<p>Vertical Guided Bone Regeneration in the Rabbit Calvarium Using Porous Nanohydroxyapatite Block Grafts Coated with rhVEGF₁₆₅ and Cortical Perforation</p>

Abstract

Introduction Vertical bone augmentation without osseous walls to support the stability of clots and bone grafts remains a challenge in dental implantology. The objectives of this study were to confirm that cortical perforation of the recipient bed is necessary and to evaluate whether nanohydroxyapatite (nHA) block grafts coated with recombinant human vascular endothelial growth factor 165 (rhVEGF 165 ) and cortical perforation can improve vertical bone regeneration. Materials and Methods We prepared nHA blocks coated with or without rhVEGF 165 on the rabbit calvarium through cortical perforation, and designated the animals as the nonperforated group (N-nHA), rhVEGF 165 group (NV-nHA), perforated group (P-nHA) and rhVEGF 165 on perforated group (PV-nHA). Micro-computed tomography (micro-CT) and fluorescence microscopy were selected to evaluate parameters of vertical bone regeneration at 4 and 6 weeks. Results The ratio of the newly formed bone volume to the titanium dome volume (BV/TV) and the bone mineral density (BMD) were significantly higher in the PV-nHA group than in the N-nHA group at 4 and 6 weeks, as determined using micro-CT. The fluorescence analysis showed slightly greater increases in new bone regeneration (NB%) and vertical height (VH%) gains in the P-nHA group than in the N-nHA group. Greater increases in NB% and VH% were observed in groups treated with rhVEGF 165 and perforation than in the blank groups, with significant differences detected at 4 and 6 weeks (N-nHA compared with PV-nHA, p<0.05). A greater VH% that was observed at the midline of the block in the PV-nHA group than in the other three groups at both time points (0.75±0.53% at 4 weeks and 0.83±0.42% at 6 weeks). Conclusion According to the present study, cortical perforation is necessary and nHA blocks coated with rhVEGF 165 and decoration could work synergistically to improve vertical bone regeneration by directly affecting primary osteoblasts and promoting angiogenesis and osteoinduction.

Structurally optimized honeycomb scaffolds with outstanding ability for vertical bone augmentation

“…In another study, the uses of brushite, monetite, combined brushite and an anabolic conjugate drug, and combined monetite and an anabolic conjugate drug augment the maximum height of new bone by 0.8 ± 0.2, 1.4 ± 0.4, 1.7 ± 0.6, and 2.7 ± 0.5 mm, respectively, at 12 weeks PI [49] . Furthermore, at 4 weeks and 6 weeks PI of the combined hydroxyapatite blocks and recombinant human vascular endothelial growth factor (rhVEGF), the percent volume of new bone was 0.8 ± 0.6% and 0.8 ± 0.5%, respectively [27] . When collagen sponges containing recombinant human BMP-2 (rhBMP-2) in conjunction with β-TCP, biphasic calcium phosphate, bovine bone mineral, or blood clot are implanted, the percent amount of new bone at 14 weeks PI is 28.7 ± 4.6%, 31.9 ± 5.1%, 18.0 ± 2.2%, and 15.3 ± 2.9%, respectively [25] .…”

“…In order to achieve this, it is necessary to improve the scaffold ability to vertically augment the new bone. To improve such ability, scaffolds have been combined with growth factors [24] , bone morphogenetic protein (BMP) [25] , [26] , [27] , and progenitor and/or stem cells [28] , [29] , [30] , [31] , [32] . However, these methods have various limitations, such as the formation of severe cyst-like tissues and swelling, excess bone resorption by osteoclasts, elaborate procedures, high cost, and/or invasive manipulation that requires surgeries at least twice [33] , [34] , [35] .…”

Honeycomb scaffolds capable of achieving barrier membrane-free guided bone regeneration

“…56 The percent volume of the newly formed bone in combined recombinant human vascular endothelial growth factor (rhVEGF) and HAp blocks at 4 and 6 weeks post-implantation was 0.8% ± 0.6% and 0.8% ± 0.5%, respectively. 57 The percent volume of new bone at 14 weeks post-implantation of recombinant human BMP 2 (rhBMP-2)containing collagen sponges in conjunction with β-TCP, biphasic calcium phosphate, bovine bone mineral, and blood clot was 28.7% ± 4.6%, 31.9% ± 5.1%, 18.0% ± 2.2%, and 15.3% ± 2.9%, respectively. 58 The percent volume of new bone formed in 3D printed porous TCP/HAp block-, anorganic bovine bone-, or TCP-filled titanium hemispheres was 23% ± 1.6%, 13.6% ± 1.5%, and 13.8% ± 1.5% at 8 weeks post-implantation and 35% ± 2%, 39% ± 2%, and 43% ± 6% at 16 weeks post-implantation, respectively.…”

“…For vertical bone augmentation, block-type scaffolds are considered favorable, because they facilitate shape forming and maintain the handleability, which are difficult when granular scaffolds are used. Various block-type scaffolds have been reported; 25,26] however, their ability for vertical bone augmentation is limited, and they need a combination of bone morphogenetic protein (BMP), [26][27][28] growth factors, 29] and stem and/or progenitor cells for favorable outcomes. [30][31][32][33][34] These combination approaches have several limitations, including severe swelling, cyst-like tissue formation, high cost, osteoclastic bone resorption, cumbersome procedures, and/or invasive manipulation requiring a minimum of two surgeries.…”

Osteopontin and Vascular Endothelial Growth Factor-Immunoreactivity in Critical Bone Defects Matrix Production: A Nano-Hydroxyapatite/Beta-Tricalcium Phosphate and Xenogeneic Hydroxyapatite Comparison

“…In a series of studies, when evaluating the response of new blood vessel formation through the VEGF in critical defects in rat calvaria, it was possible to reach the conclusion that the use of biomaterials from different sources presents more statistically relevant responses than when compared with clot use [21][22][23][24]. These results were very important for the elaboration of the methodology of this study, and we can verify that the use of nano-hydroxyapatite and micro-hydroxyapatite obtained similar results to the studies that served as support, in addition to the fact that nano-hydroxyapatite promotes a more adequate response to the protein of signaling the formation of new blood vessels.…”