Three-Dimensional Bioprinting of Functional Skeletal Muscle Tissue Using GelatinMethacryloyl-Alginate Bioinks

使用明胶甲基丙烯酰海藻酸盐生物墨水对功能性骨骼肌组织进行三维生物打印

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作者:Rasoul Seyedmahmoud, Betül Çelebi-Saltik, Natan Barros, Rohollah Nasiri, Ethan Banton, Amir Shamloo, Nureddin Ashammakhi, Mehmet Remzi Dokmeci, Samad Ahadian

Abstract

Skeletal muscle tissue engineering aims to fabricate tissue constructs to replace or restore diseased or injured skeletal muscle tissues in the body. Several biomaterials and microscale technologies have been used in muscle tissue engineering. However, it is still challenging to mimic the function and structure of the native muscle tissues. Three-dimensional (3D) bioprinting is a powerful tool to mimic the hierarchical structure of native tissues. Here, 3D bioprinting was used to fabricate tissue constructs using gelatin methacryloyl (GelMA)-alginate bioinks. Mechanical and rheological properties of GelMA-alginate hydrogels were characterized. C2C12 myoblasts at the density 8 × 106 cells/mL were used as the cell model. The effects of alginate concentration (0, 6, and 8% (w/v)) and crosslinking mechanism (UV crosslinking or ionic crosslinking with UV crosslinking) on printability, cell viability, proliferation, and differentiation of bioinks were studied. The results showed that 10% (w/v) GelMA-8% (w/v) alginate crosslinked using UV light and 0.1 M CaCl2 provided the optimum niche to induce muscle tissue formation compared to other hydrogel compositions. Furthermore, metabolic activity of cells in GelMA bioinks was improved by addition of oxygen-generating particles to the bioinks. It is hoped that such bioprinted muscle tissues may find wide applications in drug screening and tissue regeneration.

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