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3D Bioprinting using Cross-Linker Free Silk-Gelatin Bioink for Cartilage Tissue Engineering.

Yogendra Pratap Singh,A. Bandyopadhyay,B. Mandal

Published 2019 in ACS Applied Materials and Interfaces

ABSTRACT

Cartilage tissue is deprived of intrinsic self-regeneration capability, hence its damage often progresses to a chronic condition which reduces the quality of life. Towards the fabrication of functional tissue substitutes, 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 crosslinking. In this study, our goal was to develop a crosslinker free bioink with optimal rheology for polymer extrusion, aqueous and non-toxic processing and offers structural support for cartilage regeneration. Towards 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 crosslinking. 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 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 human ear enabled by optimized extrudability at adequate resolution. Altogether, the results indicate that the developed crosslinker free silk-gelatin polymer-based bioink demonstrated high potential for its 3D bioprintability and application in cartilage tissue engineering.

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