Angiogenesis and bone regeneration of porous nano-hydroxyapatite/coralline blocks coated with rhVEGF₁₆₅ in critical-size alveolar bone defects in vivo

Abstract

To improve the regenerative performance of nano-hydroxyapatite/coralline (nHA/coral) block grafting in a canine mandibular critical-size defect model, nHA/coral blocks were coated with recombinant human vascular endothelial growth factor₁₆₅ (rhVEGF) via physical adsorption (3 μg rhVEGF₁₆₅ per nHA/coral block). After the nHA/coral blocks and VEGF/nHA/coral blocks were randomly implanted into the mandibular box-shaped defects in a split-mouth design, the healing process was evaluated by histological observation and histomorphometric and immunohistological analyses. The histological evaluations revealed the ingrowth of newly formed blood vessels and bone at the periphery and cores of the blocks in both groups at both 3 and 8 weeks postsurgery, respectively. In the histomorphometric analysis, the VEGF/nHA/coral group exhibited a larger quantity of new bone formation at 3 and 8 weeks postsurgery. The percentages of newly formed bone within the entire blocks in the VEGF/nHA/coral group were 27.3%±8.1% and 39.3%±12.8% at 3 weeks and 8 weeks, respectively, and these values were slightly greater than those of the nHA/coral group (21.7%±3.0% and 32.6%±10.3%, respectively), but the differences were not significant (P>0.05). The immunohistological evaluations revealed that the neovascular density in the VEGF/nHA/coral group (146±32.9 vessel/mm²) was much greater than that in the nHA/coral group (105±51.8 vessel/mm²) at the 3-week time point (P<0.05), but no significant difference was observed at the 8-week time point (341±86.1 and 269±50.7 vessel/mm², respectively, P>0.05). The present study indicated that nHA/coral blocks might be optimal scaffolds for block grafting in critical-size mandibular defects and that additional VEGF coating via physical adsorption can promote angiogenesis in the early stage of bone healing, which suggests that prevascularized nHA/coral blocks have significant potential as a bioactive material for bone regeneration in large-scale alveolar defects.

Keywords:

• angiogenesis
• bone regeneration
• tissue engineering
• block grafting
• nano- hydroxyapatite/coralline
• critical size
• bone defect

Acknowledgments

This work was supported by the Guangdong Provincial Stomatological Hospital (Southern Medical University, People’s Republic of China), grants from the Natural Science Foundation of China (No 81170998), and the Fund of Guangdong Province Medical Science Research (C2012034).

Disclosure

The authors report no conflicts of interest related to this work.