Large-sized bone defect repair by combining a decalcified bone matrix framework and bone regeneration units based on photo-crosslinkable osteogenic microgels

Abstract

Physiological repair of large-sized bone defects is great challenging in clinic due to a lack of ideal grafts suitable for bone regeneration. Decalcified bone matrix ( DBM) is considered as an ideal bone regeneration scaffold, but low cell seeding efficiency and a poor osteoinductive microenvironment greatly restrict its application in large-sized bone regeneration. To address these problems, we proposed a novel strategy of bone regeneration units ( BRUs) based on microgels produced by photo-crosslinkable and microfluidic techniques, containing both the osteogenic ingredient DBM and vascular endothelial growth factor ( VEGF) for accurate biomimic of an osteoinductive microenvironment. The physicochemical properties of microgels could be precisely controlled and the microgels effectively promoted adhesion, proliferation, and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro. BRUs were successfully constructed by seeding BMSCs onto microgels, which achieved reliable bone regeneration in vivo. Finally, by integrating the advantages of BRUs in bone regeneration and the advantages of DBM scaffolds in 3D morphology and mechanical strength, a BRU-loaded DBM framework successfully regenerated bone tissue with the desired 3D morphology and effectively repaired a large-sized bone defect of rabbit tibia. The current study developed an ideal bone biomimetic microcarrier and provided a novel strategy for bone regeneration and large-sized bone defect repair.

Highlights

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  The photo-crosslinkable microgels contained both osteogenic ingredient DBM powders and angiogenic growth factor VEGF.

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  The photo-crosslinkable microgels effectively promote adhesion, proliferation, and osteogenic differentiation of BMSCs in vitro.

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  Bone regeneration units (BRUs) successfully achieve reliable bone regeneration in vivo.

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  The combination of DBM scaffold and BRUs successfully regenerate bone tissue with the desired 3D morphology and repair large-sized bone defect of rabbit tibia.