Faculty Bibliography

Recombinant human bone morphogenetic protein-2 (rhBMP-2) is one of the most commonly used osteogenic agents in the craniofacial skeleton. This study reviews the safety and efficacy of rhBMP-2 as applied to craniofacial reconstruction and assesses the level of scientific evidence currently available.

New resin-based restorative materials have been developed, such as computer-aided design/computer-aided manufacturing (CAD/CAM) and bulk-fill composites, as an alternative to traditional layering techniques. This study evaluated the biaxial flexural strength (BFS) before and after thermocycling of five different resin composites: one hybrid resin/ceramic CAD/CAM indirect material, Lava Ultimate CAD-CAM Restorative (LU, 3M Oral Care); a conventional composite, Filtek Z350 XT (Z350, 3M Oral Care); two bulk-fill composites, Tetric N-Ceram Bulk Fill (TBF, Ivoclar Vivadent) and Filtek Bulk Fill (FBF, 3M Oral Care); and one bulk-fill flow resin composite, Filtek Bulk Fill Flow (FBFF, 3M Oral Care). Three hundred disc-shaped specimens (6.5 mm in diameter and 0.5 mm thick) were fabricated and divided into five groups (n=30 for each composite and condition). The BFS test was performed in a universal testing machine at a crosshead speed of 0.5 mm/min immediately (i, 24 hours) and after thermocycling (a, 500 thermal cycles of 5°C to 55°C with a 30-second dwell time). The Weibull modulus (m) and characteristic stress (η) were calculated, and a contour plot was used (m vs η) to detect differences between groups (95% two-sided confidence intervals). Significantly higher characteristic stress was observed for LUi (286.6 MPa) and Z350i (248.8 MPa) compared to the bulk-fill groups (FBFi=187.9 MPa, FBFFi=175.9 MPa, TBFi=149.9 MPa), with no differences between LUi and Z350i. Thermocycling significantly decreased the characteristic stress of all groups with the highest values observed for LUa (186.7 MPa) and Z350a (188.9 MPa) and the lowest for FBFFa (90.3 MPa). Intermediate values were observed for FBFa (151.6 MPa) and TBFa (122.8 MPa). The Weibull modulus decreased only for FBFa compared to FBFi. Composition and thermocycling significantly influenced the biaxial flexural strength of resin composite materials.

AIM/OBJECTIVE:To evaluate the influence of brain-derived neurotrophic factor (BDNF) in combination with collagen sponges on periodontal tissue regeneration. METHODS:Unilateral, "box-type" (4x5mm), one-wall intrabony defects were surgically created at posterior mandibular teeth in 14 Beagle dogs. Animals received all experimental groups and the defects were randomly treated as follow: Emdogain® (positive control) [EMD]; HeliPlug®+BDNF [H/B]; RCP®+BDNF [R/B]; negative control [Control]; TeruPlug®+BDNF [Tp/B] and TeruPlug®+BDNF2 [Ts/B]. Periodontal wound healing was observed every 2 weeks by computed tomography. The animals were euthanized at 8 weeks post-surgery for microcomputed tomography and histomorphometric evaluation. RESULTS:All groups presented ∼1mm apical epithelial attachment relative to cementoenamel junction. Although linear measurements did not demonstrate significant differences between groups for cementum and periodontal ligament regeneration, semi-quantitative analysis depicted higher percentage of samples with mineralized cementum and functional PDL for Ts/B, R/B and H/B groups relative to EMD and Control (p<0.046). Irrespective of quantification method (2D or 3D), Ts/B, Control, Tp/B and H/B groups presented the highest mean percentage of new bone (not significantly different), followed by R/B and EMD groups. CONCLUSION/CONCLUSIONS:While no significant differences were detected in quantitative analyses, Ts/B combination results in significantly more samples with full periodontal tissue regeneration relative to control groups.

OBJECTIVE:To evaluate the reliability and failure mode of zirconia-reinforced lithium silicate (ZLS) molar crowns of different thicknesses. METHODS:Monolithic ZLS molar crowns (0.5mm, 1.0mm, and 1.5 mm thickness) were modeled and milled using a CAD/CAM system (n = 21/group). Crowns were cemented on dentin-like epoxy resin replicas with a resin cement. The specimens were subjected to single load-to-failure test for step-stress profiles designing. Mouth-motion step-stress accelerated-life test was performed under water by sliding an indenter 0.7 mm lingually down on the distobuccal cusp until specimen fracture or suspension. Use level probability Weibull curves and reliability were calculated and plotted. Polarized-light optical microscope and scanning electron microscope (SEM) were used to characterize fracture patterns. RESULTS:Irrespective of crown thickness, beta (β) values were higher than 1 and fatigue accelerated failures. While 0.5 mm ZLS crowns exhibited a significant reduction in the probability of survival at 200N, 300N and 400 N mission loads (69%, 41% and 19%, respectively), no significant difference was observed between 1.0 mm and 1.5 mm crowns. Both thicknesses have maintained the survivability at approximately 90%. Failure primarily comprised bulk fracture where radial cracks originated from the cementation surface beneath the indenter loading trail and propagated towards the cervical margin. SIGNIFICANCE/CONCLUSIONS:1.5 mm- and 1.0 mm-thickness monolithic ZLS crowns presented higher probability of survival compared to 0.5 mm crowns. Bulk fracture was the chief failure mode, regardless of thickness.

The study evaluated the effects of a Supercritical CO₂ (scCO₂ ) on a commercially available decellularized/delipidized naturally derived porcine pericardium collagen membrane, Vitala®. The Vitala® and scCO₂ treated experimental membranes were evaluated for guided tissue regeneration (GTR) of periodontal tissue in class III furcation defects utilizing a dog model. Physical material characterization was performed by scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). The in vivo portion of the study was allocated to three-time points (6, 12, and 24-weeks) using standardized class III furcation defects created in the upper second and third premolars. The experimental defects (n = 5) were covered with either a collagen membrane (positive control), scCO₂ -treated collagen membrane (experimental) or no membrane (negative control). Following sacrifice, histologic serial sections were performed from cervical to apical for morphologic/morphometric evaluation. Morphometric evaluation was carried out by ranking the presence of collagen membrane, amount of bone formation within the defect site and inflammatory cell infiltrate content. SEM showed the experimental scCO₂ -treated membrane to have a similar gross fibrous appearance and chemical structure in comparison to the Vitala® Collagen membrane. A significant increase in membrane thickness was noted in the scCO₂ -treated membranes (366 ± 54 μm) vs non-treated membranes (265 ± 75 μm). TGA and DSC spectra indicated no significant qualitative differences between the two membranes. For the in vivo results, both membranes indicated significantly greater amounts of newly formed bone (scCO₂ : 2.85 ± 1.1; Vitala®: 2.80 ± 1.0) within the covered defects relative to uncovered controls (0.8 ± 0.27) at 24 weeks. Both membrane types gradually degraded as time elapsed in vivo from 6 to 12 weeks, and presented nearly complete resorption at 24 weeks. The inflammatory infiltrate at regions in proximity with the membranes was commensurate with healthy tissue levels from 6 weeks in vivo on, and periodontal ligament regeneration onset was detected at 12 weeks in vivo. The effect of the supplementary scCO₂ treatment step on the collagen membrane was demonstrated to be biocompatible, allowing for the infiltration of cells and degradation over time. The treated membranes presented similar performance in GTR to non-treated samples in Class III furcation lesions. Defects treated without membranes failed to achieve regeneration of the native periodontium. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res B Part B: Appl Biomater 00B: 000-000, 2018.

Cells are transplanted to regenerate an organs' parenchyma, but how transplanted parenchymal cells induce stromal regeneration is elusive. Despite the common use of a decellularized matrix, little is known as to the pivotal signals that must be restored for tissue or organ regeneration. We report that Alx3, a developmentally important gene, orchestrated adult parenchymal and stromal regeneration by directly transactivating Wnt3a and vascular endothelial growth factor. In contrast to the modest parenchyma formed by native adult progenitors, Alx3-restored cells in decellularized scaffolds not only produced vascularized stroma that involved vascular endothelial growth factor signalling, but also parenchymal dentin via the Wnt/β-catenin pathway. In an orthotopic large-animal model following parenchyma and stroma ablation, Wnt3a-recruited endogenous cells regenerated neurovascular stroma and differentiated into parenchymal odontoblast-like cells that extended the processes into newly formed dentin with a structure-mechanical equivalency to native dentin. Thus, the Alx3-Wnt3a axis enables postnatal progenitors with a modest innate regenerative capacity to regenerate adult tissues. Depleted signals in the decellularized matrix may be reinstated by a developmentally pivotal gene or corresponding protein.

Adenosine receptor activation has been investigated as a potential therapeutic approach to heal bone. Bone has enhanced regenerative potential when influenced by either direct or indirect adenosine receptor agonism. As investigators continue to elucidate how adenosine influences bone cell homeostasis at the cellular and molecular levels, a small but growing body of literature has reported successful in vivo applications of adenosine delivery. This review summarizes the role adenosine receptor ligation plays in osteoblast and osteoclast biology and remodeling/regeneration. It also reports on all the modalities described in the literature at this point for delivery of adenosine through in vivo models for bone healing and regeneration.

This study evaluated the effect of alumina-blasted/acid-etched (AB/AE) or microabrasive blasting (C3-Microblasted) surface treatment on the osseointegration of commercially-pure Ti (grade II) and Ti-6Al-4V alloy (grade V) implants compared to as-machined surfaces. Surface characterization was performed by scanning electron microscopy and optical interferometry (IFM) to determine roughness parameters (Sa and Sq, n = 3 per group). One-hundred forty-four implants were placed in the radii of 12 beagle dogs, for histological (n = 72, bone-to-implant contact - BIC and bone-area-fraction occupancy -BAFO) and torque to interface failure test at 3 and 6 weeks (n = 72). SEM and IFM revealed a significant increase in surface texture for AB/AE and C3-Microblasted surfaces compared to machined surface, regardless of titanium substrate. Torque-to-interface failure test showed significant increase in values from as-machined to AB/AE and to C3-Microblasted. Considering time in vivo, alloy grade, and surface treatment, the C3-microblasted presented higher mean BIC values relative to AB/AE and machined surfaces for both alloy types. BAFO levels were significantly higher for both textured surfaces groups relative to the machined group at 3 weeks, but differences were not significant between the three surfaces for each alloy type at 6 weeks. Surface treatment resulted in roughness that improved osseointegration in Grade II and V titanium substrates.

This study's objective was to mechanically characterize and validate the synthesis method of a polycrystalline composite comprised of 80% alumina reinforced with 20% translucent zirconia (zirconia-toughened alumina, ZTA) and compare to an experimental translucent zirconia. Experimental ZTA (ZTA ZPEX 80/20) and translucent Y-TZP (ZPEX) green-state disc-shaped specimens were obtained via uniaxial/isostatic ceramic powder pressing technique. The discs were sintered using a predefined protocol after both sides of the discs were polished. The specimens were subjected to nanoindentation testing to acquire their elastic modulus (E) and hardness (H) before and after a simulated low temperature degradation (LTD) challenge. Subsequently, the fabricated discs had their 3D surface topographical (Sa/Sq) parameters assessed via interferometry before and after exposure to a simulated LTD aging protocol. The specimens were evaluated using X-ray diffraction (XRD) to assess the tetragonal-monoclinic phase transformation and via scanning electron microscopy (SEM) to evaluate the homogeneity of the surfaces and distribution of the grains. The apparent density was measured using Archimedes"™ principle. All of the data were statistically evaluated through repeated measures ANOVA following post-hoc comparisons using the Tukey test (p < 0.05). The XRD patterns indicated a higher increase in the monoclinic peak for ZPEX compared to ZTA ZPEX 80/20 aged. LTD aging did not have an effect on the surface roughness (Sa/Sq) for both groups (p > 0.05). A significant decrease in the E values after the aging protocol was observed for both groups (p < 0.01). While ZTA ZPEX 80/20 did not show statistically significant differences in the hardness values after the aging protocol (p = 0.36), ZPEX demonstrated a significant decrease in the H values (p = 0.03). For ZTA ZPEX 80/20, simulated LTD aging did not affect the tested properties, except for the E values. Although artificial aging did not affect the surface roughness of ZPEX, the E and H values significantly decreased after aging.

In this study, we evaluated the effect of local injection of osteoblastic cells differentiated from bone marrow or adipose tissue-mesenchymal stromal cells (BM-OB and AT-OB, respectively) on bone repair. For that, the cells were harvested from male Wistar rats (200 g), under the rules of the Committee of Ethics in Animal Research of the University of Sao Paulo. The BM-OB were obtained by osteoblastic differentiation of bone marrow-mesenchymal stromal cells for 10 days. The AT-OB were obtained by osteoblastic differentiation of adipose tissue-mesenchymal stromal cells for 10 days. Under general anesthesia, unilateral 5-mm defect was created in the calvaria of rats and in order to simulate preexisting defects only after 2 weeks the defects were treated. Each defect was locally injected with BM-OB or AT-OB (5 9 10⁶ cells/defect in 50 ll PBS). PBS without cells was injected as Control. Four weeks after cell injection, the animals were euthanized, and the bone formation was analyzed by microtomography (micro-CT) and nanoindentation assay. The data were evaluated using the ANOVA test followed by the Tukey's test when appropriated (p B 0.05). The morphometric parameters generated from micro-CT images showed that bone volume, percentage of bone volume, bone surface and trabecular number were higher in defects injected with BM-OB or AT-OB compared with Control (p = 0.001 for all). Trabecular separation was lower in defects injected with BM-OB or AT-OB compared with Control (p = 0.001). The qualitative parameters generated from nanoindentation indicated that elastic modulus and hardness of bone formed in defects injected with BM-OB or AT-OB were higher compared with Control (p = 0.05 for both). In conclusion, the use of local injection of osteoblastic cells differentiated from bone marrow or adipose tissue-mesenchymal stromal cells induced the same amount of bone formation opening new therapeutic possibilities for the treatment of bone defects