Overview of Silk Fibroin Injectable Hydrogels: Advances and Applications in Regenerative Medicine

Tissue repair following disease or injury remains a major clinical challenge, driving the search for advanced biomaterials that can effectively support tissue regeneration. Injectable hydrogels have recently gained significant attention as promising candidates in regenerative medicine due to their minimally invasive administration, ability to conform to irregular defects, and precise spatial localization, overcoming the limitations of conventional pre-formed hydrogels. Among natural polymers, silk fibroin (SF) has attracted considerable attention owing to its unique chemical structure, outstanding mechanical properties, versatile processability, biocompatibility, cost-effectiveness, and large-scale availability. Consequently, a wide variety of SF-based injectable hydrogels have been developed, either alone or in combination with other biomaterials, for diverse tissue engineering applications. This review provides an in-depth discussion of their injectability, underlying gelation mechanisms, and therapeutic advantages, including roles in tissue regeneration, drug delivery, cell therapy, immunomodulation, and angiogenesis. Furthermore, the current challenges, recent advances, and future directions for the clinical translation of SF-based injectable hydrogels are critically assessed, highlighting their potential as next-generation biomaterials for regenerative medicine.