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An in vivo preclinical study assessing biocompatibility of Pd-based bulk metallic glass

Witek, Lukasz; Vivekanand Nayak, Vasudev; Rodriguez Colon, Ricardo; Torroni, Andrea; Demetriou, Marios D; Coelho, Paulo G
BACKGROUND:The bulk metallic glass (BMG), Pd79Ag3.5P6Si9.5Ge2, has a high fracture toughness and has been found to accommodate post-yield stress, unlike most other BMG. Moreover, due to its greater noble gas composition it has a intrinsic corrosion resistance, ideal for dental and orthopedic implants. OBJECTIVE:This present study aimed to evaluate the in vivo application of Pd79Ag3.5P6Si9.5Ge2 in a large translational sheep model to assess its efficacy to be utilized as an endosteal device. METHODS:Twelve implants in the form of cylindrical rods (3 mm in diameter) were produced through rapid quenching. Each sheep (n = 12) received one osteotomy in the mandibular region using rotary instrumentation, which was subsequently filled with Pd79Ag3.5P6Si9.5Ge2. After 6- and 24-weeks the animals were euthanized, and samples collected en bloc to conduct histomorphometric analysis. The level/degrees of osseointegration were assessed through bone-to-implant contact (BIC). RESULTS:Favorable BIC was observed with fibrous connective tissue layers at both 6- and 24-weeks. Bone along with interfacial remodeling was observed in proximity with the metallic glass surface at 6 weeks with higher degrees of bone organization being observed at the later healing time, 24 weeks. CONCLUSIONS:The introduced BMG revealed potential to serve as an alternative biomaterial to commonly used Ti alloys given its unique combination of toughness and strength.
PMID: 36278332
ISSN: 1878-3619
CID: 5359252

3D printed mesoporous bioactive glass, bioglass 45S5, and β-TCP scaffolds for regenerative medicine: A comparative in vitro study

Pacheco, Maria; Ricci, John L; Mijares, Dindo; Bromage, Timothy G; Rabieh, Sasan; Coelho, Paulo G; Witek, Lukasz
BACKGROUND:While autografts to date remain the "gold standard" for bone void fillers, synthetic bone grafts have garnered attention due to their advantages such as ability to be tailored in terms of its physical and chemical properties. Bioactive glass (BG), an inorganic material, has the capacity to form a strong bond with bone by forming a bone-like apatite surface, enhancing osteogenesis. Coupled with three-dimensional printing it is possible to maximize bone regenerative properties of the BG. OBJECTIVE:The objective of this study was to synthesize and characterize 3D printed mesoporous bioactive glass (MBG), BG 45S5, and compare to β-Tricalcium phosphate (β-TCP) based scaffolds; test cell viability and osteogenic differentiation on human osteoprogenitor cells in vitro. METHODS:MBG, BG 45S5, and β-TCP were fabricated into colloidal gel suspensions, tested with a rheometer, and manufactured into scaffolds using a 3D direct-write micro-printer. The materials were characterized in terms of microstructure and composition with Thermogravimetric Analyzer/Differential Scanning Calorimeter (TGA/DSC), Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), Micro-Computed Tomography (μ-CT), Scanning Electron Microscopy (SEM), Energy Dispersive X-ray Spectroscopy (EDS), and Mattauch-Herzog-Inductively Coupled Plasma-Mass Spectrometry (MH-ICP-MS). RESULTS:Scaffolds were tested for cell proliferation and osteogenic differentiation using human osteoprogenitor cells. Osteogenic media was used for differentiation, and immunocytochemistry for osteogenic markers Runx-2, Collagen-I, and Osteocalcin. The cell viability results after 7 days of culture yielded significantly higher (p < 0.05) results in β-TCP scaffolds compared to BG 45S5 and MBG groups. CONCLUSION/CONCLUSIONS:All materials expressed osteogenic markers after 21 days of culture in expansion and osteogenic media.
PMID: 36744331
ISSN: 1878-3619
CID: 5434832

Evaluation of instrumentation and pedicle screw design for posterior lumbar fixation: A pre-clinical in vivo/ex vivo ovine model

Witek, Lukasz; Parente, Paulo Eduardo Lima; Torroni, Andrea; Greenberg, Michael; Nayak, Vasudev Vivekanand; Hacquebord, Jacques Henri; Coelho, Paulo G. G.
ISI:000915953900001
ISSN: 2572-1143
CID: 5439782

In vitro assessment of the effect of luting agents, abutment height, and fatigue on the retention of zirconia crowns luted to titanium base implant abutments

Strazzi-Sahyon, Henrico B.; Bergamo, Edmara T. P.; Gierthmuehlen, Petra C.; Lopes, Adolfo C. O.; Alves, Larissa M. M.; Jalkh, Ernesto B. Benalcazar; Zahoui, Abbas; Coelho, Paulo G.; de Carvalho, Alexandre M.; Bonfante, Estevam A.
ISI:001111792200001
ISSN: 0022-3913
CID: 5591242

The Influence of Implant Design Features on Bone Healing Pathways: An Experimental Study in Sheep

Bergamo, Edmara Tp; de Oliveira, Paula Gpf; Jimbo, Ryo; Neiva, Rodrigo; Gil, Luiz F; Tovar, Nick; Witek, Lukasz; Bonfante, Estevam A; Coelho, Paulo G
The purpose of this study was to evaluate the influence of implant design features on osseointegration parameters. Two different implant macrogeometries and surface treatments were evaluated as follows: (1) progressive buttress threads possessing the SLActive surface (SLactive/BL), and (2) inner and outer trapezoidal threads possessing nano-hydroxyapatite coating over a dual acid-etched surface (Nano/U). Implants were placed in the right ilium of 12 sheep, and histologic/metric analyses were conducted after 12 weeks in vivo. The percentage of bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO) within the threads were quantified. Histologic observations showed more intimate BIC in the SLactive/BL group compared to the Nano/U group. In contrast, the Nano/U group depicted woven bone formation generated between the wall of the osteotomy and implant threads within the healing chambers, while bone remodeling was evident at the tip of the outer thread. The SLActive/BL group presented higher BIC than the Nano/U group. On the other hand, significantly higher BAFO was observed at 12 weeks in the Nano/U group compared to the SLactive/BL group (P < .042). Differences in implant design features influenced the osseointegration pathway, which supports the need for further investigations to describe the clinical performance and differences in a timely fashion.
PMID: 36520119
ISSN: 1945-3388
CID: 5457162

A Histologic and Histomorphometric Evaluation of an Allograft, Xenograft, and Alloplast Graft for Alveolar Ridge Preservation in Humans: A Randomized Controlled Clinical Trial

Zampara, Eirini; Alshammari, Mukhlid; De Bortoli, Joao; Mullings, Otto; Gkisakis, Ioannis G; Benalcázar Jalkh, Ernesto B; Tovar, Nick; Coelho, Paulo G; Witek, Lukasz
The aim of this study was to clinically evaluate the guided bone regeneration (GBR) potential of allograft, xenograft, and alloplastic materials in combination with resorbable membranes in extraction sockets. The qualitative and quantitative assessments of this prospective study were accomplished through histologic and histomorphometric analysis. Three experimental groups and 1 control group for comparison (n = 8) received either an allograft (human cancellous bone, freeze dried, Deutsches Institut für Zell und Gewebeersatz, Berlin, Germany), xenograft (BioOss, Geistlich Pharma AG, Wolhusen, Switzerland), or alloplast (biphasic calcium sulphate, Bondbone, MIS Implants Technologies Ltd., Charlotte, NC). The negative control group received no regenerative material. Tissue samples were then qualitatively and quantitatively evaluated as a function of percentage of new vital bone, graft particles content, soft tissue, and bone marrow over time. All 3 study groups presented bone volume suitable for the successful placement of a dental implant. The xenograft group yielded significantly less amount of vital bone compared with the allograft and alloplast groups. When comparing the percentage of residual graft particles, there was significantly greater amounts associated with the xenograft group in contrast to the allograft and alloplast groups. Similarly, a significantly increased amount of soft tissue percentage was observed within the xenograft group relative to all other groups. No significant differences were observed in the percentage of residual graft particles between the allograft and alloplast groups. There were also no significant differences detected in vital bone percentage between the allograft, alloplast, and control groups. When evaluating the bone marrow percentage, the only significant difference detected was between the xenograft and alloplast materials. Overall, no complications (ie, fever, malaise, purulence or fistula) were observed during the entirety of clinical trial among all patients. The greatest GBR potential was associated with the allograft material because of the greater degree of vital bone and the lowest percentage of residual graft particles. All studied bone substitute materials resulted in bone apposition for efficient use in alveolar ridge preservation procedures.
PMID: 35446950
ISSN: 0160-6972
CID: 5433052

Laddec® versus Bio-Oss®: The effect on the healing of critical-sized defect - Calvaria rabbit model

Gil, Luiz Fernando; Nayak, Vasudev Vivekanand; Benalcázar Jalkh, Ernesto B; Tovar, Nick; Chiu, Kai-Jen; Salas, Jaime Campos; Marin, Charles; Bowers, Michelle; Freitas, Gileade; Mbe Fokam, Dejolie Christelle; Coelho, Paulo G; Witek, Lukasz
The aim of this study was to evaluate the in vivo performance of two different deproteinized bovine bone (DBB) grafting materials: DBBB (Bio-Oss®) and DBBL (Laddec®), for the regeneration of critically sized (8 mm) defects in rabbit's calvaria. Three round-shaped defects were surgically created in the calvaria of 13 New Zealand White rabbits proximal to the coronal suture in the parietal bone. Two of the defects were filled with one of the grafting materials while a third was left empty to serve as a negative control. Bone regeneration properties were evaluated at 4- and 8-weeks after implantation by means of histological and histomorphometrical analyses. Statistical analyses were performed through a mixed model analysis with fixed factors of time and material. Histological evaluation of the control group evidenced a lack of bridging bone formation across the defect sites at both evaluation time points. For the experimental groups, new bone formation was observed around the defect periphery and to progress radially inwards to the center of the defect site, regardless of the grafting material. Histomorphometric analyses at 4 weeks demonstrated higher amount of bone formation through the defect for DBBB group. However, at 8 weeks, DBBL and DBBB demonstrated osteoconductivity and low resorption rates with evidence of statistically similar bone regeneration through the complete boney defect. Finally, DBBB presented lower soft tissue migration within the defect when compared to DBBL at both evaluation time points. DBBB and DBBL presented similar bone regeneration performance and slow resorption rates. Although both materials promoted bone regeneration through the complete defect, DBBB presented lower soft tissue migration within the defects at 4- and 8-weeks.
PMID: 35857711
ISSN: 1552-4981
CID: 5279162

Effect of leukocyte-platelet-rich fibrin in bone healing around dental implants placed in conventional and wide osteotomy sites: A pre-clinical study

Benalcázar Jalkh, Ernesto B; Tovar, Nick; Arbex, Leticia; Kurgansky, Gregory; Torroni, Andrea; Gil, Luiz F; Wall, Brittany; Kohanbash, Kimia; Bonfante, Estevam A; Coelho, Paulo G; Witek, Lukasz
Leukocyte-platelet-rich fibrin (L-PRF) has been suggested for gap management for immediate implant placement when the distance is greater than 2 mm. However, there remains a paucity in hierarchically designed research to support this application. The present study aimed to evaluate the effect of L-PRF on the osseointegration parameters of dental implants placed after conventional osteotomy of surgically created bone defects that simulate post extraction sockets in a canine model after 3, 6, and 12 weeks in vivo. Eighty dental implants (Intra-Lock, Boca Raton, FL) were placed in the radius of 13 beagle dogs. The experiment consisted of 4 groups (n = 20 implants/group): 1) Regular osteotomy (Reg n/L-PRF); 2) Regular osteotomy and implant placement with L-PRF membrane (Reg L-PRF); 3) Wide osteotomy with no gap management performed, where an osteotomy/bony defect (6 mm of diameter and ~5 mm deep) was created to simulate immediate implant placement in post-extraction sockets, and the gap was left for spontaneous healing (Wide nL-PRF); and 4) Wide osteotomy with L-PRF gap management (Wide L-PRF). L-PRF membranes were obtained by blood drawn from each subject and centrifuged at 2700 rpm (408 RCF-clot) for 12 min. In the experimental groups where L-PRF was utilized, the membrane was inserted into the osteotomy site prior to implant placement. Six dogs had implants placed in the radius for 3 weeks; and 7 dogs had implants placed in the left radius for 6 weeks and in the right radius for 12 weeks. At the corresponding experimental time points, samples were harvested, and subjected to histological processing for qualitative and quantitative analyses, via bone-to-implant contact (BIC) and bone-area-fraction occupancy (BAFO). Qualitative analysis demonstrated increased amounts of bone formation around the implant and within the healing chambers over time for all groups. While comparable histological features were observed for both Reg groups (L-PRF and nL-PRF), the gap management performed in Wide L-PRF group resulted in effective gap filling with improved bone growth in close proximity to the implant surface. Quantitative analyses of BIC and BAFO yielded higher values for both variables at 3 weeks for Wide L-PRF (~38% and ~56% respectively) compared to Wide nL-PRF (~20% for BIC and BAFO) (p < .03). No statistical differences were detected between Wide groups at 6 and 12 weeks, neither between Reg groups, independent of the association with or without the L-PRF membrane at all healing times. L-PRF placed within wide osteotomies, prior to implant placement, resulted in increased early bone formation compared to unfilled wide osteotomies at the early healing time (3 weeks in vivo).
PMID: 35771197
ISSN: 1552-4981
CID: 5281272

Stability of fatigued and aged ZTA compared to 3Y-TZP and Al2O3 ceramic systems

Benalcázar Jalkh, Ernesto B; Bergamo, Edmara T P; Campos, Tiago M B; de Araújo-Júnior, Everardo N S; Lopes, Adolfo C O; Tebcherani, Sérgio M; Yamaguchi, Satoshi; Genova, Luis A; Gierthmuehlen, Petra C; Witek, Lukasz; Coelho, Paulo G; Bonfante, Estevam A
To evaluate the effect of fatigue and aging on the crystalline content and reliability of a zirconia-toughened-alumina (ZTA) composite compared to its individual counterpart materials (3Y-TZP and Al2O3). Thirty-six disc-shaped specimens per group were obtained to comply with ISO 6872:2015. Crystalline content, microstructure and reliability of experimental groups were evaluated in four stages: 1) immediate; 2) aged; 3) fatigued; 4) aged + fatigue. Aging was performed in autoclave and Step-Stress-Accelerated-Life-Testing (SSALT) was performed using three stress profiles. Weibull statistics were used to determine Weibull parameters and life-expectancy. A significant increase in monoclinic phase in 3Y-TZP was observed after aging (19.31%), fatigue (17.88%) and aging + fatigue (55.81%), while ZTA evidenced minimal variation among all conditions (<5.69%). 3Y-TZP presented higher reliability than ZTA at 300 and 500 MPa, and ZTA outperformed Al2O3 at the same stress missions. None of the ceramics yielded acceptable reliability at 800 MPa. A higher characteristic strength was observed for 3Y-TZP, followed by ZTA and Al2O3. While after aging ZTA and Al2O3 remained stable, 3Y-TZP exhibited a significant increase in the characteristic stress. Aging did not affect the reliability of ZTA and Al2O3. 3Y-TZP demonstrated an increase in monoclinic content and characteristic strength after aging.
PMID: 36162164
ISSN: 1878-0180
CID: 5374842

Patient-specific 3D printed Poly-ether-ether-ketone (PEEK) dental implant system

Sonaye, Surendrasingh Y; Bokam, Vijay K; Saini, Akshay; Nayak, Vasudev V; Witek, Lukasz; Coelho, Paulo G; Bhaduri, Sarit B; Bottino, Marco C; Sikder, Prabaha
Fused Filament Fabrication (FFF)-based 3D printing is an efficient technique for developing medical implants, but it is not very useful in developing small yet mechanically robust design-specific fixtures such as dental implants (<15 mm). Specifically, it is challenging to 3D print robust Polyetheretherketone (PEEK) small implants due to PEEK's high melting temperature and melt viscosity. However, in this study, we efficiently utilize high-temperature FFF to develop the first-of-its-kind patient-specific robust PEEK dental implants with high print resolution. Specifically, we explore the effects of critical FFF processing conditions on the mechanical properties of the implants and subsequently determine an optimized set of processing conditions that are essential in developing durable dental implant systems. Our results indicate that the 3D printed dental implants exhibit good fatigue properties and suffice the clinical and industrial requirements for dental implants. Furthermore, we prove that the 3D printed implants exhibit adequate mechanical durability even after simulated (accelerated) aging of 30 years.
PMID: 36244326
ISSN: 1878-0180
CID: 5374892