The State Key Laboratory of Fluid Power and Mechatronic Systems, and ‡Key Laboratory of 3D Printing Process and Equipment of Zhejiang Province, School of Mechanical Engineering, Zhejiang University , Hangzhou 310028, China.
ACS Appl Mater Interfaces. 2018 Feb 28;10(8):6849-6857. doi: 10.1021/acsami.7b16059. Epub 2018 Feb 15.
Methacrylated gelatin (GelMA) has been widely used as a tissue-engineered scaffold material, but only low-concentration GelMA hydrogels were found to be promising cell-laden bioinks with excellent cell viability. In this work, we reported a strategy for precise deposition of 5% (w/v) cell-laden GelMA bioinks into controlled microarchitectures with high cell viability using extrusion-based three-dimensional (3D) bioprinting. By adding gelatin into GelMA bioinks, a two-step cross-linking combining the rapid and reversible thermo-cross-linking of gelatin with irreversible photo-cross-linking of GelMA was achieved. The GelMA/gelatin bioinks showed significant advantages in processability because the tunable rheology and the rapid thermo-cross-linking of bioinks improved the shape fidelity after bioprinting. Here, the rheology, mechanical properties, and swelling of GelMA/gelatin bioinks with different concentration ratios were carefully characterized to obtain the optimized bioprinting setup. We successfully printed the 5% (w/v) GelMA with 8% (w/v) gelatin into 3D structures, which had the similar geometrical resolution as that of the structures printed by 30% (w/v) GelMA bioinks. Moreover, the cell viability of 5/8% (w/v) GelMA/gelatin bioinks was demonstrated by in vitro culture and cell printing of bone marrow stem cells (BMSCs). Larger BMSC spreading area was found on 5/8% (w/v) GelMA/gelatin scaffolds, and the BMSC viability after the printing of 5/8% (w/v) GelMA/gelatin cell-laden bioinks was more than 90%, which was very close to the viability of printing pure 5% (w/v) GelMA cell-laden bioinks. Therefore, this printing strategy of GelMA/gelatin bioinks may extensively extend the applications of GelMA hydrogels for tissue engineering, organ printing, or drug delivery.
甲基丙烯酰化明胶（GelMA）已被广泛用作组织工程支架材料，但只有低浓度的 GelMA 水凝胶被发现是具有优异细胞活力的有前途的细胞负载生物墨水。在这项工作中，我们报告了一种使用基于挤出的三维（3D）生物打印技术将 5%（w/v）细胞负载 GelMA 生物墨水精确沉积到具有高细胞活力的受控微结构中的策略。通过向 GelMA 生物墨水中添加明胶，实现了两步交联，其中包括明胶的快速可逆热交联与 GelMA 的不可逆光交联相结合。GelMA/明胶生物墨水在加工性能方面具有显著优势，因为可调的流变学特性和生物墨水的快速热交联提高了生物打印后的形状保真度。在这里，仔细表征了不同浓度比的 GelMA/明胶生物墨水的流变学、力学性能和溶胀性能，以获得优化的生物打印设置。我们成功地将 8%（w/v）明胶的 5%（w/v）GelMA 打印成 3D 结构，其几何分辨率与由 30%（w/v）GelMA 生物墨水打印的结构相似。此外，通过体外培养和骨髓间充质干细胞（BMSCs）的细胞打印，证明了 5/8%（w/v）GelMA/明胶生物墨水的细胞活力。在 5/8%（w/v）GelMA/明胶支架上发现了更大的 BMSC 扩展面积，并且在打印 5/8%（w/v）GelMA/细胞负载生物墨水后，BMSC 的活力超过 90%，与打印纯 5%（w/v）GelMA 细胞负载生物墨水的活力非常接近。因此，这种 GelMA/明胶生物墨水的打印策略可能会广泛扩展 GelMA 水凝胶在组织工程、器官打印或药物输送方面的应用。
