The efficiency of two different synthetic bone graft materials on alveolar ridge preservation after tooth extraction: a split-mouth study.

BACKGROUND: Alveolar Bone loss occurs frequently during the first six months after tooth extraction. Various studies have proposed different methods to reduce as much as possible the atrophy of the alveolar ridge after tooth extraction. Filling the socket with biomaterials after extraction can reduce the resorption of the alveolar ridge. We compared the height of the alveolar process at the mesial and distal aspects of the extraction site and the resorption rate was calculated after the application of HA/ß-TCP or synthetic co-polymer polyglycolic - polylactic acid PLGA mixed with blood to prevent socket resorption immediately and after tooth extraction. METHODS: The study was conducted on 24 extraction sockets of impacted mandibular third molars bilaterally, vertically, and completely covered, with a thin bony layer. HA/ß-TCP was inserted into 12 of the dental sockets immediately after extraction, and the synthetic polymer PLGA was inserted into 12 of the dental sockets. All sockets were covered completely with a full-thickness envelope flap. Follow-up was performed for one year after extraction, using radiographs and stents for the vertical alveolar ridge measurements. RESULTS: The mean resorption rate in the HA/ß-TCP and PLGA groups was ± 1.23 mm and ± 0.1 mm, respectively. A minimal alveolar bone height reduction of HA/ß-TCP was observed after 9 months, the reduction showed a slight decrease to 0.93 mm, while this rate was 0.04 mm after 9 months in the PLGA group. Moreover, the bone height was maintained after three months, indicating a good HA/ß-TCP graft performance in preserving alveolar bone (1.04 mm) while this rate was (0.04 mm) for PLGA. CONCLUSION: The PLGA graft demonstrated adequate safety and efficacy in dental socket preservation following tooth extraction. However, HA/ß-TCP causes greater resorption at augmented sites than PLGA, which clinicians should consider during treatment planning.

From Synthesis to Clinical Trial: Novel Bioinductive Calcium Deficient HA/ß-TCP Bone Grafting Nanomaterial.

Maxillary sinus augmentation is a commonly used procedure for the placement of dental implants. However, the use of natural and synthetic materials in this procedure has resulted in postoperative complications ranging from 12% to 38%. To address this issue, we developed a novel calcium deficient HA/ß-TCP bone grafting nanomaterial using a two-step synthesis method with appropriate structural and chemical parameters for sinus lifting applications. We demonstrated that our nanomaterial exhibits high biocompatibility, enhances cell proliferation, and stimulates collagen expression. Furthermore, the degradation of ß-TCP in our nanomaterial promotes blood clot formation, which supports cell aggregation and new bone growth. In a clinical trial involving eight cases, we observed the formation of compact bone tissue 8 months after the operation, allowing for the successful installation of dental implants without any early postoperative complications. Our results suggest that our novel bone grafting nanomaterial has the potential to improve the success rate of maxillary sinus augmentation procedures.

Concentration-Dependent Efficacy of Recombinant Human Bone Morphogenetic Protein-2 Using a HA/ß-TCP Hydrogel Carrier in a Mini-Pig Vertebral Oblique Lateral Interbody Fusion Model.

Bone morphogenetic protein-2 (BMP-2) is used in the treatment of degenerative spinal disease and vertebral fractures, spine fusion, dental surgery, and facial surgery. However, high doses are associated with side effects such as inflammation and osteophytes. In this study, we performed spinal fusion surgery on mini-pigs using BMP-2 and a HA/ß-TCP hydrogel carrier, and evaluated the degree of fusion and osteophyte growth according to time and dosage. Increasing the dose of BMP-2 led to a significantly higher fusion rate than was observed in the control group, and there was no significant difference between the 8-week and 16-week samples. We also found that the HA + ß-TCP hydrogel combination helped maintain the rate of BMP-2 release. In conclusion, the BMP-2-loaded HA/ß-TCP hydrogel carrier used in this study overcame the drawback of potentially causing side effects when used at high concentrations by enabling the sustained release of BMP-2. This method is also highly efficient, since it provides mineral matter to accelerate the fusion rate of the spine and improve bone quality.

DLP Fabrication of Zirconia Scaffolds Coated with HA/ß-TCP Layer: Role of Scaffold Architecture on Mechanical and Biological Properties.

In order to merge high-mechanical properties and suitable bioactivity in a single scaffold, zirconia porous structures are here coated with a hydroxyapatite layer. The digital light processing (DLP) technique is used to fabricate two types of scaffolds: simple lattice structures, with different sizes between struts (750, 900 and 1050 µm), and more complex trabecular ones, these latter designed to better mimic the bone structure. Mechanical tests performed on samples sintered at 1400 °C provided a linear trend with a decrease in the compressive strength by increasing the porosity amount, achieving compressive strengths ranging between 128-177 MPa for lattice scaffolds and 34 MPa for trabecular ones. Scaffolds were successfully coated by dipping the sintered samples in a hydroxyapatite (HA) alcoholic suspension, after optimizing the HA solid loading at 20 wt%. After calcination at 1300 °C, the coating layer, composed of a mixture of HA and ß-TCP (ß-TriCalcium Phospate) adhered well to the zirconia substrate. The coated samples showed a proper bioactivity, well pronounced after 14 days of immersion into simulated body fluid (SBF), with a more homogeneous apatite layer formation into the trabecular samples compared to the lattice ones.

Comparison of osteogenic differentiation potential of induced pluripotent stem cells and buccal fat pad stem cells on 3D-printed HA/ß-TCP collagen-coated scaffolds.

Production of a 3D bone construct with high-yield differentiated cells using an appropriate cell source provides a reliable strategy for different purposes such as therapeutic screening of the drugs. Although adult stem cells can be a good source, their application is limited due to invasive procedure of their isolation and low yield of differentiation. Patient-specific human-induced pluripotent stem cells (hiPSCs) can be an alternative due to their long-term self-renewal capacity and pluripotency after several passages, resolving the requirement of a large number of progenitor cells. In this study, a new biphasic 3D-printed collagen-coated HA/ß-TCP scaffold was fabricated to provide a 3D environment for the cells. The fabricated scaffolds were characterized by the 3D laser scanning digital microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, and mechanical test. Then, the osteogenesis potential of the hiPSC-seeded scaffolds was investigated compared to the buccal fat pad stem cell (BFPSC)-seeded scaffolds through in vitro and in vivo studies. In vitro results demonstrated up-regulated expressions of osteogenesis-related genes of RUNX2, ALP, BMP2, and COL1 compared to the BFPSC-seeded scaffolds. In vivo results on calvarial defects in the rats confirmed a higher bone formation in the hiPSC-seeded scaffolds compared to the BFPSC-seeded groups. The immunofluorescence assay also showed higher expression levels of collagen I and osteocalcin proteins in the hiPSC-seeded scaffolds. It can be concluded that using the hiPSC-seeded scaffolds can lead to a high yield of osteogenesis, and the hiPSCs can be used as a superior stem cell source compared to BFPSCs for bone-like construct bioengineering.

Prevention of Bone Resorption by HA/ß-TCP + Collagen Composite after Tooth Extraction: A Case Series.

After tooth extraction, alveolar ridge loss due to resorption is almost inevitable. Most of this bone loss occurs during the first six months after the extraction procedure. Many studies have indicated that applying socket-filling biomaterials after extraction can effectively reduce the resorption rate of the alveolar ridge. The purpose of this study was to investigate the clinical efficacy of the application of a hydroxyapatite/ß-tricalcium plus collagen (HA/ß-TCP + collagen) dental bone graft in dental sockets immediately after tooth extraction, so as to prevent socket resorption. The study was conducted on 57 extraction sockets located in the mandible and maxilla posterior regions in 51 patients. HA/ß-TCP + collagen was inserted into all of the dental sockets immediately after extraction, and was covered with a flap. Follow-up was performed for three months after extraction, using radiographs and stents for the vertical and horizontal alveolar ridge measurements. A minimal alveolar bone width reduction of 1.03 ± 2.43 mm (p < 0.05) was observed. The height reduction showed a slight decrease to 0.62 ± 1.46 mm (p < 0.05). Radiographically, the bone height was maintained after three months, indicating a good HA/ß-TCP + collagen graft performance in preserving alveolar bone. In conclusion, the HA/ß-TCP + collagen graft demonstrated adequate safety and efficacy in dental socket preservation following tooth extraction.

Enhancement of Osteoblastic-Like Cell Activity by Glow Discharge Plasma Surface Modified Hydroxyapatite/ß-Tricalcium Phosphate Bone Substitute.

Glow discharge plasma (GDP) treatments of biomaterials, such as hydroxyapatite/ß-tricalcium phosphate (HA/ß-TCP) composites, produce surfaces with fewer contaminants and may facilitate cell attachment and enhance bone regeneration. Thus, in this study we used argon glow discharge plasma (Ar-GDP) treatments to modify HA/ß-TCP particle surfaces and investigated the physical and chemical properties of the resulting particles (HA/ß-TCP + Ar-GDP). The HA/ß-TCP particles were treated with GDP for 15 min in argon gas at room temperature under the following conditions: power: 80 W; frequency: 13.56 MHz; pressure: 100 mTorr. Scanning electron microscope (SEM) observations showed similar rough surfaces of HA/ß-TCP + Ar-GDP HA/ß-TCP particles, and energy dispersive spectrometry analyses showed that HA/ß-TCP surfaces had more contaminants than HA/ß-TCP + Ar-GDP surfaces. Ca/P mole ratios in HA/ß-TCP and HA/ß-TCP + Ar-GDP were 1.34 and 1.58, respectively. Both biomaterials presented maximal intensities of X-ray diffraction patterns at 27° with 600 a.u. At 25° and 40°, HA/ß-TCP + Ar-GDP and HA/ß-TCP particles had peaks of 200 a.u., which are similar to XRD intensities of human bone. In subsequent comparisons, MG-63 cell viability and differentiation into osteoblast-like cells were assessed on HA/ß-TCP and HA/ß-TCP + Ar-GDP surfaces, and Ar-GDP treatments led to improved cell growth and alkaline phosphatase activities. The present data indicate that GDP surface treatment modified HA/ß-TCP surfaces by eliminating contaminants, and the resulting graft material enhanced bone regeneration.

Ticagrelor regulates osteoblast and osteoclast function and promotes bone formation in vivo via an adenosine-dependent mechanism.

As many as 10% of bone fractures heal poorly, and large bone defects resulting from trauma, tumor, or infection may not heal without surgical intervention. Activation of adenosine A2A receptors (A2ARs) stimulates bone formation. Ticagrelor and dipyridamole inhibit platelet function by inhibiting P2Y12 receptors and platelet phosphodiesterase, respectively, but share the capacity to inhibit cellular uptake of adenosine and thereby increase extracellular adenosine levels. Because dipyridamole promotes bone regeneration by an A2AR-mediated mechanism we determined whether ticagrelor could regulate the cells involved in bone homeostasis and regeneration in a murine model and whether inhibition of P2Y12 or indirect A2AR activation via adenosine was involved. Ticagrelor, dipyridamole and the active metabolite of clopidogrel (CAM), an alternative P2Y12 antagonist, inhibited osteoclast differentiation and promoted osteoblast differentiation in vitro. A2AR blockade abrogated the effects of ticagrelor and dipyridamole on osteoclast and osteoblast differentiation whereas A2BR blockade abrogated the effects of CAM. Ticagrelor and CAM, when applied to a 3-dimentional printed resorbable calcium-triphosphate/hydroxyapatite scaffold implanted in a calvarial bone defect, promoted significantly more bone regeneration than the scaffold alone and as much bone regeneration as BMP-2, a growth factor currently used to promote bone regeneration. These results suggest novel approaches to targeting adenosine receptors in the promotion of bone regeneration.-Mediero, A., Wilder, T., Reddy, V. S. R., Cheng, Q., Tovar, N., Coelho, P. G., Witek, L., Whatling, C., Cronstein, B. N. Ticagrelor regulates osteoblast and osteoclast function and promotes bone formation in vivo via an adenosine-dependent mechanism.

On the structural, mechanical, and biodegradation properties of HA/ß-TCP robocast scaffolds.

Hydroxyapatite/ß-tricalcium phosphate (HA/ß-TCP) composite scaffolds have shown great potential for bone-tissue engineering applications. In this work, ceramic scaffold with different HA/ß-TCP compositions (pure HA, 60HA/40ß-TCP, and 20HA/80ß-TCP) were fabricated by a robotic-assisted deposition (robocasting) technique using water-based hydrogel inks. A systematic study was conducted to investigate the porosity, mechanical property, and degradation of the scaffolds. Our results indicate that, at a similar volume porosity, the mechanical strength of the sintered scaffolds increased with the decreasing rod diameter. The compressive strength of the fabricated scaffolds (porosity ≈ 25-80 vol %) varied between ∼3 and ∼50 MPa, a value equal or higher than that of human cancellous bone (2-12 MPa). Although there was a slight increase of Ca and P ions in water after 5 month, no noticeable degradation of the scaffolds in SBF or water was observed. Our findings from this work indicate that composite calcium phosphate scaffolds with customer-designed chemistry and architecture may be fabricated by a robotic-assisted deposition method.