Silk Fibroin for Biomedical Applications with Emphasis on Bioimaging, Biosensing and Regenerative Systems: A Review

Biomaterials are engineered to interact with biological systems for therapeutic or diagnostic purposes. Among them, natural biomaterials offer important advantages over many synthetic polymers, including intrinsic biocompatibility, non-toxicity and biodegradability. Silk fibroin, a fibrous protein derived mainly from Bombyx mori cocoons, has re-emerged as a particularly versatile platform because it combines favourable mechanical, thermal, electrical and optical properties with aqueous processing and tuneable degradation. In this review, we first summarise the key structural, physicochemical and functional properties of regenerated silk fibroin, including its mechanical behaviour, thermal stability, dielectric and piezoelectric response, optical transparency and low autofluorescence. We then describe how extraction and regeneration protocols are used to produce defined material formats-fibres and nanofibrous mats, porous 3D scaffolds and hydrogels, sub-micron particles, thin films and microstructured devices-and outline major functionalisation strategies, ranging from physical blending and encapsulation to covalent chemistry, genetic engineering of recombinant silk variants, and enzyme-mediated conjugation approaches. Building on this foundation, we critically examine biomedical applications of silk fibroin with a particular emphasis on (i) hybrid silk-fluorophore systems for bioimaging and biosensing (nanodiamonds, quantum dots and organic dyes), (ii) optical fibre, wearable and edible sensors for health and food monitoring, (iii) wound dressings and wound-sensing platforms, and (iv) tissue engineering scaffolds and drug-delivery depots. Finally, we discuss current limitations, including process variability, the trade-offs introduced by blending and cross-linking, and the challenges posed by non-degradable inorganic fillers and clinical translation. Together, these perspectives highlight silk fibroin's potential and constraints as a multifunctional biomaterial for next-generation biomedical devices and theranostic systems.