Faculty Bibliography

BACKGROUND: Widespread application of composite tissue allotransplantation has been impeded by risks of rejection and conventional immunosuppression. The authors have developed a nonhuman primate composite tissue allotransplantation model that demonstrated reliable and long-term success necessary to progress to preclinical studies. METHODS: Composite facial subunits (e.g., skin, muscle, and bone) were transplanted between mismatched cynomolgus monkeys. Vascular supply was based on the common carotid artery and external and internal jugular veins. Facial allografts were heterotopically transplanted to the recipient's lower abdomen with end-to-side anastomoses of the common carotid artery to the common femoral artery and of both the internal and external jugular veins to the common femoral vein. Animals received tacrolimus monotherapy. Grafts were inspected daily, submitted to biopsy regularly, and studied with magnetic resonance imaging. RESULTS: Thirteen transplants were performed. Two grafts based on the common carotid artery and only the internal jugular vein failed within 3 to 5 days because of venous thrombosis not related to rejection. Subsequent transplants included anastomoses of both the internal and external jugular veins to the common femoral vein without thromboses. Immunosuppression consisted of tacrolimus monotherapy and was tolerated without complications. Long-term success was achieved with rejection-free graft survival (60 to 177 days). CONCLUSIONS: The authors have developed the first successful model of facial composite tissue allotransplantation in a nonhuman primate. Technical requirements include preservation of both internal and external jugular venous outflow. Tacrolimus monotherapy permitted prolonged rejection-free graft survival without early complications. This model provides a platform for further investigation of composite tissue allotransplantation tolerance and requirements for indefinite survival.

The complex and patient-unique geometry of posterior all-ceramic dental crowns represents a particularly interesting set of challenges to understanding stress concentration and fracture evolution in response to loading. A series of numerical and physical experiments, with both single cycle and fatigue loading, show that geometry profoundly influences the stress concentration and fracture initiation and propagation. In stylized crowns with uniform axial wall height, stresses concentrate beneath the indenter. As the height of the axial wall increases, loads to cause failure increase linearly. In crowns with variation in axial wall height around the periphery, stresses concentrate both beneath the indenter and at the margin of the core ceramic. The magnitude of the stress concentration at the margin is directly related to the amount of variation in axial wall height around the periphery of the crown. Anatomically correct veneered zirconia core crowns subjected to single-cycle loads, fracture in areas of greatest stress concentration identified by finite element models. Fractures and stress concentrations that occur in response to single-cycle loading are important indicators of initiation sites for fatigue failure. (c) 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2008

BACKGROUND: Radioprotective modalities such as dose fractionation and pharmacologic agents such as amifostine have been used to protect bone and other types of normal tissue from the damaging effects of ionizing radiation without significantly impacting tumor kill. To better understand the cellular mechanism of radioprotection of osseous tissue, the authors sought to determine the effect of dose fractionation and amifostine on isolated osteoblasts. METHODS: Isolated primary rat calvarial osteoblasts were exposed to single or fractionated doses of ionizing radiation both with and without amifostine pretreatment. Endpoints included cell growth (n = 4), vascular endothelial growth factor production as measured by enzyme-linked immunosorbent assay (n = 3), and early osteodifferentiation as measured by a quantitative alkaline phosphatase assay (n = 3). RESULTS: Both dose fractionation and amifostine protect osteoblasts from the growth inhibitory effects of ionizing radiation. Fractionation but not amifostine was protective for hypoxia-induced vascular endothelial growth factor production (used as a surrogate marker of normal osteoblast function). Neither fractionation nor amifostine could prevent the inhibitory effect of ionizing radiation on normal osteoblast osteodifferentiation as measured by alkaline phosphatase production. CONCLUSIONS: Both dose fractionation and amifostine have valid roles as radioprotectants for osteoblasts and can act in an additive fashion. Radioprotection of cell growth and viability does not necessarily correlate with preservation of normal cellular function. Combination protocols involving dose fractionation and amifostine may be effective in radioprotection of osteoblasts and normal osseous tissue.

Background: Ectopic beats are frequently associated with morphologic repolarization alterations of ensuing sinus beats. Less is known about repolarization duration alterations of post-ectopic sinus beats. In one patient who developed long QT and torsades de pointes upon exposure to a class III antiarrhythmic drug, and was later genotyped as being a carrier for long QT syndrome (LQTS) type 1, review of a pre-drug Holter monitor study revealed marked QT prolongation of post-ectopic sinus beats. In wondering whether this might be a common clue to "concealed" unexpressed LQTS, we realized that we must first characterize the range of post-ectopic QT prolongation present in normals. Prolongation beyond the upper limit of this range might then raise suspicion of possible LQTS and alter the antiarrhythmic drug selection process for the suppression of atrial fibrillation or other arrhythmias. Methods: Accordingly, we assessed the presence/degree of repolarization prolongation following premature ectopic impulses in 166 subjects with normal conduction intervals and normal repolarization on their resting 12-lead ECG, 75 of whom had no known associated cardiovascular disorder of any kind. That is, in our subjects, the maximal prolongation of the QT interval of the sinus beat following isolated ventricular and atrial premature complexes was characterized. Results: QT prolongation is common in post ectopic sinus beats. However, in our subjects the uncorrected QT interval of post-ectopic sinus beats never exceeded 480 ms in duration [which was much shorter than that seen (510-590 ms) in our gene carrier]. CONCLUSIONS: The QT interval in normal subjects may prolong following premature complexes but not to a value in excess of 480 ms.

BACKGROUND: This article aims to assess the spectrum of unfavorable events or incidents encountered during mandibular distraction and to evaluate the difference in the incident rates among the following treatment groups: (1) native bone distraction using an external device, (2) native bone distraction using an internal device, and (3) grafted bone distraction using an external device. METHODS: This retrospective study examined the records of 141 patients treated by mandibular distraction over a 16-year period. Of the total 141 patients, 56 underwent unilateral mandibular distraction and 85 underwent bilateral mandibular distraction, contributing to a total of 226 sided distraction procedures. The number of procedures performed on native bone using external devices was 149, versus 41 internal devices. There were 36 distractions performed on grafted bone with external devices. Incidents were broadly classified into three groups based on a severity index. A minor incident was one that resolved satisfactorily with minimal or no invasive intervention. A moderate incident was one that resolved satisfactorily with moderate clinical intervention. A major incident was one that did not resolve or could not be resolved with surgical intervention, and compromised treatment outcome. RESULTS: The major incident rate was 5.31 percent (total of 226 distraction procedures). A higher rate of major incidents was observed when distracting grafted bone. The overall minor incident rate was 26.99 percent and the moderate incident rate was 20.35 percent. CONCLUSION: Mandibular distraction can be considered a safe and predictable procedure for lengthening/augmenting the mandible in patients with lower jaw deficiencies

Among dental implant design alterations, surface modifications have been by far the most investigated topic. Regarding implant surface research, the lack of hierarchical approaches relating in vitro, in vivo, clinical trials, and ex vivo analyses has hindered biomaterials scientists with clear informed rationale guidelines for implant surface design. This manuscript provides a critical hierarchical overview of the in vitro, laboratory in vivo, clinical, and ex vivo methodologies used to investigate the performance of novel biomaterials aiming to allow dental professionals to better evaluate the past, present, and future dental implant surface research. This manuscript also contains an overview of the commercially available surface texture and chemistry modifications including novel nanotechnology-based fabrication processes. Over the last decade, surface texturing has been the most utilized parameter for increasing the host-to-implant response. Recently, dental implant surfaces utilizing reduced length scale physico/chemical features (atomic and nanometric) have shown the potential to synergistically use both texture and the inclusion of bioactive ceramic components on the surface. Although surface modifications have been shown to enhance osseointegration at early implantation times, information concerning its long-term benefit to peri-implant tissues is lacking due to the reduced number of controlled clinical trials. Given the various implants/surfaces under study, the clinician should ask, founded on the basic hierarchical approach described for the in vitro, laboratory in vivo data, as well as the results of clinical studies to effectiveness before use of any dental implant