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Effect of Secondary Non-Thermal Plasma Decontamination on Ethanol-Treated Endosteal Implant Surfaces: An In Vivo Study of Osseointegration
Sandino, Adriana I; Kawase De Queiroz Goncalves, Joao Arthur; Pathagamage, Pawan; Brochu, Baylee M; Sturm, Savanah R; Castellano, Arthur; Nayak, Vasudev Vivekanand; Witek, Lukasz; Coelho, Paulo G
Effective surface treatment of implants is essential for enhancing osseointegration outcomes. This study assessed the influence of alcohol decontamination both with and without secondary argon-based non-thermal plasma (NTP) treatment on osseointegration of endosteal implants in a large translational (sheep) model. Ti6Al4V dental implants were utilized either as received (CTRL), or subjected to ethanol cleaning (for 60 s) followed by NTP (for 60 s) (Clean+Plasma); or treated with NTP alone (Plasma) for 60 s. X-ray photoelectron spectroscopy was used for surface elemental analysis, followed by interferometry and sessile drop tests to measure changes in surface roughness and surface energy, respectively. Twelve sheep received implants (one implant per group per sheep) in the iliac crest, and bone healing was evaluated after 3 and 12 weeks using histomorphometric analysis (six sheep/time point). No significant differences in surface roughness (arithmetic mean (Sa) and root mean square (Sq) height: p > 0.161 and p > 0.173, respectively) or topographies were detected between implant surfaces. However, both NTP treated groups presented higher surface energies and lower water contact angle values relative to CTRL surface (p < 0.001). Compared to the CTRL, both NTP-treated groups exhibited reduced levels of Carbon and elevated levels of Oxygen. No significant differences in Bone-to-Implant Contact (BIC) or Bone Area Fractional Occupancy (BAFO) were observed among groups at 3 weeks. At the 12-week time point, Plasma implants demonstrated significantly higher BAFO (p = 0.014) compared to the CTRL group, as well as an increase in both BIC and BAFO over time (3 vs. 12 weeks in vivo) (p = 0.041 and p = 0.043, respectively). Building on the existing literature, the current study suggests that NTP treatment alone may be adequate to successfully enhance osseointegration while minimizing contamination risks, thereby eliminating the need for additional cleaning protocols.
PMID: 40742223
ISSN: 1552-4981
CID: 5902822
The Effect of Three-Dimensional Stabilization Thread Design on Biomechanical Fixation and Osseointegration in Type IV Bone
Iglesias, Nicholas J; Nayak, Vasudev Vivekanand; Castellano, Arthur; Witek, Lukasz; Souza, Bruno Martins de; Bergamo, Edmara T P; Almada, Ricky; Slavin, Blaire V; Bonfante, Estevam A; Coelho, Paulo G
Achieving the appropriate primary stability for immediate or early loading in areas with low-density bone, such as the posterior maxilla, is challenging. A three-dimensional (3D) stabilization implant design featuring a tapered body with continuous cutting flutes along the length of the external thread form, with a combination of curved and linear geometric surfaces on the thread's crest, has the capacity to enhance early biomechanical and osseointegration outcomes compared to implants with traditional buttressed thread profiles. Commercially available implants with a buttress thread design (TP), and an experimental implant that incorporated the 3D stabilization trimmed-thread design (TP 3DS) were used in this study. Six osteotomies were surgically created in the ilium of adult sheep (N = 14). Osteotomy sites were randomized to receive either the TP or TP 3DS implant to reduce site bias. Subjects were allowed to heal for either 3 or 12 weeks (N = 7 sheep/time point), after which samples were collected en bloc (including the implants and surrounding bone) and implants were either subjected to bench-top biomechanical testing (e.g., lateral loading), histological/histomorphometric analysis, or nanoindentation testing. Both implant designs yielded high insertion torque (ITV ≥ 30 N⋅cm) and implant stability quotient (ISQ ≥ 70) values, indicative of high primary stability. Qualitative histomorphological analysis revealed that the TP 3DS group exhibited a continuous bone-implant interface along the threaded region, in contrast to the TP group at the early, 3-week, healing time point. Furthermore, TP 3DS's cutting flutes along the entire length of the implant permitted the distribution of autologous bone chips within the healing chambers. Histological evaluation at 12 weeks revealed an increase in woven bone containing a greater presence of lacunae within the healing chambers in both groups, consistent with an intramembranous-like healing pattern and absence of bone dieback. The TP 3DS macrogeometry yielded a ~66% increase in average lateral load during pushout testing at baseline (T = 0 weeks, p = 0.036) and significantly higher bone-to-implant contact (BIC) values at 3 weeks post-implantation (p = 0.006), relative to the traditional TP implant. In a low-density (Type IV) bone model, the TP 3DS implant demonstrated improved performance compared to the conventional TP, as evidenced by an increase in baseline lateral loading capacity and increased BIC during the early stages of osseointegration. These findings indicate that the modified implant configuration of the TP 3DS facilitates more favorable biomechanical integration and may promote more rapid and stable bone anchorage under compromised bone quality conditions. Therefore, such improvements could have important clinical implications for the success and longevity of dental implants placed in regions with low bone density.
PMCID:12190597
PMID: 40558364
ISSN: 2313-7673
CID: 5874542
Effect of bulk material on the reliability and failure mode of narrow implants
Benalcázar-Jalkh, Ernesto B; Lopes, Adolfo C O; Bergamo, Edmara T P; de Carvalho, Laura F; Witek, Lukasz; Coelho, Paulo G; Zahoui, Abbas; Bonfante, Estevam A
The aim of the study was to assess the effect of bulk material on the reliability and failure modes of narrow-diameter implants. Narrow implants (Ø3.5 × 10 mm - 11° internal conical connection) were manufactured from three different bulk materials: commercially pure titanium grade-IV (CP4), cold-worked titanium (CW), and 4Titude (4Ti), and were evaluated under fatigue testing. Eighteen samples per group were tested under step-stress accelerated life testing through 30° off-axis load application in mild, moderate, and aggressive loading profiles. The number of cycles and load at failure were used to calculate use-level probability curves and reliability for missions of 100,000 cycles up to 200 N, followed by fractographic analyses. Beta values suggested that damage accumulation dictated failures. Reliability analyses at 80, 120, and 150 N evidenced high reliability for narrow implants independent of bulk material. At 200 N, a decrease in reliability was observed for all groups (∼46%). Failure mode analysis depicted similar failures for all groups and comprised implant fracture, abutment fracture, and implant + abutment fractures. Narrow implants presented high reliability for physiologic masticatory forces in the anterior region. Characteristic strength, reliability, and failure modes were similar regardless of bulk material, suggesting that fatigue damage accumulation at thin wall implants dictated failure over bulk material strength.
PMID: 40500134
ISSN: 1600-0722
CID: 5869432
Exploring Denosumab in the Treatment of Giant Cell Tumors: Clinical Evidence and Controversies
Brochu, Baylee M; Mirsky, Nicholas A; Nayak, Vasudev Vivekanand; Witek, Lukasz; Thaller, Seth R; Carlini, Joao L; Coelho, Paulo G
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.
PMID: 39813592
ISSN: 1536-3732
CID: 5776892
Application of 3D Printing in Cleft Lip and Palate Repair
Kelly, Sophie S; Suarez, Camila A; Mirsky, Nicholas A; Slavin, Blaire V; Brochu, Baylee; Vivekanand Nayak, Vasudev; El Shatanofy, Muhammad; Witek, Lukasz; Thaller, Seth R; Coelho, Paulo G
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.
PMID: 38738906
ISSN: 1536-3732
CID: 5664282
Comparative Evaluation of Bovine- and Porcine-Deproteinized Grafts for Guided Bone Regeneration: An In Vivo Study
Slavin, Blaire V; Nayak, Vasudev Vivekanand; Parra, Marcelo; Spielman, Robert D; Torquati, Matteo S; Iglesias, Nicholas J; Coelho, Paulo G; Witek, Lukasz
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.
PMCID:12108621
PMID: 40428078
ISSN: 2306-5354
CID: 5855242
Impact of three-dimensional stabilization thread design on biomechanical fixation and osseointegration of endosteal implants
Slavin, Blaire V; Nayak, Vasudev Vivekanand; Bergamo, Edmara T P; Costello, Joseph P; Ehlen, Quinn T; Stauber, Zachary M; Fullerton, Natalia; Witek, Lukasz; Coelho, Paulo G
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.
PMID: 40245678
ISSN: 1878-0180
CID: 5828742
Experimental bilayer zirconia systems after aging: Mechanical, optical, and microstructural characterization
Sousa, Edisa O; Alves, Larissa M M; Campos, Tiago M B; Bergamo, Edmara T P; Benalcazar-Jalkh, Ernesto B; Marun, Manoela M; Galli, Mateus Z; Carvalho, Laura F; Dos Santos, Claudinei; Tebcherani, Sergio M; Thim, Gilmar Patrocínio; Zhang, Yu; Yamaguchi, Satoshi; Witek, Lukasz; Coelho, Paulo G; Bonfante, Estevam A
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).
PMID: 39809617
ISSN: 1879-0097
CID: 5776622
Novel bilayered zirconia systems using recycled 3Y-TZP for dental applications
Benalcázar-Jalkh, Ernesto B; Campos, Tiago M B; Dos Santos, Claudinei; Alves, Larissa M M; Carvalho, Laura F; Bergamo, Edmara T P; Tebcherani, Sergio M; Witek, Lukasz; Coelho, Paulo G; Thim, Gilmar P; Yamaguchi, Satoshi; Sousa, Edisa O; Marcolino, Giovana A; Bonfante, Estevam A
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.
PMID: 39827061
ISSN: 1879-0097
CID: 5777982
Synergistic Effect of Implant Surface Physicochemical Modifications and Macrogeometry on the Early Stages of Osseointegration: An In Vivo Preclinical Study
Benalcázar-Jalkh, Ernesto B; Nayak, Vasudev Vivekanand; Slavin, Blaire V; Balderrama, Isis Fatima; Bonfante, Estevam A; Coelho, Paulo G; Witek, Lukasz
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.
PMID: 40156250
ISSN: 1552-4981
CID: 5814442