Faculty Bibliography

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.

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).

Giant cell tumors (GCTs) are benign but locally aggressive bone neoplasms that primarily affect skeletally mature individuals. They are characterized by a tendency for recurrence and being associated with significant morbidity. Traditional treatment has focused on surgical resection; however, the role of medical therapies, such as Denosumab, a bone anti-resorptive drug, which has been Food and Drug Administration (FDA)-approved for unresectable GCTs since 2013, recently has gained prominence. Denosumab is a human monoclonal antibody that inhibits receptor activator of nuclear factor kappa B ligand (RANKL). This article aims to consolidate the current literature on Denosumab's efficacy in treating GCTs, highlighting its mechanism of action, clinical evidence, and potential complications. Clinical studies have demonstrated that Denosumab effectively reduces tumor size improving patient outcomes. Yet, some clinicians maintain concerns and reservations regarding local recurrence and malignant transformation. This review discusses the biochemical background of GCTs, current treatment guidelines, challenges, and future directions for research. Ultimately, Denosumab represents a potentially viable advancement in the management of GCTs, particularly in cases where surgical options are limited.

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.

This manuscript reviews the transformative impact of 3-dimensional (3D) printing technologies in the treatment and management of cleft lip and palate (CLP), highlighting its application across presurgical planning, surgical training, implantable scaffolds, and postoperative care. By integrating patient-specific data through computer-aided design and manufacturing, 3D printing offers tailored solutions that improve surgical outcomes, reduce operation times, and enhance patient care. The review synthesizes current research findings, technical advancements, and clinical applications, illustrating the potential of 3D printing to revolutionize CLP treatment. Further, it discusses the future directions of combining 3D printing with other innovative technologies like artificial intelligence, 4D printing, and in situ bioprinting for more comprehensive care strategies. This paper underscores the necessity for multidisciplinary collaboration and further research to overcome existing challenges and fully utilize the capabilities of 3D printing in CLP repair.

This study explores the novel application of pyronin Y for fluorescently labeling extracellular matrices (ECMs) and gelatin cryogels, providing a simple and reliable method for laser scanning confocal microscopy. Pyronin Y exhibited remarkable staining ability of the porous structures of gelatin cryogels, indicating its potential as a reliable tool for evaluating such biomaterials. Confocal imaging of pyronin Y-stained cryogels produced high signal-to-noise ratio images suitable for quantifying pores using Fiji/Image J. Importantly, pyronin Y enabled effective dual-color imaging of cryogel-labeled mesenchymal stem cells, expanding its utility beyond traditional RNA assays. Traditional staining methods like Mason's trichrome and Sirius Red have limitations in cryogel applications. Pyronin Y emerges as a powerful alternative due to its water solubility, minimal toxicity, and stability. Our results demonstrate pyronin Y's ability to specifically stain gelatin cryogel's porous structures, surpassing its weak staining of ECMs in 2D. Confocal imaging revealed enduring staining even under rigorous scanning, with no notable photobleaching observed. Furthermore, pyronin Y's combination with Alexa Fluor 647 for dual-color imaging showed promising results, validating its versatility in fluorescence microscopy. In conclusion, this study establishes pyronin Y as a cost-effective and rapid option for fluorescent staining of gelatin cryogels. Its simplicity, efficacy, and compatibility with confocal microscopy make it a valuable tool for characterizing and evaluating gelatin-based biomaterials, contributing significantly to the field of cryogel imaging. The study opens new avenues for dual-color imaging in biomaterial research and tissue engineering, advancing our understanding of cellular interactions within scaffolds. Key features • Fluorescent staining of gelatin-based cryogels with an inexpensive yet less time-consuming protocol. • Pyronin Y staining is suitable for dual-color confocal imaging by combining with far-red fluorophores (such as Alexa Fluor 647). • The method is conducted routinely. Graphical overview Gelatin cryogel staining using pyronin Y.

Large osseous defects resulting from trauma, tumor resection, or fracture render the inherent ability of the body to repair inadequate and necessitate the use of bone grafts to facilitate the recovery of both form and function of the bony defect sites. In the United States alone, a large number of bone graft procedures are performed yearly, making it an essential area of investigation and research. Synthetic grafts represent a potential alterative to autografts due to their patient-specific customizability, but currently lack widespread acceptance in the clinical space. Early in their development, non-autologous bone grafts composed of metals such as stainless steel and titanium alloys were favorable due to their biocompatibility, resistance to corrosion, mechanical strength, and durability. However, since their inception, bioceramics have also evolved as viable alternatives. This review aims to present an overview of the fundamental prerequisites for tissue engineering devices using bioceramics as well as to provide a comprehensive account of their historical usage and significant advancements over time. This review includes a summary of commonly used manufacturing techniques and an evaluation of their use as drug carriers and bioactive coatings-for therapeutic ion/drug release, and potential avenues to further enhance hard tissue regeneration.