Faculty Bibliography

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

As many as 10% of bone fractures heal poorly, and large bone defects resulting from trauma, tumor, or infection may not heal without surgical intervention. Activation of adenosine A2A receptors (A2AR) stimulates bone formation. Ticagrelor and dipyridamole inhibit platelet function by inhibiting P2Y12 receptors and platelet phosphodiesterase, respectively, but share the capacity to inhibit cellular uptake of adenosine and thereby increase extracellular adenosine levels. Because dipyridamole promotes bone regeneration by an A2AR-mediated mechanism we determined whether ticagrelor could regulate the cells involved in bone homeostasis and regeneration in a murine model and whether inhibition of P2Y12 or indirect A2AR activation via adenosine was involved. Ticagrelor, dipyridamole and the active metabolite of clopidogrel (CAM), an alternative P2Y12 antagonist, inhibited osteoclast differentiation and promoted osteoblast differentiation in vitro. A2AR blockade abrogated the effects of ticagrelor and dipyridamole on osteoclast and osteoblast differentiation whereas A2BR blockade abrogated the effects of CAM. Ticagrelor and CAM, when applied to a 3-dimentional printed resorbable calcium-triphosphate/hydroxyapatite scaffold implanted in a calvarial bone defect, promoted significantly more bone regeneration than the scaffold alone and as much bone regeneration as BMP-2, a growth factor currently used to promote bone regeneration. These results suggest novel approaches to targeting adenosine receptors in the promotion of bone regeneration.-Mediero, A., Wilder, T., Reddy, V. S. R., Cheng, Q., Tovar, N., Coelho, P. G., Witek, L., Whatling, C., Cronstein, B. N. Ticagrelor regulates osteoblast and osteoclast function and promotes bone formation in vivo via an adenosine-dependent mechanism.

A bone drilling concept, namely osseodensification, has been introduced for the placement of endosteal implants to increase primary stability through densification of the osteotomy walls. This study investigated the effect of osseodensification on the initial stability and early osseointegration of conical and parallel walled endosteal implants in low density bone. Five male sheep were used. Three implants were inserted in the ilium, bilaterally, totaling 30 implants (n=15 conical, and n=15 parallel). Each animal received 3 implants of each type, inserted into bone sites prepared as follows: (i) regular-drilling (R: 2mm pilot, 3.2mm, and 3.8mm twist drills), (ii) clockwise osseodensification (CW), and (iii) counterclockwise (CCW) osseodensification drilling with Densah Bur (Versah, Jackson, MI, USA): 2.0mm pilot, 2.8mm, and 3.8mm multi-fluted burs. Insertion torque as a function of implant type and drilling technique, revealed higher values for osseodensification relative to R-drilling, regardless of implant macrogeometry. A significantly higher bone-to-implant contact (BIC) for both osseodensification techniques (p<0.05) was observed compared to R-drilling. There was no statistical difference in BIC as a function of implant type (p=0.58), nor in bone-area-fraction occupancy (BAFO) as a function of drilling technique (p=0.22), but there were higher levels of BAFO for parallel than conic implants (p=0.001). Six weeks after surgery, new bone formation along with remodeling sites was observed for all groups. Bone chips in proximity with the implants were seldom observed in the R-drilling group, but commonly observed in the CW, and more frequently under the CCW osseodensification technique. In low-density bone, endosteal implants present higher insertion torque levels when placed in osseodensification drilling sites, with no osseointegration impairment compared to standard subtractive drilling methods.

OBJECTIVES: To evaluate the influence of implant-abutment interface (IAI) placement depth on bone remodeling around implants with two different types of tapered internal IAI: screwed-in (SI) and tapped-in (TI) connections in dogs. MATERIALS AND METHODS: Eight weeks post mandibular tooth extraction in six beagle dogs, two SI implants (OsseoSpeed , Astra Tech, DENTSPLY) and two TI implants (Integra-CP , Bicon LLC) were placed in one side of the mandible. The four experimental groups were as follows: (i) SI-placed equicrestally (SIC); (ii) TI-placed equicrestally (TIC); (iii) SI-placed 1.5 mm subcrestally (SIS); and (iv) TI-placed 1.5 mm subcrestally (TIS). Healing abutments were connected 12 weeks after implant placement. Sixteen weeks later, the dogs were sacrificed and histomorphometric analysis was performed. Histometrical outcomes were evaluated using a nonparametric Brunner-Langer model. RESULTS: Mean distance from the IAI to first bone-implant contact (IAI-fBIC) was 0.88 mm (median: 0.77; SD: 0.54) for SIC group, 1.23 mm (median: 1.22; SD: 0.66) for TIC group, 0.41 mm (median: 0.31; SD: 0.36) for SIS group, and 0.41 mm (median: 0.26; SD: 0.45) for TIS group. Subcrestal groups showed lower IAI-fBIC compared with equicrestal groups (P < 0.001). Connective tissue presented similar measurements regardless of the IAI placement depth and IAI type (P > 0.05), but the epithelium length and peri-implant soft tissue length in subcrestal groups were significant larger than that in the equicrestal groups (P < 0.001 and P = 0.004, respectively). CONCLUSION: Subcrestal implant placement with tapered internal IAI is beneficial for bone contact with the implant neck, and concurrently, it may not increase the soft tissue inflammation around IAI.

PURPOSE:: To investigate the bone regenerative effect of polymer and collagen incorporation to synthetic bone graft materials. MATERIALS AND METHODS:: The bone ingrowth of biphasic graft materials was tested in a rabbit calvaria defect model after chemical characterization: HA/TCP (25%/75%) with collagen, HA/TCP (25%/75%) without collagen, (HA/TCP)/PLGA (85%/15%) with collagen, (HA/TCP)/PLGA (65%/35%) with collagen and a commercially available (HA/TCP)/PLGA (50%/50%) was used as control. After 4 and 8 weeks, the retrieved samples were subjected to histomorphometrical analysis. RESULTS:: Histomorphometry presented no significant differences concerning the bone formation between the different groups at both 4 and 8 weeks. Evidently, the (HA/TCP)/PLGA (65%/35%) with collagen presented the least amount of soft tissue incorporation within the defect. The same group possessed higher amounts of bone graft material within the defect throughout the 8-week observation period, whereas the other groups seemed to decrease in volume from 4 to 8 weeks. CONCLUSION:: Increase of the PLGA percentage within the biphasic graft material seemed to maintain its volume and prevented soft tissue migration, which could be clinically beneficial.

This study assessed the osseointegrative effects of atmospheric pressure plasma (APP) surface treatment for implants in a canine model. Control surfaces were untreated textured titanium (Ti) and calcium phosphate (CaP). Experimental surfaces were their 80-second air-based APP-treated counterparts. Physicochemical characterization was performed to assess topography, surface energy, and chemical composition. One implant from each control and experimental group (four in total) was placed in one radius of each of the seven male beagles for three weeks, and one implant from each group was placed in the contralateral radius for six weeks. After sacrifice, bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO) were assessed. X-ray photoelectron spectroscopy showed decreased surface levels of carbon and increased Ti and oxygen, and calcium and oxygen, posttreatment for Ti and CaP surfaces, respectively. There was a significant (P < 0.001) increase in BIC for APP-treated textured Ti surfaces at six weeks but not at three weeks or for CaP surfaces. There were no significant (P = 0.57) differences for BAFO between treated and untreated surfaces for either material at either time point. This suggests that air-based APP surface treatment may improve osseointegration of textured Ti surfaces but not CaP surfaces. Studies optimizing APP parameters and applications are warranted.

Numerous studies have demonstrated that Schwann cells (SCs) play a role in nerve regeneration; however, their role in innervating a bioceramic scaffold for potential application in bone regeneration is still unknown. Here we report the cell growth and functional behavior of SCs on beta-tricalcium phosphate (beta-TCP) scaffolds arranged in 3D printed-lattice (P-beta-TCP) and randomly-porous, template-casted (N-beta-TCP) structures. Our results indicate that SCs proliferated well and expressed the phenotypic markers p75LNGFR and the S100-beta subunit of SCs as well as displayed growth morphology on both scaffolds, but SCs showed spindle-shaped morphology with a significant degree of SCs alignment on the P-beta-TCP scaffolds, seen to a lesser degree in the N-beta-TCP scaffold. The gene expressions of nerve growth factor (beta-ngf), neutrophin-3 (nt-3), platelet-derived growth factor (pdgf-bb), and vascular endothelial growth factor (vegf-a) were higher at day 7 than at day 14. While no significant differences in protein secretion were measured between these last two time points, the scaffolds promoted the protein secretion at day 3 compared to that on the cell culture plates. These results together imply that the beta-TCP scaffolds can support SC cell growth and that the 3D-printed scaffold appeared to significantly promote the alignment of SCs along the struts. Further studies are needed to investigate the early and late stage relationship between gene expression and protein secretion of SCs on the scaffolds with refined characteristics, thus better exploring the potential of SCs to support vascularization and innervation in synthetic bone grafts.

This study investigated whether the use of a dual-layer polytetrafluoroethylene (PTFE)/porcine-derived bioresorbable pericardium membrane enhances the osseointegration around implants compared to a single-layer porcine-derived bioresorbable pericardium membrane and a no-membrane control group. Endosseous implants were placed in the fresh extraction sockets of beagles. At 6 weeks, bone loss and apical soft tissue migration occurred in the control group, whereas bone successfully formed to the neck of the implant for the single-layer porcine-derived bioresorbable pericardium membrane group. The dual-layer PTFE/ porcine-derived bioresorbable pericardium membrane showed bone growth coronal to the neck of the implant. Bone-to-implant contact and buccal bone loss were respectively higher and lower relative to the single-layer but not statistically different.

In this study, the physicochemical characteristics of calcium phosphate based bioactive ceramics of different compositions and blends presenting similar micro/nanoporosity and micrometer scale surface texture were characterized and evaluated in an in vivo model. Prior to the animal experiment, the porosity, surface area, particle size distribution, phase quantification, and dissolution of the materials tested were evaluated. The bone regenerative properties of the materials were evaluated using a rabbit calvaria model. After 2, 4, and 8weeks, the animals were sacrificed and all samples were subjected to histologic observation and histomorphometric analysis. The material characterization showed that all materials tested presented variation in particle size, porosity and composition with different degrees of HA/TCP/lower stoichiometry phase ratios. Histologically, the calvarial defects presented temporal bone filling suggesting that all material groups were biocompatible and osteoconductive. Among the different materials tested, there were significant differences found in the amount of bone formation as a function of time. At 8weeks, the micro/nanoporous material presenting ~55%TCP:45%HA composition ratio presented higher amounts of new bone regeneration relative to other blends and a decrease in the amount of soft tissue infiltration.