的生物致动器,并能提高力输出。我们使用不同的生物材料证明了该技术的多功能性,显示了其开发功能更强、更复杂的生物杂化组织结构的潜力。
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Bioengineering Fascicle-like Skeletal Muscle Bioactuators via Pluronic-Assisted Co-axial 3D Bioprinting
Advances in 3D bioprinting have opened new possibilities in the development of bioengineered muscle models that mimic the structure and functionality of native tissues. The combination of skeletal muscle tissue and artificial elements promotes diverse innovative solutions of interest in both the biomedical field and the development of biohybrid actuators. However, current bioengineering approaches do not fully recreate the complex fascicle-like hierarchical organization of skeletal muscle, impacting on the muscle maturation process due to a lack of oxygen and nutrients supply in the scaffold inner regions. Here we explored co-axial 3D bioprinting as a strategy towards overcoming this challenge, creating individual/non-fused filaments with controlled thickness that present a fascicle-like organization. Compared to conventional 3D-bioprinting, where cell-laden bioink is disposed by a single syringe, our Pluronic-assisted co-axial 3D-bioprinting system (PACA-3D) creates a physical confinement of the bioink during the extrusion process, effectively obtaining thin and independent printed fibers with controlled shape. Fabrication of skeletal muscle-based actuators with PACA-3D resulted in improved cell differentiation, obtaining stronger bioactuators with increased force output when compared to bioactuators fabricated by conventional 3D bioprinting. The versatility of our technology has been demonstrated using different biomaterials, showing its potential to develop more complex biohybrid tissue-based architectures with improved functionality.
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