Evaluation of a Novel HA/ZrO2-Based Porous Bioceramic Artificial Vertebral Body Combined with a rhBMP-2/Chitosan Slow-Release Hydrogel

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.

The Impact of Bioceramic Scaffolds on Bone Regeneration in Preclinical In Vivo Studies: A Systematic Review

“…Although studies in dogs, minipigs, sheep, and non-human primates, could provide a better insight into new bone formation and scaffold effectiveness thanks to the closer resemblance to the human bone, only studies employing rat and rabbit models were found to satisfy eligibility criteria, and were, therefore, included in the present systematic review [21,[27][28][29]126]. Even though after the first step of screening, studies in dogs, sheep, and pigs were included, the full-text analysis revealed that most of these studies did not meet the selection criteria due to a reduced sample size (n < 6 animals per group) or the non-critical dimensions of the bone defects [94,100,102,103,106]. Among the papers included, the most frequently used CSD model was the CSD in rat calvaria, which is one of the most commonly used animal models for evaluating bone healing [23,127].…”

Effects of a bone graft substitute consisting of porous gradient HA/ZrO2and gelatin/chitosan slow‐release hydrogel containing BMP‐2 and BMSCs on lumbar vertebral defect repair in rhesus monkey

“…Therefore, the BMP‐2 release rate is an important factor in inducing effective bone regeneration (Seo, Koh, & Song, ). Our previous study showed that 28% and 49% of recombinant human BMP‐2 was released on Days 1 and 3, respectively, after BMP‐2 was added into gelatin/chitosan slow‐release hydrogel and was then released slowly from Days 3 to 15, with a cumulative release of 74% by Day 12 and 77% by Day 15 (Shi et al, ). In the present study, loading of BMP‐2 in the gelatin/chitosan slow‐release hydrogel was performed using the technology of complex emulsion cross‐linking, thereby reducing the BMP‐2 release rate and improving its biological effects.…”

“…by Day 12 and 77% by Day 15 (Shi et al, 2016). In the present study, loading of BMP-2 in the gelatin/chitosan slow-release hydrogel was performed using the technology of complex emulsion cross-linking, thereby reducing the BMP-2 release rate and improving its biological effects.…”

Zirconia-Based Biomaterials for Hard Tissue Reconstruction

“…79 In addition, zirconia/HA-based porous bioceramics loaded with recombinant human BMP-2 promote the repair of bony defect and facilitate bone growth in vivo, which might substitute the use of iliac bone grafts in routine clinical practice. 80 Taken together, zirconia-based scaffolds show good mechanical performances and biocompatibility and are promising biomaterials to be used in bone reconstruction needed in the treatment of load-bearing large bone defects.…”