3D biomimetic artificial bone scaffolds with dual-cytokines spatiotemporal delivery for large weight-bearing bone defect repair

• Published in: Scientific reports Vol. 7; no. 1; pp. 7814 - 13
• Main Authors: Bao, Xiaogang, Zhu, Lingjun, Huang, Xiaodong, Tang, Dezhi, He, Dannong, Shi, Jiangang, Xu, Guohua
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10.08.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 140/131; 38/77; 59; 59/78; 631/61/54/990; 64/60; 692/698/1671/63; Anatomy; Biodegradability; Biodegradation; Biomimetics; Bone grafts; Bone growth; Bone morphogenetic protein 2; Controlled release; Cytokines; Defects; Humanities and Social Sciences; Hydrogels; multidisciplinary; Ossification (ectopic); Osteoconduction; Regeneration; Science; Science (multidisciplinary); Skin & tissue grafts; Structure-function relationships; Synergistic effect; Vascular endothelial growth factor
• DOI: 10.1038/s41598-017-08412-0
• ISSN: 2045-2322

It is a great challenge to prepare “functional artificial bone” for the repair of large segmental defect, especially in weight-bearing bones. In this study, bioactive HA/PCL composite scaffolds that possess anatomical structure as autogenous bone were fabricated by CT-guided fused deposition modeling technique. The scaffolds can provide mechanical support and possess osteoconduction property. Then the VEGF-165/BMP-2 loaded hydrogel was filled into biomimetic artificial bone spatially to introduce osteoinduction and angioinduction ability via sustained release of these cytokines. It has been revealed that the cytokine-loaded hydrogel possessed good biodegradability and could release the VEGF-165/BMP-2 sustainedly and steadily. The synergistic effect of these two cytokines showed significant stimulation on the osteogenic gene expresssion of osteoblast in vitro and ectopic ossification in vivo . The scaffolds were then implanted into the rabbit tibial defect sites (1.2 cm) for bone regeneration for 12 weeks, indicating the best repair of defect in vivo , which was superior to the pure hydrogel/scaffolds or one-cytokine loaded hydrogel/scaffolds and close to autogenous bone graft. The strategy to construct an “anatomy-structure-function” trinity system as functional artificial bone shows great potential in replacing autogenous bone graft and applying in large bone defect repair clinically in future.