Faculty Bibliography

The present study describes the development of a microsphere capsule based on polylactide-co-glycolide (PLGA) loaded with simvastatin that was subsequently incorporated into synthetic bone cement. The osteogenic effect of simvastatin-loaded bone cement was in a critical sized defect in vivo to test the hypothesis the biologic response would be different depending on the dosage of simvastatin applied to bone cement. Our results showed that simvastatin loaded PLGA microspheres can be successfully obtained through O/W emulsion/solvent evaporation method with appropriate morphologic characteristics and high encapsulation efficiency for incorporation in bone cements. The biodegradable characteristic of the microspheres successfully presented a slow release and the duration of the release lasted for more than 1 month. The in vivo experiment revealed that the microspheres containing simvastatin significantly enhanced bone formation in the rabbit calvaria critical size defect.

Particulate bone augmentation is an established clinical alternative to regenerate bone. However, in regions of poor bone quality or previously infected sites, the clinical outcomes are more inconsistent. For that purpose, peptides have been added to particulate materials in an attempt to render them with antibacterial properties or to improve their osseoconductivity. For instance, competence-stimulating peptide (CSP) has been studied to decrease the division rate of Streptococcus mutans. Also, the addition of a specific short amino acid sequence peptide derived from type I collagen (P-15) to the bone substitutes has been introduced in an attempt to increase its osseoconductivity. The present study hypothesized that xenogeneic graft materials with and without CSP would present improved host-to-biomaterial response when used in combination with P-15. Particulate graft materials with and without P-15, OsteoGraf with CSP and OsteoGraf, were implanted in an 8-mm rabbit calvarial defect for 4 weeks, and thereafter, histological and histomorphometrical evaluation was performed. The results showed that both OsteoGraf and CSP groups with the addition of P-15 induced bone growth towards the center of the defect. Furthermore, the addition of CSP to Osteograf showed a tendency to increase its osteoconductivity when combined with P-15. The results of the current study suggested that P-15 had some impact on osteogenesis; however, the effect differed between different bone substitute materials. Further investigation is necessary to clarify its effectiveness when used in combination with bone substitutes.

Purpose: To evaluate the effect of the presence of a prefabricated cobalt-chromium (CoCr) margin in a universal castable long abutment (UCLA) on the sealing capability and fit of the implant-abutment interface. Materials and Methods: One-hundred twenty external hexagon implants (SIN) were divided into two groups (n = 60 each) to receive UCLA abutments from six manufacturers (n = 10 each) either with or without a CoCr margin (n = 60 each). Abutments were cast and 12 groups were formed: M (Microplant), I (Impladen), S (SIN), Sv (Signo Vinces), T (TitaniumFix), and B (Bionnovation). Sealing was determined by placing 0.7 microL of 0.1% toluidine blue in the implant wells before abutment torquing. Implant-abutment samples were placed into 2.0-mL vials containing 0.7 mL of distilled water to maintain the implant-abutment interface, and aliquots of 100 microL of water were retrieved at 1, 3, 6, 24, 48, 72, 96, and 144 hour incubation times for measurement of absorbance in a spectrophotometer, and returned for repeated measurements. Two-way ANOVA (P < .05) and Tukey's test were used. Scanning electron microscopy (SEM) was used for observation of the implant-abutment fit. Results: Groups M, Sv, and T without the CoCr margin resulted in complete release of toluidine blue at 1 hour, whereas I, S, and B did so at 3, 24, and 96 hours, respectively. Complete leakage in abutments with the prefabricated margin occurred at 6 hours for S; 24 hours for Sv, T, and B; and 72 hours for M and I. Implant-abutment gaps were observed in all groups. A poorer fit was depicted for groups M and T without the CoCr margin. Conclusion: Complete leakage was observed for all UCLA abutments regardless of the presence of the CoCr margin. Implant-abutment gaps were observed in all groups.

This study aimed to observe the regenerative effect of brain-derived neurotrophic factor (BDNF) in a non-human primate furcation defect model. Class II furcation defects were created in the first and second molars of 8 non-human primates to simulate a clinical situation. The defect was filled with either, Group A: BDNF (500 microg/ml) in high-molecular weight-hyaluronic acid (HMW-HA), Group B: BDNF (50 microg/ml) in HMW-HA, Group C: HMW-HA acid only, Group D: empty defect, or Group E: BDNF (500 microg/ml) in saline. The healing status for all groups was observed at different time-points with micro computed tomography. The animals were euthanized after 11 weeks, and the tooth-bone specimens were subjected to histologic processing. The results showed that all groups seemed to successfully regenerate the alveolar buccal bone, however, only Group A regenerated the entire periodontal tissue, i.e., alveolar bone, cementum and periodontal ligament. It is suggested that the use of BDNF in combination with a scaffold such as the hyaluronic acid in periodontal furcation defects may be an effective treatment option.

BACKGROUND: It is known that physico/chemical alterations on biomaterial surfaces have the capability to modulate cellular behavior, affecting early tissue repair. Such surface modifications are aimed to improve early healing response and, clinically, offer the possibility to shorten the time from implant placement to functional loading. Since FAK and Src are intracellular proteins able to predict the quality of osteoblast adhesion, this study evaluated the osteoblast behavior in response to nanometer scale titanium surface texturing by monitoring FAK and Src phosphorylations. METHODOLOGY: Four engineered titanium surfaces were used for the study: machined (M), dual acid-etched (DAA), resorbable media microblasted and acid-etched (MBAA), and acid-etch microblasted (AAMB). Surfaces were characterized by scanning electron microscopy, interferometry, atomic force microscopy, x-ray photoelectron spectroscopy and energy dispersive X-ray spectroscopy. Thereafter, those 4 samples were used to evaluate their cytotoxicity and interference on FAK and Src phosphorylations. Both Src and FAK were investigated by using specific antibody against specific phosphorylation sites. PRINCIPAL FINDINGS: The results showed that both FAK and Src activations were differently modulated as a function of titanium surfaces physico/chemical configuration and protein adsorption. CONCLUSIONS: It can be suggested that signaling pathways involving both FAK and Src could provide biomarkers to predict osteoblast adhesion onto different surfaces.

Several histologic studies regarding peri-implant soft tissues and biological width around dental implants have been done in animals. However, these findings in human peri-implant soft tissues are very scarce. Therefore, the aim of this case series was to compare the biological width around unloaded one- and two-piece implants retrieved from human jaws. Eight partially edentulous patients received 2 test implants in the posterior mandible: one-piece (solid implants that comprise implant and abutment in one piece) and two-piece (external hexagon with a healing abutment) implants. After 4 months of healing, the implants and surrounding tissue were removed for histologic analysis. The retrieved implants showed healthy peri-implant bone and exhibited early stages of maturation. Marginal bone loss, gaps, and fibrous tissue were not present around retrieved specimens. The biologic width dimension ranged between 2.55 +/- 0.16 and 3.26 +/- 0.15 to one- and two-piece implants, respectively (P < 0.05). This difference was influenced by the connective tissue attachment, while sulcus depth and epithelial junction presented the same dimension for both groups (P > 0.05). Within the limits of this study, it could be shown that two-piece implants resulted in the thickening of the connective tissue attachment, resulting in the increase of the biological width, when compared to one-piece implants.

Bone is a viscoelastic connective tissue composed primarily of mineral and type I collagen, which interacts with water, affecting its mechanical properties. Therefore, both the level of hydration and the loading rate are expected to influence the measured nanomechanical response of bone. In this study, we investigated the influence of three distinct hydration conditions, peak loads and loading/unloading rates on the elastic modulus and hardness of canine femoral cortical bone via nanoindentation. Sections from three canine femurs from multiple regions of the diaphysis were tested for a total of 670 indentations. All three hydration conditions (dry, moist and fully hydrated tissue) were tested at three different loading profiles (a triangular loading profile with peak loads of 600, 800 and 1000muN at loading/unloading rate of 60, 80 and 100muN/s, respectively; each test was 20s in duration). Significant differences were found for both the elastic modulus and hardness between the dry, moist and fully hydrated conditions (p0.05). However, in both the moist and fully hydrated conditions, the elastic modulus and hardness were significantly different under all loading profiles (with the exception of the moist condition at the 600- and 800-muN peak load). Given these findings, it is critical to perform nanoindentation of bone under fully hydrated conditions to ensure physiologically relevant results. Furthermore, this work found that a 20-s triangular loading/unloading profile was sufficient to capture the viscoelastic behavior of bone in the 600- to 1000-muN peak load range. Lastly, specific peak load values and loading rates need to be selected based on the structural region for which the mechanical properties are to be measured.