Elucidating role of silk-gelatin bioink to recapitulate articular cartilage differentiation in 3D bioprinted constructs

Abstract

Tissue engineered cartilage has never been evaluated with an aim to distinguish between transient and articular cartilage. A major drawback of existing state-of-the art engineered cartilage is cellular hypertrophy, leading to development of transient cartilage which ultimately undergoes endochondral ossification to form bone trabeculae. As a paradigm shift, using 3D bioprinting, we have evaluated six different conditions for best outcome vis-à-vis articular cartilage differentiation as assessed by expression of a constellation of markers (like Autotaxin, lubricin etc). Our study strongly suggests that BMSCs undergo hypertrophic differentiation in the presence of TGF-β1, while in the absence of TGF-β1 BMSCs encapsulated in 3D bioprinted silk-gelatin bioink matrix undergo articular cartilage differentiation. Our study provides novel insights into direct regulatory role of silk-gelatin bioink on IHH and Wnt signaling pathways in controlling hypertrophy during chondrogenic differentiation of BMSCs. 3D bioprinted silk-gelatin constructs enabled adequate cellular attachment, proliferation and most importantly, articular cartilage differentiation. Interestingly, we observed close similarities between the signaling pathways associated with the 3D bioprinted constructs with respect to the signaling pathways with embryonic cartilage development suggesting our engineered cartilage tissue to be a prospective tissue equivalent with potential of providing the essential instructive elements for activating pathways of organogenesis in patient-specific manner.