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

Abstract 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.