Faculty Bibliography

PURPOSE: Orthopedic and maxillofacial bone fractures are routinely treated by titanium internal fixation, which may be prone to exposure, infection or intolerance. Magnesium (Mg) and its alloys represent promising alternatives to produce biodegradable osteosynthesis devices, with biocompatibility and, specifically, hydrogen gas production during the degradation process, being the main drawback. Aim of this study is to test and compare biocompatibility, degradation rate and physiscochemical properties of two Mg-alloys to identify which one possesses the most suitable characteristics to be used as resorbable hardware in load-bearing fracture sites. MATERIALS AND METHODS: As-cast (WE43) and T5 Mg-alloys were tested for biocompatibility, physical, mechanical and degradation properties. Microstructure was assessed by optical microscopy, scanning electron microscopy (SEM) and energy-dispersive spectroscopy (EDS); mechanical properties were tested utilizing quasi-static compression and failure analysis. Locoregional biocompatibility was tested by sub-periosteal implantation on the fronto-nasal region of large-animal model (sheep): regional immunoreaction and metal accumulation was analyzed by LA-ICP of tributary lymph-nodes, local reactions were analyzed through histological preparation including bone, implant and surrounding soft tissue. RESULTS: Mechanically, T5 alloy showed improvement in strength compared to the as-cast. Lymph-node Mg accumulation depicted no differences between control (no implant) and study animals. Both alloys showed good biocompatibility and osteogenesis-promoting properties. CONCLUSION: This study demonstrated excellent biocompatibility and osteogenesis-promoting capabilities of the tested alloys, providing a platform for further studies to test them in a maxillofacial fracture setting. T-5 alloy displayed more stability and decreased degradation rate than the as-cast.

PURPOSE: Based on the current evidence, the effect of implant macrogeometry has a significant influence on osseointegration. Thus, this study evaluated histomorphometrically and histologically the bone response to acid-etched in comparison to grit-blasted/acid-etched (GB) and machined control (C) surfaced implants possessing identical macrogeometry placed in high-density bone. MATERIALS AND METHODS: Implant surface topography of the 3 different surfaced implants has previously been characterized. The macrogeometry of the implants were conical, and healing chambers were created in the cortical regions. The 3 groups were placed in the external mandibular body of adult male sheep (n = 5). After 6 weeks in vivo, all samples were retrieved for histologic observation and histomorphometry (eg, bone-to-implant contact [BIC] and bone area fraction occupancy [BAFO]). RESULTS: No statistical difference was observed for BIC and for BAFO, although there was a tendency that the mean values for BAFO was higher for the textured surface groups. CONCLUSIONS: It is suggested that the effect of surface topography is minimal in high-density bone and osseointegration seemed to be macrogeometry dependent.

Background/Purpose: Autogenous ear reconstruction remains one of the most technically challenging procedures in plastic surgery. Current methods to autogenous ear construct design entail tracing the contralateral (unaffected) ear, if available, and using this 2 dimensional outline as a surgical model. This study explores the feasibility of creating in-house patient specific intraoperative 3D models of autogenous ear reconstruction. Methods/Description: A 3 dimensional photograph of the unaffected ear (3DMD, Atlanta, GA) of a patient with unilateral microtia was uploaded into Amira (FEI Company, Hillsboro, Oregon, USA) and transformed to a (.stl) digital model. After rendering the (.stl) model of the ear, it was imported into Blendere (Amsterdam, The Netherlands) where it was inverted along the vertical axis to create a working template of the contralateral ear. The depths of the scapha, triangular fossa and cymba were all deepened to accentuate these contours. Additional relief was added to the helical root to further define this structure. The final template was digitally separated to create the requisite auricular components for the Nagata technique reconstruction: helix; antihelical fold with the superior and inferior crus; base frame. The patient had an intact tragus. The helix was digitally straightened to optimize its use as a model. The complete auricular model and the separated auricular components were all individually 3D printed (Builder Premium 3D Printer, Noordwijkerhout, The Netherlands) using a polylactic acid filament and sterilized following the manufacturer's specifications (1218C for 1 hour and 30 minute dry cycle). Results: The total time of digital preparation was 5 hours. Total time of 3D printing was 5.5 hours. Total cost of manufacturing was $0.78. On the day of surgery these sterilized, patient-specific 3 dimensional models were brought to the operating room and placed on the back table with the ear sculpting tools and carving block. The sterilized models were placed on the cartilage grafts and the forms and relief of the cartilage construct was easily appreciated and incorporated into the cartilage shape. Compared to the classic auricular tracings also present during this surgery these 3D printed models contained more detailed anatomic information which eliminated much of the guesswork from auricular reconstruction and resulted in a more efficient and precise operation. Conclusions: Leveraging hardware, expertise and software platforms already existing within an academic medical center, affordable, sterilizable, patient-specific 3D auricular models can be manufactured and used during autogenous ear construction

Organ development requires complex signaling by cells in different tissues. Epithelium and mesenchyme interactions are crucial for the development of skin, hair follicles, kidney, lungs, prostate, major glands, and teeth. Despite myriad literature on cell-cell interactions and ligand-receptor binding, the roles of extracellular vesicles in epithelium-mesenchyme interactions during organogenesis are poorly understood. Here, we discovered that approximately 100 nm exosomes were secreted by the epithelium and mesenchyme of a developing tooth organ and diffused through the basement membrane. Exosomes were entocytosed by epithelium or mesenchyme cells with preference by reciprocal cells rather than self-uptake. Exosomes reciprocally evoked cell differentiation and matrix synthesis: epithelium exosomes induce mesenchyme cells to produce dentin sialoprotein and undergo mineralization, whereas mesenchyme exosomes induce epithelium cells to produce basement membrane components, ameloblastin and amelogenenin. Attenuated exosomal secretion by Rab27a/b knockdown or GW4869 disrupted the basement membrane and reduced enamel and dentin production in organ culture and reduced matrix synthesis and the size of the cervical loop, which harbors epithelium stem cells, in Rab27aash/ash mutant mice. We then profiled exosomal constituents including miRNAs and peptides and further crossed all epithelium exosomal miRNAs with literature-known miRNA Wnt regulators. Epithelium exosome-derived miR135a activated Wnt/beta-catenin signaling and escalated mesenchymal production of dentin matrix proteins, partially reversible by Antago-miR135a attenuation. Our results suggest that exosomes may mediate epithelium-mesenchyme crosstalk in organ development, suggesting that these vesicles and/or the molecular contents they are transporting may be interventional targets for treatment of diseases or regeneration of tissues.

PURPOSE: The present study hypothesized that different bone healing patterns through initial stages of osseointegration would be observed when three distinct commercially available implant systems (Nobel Groovy, Implacil, and Zimmer TSV) were used, leading to significant variations in histometric levels of total bone and new bone formation during the osseointegration process. MATERIALS AND METHODS: A total of 48 implants were placed bilaterally on the tibias of eight beagle dogs and allowed to heal for 2 and 6 weeks. Following euthanasia, nondecalcified specimens were processed for morphologic and histometric evaluation. Bone-to-implant contact (BIC) and new bone area fraction occupancy (BAFO) analyses for native and new bone were performed along the whole perimeter of each implant and separately for the cortical and trabecular bone regions. RESULTS: Morphologic evaluation of cortical bone presented different healing patterns and osseointegration levels for different implant systems as time elapsed in vivo. Interfacial remodeling was the chief healing pattern in Zimmer implants, while a combination of interfacial remodeling and healing chambers was observed in Nobel and Implacil implants. When trabecular bone was evaluated, similar bone healing patterns were observed between systems despite different levels of osseointegration observed as a function of implantation time, implant system, and native and/or new bone BIC and BAFO. CONCLUSION: Different implant systems led to different healing patterns during early stages of osseointegration. Such variation in pattern was more noticeable in the cortical regions compared to the trabecular regions. The variation in bone healing pattern did significantly influence overall indicators of native and new BIC and BAFO during the osseointegration process. The postulated hypothesis was accepted.

OBJECTIVE: This work aims to present a pilot study of a non-destructive dental histo-anatomical analysis technique as well as to push the boundaries of the presently available restorative workflows for the fabrication of highly customized ceramic restorations. MATERIALS AND METHODS: An extracted human maxillary central incisor was subject to a micro computed tomography scan and the acquired data was transferred into a workstation, reconstructed, segmented, evaluated and later imported into a Computer-Aided Design/Computer-Aided Manufacturing software for the fabrication of a ceramic resin-bonded prosthesis. RESULTS: The obtained prosthesis presented an encouraging optical behavior and was used clinically as final restoration. CONCLUSION: The digitally layered restorative replication of natural tooth morphology presents today as a clear possibility. New clinical and laboratory-fabricated, biologically inspired digital restorative protocols are to be expected in the near future. CLINICAL SIGNIFICANCE: The digitally layered restorative replication of natural tooth morphology presents today as a clear possibility. This pilot study may represent a stimulus for future research and applications of digital imaging as well as digital restorative workflows in service of esthetic dentistry.

OBJECTIVE: To evaluate the effect of light-curing wavelengths on composite filler particle displacement, and thus to visualize localized polymerization shrinkage in a resin-based composite (RBC) containing camphorquinone (CQ) and Lucirin TPO (TPO). METHODS: Three light-curing units (LCUs) were used to light-cure a RBC containing CQ and TPO: a violet-only, a blue-only, and a dual-wavelength, conventional (Polywave(R), emitting violet and blue wavelengths simultaneously). Zirconia fillers were added to the RBC to act as filler particle displacement tracers. LCUs were characterized for total emitted power (mW) and spectral irradiant output (mW/cm2/nm). 2-mm high, 7-mm diameter silanized glass cylindrical specimens were filled in a single increment with the RBC, and micro-computed tomography (mu-CT) scans were obtained before and after light-curing, according to each LCU (n=6). Filler particle movement identified polymerization shrinkage vectors, traced using software, at five depths (from 0 up to 2mm): top, top-middle, middle, middle-bottom and bottom. RESULTS: Considering different RBC depths within the same LCU, use of violet-only and conventional LCUs showed filler particle movement decreased with increased depth. Blue-only LCU showed homogeneous filler particle movement along the depths. Considering the effect of different LCUs within the same depth, filler particle movement within LCUs was not statistically different until the middle of the samples (P>.05). However, at the middle-bottom and bottom depths (1.5 and 2mm, respectively), blue-only LCU compared to violet-only LCU showed higher magnitude of displacement vector values (P<.05). Use of the conventional LCU showed filler displacement magnitudes that were not significantly different than blue-only and violet-only LCUs at any depth (P>.05). With respect to the direction of particle movement vectors, use of violet-only LCU showed a greater displacement when close to the incident violet LED; blue-only LCU showed equally distributed particle displacement values within entire depth among the samples; and the conventional LCU showed greater filler displacement closer to the blue LED locations. SIGNIFICANCE: Filler particle displacement in a RBC as a result of light-curing is related to localized application of light wavelength and total emitted power of the light emitted on the top surface of the RBC. When the violet LED is present (violet-only and conventional LCUs), filler particle displacement magnitude decreased with increased depth, while results using the blue-only LED show a more consistent pattern of displacement. Clinically, these results correlate to production of different characteristics of curing within a RBC restoration mass, depending on localized wavelengths applied to the irradiated surface.

PURPOSE: Currently, surgeons approach autogenous microtia repair by creating a two-dimensional (2D) tracing of the unaffected ear to approximate a three-dimensional (3D) construct, a difficult process. To address these shortcomings, this study introduces the fabrication of patient-specific, sterilizable 3D printed auricular model for autogenous auricular reconstruction. METHODS: A high-resolution 3D digital photograph was captured of the patient's unaffected ear and surrounding anatomic structures. The photographs were exported and uploaded into Amira, for transformation into a digital (.stl) model, which was imported into Blender, an open source software platform for digital modification of data. The unaffected auricle as digitally isolated and inverted to render a model for the contralateral side. The depths of the scapha, triangular fossa, and cymba were deepened to accentuate their contours. Extra relief was added to the helical root to further distinguish this structure. The ear was then digitally deconstructed and separated into its individual auricular components for reconstruction. The completed ear and its individual components were 3D printed using polylactic acid filament and sterilized following manufacturer specifications. RESULTS: The sterilized models were brought to the operating room to be utilized by the surgeon. The models allowed for more accurate anatomic measurements compared to 2D tracings, which reduced the degree of estimation required by surgeons. Approximately 20 g of the PLA filament were utilized for the construction of these models, yielding a total material cost of approximately $1. CONCLUSION: Using the methodology detailed in this report, as well as departmentally available resources (3D digital photography and 3D printing), a sterilizable, patient-specific, and inexpensive 3D auricular model was fabricated to be used intraoperatively. This technique of printing customized-to-patient models for surgeons to use as 'guides' shows great promise.