A Stone-Cottage-Inspired Printing Strategy to Build Microsphere Patterned Scaffolds for Accelerated Bone Regeneration

The physical microtopography, in an effective and stable manner, can powerfully confer biomaterials with enhanced osteoconduction for the repair of critical-sized bone defects. However, the realization of the osteoconductive microtopography within a 3D porous scaffold is still unmet. Herein, this work presents a stone-cottage-inspired printing strategy to build microsphere patterned scaffolds with a tunable microtopography for accelerated bone regeneration. The customized composite inks of poly (lactic- co -glycolic acid) microspheres as “Stone” and alginate hydrogels as “Mortar” endow the fibers of as-printed scaffolds with a stable and tunable groove-ridge microstructure. Owing to this microtopography, microsphere patterned scaffolds significantly promote cell recruitment, immune response, angiogenesis, and osteogenesis. Meanwhile, compared to 55 and 85 µm, 25 µm width of groove-ridge microstructure displays the most osteoconduction for repair of critical bone defects. Mechanistically, while cells prefer to adhere to microstructure with a bigger width and higher modulus in the early phase, this microstructure should also act as a barrier for cell growth and its smaller width is more beneficial for cell communication and differentiation in the later phase. Overall, it provides a robust strategy to fabricate the osteoconductive microtopography within a 3D scaffold, broadening the manipulation of physical morphology in tissue engineering.