Faculty Bibliography

Hearing loss affects approximately 70 % of individuals with osteogenesis imperfecta (OI), a genetic connective tissue disorder characterized by bone fragility and deformities. No effective treatments exist for OI hearing loss, and its etiology is unknown limiting the development of new targeted therapies. This work investigates the impact of OI type I collagen mutations on the ossicle bone properties in the homozygous oim mouse model of severe OI, which is known to exhibit hearing loss. The morphology and porosity of the ossicles of 14-week-old oim and wild-type mice were analyzed using high-resolution synchrotron radiation microtomography. Additionally, the collagen fibers structure, bone tissue composition and mechanical properties were evaluated through second harmonic generation microscopy, Raman spectroscopy, and nanoindentation. The results demonstrated that oim ossicles are small, highly porous with an elevated lacunar number density, a flat stapes footplate and a small malleal processus brevis. One-in-two oim ossicles had incudomalleal joint abnormalities, exhibiting either a localized fracture in the incus head or a joint space widening. No differences were observed in collagen fibers structure, bone tissue composition and mechanical properties. These findings suggest that bone fractures observed in the oim incus may contribute to their reported hearing loss. However, the underlying mechanism for these fracture development remains to be investigated, as they do not appear to result from changes in bone tissue properties (collagen fibers organization, tissue composition or mechanical properties). Instead, they may be associated with joint space widening, and possibly altered ossicle chain kinematics.

BACKGROUND:Implant's primary stability is determined by the intimate and immediate contact between the implant and osteotomy wall, whereas secondary stability is primarily influenced by healing chambers that facilitate the bone formation and remodeling processes following placement. Therefore, modifications to macro-geometric parameters are essential to elicit the desired in vivo response and to ensure successful osseointegration. Three-dimensional (3D) stabilization thread forms comprise both curved and linear geometric surfaces across the thread's crest maximizing retention forces while constraining lateral movement under load relative to conventional buttress-threaded implants. METHODS:This study utilized Ti-6Al-4V ELI implants with (i) a buttress thread design [Tapered Pro, BioHorizons®, Birmingham, AL, USA] (TP - control) compared to (ii) a novel, patented, 3D stabilization trimmed-thread design (TP 3DS - experimental). Implants were placed in the mandible of sheep (N = 14 sheep, 6 implants per group per sheep) and allowed to heal for 3- and 12-weeks (N = 7 sheep per time point). During implant placement (T = 0 weeks), the maximum insertion torque value (ITV) and implant stability quotient (ISQ) were measured by torque-in testing and resonance frequency analysis, respectively. After the healing periods, subjects were euthanized, and samples harvested en bloc for biomechanical evaluation via lateral loading tests in addition to histomorphometric and nanoindentation analysis. RESULTS:ITV values were significantly lower in the TP 3DS group compared to TP (p < 0.001). Both groups presented ISQ values ≥ 70, indicating high primary stability. Relative to the TP group, TP 3DS exhibited a significant (∼1.85-fold) increase in lateral load at 3 weeks (p = 0.029) and comparable load values at 12 weeks (p > 0.05). No quantitative differences in percentage of bone-to-implant contact (BIC) and bone-area-fraction-occupancy (BAFO) were observed at either time points between the two thread designs (p > 0.05). Similarly, no differences in bone's mechanical properties (Young's modulus (E) and Hardness (H)) between TP and TP 3DS were observed at 3- and 12- weeks (p > 0.05). Qualitatively, scattered microcracks were apparent at the outer threads of the implant, particularly within the TP group, whereas small bone chips were interspersed between threads of the 3DS implant serving as additional nucleation sites for bone formation. CONCLUSION/CONCLUSIONS:The TP 3DS design reduced insertion torque, improved lateral loading competence, and resulted in a healing pattern, that are beneficial during early stages of osseointegration compared to TP implants.

This preclinical, in vivo study aimed to histologically and histomorphometrically evaluate the effect of implant design features on bone healing during the early stages of osseointegration. Three different implant macrogeometries and surface treatments were evaluated: (1) trapezoidal threads with decompressing vertical chambers and blasted acid-etched surface (Maestro/Blasted+AE); (2) large thread pitch implant with deep and wide threads, with TiUnite surface (RS/TiUnite); and (3) progressive buttress threads with SLActive surface (BL/SLActive). Implant surfaces were characterized by scanning electron microscopy, profilometry, and energy-dispersive X-ray spectroscopy. Implants were placed in the iliac bone of 12 female sheep (~65 kg and 2 years old). Following healing times of 3- and 6- weeks, samples were harvested and subjected to qualitative and quantitative histological/histomorphometric evaluations. Percentages of bone-to-implant contact (%BIC) along the implant's perimeter and bone area fraction occupancy (%BAFO) within implant threads were measured, and results were analyzed using a linear mixed model analysis. All implants, irrespective of differences in macrogeometry and surface treatment, at both healing times demonstrated successful osseointegration. Evaluations of %BIC yielded no statistically significant differences among groups at 3 and 6 weeks (p > 0.052). While no significant differences were detected among groups for %BAFO at 3 weeks (p > 0.249), Maestro/Blasted+AE yielded significantly higher degrees of bone formation within implant threads relative to RS/TiUnite (p = 0.043) and BL/SLActive group (p = 0.032) at the 6-week time point. Qualitative histological analyses depicted different osseointegration features for the different implants. While Maestro/Blasted+AE portrayed evidence of an intramembranous-like osseointegration pathway in the healing chambers and interfacial remodeling at thread tips, BL/SLActive and RS/TiUnite groups predominantly presented an interfacial bone remodeling healing pathway. Implant design features influenced the osseointegration pathway, where implants with decompressing vertical chambers enhanced bone formation between implant threads.

OBJECTIVE:To synthesize bilayer zirconia systems based on commercial or recycled 3Y-TZP obtained from non-milled remnants and to compare their optical and mechanical properties before and after aging. METHODS:Bilayer zirconia samples were fabricated using either recycled 3Y-TZP (3Y-R/4Y and 3Y-R/5Y) or commercial powders (3Y/4Y and 3Y/5Y). Microstructure and phase composition were analyzed using ScanningElectronMicroscopy (SEM) and X-Ray Diffraction (XRD). Optical and mechanical properties were assessed via reflectance and biaxial flexural strength tests (BFS), followed by fractographic analysis. Optical properties and BFS data were analyzed using two-way ANOVA and Tukey test, and Weibull statistics, respectively. RESULTS:Recycled powder exhibited particle sizes < 2.07μm. SEM micrographs depicted dense surfaces with largest grains in the 5Y, followed by recycled-3Y, 4Y, and commercial-3Y. XRD analysis revealed tetragonal peaks in commercial and recycled 3Y-TZPs, and tetragonal and cubic phases in the 4Y and 5Y surfaces. Aging induced significant phase transformation in 4Y (∼40 %), commercial- (58 %) and recycled-3Y (53 %), with no effect in 5Y surfaces. Commercial bilayers exhibited higher translucency and strength (∼1130 MPa) compared to recycled bilayers (∼935 MPa), with no significant differences within commercial, nor within recycled groups. Aging decreased contrast ratio for recycled groups and increased the strength of all groups. While all groups presented high reliability up to 500MPa, commercial bilayers outperformed recycled systems at 800-MPa. SIGNIFICANCE/CONCLUSIONS:The synthesis of bilayered systems using recycled-3Y was successful, resulting in high reliability in missions up to 500MPa. Bilayers based on commercial powder demonstrated superior translucency, strength, and reliability at 800MPa compared to their recycled counterparts.

OBJECTIVES/OBJECTIVE:To characterize two experimental zirconia bilayer materials compared to their monolithic controls, before and after hydrothermal aging. METHODS:Commercial zirconia powders were utilized to fabricate two bilayer materials: 3Y-TZP+ 5Y-PSZ (3Y+5Y/BI) and 4Y-PSZ+ 5Y-PSZ (4Y+5Y/BI), alongside control groups 3Y-TZP (3Y/C), 4Y-PSZ (4Y/C), and 5Y-PSZ (5Y/C). Compacted specimens were sintered (1550 °C- 2 h, 3 °C/min), and half of them underwent hydrothermal aging (134 °C-20h, 2.2 bar). Characterizations were performed through scanning-electron microscopy (SEM), X-ray diffraction (XRD), Raman spectroscopy, reflectance tests and biaxial flexural strength test (ISO:6872). Weibull statistics were applied to determine the characteristic strength and Weibull modulus. Grain size and optical properties were analyzed using two-way ANOVA followed by the Tukey test. RESULTS:Degradation regions and monoclinic phase were observed at aged 3Y-TZP and 4Y-PSZ surfaces. Significant differences were observed in the evaluation of optical properties between the bilayer and control groups. The bilayer materials presented intermediate characteristic strength values compared to their controls and aging significantly increased the strength of some groups. SIGNIFICANCE/CONCLUSIONS:Experimental bilayer materials presented lower mechanical properties than monolithic controls, 3Y/C and 4Y/C. Hydrothermal aging increased the characteristic strength of bilayered and monolithic controls, except for 5Y-PSZ. Both experimental bilayer systems, as well as monolithic controls, met the ISO 6872:2015 requirements for single-unit crowns (100 MPa), 3-unit fixed dental prostheses (FDPs) up to premolars (300 MPa), and 3-unit FDPs involving molars (500 MPa). However, for FDPs with four or more units, only monolithic 3Y-TZP and 4Y-PSZ, and bilayered 3Y+5Y met the required minimum flexural strength (≥800 MPa).

BACKGROUND:The preservation of the alveolar ridge following tooth extraction is crucial to prevent atrophy and maintain structural integrity, facilitating future dental rehabilitations. This study compared the use of two different polymeric, resorbable membranes: polylactic acid (PLA), and 5% polylactic acid + 95% polycaprolactone (PLA/PCL), relative to unassisted socket healing (negative control). MATERIAL AND METHODS/METHODS:A preclinical model involving healthy, skeletally mature beagles (n=7) were used in this study. Surface topography and thermal degradation of the membranes were assessed, followed by in vivo evaluation of socket preservation in extracted maxillary premolars. Histomorphometric analysis was employed to measure bone formation and total socket area. Data was analyzed through linear mixed models with fixed factor of treatment following a post-hoc comparison by the Tukey test. Ranked data of residual membrane presence and inflammatory infiltrate were analyzed through Kruskal-Wallis non-parametric test. All analyses were conducted with statistical significance set at p-value ≤ 0.05. RESULTS:Surface topography depicted a distinctive fibrous network structure for PLA membrane relative to PLA/PCL which exhibited a more porous architecture. Thermal degradation behavior/profile, observed through TGA and DSC, for both membranes was similar. Histomorphometric analysis of bone formation within the induced socket yielded 36.1 ±7.7%, 35.6 ±7.2% and 32.8 ±7.7% for control, PLA and PLA/PCL groups, respectively, with no statistically significant differences between groups (p = 0.796). Analysis of total socket area (mean ± 95% confidence intervals) yielded significantly higher values for experimental groups, PLA (8.95 ± 1.7 mm2) and PLA/PCL (8.8 ± 1.76 mm2), relative to control (6.7 ± 1.8 mm2) (p = 0.041). Residual membrane, along with mild inflammatory infiltrate was observed after the healing period irrespective of membrane type utilized. CONCLUSIONS:Guided bone regeneration (GBR) with PLA and PLA/PCL membranes did not yield higher bone formation within the socket relative to the control group. However, an improvement in the preservation of the socket's architecture was observed.

In recognizing the critical role of vitamin D in bone metabolism and osseointegration, research aims to identify whether preoperative vitamin D deficiency serves as a risk factor for early implant failure. By analyzing patient outcomes and their serum vitamin D levels, studies seek to establish evidence-based recommendations for vitamin D assessment and management in the preoperative period, with the ultimate goal of enhancing implant success rates and patient outcomes in dental implantology. Given these insights, it is important for clinicians to incorporate the preoperative evaluation of vitamin D serum levels into their standard protocol for patients undergoing dental implant procedures. The objective of this study is to review and investigate the correlation between early dental implant failure (EDIF) and reduced serum levels of vitamin D, and to evaluate the potential benefits of preoperative screening and supplementation of vitamin D in patients undergoing dental implant surgery. A literature review was performed using a selected database-PubMed, Google Scholar, Cochrane, and SCOPUS-to assess the effect of vitamin D3 level on EDIF and biological factors (i.e., peri-implant bone level). Studies were limited to peer-reviewed, indexed journals. Subsequently, a hypothesis was proposed that vitamin D3 supplementation would mitigate the negative effect of vitamin D3 deficiency. The potential benefit of vitamin D3 supplementation-systemic and topical-was assessed in terms of bone-to-implant contact (BIC) and peri-implant bone level. The deleterious effects of low vitamin D serum levels on osseointegration of dental implants and immune system modulation are increasingly accepted. Evidence has displayed that deficiency of this vitamin can result in impaired peri-implant bone formation. Vitamin D deficiency resulted in nearly a fourfold increase in overall EDIF incidence. Presurgical supplementation of vitamin D3 demonstrated increased levels of implant osseointegration, increased bone-implant contact, enhanced bone level maintenance, and decreased EDIF even in at-risk demographics (i.e., diabetic subjects). The findings of this study reinforce the role of vitamin D in dental implant osseointegration. Our study, particularly, emphasizes the necessity of vitamin D supplementation for individuals with sub-physiologic vitamin D serum levels (≤ 30 ng/mL) and those within specific risk categories: smokers, diabetics, obese individuals, and those with compromised immune systems. Adopting a proactive management plan, including screening and supplementation in these patients, may substantially enhance the clinical outcomes in dental implant surgery.

Preclinical testing of tissue engineering modalities are commonly performed in a healthy wound bed. These conditions do not represent clinically relevant compromised oral wound environments due to radiation treatments seen clinically. This study aimed to characterize the bone regeneration outcomes in critical-sized mandibular defects using particulate grafting in an irradiated preclinical model of compromised wound healing. Sixteen New Zealand white rabbits were divided into two groups (n = 8/group), namely (i) irradiated (experimental) and (ii) non-irradiated (control). The rabbits in the experimental group received a total of 36 Gy radiation, followed by surgical intervention to create critical-sized (10 mm), full-thickness mandibular defects. The control group was subjected to the same surgical intervention. All defects were filled with bovine bone grafting material (Bio-Oss, Geistlich, Princeton, NJ, USA) and allowed to heal for 8 weeks. At the study endpoint, rabbits were euthanized, and their mandibles were harvested for micro-computed tomographic, histological, and histomorphometric processing and analysis. Qualitative histological analysis revealed increased levels of bone formation and bridging in the control group relative to the experimental group. This was accompanied by increased levels of soft tissue presence in the experimental group. Volumetric reconstruction showed a significantly higher degree of bone in the control group (27.59% ± 2.71), relative to the experimental group (22.02% ± 2.71) (p = 0.001). The irradiated rabbit model exhibited decreased bone regeneration capacity relative to the healthy subjects, highlighting its suitability as a robust compromised wound healing environment for further preclinical testing involving growth factors or customized, high-fidelity 3D printed tissue engineering scaffolds.

Sodium-glucose transporter-2 inhibitor (SGLT2i) drugs are widely used for lowering blood glucose levels independent of insulin. Beyond this, these drugs induce various metabolic changes, including weight loss and impaired bone integrity. There is a significant gap in understanding SGLT2i-induced skeletal changes, as SGLT2 is not expressed in osteoblasts or osteocytes, which use glucose to remodel the bone matrix. We studied the impact of 1, 3, or 6 months of canagliflozin (CANA), an SGLT2i treatment, on the skeleton of 6-month-old genetically heterogeneous UM-HET3 mice. Significant metabolic adaptations to CANA were evident as early as 1.5 months post-treatment, specifically in male mice. CANA-treated male mice exhibited notable reductions in body weight and decreased proinflammatory and bone remodeling markers associated with reduced cortical bone remodeling indices. Bone tissue metabolome indicated enrichment in metabolites related to amino acid transport and tryptophan catabolism in CANA-treated male mice. In contrast, CANA-treated female mice showed increases in nucleic acid metabolism. An integrOmics approach of source-matched bone tissue metabolome and bone marrow RNAseq indicated a positive correlation between the two omics data sets in male mice. Three clusters of transcripts and metabolites involved in energy metabolism, oxidative stress response, and cellular proliferation and differentiation were reduced in CANA-treated male mice. In conclusion, CANA affects bone metabolism mainly via the 'glucose restriction state' it induces and impacts bone cell proliferation and differentiation. These findings underline the effects of SGLT2i on bone health and highlight the need to consider sex-specific responses when developing clinical treatments that alter substrate availability.

BACKGROUND/UNASSIGNED:Polylactic acid (PLA) has been extensively used in tissue engineering. However, poor mechanical properties and low cell affinity have limited its pertinence in load bearing bone tissue regeneration (BTR) devices. OBJECTIVE/UNASSIGNED:Augmenting PLA with β-Tricalcium Phosphate (β-TCP), a calcium phosphate-based ceramic, could potentially improve its mechanical properties and enhance its osteogenic potential. METHODS/UNASSIGNED:Gels of PLA and β-TCP were prepared of different % w/w ratios through polymer dissolution in acetone, after which polymer-ceramic membranes were synthesized using the gel casting workflow and subjected to characterization. RESULTS/UNASSIGNED:Gel-cast polymer-ceramic constructs were associated with significantly higher osteogenic capacity and calcium deposition in differentiated osteoblasts compared to pure polymer counterparts. Immunocytochemistry revealed cell spreading over the gel-cast membrane surfaces, characterized by trapezoidal morphology, distinct rounded nuclei, and well-aligned actin filaments. However, groups with higher ceramic loading expressed significantly higher levels of osteogenic markers relative to pure PLA membranes. Rule of mixtures and finite element models indicated an increase in theoretical mechanical strength with an increase in β-TCP concentration. CONCLUSION/UNASSIGNED:This study potentiates the use of PLA/β-TCP composites in load bearing BTR applications and the ability to be used as customized patient-specific shape memory membranes in guided bone regeneration.