Three-dimensional
(3D) bioprinting is a highly innovative and promising technology to
render precise positioning of biologics together with living cells
and extracellular matrix (ECM) constituents. In spite of such enthralling
potential, the fabrication of a clinically relevant engineered tissue
is quite challenging. A constellation of factors simulating the complex
architecture of the native tissue, selection of the “ideal
bioink”, optimization of the biochemical, mechanical, and topographical
functions of the cell-laden printed construct, cellular differentiation,
their self-assembly, and remodeling into the desired lineage postprinting
present major complications. Keeping this in view, we have attempted
to highlight the use of silk fibroin (SF) protein from Bombyx
mori silkworm as a promising biomaterial of choice for the
formulation of bioink owing to its distinct characteristics involving
rheology behavior, self-supporting filamentous extrusion, and a suitable
biomaterial to achieve resolution printing. Further, we have elaborated
on how SF gelatin bioink can in specific regulate the cellular differentiation
pathway of progenitor cells, the mechanism of cellular self-assembly,
cell migration, matrix remodeling, and self-orientation, leading to
the desired tissue-specific construct. How features of bioink and
fabrication design aspects can induce in vitro tissue
patterning and anatomically relevant tissue organization have also
been explored in this review. Importantly, we have tried to shift
the understanding of bioprinted tissue regeneration from a cell-proliferation-centric
and gene-expression-centric point of view to the complex role of the
microenvironment present within the bioprinted constructs. We believe
that shedding light on these factors would help in achieving the so-called
“ideal 3D bioprinted construct” to meet the shortages
of high-quality donor tissues for the regeneration of the damaged
and diseased ones.