Cartilage tissue
is deprived of intrinsic self-regeneration capability;
hence, its damage often progresses to a chronic condition which reduces
the quality of life. Toward the fabrication of functional tissue substitutes,
three-dimensional (3D) bioprinting has progressed vastly over the
last few decades. However, this progress is challenged by the difficulty
in developing suitable bioink materials as most of them require toxic
chemical cross-linking. In this study, our goal was to develop a cross-linker-free
bioink with optimal rheology for polymer extrusion, aqueous, and nontoxic
processing and offers structural support for cartilage regeneration.
Toward this, we use the self-gelling ability of silk fibroin blends
(Bombyx mori and Philosamia
ricini) along with gelatin as a bulking agent. Silk
and gelatin interact with each other through entanglement and physical
cross-linking. The ink was rheologically and structurally optimized
for printing efficiency in printing grid-like structures. The printed
3D constructs show optimal swelling capability, degradability, and
compressive strength. Further, the construct supports the growth and
proliferation of encapsulated chondrocytes and formation of the cartilaginous
extracellular matrix as indicated by the increased sulfated glycosaminoglycan
and collagen contents. This was further corroborated by the upregulation
of chondrogenic gene expression with minimal hypertrophy of chondrocytes.
Additionally, the construct demonstrates in vitro and in vivo biocompatibility.
Notably, the ink demonstrates good print fidelity for printing anatomical
structures such as the human ear enabled by optimized extrudability
at adequate resolution. Altogether, the results indicate that the
developed cross-linker-free silk–gelatin polymer-based bioink
demonstrated high potential for its 3D bioprintability and application
in cartilage tissue engineering.