Lin Zening, Hong Yang, Jiang Tao, Yang Yun, Gao Yuan, Xie Hang, Luo Zirong
College of Intelligence Science and Technology, National University of Defense Technology, Changsha, 410073, China.
J Mater Chem B. 2025 Aug 13;13(32):9824-9837. doi: 10.1039/d5tb00912j.
In recent years, Matrigel-fibrinogen-thrombin (MFT) hydrogels have gained prominence in muscle tissue regeneration and biohybrid robotics owing to their remarkable bioactivity. Nevertheless, addressing their disadvantages-the instability of Matrigel, inadequate mechanical strength, complex fabrication processes, and limited structural tunability of MFT hydrogels-while maintaining biocompatibility remains challenging. In this study, sodium alginate and gelatin are used to formulate an alginate-gelatin-fibrinogen hydrogel that avoids the operational complexity associated with the initial cross-linking of thrombin and the instability of Matrigel. Notably, the alginate-gelatin-fibrinogen hydrogel showed significant shear-thinning behavior and exhibited good printability for different structures. This approach overcomes the critical limitations of extrusion printing using MFT hydrogels to fabricate muscle tissue structures with different requirements. We also used a novel quality assessment method proposed in our previous study, which incorporates the relative mean width () and relative standard deviation () of extruded filaments to quantitatively evaluate printing quality. This approach enables the realization of an ideal printing boundary. In addition, a comparison with the Young's modulus of MFT hydrogels revealed that alginate-gelatin-fibrinogen hydrogels crosslinked with calcium chloride possessed significantly improved mechanical properties. The dual-crosslinking mechanism achieved enzymatic and/or ionic methods resulted in flexible tunability of the modulus and porosity of the material. Experimental findings using C2C12 myoblast cells grown on the alginate-gelatin-fibrinogen hydrogel surface demonstrate that this biomaterial facilitates 3D bioprinting of anatomically complex muscle tissue constructs and biohybrid robotic systems. Overall, this study provides a novel strategy for the application in muscle tissue construction, repair, and bio-robotics through designing alginate-gelatin-fibrinogen composite hydrogels.
近年来，基质胶-纤维蛋白原-凝血酶（MFT）水凝胶因其卓越的生物活性在肌肉组织再生和生物杂交机器人领域备受关注。然而，在保持生物相容性的同时，解决其缺点——基质胶的不稳定性、机械强度不足、制备过程复杂以及MFT水凝胶的结构可调性有限——仍然具有挑战性。在本研究中，海藻酸钠和明胶被用于制备一种海藻酸钠-明胶-纤维蛋白原水凝胶，该水凝胶避免了与凝血酶初始交联相关的操作复杂性以及基质胶的不稳定性。值得注意的是，海藻酸钠-明胶-纤维蛋白原水凝胶表现出显著的剪切变稀行为，并且对不同结构具有良好的可打印性。这种方法克服了使用MFT水凝胶进行挤出打印以制造具有不同要求的肌肉组织结构的关键限制。我们还使用了我们先前研究中提出的一种新颖的质量评估方法，该方法结合了挤出细丝的相对平均宽度（）和相对标准偏差（）来定量评估打印质量。这种方法能够实现理想的打印边界。此外，与MFT水凝胶的杨氏模量比较表明，用氯化钙交联的海藻酸钠-明胶-纤维蛋白原水凝胶具有显著改善的机械性能。通过酶促和/或离子方法实现的双重交联机制导致材料的模量和孔隙率具有灵活的可调性。在海藻酸钠-明胶-纤维蛋白原水凝胶表面培养C2C12成肌细胞的实验结果表明，这种生物材料有助于对解剖结构复杂的肌肉组织构建体和生物杂交机器人系统进行3D生物打印。总体而言，本研究通过设计海藻酸钠-明胶-纤维蛋白原复合水凝胶，为肌肉组织构建、修复和生物机器人学的应用提供了一种新策略。
