Faculty Bibliography

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.

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.

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).

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.

BACKGROUND/UNASSIGNED:performance of a novel electrospun composite scaffold coated in a recombinant variant of human bone morphogenetic protein-2 (OsteoAdapt) relative to a porcine-derived xenograft. Further, it sought to determine if OsteoAdapt would remain within the defect without a membrane in place, as this is not feasible with the particulate xenograft currently used in clinical practice. METHODS/UNASSIGNED:, bone regeneration was assessed through qualitative volumetric reconstruction, qualitative and quantitative histological analyses. RESULTS/UNASSIGNED:= 0.982, respectively). However, qualitative analysis of the histological micrographs demonstrated advanced bone healing characterized by an abundance of nucleation sites for regeneration to occur in defects treated with OA relative to the CTRL. Bone overgrowth beyond the limits of defect borders was observed in groups treated OA/ZM and OA/P/ZM. In contrast to the treatment groups, minimal woven bone was visualized in the CTRL group. CONCLUSION/UNASSIGNED:. This suggests that the novel combination of AMP-2 and a bioceramic/synthetic polymer-based electrospun scaffold is a suitable candidate for GBR procedures, without a barrier membrane to secure its place within a defect.

The unique screw-shape design and microstructure of implants pose a challenge for mechanical debridement in removing biofilms. Biofilms exhibit increased resistance to antimicrobials relative to single planktonic cells, emphasizing the need for effective biofilm removal during periodontal therapy for peri-implantitis treatment. To tackle this issue, our team evaluated the effectiveness of low-temperature plasma (LTP) for disinfecting titanium discs contaminated with multispecies biofilms associated with peri-implantitis, specifically focusing on biofilms matured for 14 and 21 days as well as biofilms that had formed on Straumann^Ⓡ Ti-SLA implants for 21 days. The biofilms included Actinomyces naeslundii, Porphyromonas gingivalis, Streptococcus oralis, and Veillonella dispar, which were grown in anaerobic conditions. These biofilms were subjected to LTP treatment for 1, 3, and 5 min, using distances of 3 or 10 mm from the LTP nozzle to the samples. Control groups included biofilms formed on Ti discs or implants that received no treatment, exposure to argon flow at 3 or 10 mm of distance for 1, 3, or 5 min, application for 1 min of 14 μg/mL amoxicillin, 140 μg/mL metronidazole, or a blend of both, and treatment with 0.12% chlorhexidine (CHX) for 1 min. For the implants, 21-day-old biofilms were treated with 0.12% CHX 0.12% for 1 min and LTP for 1 min at a distance of 3 mm for each quadrant. Biofilm viability was assessed through bacterial counting and confocal laser scanning microscopy. The impact of LTP was investigated on reconstituted oral epithelia (ROE) contaminated with P. gingivalis, evaluating cytotoxicity, cell viability, and histology. The results showed that a 1 min exposure to LTP at distances of 3 or 10 mm significantly lowered bacterial counts on implants and discs compared to the untreated controls (p < 0.017). LTP exposure yielded lower levels of cytotoxicity relative to the untreated contaminated control after 12 h of contamination (p = 0.038), and cell viability was not affected by LTP (p ≥ 0.05); thus, LTP-treated samples were shown to be safe for tissue applications, with low cytotoxicity and elevated cell viability post-treatment, and these results were validated by qualitative histological analysis. In conclusion, the study's results support the effectiveness of 1 min LTP exposure in successfully disinfecting mature peri-implantitis multispecies biofilms on titanium discs and implants. Moreover, it validated the safety of LTP on ROE, suggesting its potential as an adjunctive treatment for peri-implantitis.

Bone nonunion following a fracture represents a significant global healthcare challenge, with an overall incidence ranging between 2 and 10% of all fractures. The management of nonunion is not only financially prohibitive but often necessitates invasive surgical interventions. This comprehensive manuscript aims to provide an extensive review of the published literature involving growth factors, stem cells, and novel delivery mechanisms for the treatment of fracture nonunion. Key growth factors involved in bone healing have been extensively studied, including bone morphogenic protein (BMP), vascular endothelial growth factor (VEGF), and platelet-derived growth factor. This review includes both preclinical and clinical studies that evaluated the role of growth factors in acute and chronic nonunion. Overall, these studies revealed promising bridging and fracture union rates but also elucidated complications such as heterotopic ossification and inferior mechanical properties associated with chronic nonunion. Stem cells, particularly mesenchymal stem cells (MSCs), are an extensively studied topic in the treatment of nonunion. A literature search identified articles that demonstrated improved healing responses, osteogenic capacity, and vascularization of fractures due to the presence of MSCs. Furthermore, this review addresses novel mechanisms and materials being researched to deliver these growth factors and stem cells to nonunion sites, including natural/synthetic polymers and bioceramics. The specific mechanisms explored in this review include BMP-induced osteoblast differentiation, VEGF-mediated angiogenesis, and the role of MSCs in multilineage differentiation and paracrine signaling. While these therapeutic modalities exhibit substantial preclinical promise in treating fracture nonunion, there remains a need for further research, particularly in chronic nonunion and large animal models. This paper seeks to identify such translational hurdles which must be addressed in order to progress the aforementioned treatments from the lab to the clinical setting.