Faculty Bibliography

BACKGROUND:Three-dimensionally-printed bioceramic scaffolds composed of β-tricalcium phosphate delivering the osteogenic agent dipyridamole can heal critically sized calvarial defects in skeletally mature translational models. However, this construct has yet to be applied to growing craniofacial models. In this study, the authors implanted three-dimensionally-printed bioceramic/dipyridamole scaffolds in a growing calvaria animal model and evaluated bone growth as a function of geometric scaffold design and dipyridamole concentration. Potential adverse effects on the growing suture were also evaluated. METHODS:Bilateral calvarial defects (10 mm) were created in 5-week-old (approximately 1.1 kg) New Zealand White rabbits (n = 16 analyzed). Three-dimensionally-printed bioceramic scaffolds were constructed in quadrant form composed of varying pore dimensions (220, 330, and 500 μm). Each scaffold was coated with collagen and soaked in varying concentrations of dipyridamole (100, 1000, and 10,000 μM). Controls consisted of empty defects. Animals were killed 8 weeks postoperatively. Calvariae were analyzed using micro-computed tomography, three-dimensional reconstruction, and nondecalcified histologic sectioning. RESULTS:Scaffold-induced bone growth was statistically greater than bone growth in empty defects (p = 0.02). Large scaffold pores, 500 μm, coated in 1000 μM dipyridamole yielded the most bone growth and lowest degree of scaffold presence within the defect. Histology showed vascularized woven and lamellar bone along with initial formation of vascular canals within the scaffold lattice. Micro-computed tomographic and histologic analysis revealed patent calvarial sutures without evidence of ectopic bone formation across all dipyridamole concentrations. CONCLUSION/CONCLUSIONS:The authors present an effective pediatric bone tissue-engineering scaffold design and dipyridamole concentration that is effective in augmentation of calvarial bone generation while preserving cranial suture patency.

AIM/OBJECTIVE:Die silicone materials are used to build chairside composite restorations. The purpose of this study was to compare the flowability, dimension accuracy, and tear strength of four elastomeric die materials. MATERIAL AND METHODS/METHODS:Materials were divided into four groups: Mach-2 (M2), Scan Die (SD), GrandioSO Inlay System (GIS), and Impregum-F (IM). Flowability analysis was carried out using the shark fin test (SFT). For dimension accuracy, impressions were taken from a premolar Class I preparation and an elastomeric model was cast. Composite resin restorations were built and positioned into the premolar for gap measurement. The mean gap length was divided into three levels: acceptable (A), not acceptable (NA), and misfit (M). For tear strength, strip specimens were made with a V-shaped notch (n = 6). The specimens were tested in a universal machine until tear. All data were analyzed statistically with a confidence interval of 95%. RESULTS:GIS showed the lowest flowability values, with no differences between IM, M2, and SD. For dimension accuracy, IM showed 100% 'A' gap values, followed by M2 (80%), SD (60%), and GIS (60%). For tear strength, IM showed the highest values, followed by M2, GIS, and SD. CONCLUSIONS:M2, SD, and IM had similar flowability, while GIS had the lowest. IM presented higher tear strength than M2, followed by GIS and SD. IM showed the highest degrees of acceptable gap filling, followed by M2.

This study investigates a comprehensive model of bone regeneration capacity of dypiridamole-loaded 3D-printed bioceramic (DIPY-3DPBC) scaffolds composed of 100% beta-tricalcium phosphate (β -TCP) in an immature rabbit model through the time of facial maturity. The efficacy of this construct was compared to autologous bone graft, the clinical standard of care in pediatric craniofacial reconstruction, with attention paid to volume of regenerated bone by 3D reconstruction, histologic and mechanical properties of regenerated bone, and long-term safety regarding potential craniofacial growth restriction. Additionally, long-term degradation of scaffold constructs was evaluated. At 24 weeks in vivo, DIPY-3DPBC scaffolds demonstrated volumetrically significant osteogenic regeneration of calvarial and alveolar defects comparable to autogenous bone graft with favorable biodegradation of the bioactive ceramic component in vivo. Characterization of regenerated bone reveals osteogenesis of organized, vascularized bone with histologic and mechanical characteristics comparable to native bone. Radiographic and histologic analyses were consistent with patent craniofacial sutures. Lastly, through application of 3D morphometric facial surface analysis, our results support that DIPY-3DPBC scaffolds do not cause premature closure of sutures and preserve normal craniofacial growth. Based on this novel evaluation model, this DIPY-3DPBC scaffold strategy is a promising candidate as a safe, efficacious pediatric bone tissue engineering strategy.

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.

BACKGROUND:Surgical fixation of implants into bone for the correction of bone deformities or defects is a traditional approach for skeletal stabilization. Important measures of efficacy of implants include implant stability and osseointegration-the direct interaction between living bone and an implant. Osseointegration depends on successful implant placement and subsequent bone remodeling. This study utilized osseodensification drilling (OD) in a low bone density model using trabecular metal (TM) implants. MATERIAL AND METHODS/METHODS:Three osteotomy sites, Regular, OD-CW (clockwise), and OD-CCW (counterclockwise), were prepared in each ilium of three female sheep. Drilling was performed at 1100rpm with saline irrigation. Trabecular metal (TM) (Zimmer, Parsippany, NJ, USA) implants measuring 3.7mm in diameter x 10mm length were placed into respective osteotomies. A three-week period post-surgery was given to allow for healing to take place after which all three sheep were euthanized and the ilia were collected. Samples were prepared, qualitatively and quantitatively analyzed using histology micrographs and image analysis software (ImageJ, NIH, Bethesda, MD). Bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO) were quantified to evaluate the osseointegration parameters. RESULTS:All implants exhibit successful bone formation in the peri-implant environment as well as within the open spaces of the trabecular network. Osseointegration within the TM (quantified by %BIC) as a function of drilling technique was more pronounced in OD samples(p>0.05). The %BAFO however shows a significant difference (p=0.036) between the CCW and R samples. Greater bone volume and frequency of bone chips are observed in OD samples. CONCLUSION/CONCLUSIONS:The utilization of OD as a design for improved fixation of hardware was supported by increased levels of stability, both primary and secondary. Histological data with OD provided notably different results from those of the regular drilling method.

OBJECTIVES/OBJECTIVE:To evaluate the three-dimensional fit of abutments fabricated by the industry to those either milled or cast by a commercial laboratory and to correlate the implant-abutment connection fit with stress at fatigue failure of prostheses. Probability of survival (reliability) and fractography to characterize failure modes were also performed for cemented and screw-retained prostheses. METHODS:One-hundred and twenty-six maxillary central incisor crowns were milled to restore implants and divided in 3 cemented and 3 screwed-retained groups (n = 21/each), as follows: [Digital-Sc]: milled one-piece monolithic abutment/crown; [TiB-Sc]: milled crowns cemented onto Ti-base abutments; [UCLA]: screw-retained crown using UCLA abutments; [Digital-Ce]: milled two-piece assembly comprised by screwed monolithic abutment and a cemented crown; [TiB-Ce]: milled coping cemented onto Ti-base abutments to receive a cemented crown; [UCLA-Ce]: UCLA abutments that received an overcast coping and a cemented crown. Implant-abutment volume misfit was assessed by micro-computed tomography using the silicone replica technique. Implant/crown systems were subjected to step-stress accelerated life testing (SSALT) in water. The use-level probability Weibull curves and reliability for a mission of 50,000 cycles at calculated stress at failure of 2,300, 3300 and 4300 MPa were plotted. Fractographic analysis was performed with scanning electron microscopy. Internal misfit was analyzed through one-way ANOVA following post-hoc comparisons by Tukey test (p < 0.05). Correlation between misfit volume and the stress at fatigue failure was assessed by Pearson test. RESULTS:). The mean β values were: 1.68, 1.39, 1.48, 2.41, 2.27 and 0.71 for Digital-Sc, TiB-Sc, UCLA, Digital-Ce, TiB-Ce and UCLA-Ce, respectively, indicating that fatigue was an accelerating factor for failure of all groups. Higher stress at failure decreased the reliability of all groups, more significantly for screw compared to cement-retained groups, especially for Digital-Sc that demonstrated the lowest reliability. The failure mode was restricted to abutment screw fracture. A negative correlation was observed between misfit values and stress at failure (r = -0.302, p = 0.01). CONCLUSIONS:Abutments milled by a commercial lab presented higher misfit compared to those provided by the industry and a moderate correlation was observed between higher misfit and lower stress at failure during fatigue. Probability of survival decreased at higher stress, especially for screw compared to cement-retained groups, and failures were confined to abutment screws.

This paper is aimed to present a biomaterials perspective in implant therapy that fosters improved bone response and long-term biomechanical competence from surgical instrumentation to final prosthetic rehabilitation. Strategies to develop implant surface texturing will be presented and their role as an ad hoc treatment discussed in light of the interplay between surgical instrumentation and implant macrogeometric configuration. Evidence from human retrieved implants in service for several years and from in vivo studies will be used to show how the interplay between surgical instrumentation and implant macrogeometry design affect osseointegration healing pathways, and bone morphologic and long-term mechanical properties. Also, the planning of implant-supported prosthetic rehabilitations targeted at long-term performance will be appraised from a standpoint where personal preferences (eg, cementing or screwing a prosthesis) can very often fail to deliver the best patient care. Lastly, the acknowledgement that every rehabilitation will have its strength degraded over time once in function will be highlighted, since the potential occurrence of even minor failures is rarely presented to patients prior to treatment.

AIM/OBJECTIVE:To evaluate the influence of brain-derived neurotrophic factor (BDNF) in combination with collagen sponges on periodontal tissue regeneration. METHODS:Unilateral, "box-type" (4x5mm), one-wall intrabony defects were surgically created at posterior mandibular teeth in 14 Beagle dogs. Animals received all experimental groups and the defects were randomly treated as follow: Emdogain® (positive control) [EMD]; HeliPlug®+BDNF [H/B]; RCP®+BDNF [R/B]; negative control [Control]; TeruPlug®+BDNF [Tp/B] and TeruPlug®+BDNF2 [Ts/B]. Periodontal wound healing was observed every 2 weeks by computed tomography. The animals were euthanized at 8 weeks post-surgery for microcomputed tomography and histomorphometric evaluation. RESULTS:All groups presented ∼1mm apical epithelial attachment relative to cementoenamel junction. Although linear measurements did not demonstrate significant differences between groups for cementum and periodontal ligament regeneration, semi-quantitative analysis depicted higher percentage of samples with mineralized cementum and functional PDL for Ts/B, R/B and H/B groups relative to EMD and Control (p<0.046). Irrespective of quantification method (2D or 3D), Ts/B, Control, Tp/B and H/B groups presented the highest mean percentage of new bone (not significantly different), followed by R/B and EMD groups. CONCLUSION/CONCLUSIONS:While no significant differences were detected in quantitative analyses, Ts/B combination results in significantly more samples with full periodontal tissue regeneration relative to control groups.

OBJECTIVE:To compare hard-tissue healing after 3 exodontia approaches. MATERIALS AND METHODS/METHODS:Premolars of dogs were extracted: (1) flapless, (2) flap, and (3) flap + socket coverage with polytetrafluoroethylene (dPTFE) nonresorbable membrane (flap + dPTFE). Animals were euthanized at 1 and 4 weeks. Amount of bone formation within socket and socket total area were measured. RESULTS:Amount of bone formation revealed significant difference between 1 and 4 weeks; however, there was no differences among groups. Socket total area decreased after 4 weeks, and the flap + dPTFE group showed significantly higher socket total area. As a function of time and group, flap + dPTFE 4 weeks presented similar socket total area values relative to flap + dPTFE at 1 week, and significantly higher socket total area than flapless and flap. The histological sections revealed almost no bone formation within socket after 1 week, which increased for all groups at 4 weeks. CONCLUSION/CONCLUSIONS:Socket coverage with polytetrafluoroethylene (dPTFE) membrane showed to effectively preserve bone architecture. Bone formation within sockets was not influenced by tooth extraction technique.