Faculty Bibliography

PURPOSE:To evaluate the effect of two surface modifications on early osseointegration parameters of conical implants in a translational pre-clinical model. MATERIALS AND METHODS:), surface energy and contact angle. Subsequently, implants were installed in the ilium crest of nine female sheep (weighing ~65 kg). Torque out, histological and histomorphometric analyses were conducted after 3 and 6 weeks in-vivo. The percentage of bone to implant contact (%BIC) and bone area fraction occupancy within implant threads (%BAFO) were quantified, and the results were analyzed using a general linear mixed model analysis as function of surface treatment and time in-vivo. RESULTS:. Torque-out testing yielded significantly higher values for IMP Sur + AE in comparison to the IMP Sur at 3- (62.78 ± 15 and 33.49 ± 15 N.cm, respectively) and 6-weeks (60.74 ± 15 and 39.80 ± 15 N.cm, respectively). Histological analyses depicted similar osseointegration features for both surfaces, where an intramembranous-type healing pattern was observed. At histomorphometric analyses, IMP Sur + AE implants yielded higher values of BIC in comparison to IMP Sur at 3- (40.48 ± 38 and 27.98 ± 38%, respectively) and 6-weeks (45.86 ± 38 and 34.46 ± 38%, respectively). Both groups exhibited a significant increase in %BAFO from 3 (~35%) to 6 weeks (~44%), with no significant differences between surface treatments. CONCLUSION:Supplemental acid-etching and its interplay with implant thread design, positively influenced the BIC and torque-out resistance at early stages of osseointegration.

Robin sequence (RS) is diagnosed in infants born with micrognathia, glossoptosis and varying degrees of upper airway obstruction (UAO). Due to the variable levels of hypoxia, severe breathing and feeding problems can occur. Treatment is determined by clinical severity, ranging from conservative interventions for mild cases to surgical interventions for severe cases. Mandibular distraction osteogenesis (MDO) is a surgical technique that gradually lengthens the mandible after an osteotomy by using an internal or external distraction device, directly correcting the micrognathia. This review will focus on advantages and disadvantages of mandibular distraction in infants with RS.

Oral squamous cell carcinoma (SCC) pain is more prevalent and severe than pain generated by any other form of cancer. We previously showed that protease-activated receptor-2 (PAR₂) contributes to oral SCC pain. Cathepsin S is a lysosomal cysteine protease released during injury and disease that can activate PAR₂. We report here a role for cathepsin S in PAR₂-dependent cancer pain. We report that cathepsin S was more active in human oral SCC than matched normal tissue, and in an orthotopic xenograft tongue cancer model than normal tongue. The multiplex immunolocalization of cathepsin S in human oral cancers suggests that carcinoma and macrophages generate cathepsin S in the oral cancer microenvironment. After cheek or paw injection, cathepsin S evoked nociception in wild-type mice but not in mice lacking PAR₂ in Na_v1.8-positive neurons (Par₂Na_v1.8), nor in mice treated with LY3000328 or an endogenous cathepsin S inhibitor (cystatin C). The human oral SCC cell line (HSC-3) with homozygous deletion of the gene for cathepsin S (CTSS) with CRISPR/Cas9 provoked significantly less mechanical allodynia and thermal hyperalgesia, as did those treated with LY3000328, compared to the control cancer mice. Our results indicate that cathepsin S is activated in oral SCC, and that cathepsin S contributes to cancer pain through PAR₂ on neurons.

OBJECTIVE:Evaluate the effect of aging using two different methods on the three-dimensional fit of zirconia abutments at the implant-abutment connection and estimate the probability of survival of anterior crowns supported by straight and 17-degree angled abutments. MATERIALS AND METHODS/METHODS:Two different zirconia abutment designs, straight and 17-degree angled abutments (n = 63/group), were evaluated in the current study. The abutments were randomly allocated into three experimental groups according to laboratory aging condition (134°C, 2.2 bar, 20 h): (i) control, (ii) autoclave aging, and (iii) hydrothermal reactor aging. Crystalline content was determined by X-Ray diffraction (XRD) and Raman spectroscopy, and microstructure was analyzed using field-emission gun scanning electron microscope (FEG-SEM). Implant-abutment volume misfit was determined in the straight abutments by micro-computed tomography using the silicone replica technique. For fatigue testing, abutments were torqued to the implants and connected to standardized maxillary incisor zirconia crowns. The assemblies were subjected to step-stress accelerated life testing (SSALT) in water until fracture or suspension. The use level probability Weibull curves and probability of survival for a mission of 50,000 cycles at 50, 100, 150 and 200 N were calculated and plotted. Fractured samples were analyzed using a stereomicroscope and scanning electron microscope. RESULTS:). The beta (β) values indicated that failures were predominantly controlled by material strength rather than fatigue damage accumulation for all groups, except for straight control abutments. Irrespective of aging, the probability of survival of straight and angled zirconia abutments was up to 95% (95-100%) at 50 and 100 N. A 50N-increase in the load resulted in wider range of survival estimate, with straight autoclave abutments percentage significantly lower probability of survival (77%) than angled hydrothermal reactor abutments (99%). At 200N, angled hydrothermal reactor (97%) or autoclave (82%) aged abutments demonstrated the highest probability of survival, angled control (71%) and straight hydrothermal reactor (69%) abutments intermediate values, and straight autoclave (23%) and control (7%) abutments the lowest estimate. The failure mode predominantly involved abutment and/or abutment screw fracture for both straight and angled abutments. CONCLUSIONS:Hydrothermal aging significantly influenced volume misfit, as well as the probability of survival of zirconia abutments at higher loads for both angled and straight abutments.

Bone defects are often linked to congenital disorders, high impact traumas, tumors or oncological resections. Potential treatment options include autografts, allografts, or synthetic grafts, such as bioactive ceramic-based materials which have been successfully utilized in an effort to regenerate bone. β-tricalcium phosphate (β-TCP), is a commonly utilized bioactive ceramic for regenerative purposes with favorable osteoconductive properties. Alternatively, Synthetic Bone Mineral (SBM) has been previously utilized in in vivo experiments as a supplement for bone loss treatment. As a potential alternative to β-TCP, it is also a bioactive ceramic, which consists of a carbonate hydroxyapatite with ionic substitutions such as F^−, Zn²⁺ and Mg²⁺. The objective of this work was to characterize the physiochemical properties of the colloidal gel obtained from a formulation of SBM and compare the properties directly to β-TCP. Mechanical properties were evaluated for both materials in bulk, using Biaxial Flexural Strength tests. Scanning electron microscopy and micro-computed tomography were utilized to explore the structure of the bulk material and the three dimensionally (3D) printed scaffolds. Inductive coupled plasma (ICP), X-ray diffraction (XRD), and Fourier transform infrared spectrometry (FT-IR), were utilized to determine the calcium-phosphorous ratio (Ca:P), quantitative analysis of crystalline phases, and functional groups, respectively. Thermogravimetric analysis (TGA) was used to quantify the weight percent of water, organic components, carbonate and mineral in the SBM colloidal gel. Flexural strength of SBM discs sintered at 700°C were statistically analogous to β-TCP sintered at 900°C. The Ca:P ratio of the sintered SBM was found to be 1.47 ± 0.04, statistically different from β-TCP sintered at higher temperatures. The carbonate content of the SBM was determined to be ~2.8% ± 0.9. The novel SBM colloidal gel has hence been characterized chemically and physically for its potential use in 3D printing grafts to repair critical sized bone defects.

BACKGROUND:Implant-based breast reconstruction accounts for the vast majority of breast reconstruction procedures and is commonly performed with human acellular dermal matrix. There is no consensus as to the optimal human acellular dermal matrix preparation, and high-quality evidence concerning comparative effectiveness is lacking. This study is the first prospective, multicenter, randomized controlled clinical trial to compare human acellular dermal matrix-related complications of the two most commonly used human acellular dermal matrices in implant-based breast reconstruction. The authors hypothesize that there will be no difference in infection, seroma, and reconstructive failure between FlexHD Pliable and AlloDerm RTU. METHODS:The authors conducted a Level 1 prospective, randomized, controlled, multicenter clinical trial to assess complications associated with the use of two human acellular dermal matrices in immediate postmastectomy implant-based breast reconstruction across seven clinical sites. Group A patients received FlexHD Pliable (113 patients with 187 breast reconstructions), and group B patients received AlloDerm RTU (117 patients with 197 breast reconstructions). RESULTS:There was no significant difference with respect to patient demographics, indications, comorbidities, and reconstruction approach between groups. Mean follow-up time was 10.7 ± 3.2 months. There was no statistical difference in the overall matrix-related complications between groups A and B (4.3 percent versus 7.1 percent, p = 0.233). Obesity (OR, 1.14; 95 percent CI, 1.05 to 1.24; p = 0.001) and prepectoral placement of matrix (OR, 4.53; 95 percent CI, 1.82 to 11.3; p = 0.001) were independently associated with greater risks of overall matrix-related complications. CONCLUSION/CONCLUSIONS:This work supports the use of human acellular dermal matrices in implant-based breast reconstruction and demonstrates no significant difference in matrix-related complication rates between FlexHD Pliable and AlloDerm RTU.

Introduction: Diabetic neuropathy (DN) is a debilitating disorder characterized by sensory loss and pain. Although common, DN has no effective treatment. A notable pathologic finding of DN is loss of sensory apparatus in the skin, causing sensory abnormalities and pain. Given that diabetic patients frequently develop skin complications, we hypothesize that skin microenvironment is important for the pathogenesis of DN.
Method(s): Our investigation focused on a skin molecule epidermal sirtuin 1 (SIRT1), which is an NAD + -dependent deacetylase known to regulate metabolism and senescence. To address the role of epidermal SIRT1 in neuroprotection against DN, we created a tamoxifeninducible epidermal SIRT1 knockout (KO) and a doxycycline-inducible epidermal SIRT1 overexpression (OE) mouse model. The KO and control mice were placed on high-fat diets (HFDs), and were subsequently assessed by behavioral, morphologic and transcriptome analyses. SIRT1 overexpression was induced in mice after three months of HFDs.
Result(s): The DN phenotype was greatly exacerbated by depletion of epidermal SIRT1, as mice developed extreme mechanical allodynia after HFD. There was also evidence of large-fiber neuropathy, including loss of Meissner corpuscles, tail sensory nerve conduction defects and degeneration of large-diameter axons, while small nerve fibers and the corresponding nociception were largely intact. The phenotype could not be rescued by treatment with the NAD+ precursor nicotinamide riboside. In comparison, induction of epidermal SIRT1 overexpression alleviated the diabetic mechanical allodynia in mice. One potential mechanism of achieving epidermal SIRT1-mediated neuroprotection is increasing the expression of epidermal brainderived neurotrophic factor (BDNF), which could preserve the morphologic and functional integrity of Meissner corpuscles.
Conclusion(s): Our data suggest an important role of epidermal SIRT1 in maintaining skin sensory apparatus and preventing mechanical allodynia in the setting of diabetes. The findings also highlight epidermal SIRT1 as a promising therapeutic target for DN due to easy accessibility of SIRT1 in skin keratinocytes

PURPOSE/OBJECTIVE:The purpose of this study was to measure the association between the magnitude of advancement and dental and skeletal relapse in patients with cleft lip and palate (CLP). METHODS:A single-institution retrospective cohort study of skeletally matured patients with CLP who underwent isolated Le Fort I advancement surgery between 2013 and 2019 was studied. Patients were included if they had lateral cephalograms or cone-beam computed tomography (CBCT) at preoperative (T1), immediately postoperative (T2), and 1-year follow-up (T3). Lateral cephalometric landmarks were digitized and measured. The sample was divided on the basis of the magnitude of skeletal advancement: minor (<5 mm), moderate (≥5 but <10 mm), and major (≥10 mm) advancement groups. The mean advancement and relapse were compared between groups using 1-way ANOVA. Correlation between the amount of surgical advancement and relapse was evaluated. RESULTS:Forty-nine patients with nonsyndromic CLP with hypoplastic maxilla met inclusion criteria and the sample consisted of 36 males and 13 females with the mean age of 19.5 years. In the minor, moderate, and major advancement groups, the mean advancement at point A was +4.1 ± 0.4, + 7.5 ± 1.4, and +11.3 ± 1.3 mm, respectively. At 1-year follow-up, the mean relapse at point A was -1.3 ± 1.2, -1.1 ± 1.2, and -1.7 ± 1.5 mm, respectively. There was no significant difference in the relapse amount between all surgical groups. No correlation between the magnitude of advancement and relapse was found. CONCLUSIONS:This study demonstrated no statistically significant difference in skeletal stability between a minor (<5 mm), moderate (≥5 but <10 mm), and major (≥10 mm) Le Fort I advancement groups in patients with clefts. Regardless of the degree of advancement, mild skeletal relapse was observed in all 3 groups.