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 factor 165 (rhVEGF) via physical adsorption (3 μg rhVEGF 165 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/mm 2 ) was much greater than that in the nHA/coral group (105±51.8 vessel/mm 2 ) 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/mm 2 , 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.

Synthetic Blocks for Bone Regeneration: A Systematic Review and Meta-Analysis

“…The main characteristics of the defect treated, bone graft material characteristics, study outcome, and follow-up time for each animal model are summarized in Table 1, Table 2, Table 3, Table 4, Table 5 and Table 6. Thirty-seven studies (97.3%) performed histologic evaluation of the samples retrieved [18,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60], 26 studies (68.4%) reported histomorphometric analysis, 1 study performed fluorescence microscopy analyses of bone samples [18]. Two studies [47,56] described a scanning electron microscope (SEM) evaluation.…”

“…Eleven articles [28,29,30,31,32,39,40,51,54,59,61] also performed microcomputed tomography (micro-CT), five a radiographic assessment [18,38,44,55,62], and one article [50] reported an angiogram evaluation. One study also reported X-ray diffraction evaluation [42]. An analytic description of the evaluation techniques is provided in Table 1, Table 2, Table 3, Table 4, Table 5 and Table 6.…”

Cationic Substitutions in Hydroxyapatite: Current Status of the Derived Biofunctional Effects and Their In Vitro Interrogation Methods

“…One possibility for generating blood vessels in the scaffold is to use recombinant pro-angiogenic growth factors such as, VEGF, PDGF, IGF, or TGF-β1 & TGF-β2 adsorbed into the scaffold [502,509]. These proteic substances are difficult to manage and manipulate, expensive and would require a complex authorization and quality control.…”

Synthetic and Marine-Derived Porous Bone Graft Substitutes

“…The histological evaluation and the histomorphometric analysis revealed enhanced neovascular density and a larger quantity of new bone formation at 3 and 8 weeks postsurgery. The results suggest that nHA/coral blocks might be satisfactory 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 [164,165]. 6.1.1.4.…”