Porous nanofibrous scaffold incorporated with S1P loaded mesoporous silica nanoparticles and BMP-2 encapsulated PLGA microspheres for enhancing angiogenesis and osteogenesis.

Repair of bone defects remains a major clinical challenge due to inadequate or abnormal vascularization in bone substitutes, which commonly leads to inferior bone formation or bone nonunion. Therefore, healing of bone defects requires the coordinated processes of angiogenesis and osteogenesis. In this study, sphingosine-1-phosphate (S1P) was initially loaded into mesoporous silica nanoparticles (MSNs) to form angiogenic microcarriers, which were subsequently embedded into porous nanofibrous poly-l-lactide (PLLA) scaffolds during a thermally induced phase separation (TIPS) process, while bone morphogenetic protein-2 (BMP-2) was encapsulated into poly(lactic-co-glycolic acid) (PLGA) microspheres to obtain osteogenic microcarriers, which were then integrated onto a MSNs/PLLA nanofibrous scaffold by a post seeding method. The osteogenic and angiogenic activities of the resulting dual-bioactive factor containing scaffolds were evaluated both in vitro and in vivo. The simulated drug release studies indicated that both bioactive factors will be released simultaneously and continuously from the fabricated composite scaffold. Moreover, the ectopic bone formation results showed that the sustained release of S1P and BMP-2 from the composite scaffold resulted in a synergistic effect on blood vessel formation and bone regeneration. Taken together, the results showed the promising application of the dual-bioactive factor loaded nanofibrous scaffold for enhanced bone regeneration.