Fine-tuning of porous microchannelled silk fibroin scaffolds for optimal tissue ingrowth

Abstract

Physical attributes of implantable scaffold materials such as pore architecture and pore size modulate regenerative outcomes by influencing vascularization and integration with host tissue. Silk fibroin (SF), renowned for its abundant availability and exceptional biocompatibility, has emerged as a choice material for scaffold fabrication, showcasing promising biomedical applications in tissue engineering and regenerative medicine. However, there remains a challenge in the design and manufacture of SF scaffolds with precisely tailored pore structures. Here, we combined sacrificial 3D-printed polymer template leaching and freeze-drying techniques to engineer SF scaffolds with controllable microchannel and pore structures. The resultant highly porous SF scaffolds were characterized by their directional microchannels and pore interconnectivity. We found that scaffold spanning microchannel incorporation combined with larger interconnecting pore structures elicited superior promotive effects on cell migration into the scaffold interior, enhancing rapid formation of vascular networks, and yielding the deposition of organized collagen matrices. Additionally, the porous nature of the scaffolds accelerated scaffold degradation through the enhanced recruitment of reparative M2-like macrophages, thereby contributing to neo-tissue formation. Our study advances the conceptual frameworks and strategies for fabricating and tuning porous SF scaffolds, offering a move toward expediting the clinical translation of tailored SF-based biomaterials.