Engineering Injectable and Highly Interconnected Porous Silk Fibroin Microspheres for Tissue Regeneration

Injectable porous microspheres represent a promising therapeutic platform for cell delivery, drug delivery, and tissue regeneration. Yet, the engineering of silk fibroin microspheres with a highly interconnected porous structure remains an unsolved challenge. In this study, a simple and efficient method is developed that does not require the use of organic solvents to prepare silk fibroin microspheres with a predictable structure. Through extensive screening, the addition of glucose is found to direct the formation of a highly interconnected porous structure from the interior to the surface of silk fibroin microspheres. Compared to silk fibroin microspheres (SF microspheres) produced through a combination of electro-spray, cryopreservation, and freeze drying, silk fibroin-glucose microspheres (SF-Glu microspheres) demonstrates enhanced capabilities in promoting cell adhesion and proliferation in vitro. Both SF-Glu and SF microspheres exhibit the capacity to maintain the sustained release kinetics of the loaded model drug. Furthermore, SF-Glu microspheres facilitate the recruitment of endogenous cells, capillary migration, and macrophage phenotype switch following subcutaneous injection in the rats. This study opens a new avenue for the construction of porous silk fibroin microspheres, which could lead to a broader range of applications in regenerative medicine.