Faculty Bibliography

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.

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.

Guided bone regeneration (GBR) procedures have been indicated to enhance bone response, reliably regenerate lost tissue, and create an anatomically pleasing ridge contour for biomechanically favorable and prosthetically driven implant placement. The aim of the current study was to evaluate and compare the bone regenerative performance of deproteinized bovine bone (DBB) and deproteinized porcine bone (DPB) grafts in a beagle mandibular model for the purposes of GBR. Four bilateral defects of 10 mm × 10 mm were induced through the mandibular thickness in each of the 10 adult beagle dogs being studied. Two of the defects were filled with DPB, while the other two were filled with DBB, after which they were covered with collagen-based membranes to allow compartmentalized healing. Animals were euthanized after 6, 12, 24, or 48 weeks postoperatively. Bone regenerative capacity was evaluated by qualitative histological and quantitative microtomographic analyses. Microcomputed tomography data of the bone (%), graft (%), and space (%) were compared using a mixed model analysis. Qualitatively, no histomorphological differences in healing were observed between the DBB and DPB grafts at any time point. By 48 weeks, the xenografts (DBB and DPB) were observed to have osseointegrated with regenerating spongy bone and a close resemblance to native bone morphology. Quantitatively, a higher amount of bone (%) and a corresponding reduction in empty space (space (%)) were observed in defects treated by DBB and DPB grafts over time. However, no statistically significant differences in bone (%)were observed between DBB (71.04 ± 8.41 at 48 weeks) and DPB grafts (68.38 ± 10.30 at 48 weeks) (p > 0.05). GBR with DBB and DPB showed no signs of adverse immune response and led to similar trends in bone regeneration over 48 weeks of permitted healing.

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.

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).

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.

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.

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.

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.