Fabrication and application of novel porous scaffold in situ-loaded graphene oxide and osteogenic peptide by cryogenic 3D printing for repairing critical-sized bone defect

Abstract

Osteogenic peptides have been reported as highly effective in directing mesenchymal stem cell osteogenic differentiation in vitro and bone formation in vivo. Therefore, developing novel biomaterials for the controlled delivery of osteogenic peptides in scaffolds without lowering the peptide's biological activity is highly desirable. To repair a critical-sized bone defect to efficiently achieve personalized bone regeneration, a novel bioactive poly(lactic-co-glycolic acid) (PLGA)/β-tricalcium phosphate (β-TCP) composite scaffold, in which graphene oxide (GO) and bone morphogenetic protein (BMP)-2-like peptide were loaded in situ (PTG/P), was produced by an original cryogenic 3D printing method. The scaffolds were mechanically comparable to human cancellous bone and hierarchically porous. The incorporation of GO further improved the scaffold wettability and mechanical strength. The in situ loaded peptides retained a high level of biological activity for an extended time, and the loading of GO in the scaffold further tuned the peptide release so that it was more sustained. Our in vitro study showed that the PTG/P scaffold promoted rat bone marrow-derived mesenchymal stem cell ingrowth into the scaffold and enhanced osteogenic differentiation. Moreover, the in vivo study indicated that the novel PTG/P scaffold with sustained delivery of the peptide could significantly promote bone regeneration in a critical bone defect. Thus, the novel bioactive PTG/P scaffold with a customized shape, improved mechanical strength, sustainable peptide delivery, and excellent osteogenic ability has great potential in bone tissue regeneration.