Protein-based macromolecules such as keratin, silk fibroin, collagen, gelatin, and
fibrin have emerged as potential candidate materials with unique structural and functional
characteristics. Despite many advantages, the development of tissue-engineered constructs
that can match the biological context of real tissue matrix remains a challenge in
tissue engineering (TE). The tissue-engineered constructs should also support vascularization.
Protein-based macromolecules, in pristine or combine form, provide a promising platform
to engineer constructs with unique design and functionalities which are highly essential
for an appropriate stimulation and differentiation of cells in a specific TE approach.
However, much work remains to be undertaken with particular reference to in-depth
interactions between constructed cues and target host tissues. Thus, modern advancements
are emphasizing to understand critiques and functionalization of protein-based macromolecule
that organize not only cellular activities but also tissue regenerations. In this
review, numerous physicochemical, functional, and structural characteristics of protein-based
macromolecules such as keratin, silk fibroin, collagen, gelatin, and fibrin are discussed.
This review also presents the hope vs. hype phenomenon for tissue engineering. Later
part of the review focuses on different requisite characteristics and their role in
TE. The discussion presented here could prove highly useful for the construction of
scaffolds with requisite features.