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As an FDA-approved biopolymer, silk has been contemplated for a wide range of applications based on its unique merits, such as biocompatibility, biodegradability, and piezoelectricity. As silk, in both crystalline structure and amorphous state, exhibits unique physical, mechanical, and biological properties (promoting cell migration, differentiation, growth, and protein-surface interaction), it is fruitful to understand its potential applications. Sensors, actuators, and drug delivery systems are the best in case. As such, the current effort first introduces silk fibroin (SF) and delineates its characteristics. It then explores the extensive use of this biomaterial in tissue engineering approaches, in addition to its biosensor and electro-active wearable bioelectronic application. To this end, the SF application in cardiovascular, skin, cartilage, and drug delivery systems for cancer therapy and wound healing was studied precisely …