Faculty Bibliography

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.

BACKGROUND:Alveolar clefts are traditionally treated with secondary bone grafting, but this is associated with morbidity and graft resorption. Although recombinant human bone morphogenetic protein-2 (rhBMP-2) is under investigation for alveolar cleft repair, safety concerns remain. Dipyridamole is an adenosine receptor indirect agonist with known osteogenic potential. This study compared dipyridamole to rhBMP-2 at alveolar cleft defects delivered using bioceramic scaffolds. METHODS:Skeletally immature New Zealand White rabbits underwent unilateral, 3.5 × 3.5-mm alveolar resection adjacent to the growing suture. Five served as negative controls. The remaining defects were reconstructed with three-dimensionally printed bioceramic scaffolds coated with 1000 μm of dipyridamole (n = 6), 10,000 μm of dipyridamole (n = 7), or 0.2 mg/ml of rhBMP-2 (n = 5). At 8 weeks, new bone was quantified. Nondecalcified histologic evaluation was performed, and new bone was evaluated mechanically. Statistical analysis was performed using a generalized linear mixed model and the Wilcoxon rank sum test. RESULTS:Negative controls did not heal, whereas new bone formation bridged all three-dimensionally printed bioceramic treatment groups. The 1000-μm dipyridamole scaffolds regenerated 28.03 ± 7.38 percent, 10,000-μm dipyridamole scaffolds regenerated 36.18 ± 6.83 percent (1000 μm versus 10,000 μm dipyridamole; p = 0.104), and rhBMP-2-coated scaffolds regenerated 37.17 ± 16.69 percent bone (p = 0.124 versus 1000 μm dipyridamole, and p = 0.938 versus 10,000 μm dipyridamole). On histology/electron microscopy, no changes in suture biology were evident for dipyridamole, whereas rhBMP-2 demonstrated early signs of suture fusion. Healing was highly cellular and vascularized across all groups. No statistical differences in mechanical properties were observed between either dipyridamole or rhBMP-2 compared with native bone. CONCLUSION/CONCLUSIONS:Dipyridamole generates new bone without osteolysis and early suture fusion associated with rhBMP-2 in skeletally immature bone defects.

There are over 2 million long bone defects treated in the USA annually, of which ~5% will not heal without significant surgical intervention. While autogenous grafting is standard of care in simple defects, a customized scaffold for large defects in unlimited quantities is not available. Recently, a three-dimensionally (3D) printed bioactive ceramic (3DPBC) scaffold has been successfully utilized in the of repair critical sized long bone defects in vivo. In this study, 3DPBC scaffolds were augmented with Dipyridamole, an adenosine A2A receptor (A_2A R) indirect agonist, because of its known effect to enhance bone formation. Critical-sized full thickness segmental defects (~11mm x full thickness) defects were created in the radial diaphysis in New Zealand White rabbits (n=24). A customized 3DPBC scaffold composed of β-tricalcium phosphate was placed into the defect site. Groups included scaffolds that were collagen-coated (COLL), or immersed in 10μM, 100μM, or 1000μM Dipyridamole solution. Animals were euthanized 8 weeks post-operatively and the radii/ulna-scaffold complex retrieved, en bloc, for micro-CT, histological and mechanical analysis. Bone growth was assessed exclusively within scaffold pores and evaluated by microCT and advanced reconstruction software. Biomechanical properties were evaluated utilizing nanoindentation to assess the newly regenerated bone for elastic modulus (E) and hardness (H). MicroCT reconstructions illustrated bone in-growth throughout the scaffold, with an increase in bone volume dependent on the Dipyridamole dosage. Histological evaluation did not indicate any adverse immune response while revealing progressive remodeling of bone. These customized biologic 3DPBC scaffolds have the potential of repairing and regenerating bone. This article is protected by copyright. All rights reserved.

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.

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.

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