A dual aperture (mesoporous and macroporous) system loaded with cell-free fat extract to optimize bone regeneration microenvironment

Injured bone regeneration requires a systemically and carefully orchestrated series of events involving inflammation, angiogenesis, and osteogenesis. Thus, we designed a multifunctional cell-supporting and drug-retarding dual-pore system: cell-free fat extract (Ceffe)-mesoporous silica nanoparticle (MSN)@poly(lactic-co-glycolic acid) (PLGA) (Ceffe-MSN@PLGA) to mimic the developmental spatial structure, the microenvironment of bone regeneration and integration during injured bone regeneration. In this system, a macroporous scaffold (pore size 200-250 μm) of PLGA is combined with mesoporous MSN (pore size 2-50 nm), aiming at realizing the slow release of Ceffe. Besides, PLGA and MSN are used to recruit the temporary support of cells that are able to degrade simultaneously with bone regeneration and provide space for bone tissue regeneration. And the Ceffe isolated from fresh human adipose tissue has a therapeutic effect in regulating the important functions of early inflammatory cell transformation, neovascularization and eventual osteogenic differentiation. Our results suggest that the mesoporous and macroporous Ceffe-MSN@PLGA system represents a promising strategy to better fit the regeneration of injured bone tissue.