Printability Optimization of Gelatin-Alginate Bioinks by Cellulose Nanofiber Modification for Potential Meniscus Bioprinting

Meniscal injury is more likely to cause a permanent alteration of the biomechanical and biological environment of the knee joint, mainly due to the morphological mismatch and substantial loss of meniscal tissues. Herein, to overcome this challenge, we developed an improved bioink with enhanced printability, while maintaining the biocompatibility of major cellular component of the meniscus, namely fibrochondrocytes. Firstly, cellulose nanofiber (CNF) was mixed with gelatin-alginate thermal-responsive bioinks to improve the printability. Afterward, individual-specific meniscal prototypes based on the 3D reconstruction of MRI data were bioprinted using our bioink. The rheological and printability properties of the bioinks were characterized to select proper bioink content and bioprinting parameters. And then, a series of biological characterizations of the bioprinted samples, such as cell viability, metabolic activity, and extracellular matrix accumulation, were carried out in vitro. The results indicated that superior rheological performance and printability of CNF-modified bioink were achieved, ensuring high-precision bioprinting of specific-designed meniscal prototype when compared with the non-CNF-containing counterparts. Meanwhile, biological tests indicated that fibrochondrocytes encapsulated within the CNF-modified bioink maintained long-term cellular viability as well as acceptable extracellular matrix accumulation. This study demonstrates that the CNF-modified bioink is in favor of the printing fidelity of specific meniscus by improved rheological properties, minimizing the mismatch between artificial meniscal implants and native knee joint tissues, thereby permitting the evolution of clinical therapeutic methods of meniscal reconstruction.