Abstract

A new HA/ZrO2-based porous bioceramic artificial vertebral body (AVB), carried a recombinant human bone morphogenetic protein-2 (rhBMP-2)/chitosan slow-release hydrogel was prepared to repair vertebral bone defect in beagles. An ionic cross-linking was used to prepare the chitosan hydrogel (CS gel) as the rhBMP-2 slow-release carrier. The vertebral body defects were implanted with the rhBMP-2-loaded AVB in group A, or a non-drug-loaded AVB in group B, or autologous iliac in group C. The encapsulation rate of rhBMP-2 in rhBMP-2-loaded CS gel was 91.88±1.53%, with a drug load of 39.84±2.34 ng/mg. At 6, 12, 24 weeks postoperatively, radiography showed that the bone calluses gradually increased with time in group A, where the artificial vertebral body had completely fused with host-bone at 24 weeks after surgery. In group C, an apparent bone remodeling was occurred in the early stages, and the graft-bone and host-bone had also fused completely at 24 weeks postoperatively. In group B, fusion occurred less than in groups A and C. At 24 weeks after surgery, micro-computed tomography (Micro-CT) revealed that the volume of newly-formed bone in group A was significantly more than in group B (p<0.05). At 24 weeks after surgery, ultra-compressive strengths of the operated segments were 14.03±1.66 MPa in group A, 8.62±1.24 MPa in group B, and 13.78±1.43 MPa in group C. Groups A and C were both significantly higher than group B (p < 0.05). At 24 weeks postoperatively, the hard tissue sections showed that the AVB of group A had tightly fused with host bone, and that pores of the AVB had been filled with abundant nearly mature bone, and that the new bone structured similarly to a trabecular framework, which was similar to that in group C. In contrast, implant fusion of the AVB in group B was not as apparent as group A. In conclusion, the novel HA/ZrO2-based porous bioceramic AVB carried the rhBMP-2-loaded CS gel can promote the repair of bony defect, and induce bone tissue to grow into the pores, which may replace iliac bone grafts as commonly applied in clinical practice.

Highlights

  • In current clinical practice, artificial bone grafting is commonly used to repair large bone defects

  • Sufficient new bone must form at the graft site and a strong connection must be formed between the graft-bone and the host-bone tissue, while most of current bone grafts act as bone substitutes

  • The cumulative release of recombinant human bone morphogenetic protein-2 (rhBMP-2) was expressed as the percentage of released rhBMP-2 compared with the loaded total

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Summary

Introduction

Artificial bone grafting is commonly used to repair large bone defects. The key factor for successful grafting is the ability of new bone tissues to grow into the grafts postoperatively [1]. The repair of large bone-defect is complicated, and need longer fusion time with an increasing risk of infection and implant collapse. Improving osteogenesis and fusion rates of artificial bone grafts will certainly promote the success of bone graft surgeries [2,3,4,5]. The ZrO2-HA containing AVB had superior bone conduction activity, with excellent mechanical properties and plenty new bone growing into the designed pores would be desired as an ideal bone scaffold

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