Bioinspired trimodal macro/micro/nano-porous scaffolds loading rhBMP-2 for complete regeneration of critical size bone defect

Critical size bone defects raise great demands for efficient bone substitutes. Mimicking the hierarchical porous architecture and specific biological cues of natural bone has been considered as an effective strategy to facilitate bone regeneration. Herein, a trimodal macro/micro/nano-porous scaffold loaded with recombinant human bone morphogenetic protein-2 (rhBMP-2) was developed. With mesoporous bioactive glass (MBG) as matrix, a trimodal MBG scaffold (TMS) with enhanced compressive strength (4.28MPa, porosity of 80%) was prepared by a “viscosity controlling” and “homogeneous particle reinforcing” multi-template process. A 7.5nm, 3D cubic (Im3m) mesoporous structure was tailored for a “size-matched entrapment” of rhBMP-2 to achieve sustained release and preserved bioactivity. RhBMP-2-loaded TMS (TMS/rhBMP-2) induced excellent cell attachment, ingrowth and osteogenesis in vitro. Further in vivo ectopic bone formation and orthotopic rabbit radius critical size defect results indicated that compared to the rhBMP-2-loaded bimodal macro/micro- and macro/nano-porous scaffolds, TMS/rhBMP-2 exhibited appealing bone regeneration capacity. Particularly, in critical size defect, complete bone reconstruction with rapid medullary cavity reunion and sclerotin maturity was observed on TMS/rhBMP-2. On the basis of these results, TMS/rhBMP-2 developed here represents a promising bone substitute for clinical application and the concepts proposed in this study might provide new thoughts on development of future orthopedic biomaterials.