Vol. 9, Issue 8, Part J (2025)

Silk has long been revered as a natural fiber with exceptional mechanical strength, elasticity, biodegradability, and biocompatibility, making it highly desirable for diverse applications ranging from textiles to biomedical engineering. However, traditional silk production through sericulture is labor-intensive, season-dependent and environmentally demanding. In response to these limitations, scientific efforts have increasingly focused on replicating the silk production process in vitro through synthetic silk gland models that emulate the physiological and biochemical mechanisms of native silk glands in Bombyx mori and spiders. This review provides a comprehensive overview of the biomimetic strategies employed to develop artificial silk-spinning systems, including microfluidic devices that replicate the gland’s tapering structure and fluid shear environment and modular bioreactors that integrate protein expression with spinning. It also discusses innovations in wet-spinning, electrospinning and advanced spinneret technologies such as multi-lumen nozzles and 3D-printed extrusion systems that have enabled the fabrication of silk fibers with properties approaching those of natural silk. The role of recombinant protein expression in microbial hosts like E. coli, Pichia pastoris, and Bacillus subtilis is explored, highlighting advances in the scalable production of spidroins and fibroins tailored for biomimetic processing. Challenges such as achieving native-like hierarchical structures, improving fiber uniformity and mechanical properties and replicating the controlled chemical gradients of the natural gland are critically analyzed. Overall, synthetic silk gland technologies hold immense promise for revolutionizing silk production by offering eco-friendly, controllable and scalable alternatives to sericulture. These systems not only pave the way for high-performance artificial silk fibers but also establish a platform for producing customizable biomaterials for future use in tissue engineering, drug delivery, bioelectronics, and smart textiles.