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Tissue Engineering Strategies for Craniomaxillofacial Surgery: Current Trends in 3D-Printed Bioactive Ceramic Scaffolds

Chapter by: Witek, Lukasz; Nayak, Vasudev Vivekanand; Runyan, Christopher M; Tovar, Nick; Elhage, Sharbel; Melville, James C; Young, Simon; Kim, David H; Cronstein, Bruce N; Flores, Roberto L; Coelho, Paulo G
in: Innovative Bioceramics in Translational Medicine II by Choi, Andy H; Ben-Nissan, Besim [Eds]
Cham : Springer, 2022
pp. 55-74
ISBN: 978-981-16-7438-9
CID: 5457532

The Influence of Surface Treatment on Osseointegration of Endosteal Implants Presenting Decompressing Vertical Chambers: An In Vivo Study in Sheep

Parra, Marcelo; Benalcázar Jalkh, Ernesto B; Tovar, Nick; Torroni, Andrea; Badalov, Rafael M; Bonfante, Estevam A; Nayak, Vasudev; Castellano, Arthur; Coelho, Paulo G; Witek, Lukasz
PURPOSE/OBJECTIVE:blasting + maleic + HCl) in a large translational animal model at 3 and 6 weeks in vivo. MATERIALS AND METHODS/METHODS:Nine female sheep were used, and 72 implants with trapezoidal threads and decompressing vertical chambers of 0.6 mm in diameter and 0.2 mm in depth were placed in the ilium crest. After 3 and 6 weeks, the animals were euthanized, and biomechanical and histomophometric analyses were performed. RESULTS:Survey histologic evaluation indicated intimate contact between the bone and the implants independent of surface treatment at both times in vivo. Bone formation at both time points depicted an intramembranous-type healing pattern between the implant threads. The mean removal torque values for all groups showed a relative increase in removal torque from 3 to 6 weeks. In terms of bone area fraction occupancy analysis, significant differences were found at 6 weeks between surface treatments (P = .046), where the experimental surface yielded higher degrees of bone area fraction occupancy. CONCLUSION/CONCLUSIONS:Conical implants with decompressing vertical chambers between threads presented similar osseointegration parameters regarding bone-toimplant contact and torque-out test values irrespective of surface treatment. However, shifting from a minimally rough to a moderately rough surface (experimental surface with supplemental acid-etching) resulted in significantly improved bone area fraction occupancy at 6 weeks.
PMID: 36170307
ISSN: 1942-4434
CID: 5439392

Residual stress estimated by nanoindentation in pontics and abutments of veneered zirconia fixed dental prostheses

Fardin, Vinicius Pavesi; Bonfante, Gerson; Coelho, Paulo G; Bergamo, Edmara T P; Bordin, Dimorvan; Janal, Malvin N; Tovar, Nick; Witek, Lukasz; Bonfante, Estevam A
Glass ceramics' fractures in zirconia fixed dental prosthesis (FDP) remains a clinical challenge since it has higher fracture rates than the gold standard, metal ceramic FDP. Nanoindentation has been shown a reliable tool to determine residual stress of ceramic systems, which can ultimately correlate to failure-proneness.
PMCID:9041093
PMID: 35476114
ISSN: 1678-7765
CID: 5206382

Effect of different tightening protocols on the probability of survival of screw-retained implant-supported crowns

Fardin, Vinicius P; Bergamo, Edmara T P; Bordin, Dimorvan; Hirata, Ronaldo; Bonfante, Estevam A; Bonfante, Gerson; Coelho, Paulo G
PURPOSE/OBJECTIVE:This study evaluated the effect of different tightening protocols on the probability of survival of screw-retained implant-supported anterior crowns. MATERIALS AND METHODS/METHODS:Seventy-two implants with internal conical connections (4.0 × 10mm, Ti-6Al-4V, Colosso, Emfils) were divided into four groups (n = 18 each): 1) Manufacturer's recommendations torque (25 N.cm for abutment's screw and 30 N.cm for crown's screw) (MaT); 2) Retightening after 10 min (ReT); 3) Torque 16% below recommended to simulate an uncalibrated wrench (AgT), and; 4) Temporary crown simulation (TeT), where crowns were torqued to 13 N.cm to simulate manual tightening, subjected to 11,200 cycles to simulate temporary crown treatment time (190 N), and then retightened to manufacturer torque (TeT). All specimens were subjected to cyclic fatigue in distilled water with a load of 190 N until 250,000 cycles or failure. The probability of survival (reliability) to complete a mission of 50,000 cycles was calculated and plotted using the Weibull 2-Parameter analysis. Weibull modulus and number of cycles at which 62.3% of the specimens would fail were also calculated and plotted. The failure mode was characterized in stereo and scanning electron microscopes (SEM). RESULTS:The probability of survival was 69.3% for MaT, 70% for ReT, 54.8% for AgT, and 40.3% for TeT, all with no statistically significant difference. Weibull modulus was approximately 1.0 for all groups. The characteristic number of cycles for failure was 105,000 cycles for MaT, 123,000 for ReT, 82,000 cycles for AgT, and 54,900 cycles for TeT, with no significant difference between groups. The chief failure mode for MaT, ReT, AgT groups was crown screw fracture, whereas abutment screw fracture was the chief failure mode for the TeT group. CONCLUSION/CONCLUSIONS:Tightening protocol did not influence the probability of survival of the screw-retained anterior crowns supported by internal conical implants (Ti-6Al-4V, Colosso, Emfils).
PMID: 34875501
ISSN: 1878-0180
CID: 5099562

Transforming the Degradation Rate of β-tricalcium Phosphate Bone Replacement Using 3-Dimensional Printing

Shen, Chen; Wang, Maxime M; Witek, Lukasz; Tovar, Nick; Cronstein, Bruce N; Torroni, Andrea; Flores, Roberto L; Coelho, Paulo G
BACKGROUND:β-Tricalcium phosphate (β-TCP) is one of the most common synthetic bone grafting materials utilized in craniofacial reconstruction; however, it is limited by a slow degradation rate. The aim of this study was to leverage 3-dimensional (3D) printing in an effort to accelerate the degradation kinetics of β-TCP. METHODS:Twenty-two 1-month-old New Zealand white rabbits underwent creation of calvarial and alveolar defects, repaired with 3D-printed β-TCP scaffolds coated with 1000 μM of osteogenic agent dipyridamole. Rabbits were euthanized after 2, 6, and 18 months after surgical intervention. Bone regeneration, scaffold degradation, and bone mechanical properties were quantified. RESULTS:Histological analysis confirmed the generation of vascularized and organized bone. Microcomputed tomography analysis from 2 to 18 months demonstrated decreased scaffold volume within calvarial (23.6% ± 2.5%, 5.1% ± 2.2%; P < 0.001) and alveolar (21.5% ± 2.2%, 0.2% ± 1.9%; P < 0.001) defects, with degradation rates of 54.6%/year and 90.5%/year, respectively. Scaffold-inducted bone generation within the defect was volumetrically similar to native bone in the calvarium (55.7% ± 6.9% vs 46.7% ± 6.8%; P = 0.064) and alveolus (31.4% ± 7.1% vs 33.8% ± 3.7%; P = 0.337). Mechanical properties between regenerated and native bone were similar. CONCLUSIONS:Our study demonstrates an improved degradation profile and replacement of absorbed β-TCP with vascularized, organized bone through 3D printing and addition of an osteogenic agent. This novel additive manufacturing and tissue engineering protocol has implications to the future of craniofacial skeletal reconstruction as a safe and efficacious bone tissue engineering method.
PMCID:8616850
PMID: 34611100
ISSN: 1536-3708
CID: 5072082

Effects of relative centrifugation force on L-PRF: An in vivo submandibular boney defect regeneration study

Tovar, Nick; Benalcázar Jalkh, Ernesto B; Ramalho, Ilana S; Rodriguez Colon, Ricardo; Kim, Heoijin; Bonfante, Estevam A; Torroni, Andrea; Coelho, Paulo G; Witek, Lukasz
Properties and composition of leukocyte- and platelet-rich fibrin (L-PRF) clots may be largely affected by centrifugation protocols (function of relative centrifugal force [RCF]), which may impact biological potential repair in bone regeneration. The present in vivo study sought to assess the effect of the RCF on the composition of L-PRF clots, as well as to compare the repair potential of L-PRF clots obtained with different RCF protocols in submandibular boney defects using PLGA scaffolds for bone regeneration. Complete blood count and volumetric evaluations were performed on L-PRF clots obtained through centrifugation for 12 min at 200, 400, and 600 RCF-clot centrifugation speeds. These evaluations were completed from blood collected immediately prior to any surgical procedures. The in vivo portion comprised of three submandibular unilateral, full thickness, osteotomies (~0.40cm3 ) which were created in the submandibular region of six sheep, using rotary instrumentation under continuous irrigation. Subsequently, poly(lactic-co-glycolic acid) (PLGA) scaffolds were enveloped in a L-PRF membrane from one of the three spinning speeds (n = 6/RCF) and inserted into the defect (sites were interpolated to avoid site bias). Six-weeks after surgery, the mandibles were harvested en bloc and prepared for volumetric and histomorphometric evaluations. Membranes harvested from 600 RCF produced significantly larger L-PRF clots (6.97g ± 0.95) in comparison to the lower 200 RCF (5.7g ± 0.95), with no significant differences between 600 and 400, and from 400 and 200 RCF. The three tested RCFs did not alter the platelet count of the L-PRF clot. For the in vivo component, quantitative bone regeneration analyses demonstrated significantly higher values obtained with L-PRF membranes extracted post 600 RCF (27.01 ± 8%) versus 200 RCF (17.54 ± 8%), with no significant differences regarding 400 RCF (~23 ± 8%). At the qualitative histological analyses, L-PRF membranes obtained at 600 and 400 RCFs yielded improved healing throughout the defect, where the L-PRF sourced from the lowest speed, 200 RCF, presented healing primarily at the margins along with the presence of connective tissue at the central aspect of the surgical defect. Higher 600 RCF yielded larger L-PRF clots/membranes, resulting in enhanced bone repair potential in association with PLGA scaffolds for the treatment of critical size bone defects.
PMID: 34080775
ISSN: 1552-4981
CID: 4905812

Performance of crowns cemented on a fiber-reinforced composite framework 5-unit implant-supported prostheses: in silico and fatigue analyses

Bergamo, Edmara T P; Yamaguchi, Satoshi; Lopes, Adolfo C O; Coelho, Paulo G; de Araújo-Júnior, Everardo N S; Benalcázar Jalkh, Ernesto B; Zahoui, Abbas; Bonfante, Estevam A
OBJECTIVE:To characterize the biomechanical performance of fiber-reinforced composite 5-unit implant-supported fixed dental prostheses (FDPs) receiving individually milled crowns by insilico and fatigue analyses. METHODS:Eighteen implant-supported five-unit fiber-reinforced composite frameworks with an individually prepared abutment design were fabricated, and ninety resin-matrix ceramic crowns were milled to fit each abutment. FDPs were subjected to step-stress accelerated-life testing with load delivered at the center of the pontic and at 2nd molar and 1st premolar until failure. The reliability of the prostheses combining all loaded data and of each loaded tooth was estimated for a mission of 50,000 cycles at 300, 600 and 900 N. Weibull parameters were calculated and plotted. Fractographic and finite element analysis were performed. RESULTS:Fatigue analysis demonstrated high probability of survival at 300 N, with no significant differences when the set load was increased to 600 and 900 N. 1st and 2nd molar dataset showed high reliability at 300 N, which remained high for the higher load missions; whereas 1st premolar dataset showed a significant decrease when the reliability at 300 N was compared to higher load missions. The characteristic-strength of the combined dataset was 1252 N, with 1st molar dataset presenting higher values relative to 2nd molar and 1st premolar, both significantly different. Failure modes comprised chiefly cohesive fracture within the crown material originated from cracks at the occlusal area, matching the maximum principal strain location. SIGNIFICANCE/CONCLUSIONS:Five-unit implant-supported FDP with crowns individually cemented in a fiber-reinforced composite framework presented a high survival probability. Crown fracture comprised the main failure mode.
PMID: 34588130
ISSN: 1879-0097
CID: 5067492

Microtomographic reconstruction of mandibular defects treated with xenografts and collagen-based membranes: A pre-clinical minipig model

Gomez, J; Bergamo, E-T; Tovar, N; Talib, H-S; Pippenger, B-E; Herdia, V; Cox, M; Coelho, P-G; Witek, L
BACKGROUND:The goal of this study was to evaluate hard tissue response following guided bone regeneration using commercially available bovine bone grafts and collagen membranes; bilayer collagen membrane and porcine pericardium-based membrane, by means of a non-destructive three-dimensional (3D) computerized volumetric analysis following microtomography reconstruction. MATERIAL AND METHODS/METHODS:Bone regenerative properties of various bovine bone graft materials were evaluated in the Göttingen minipig model. Two standardized intraosseous defects (15mm x 8mm x 8mm) were created bilaterally of the mandible of eighteen animals (n=72 defects). Groups were nested within the same subject and randomly distributed among the sites: (i) negative control (no graft and membrane), (ii) bovine bone graft/bilayer collagen membrane (BOB) (iii) Bio-Oss® bone graft/porcine pericardium-based membrane (BOJ) and (iv) cerabone® bone graft/porcine pericardium-based membrane (CJ). Samples were harvested at 4, 8, and 12-week time points (n=6 animal/time point). Segments were scanned using computerized microtomography (μCT) and three dimensionally reconstructed utilizing volumetric reconstruction software. Statistical analyses were performed using IBM SPSS with a significance level of 5%. RESULTS:From a temporal perspective, tridimensional evaluation revealed gradual bone ingrowth with the presence of particulate bone grafts bridging the defect walls, and mandibular architecture preservation over time. Volumetric analysis demonstrated no significant difference between all groups at 4 weeks (p>0.127). At 8 and 12 weeks there was a higher percentage of new bone formation for control and CJ groups when compared to BOB and BOJ groups (p<0.039). The natural bovine bone graft group showed more potential for graft resorption over time relative to bovine bone graft, significantly different between 4 and 8 weeks (p<0.003). CONCLUSIONS:Volumetric analysis yielded a favorable mandible shape with respect to time through the beneficial balance between graft resorption/bone regenerative capacity for the natural bovine bone graft.
PMID: 34564687
ISSN: 1698-6946
CID: 5039602

Nanoscale physico-mechanical properties of an aging resistant ZTA composite

Benalcázar Jalkh, E B; Coelho, P G; Witek, L; Bergamo, E T P; Lopes, A C O; Monteiro, K N; Cesar, P F; Genova, L A; Lisboa-Filho, P N; Abreu, J L B; Campos, T M B; Canteenwala, A; Bonfante, E A
OBJECTIVE:To characterize the effects of aging on the nanomechanical properties and 3D surface topographical parameters of an experimental Zirconia Toughened Alumina (ZTA) composite compared to its respective individual counterpart materials. METHODS:), while X-ray diffraction (XRD) and scanning electron microscope (SEM) assessed the crystalline content and microstructure. All tests were performed before and after simulated aging (134°C, 2.2 bar, 20 h). Statistical analyses were performed using linear mixed-model and least square difference pos-hoc tests (α = 5%). RESULTS:yielded the highest H and E values (H:21 GPa, E: 254 GPa), followed by ZTA 70/30 (H: 13 GPa, E: 214 GPa) and Zpex (H:11 GPa, E: 167 GPa), all significantly different (p < 0.03). CONCLUSION/CONCLUSIONS:presented high hydrothermal stability with respect to all evaluated variables, where artificial aging significantly increased the monoclinic content and surface roughness of Zpex.
PMID: 34385065
ISSN: 1878-0180
CID: 4999352

Comparative barrier membrane degradation over time: Pericardium versus dermal membranes

Bornert, Fabien; Herber, Valentin; Sandgren, Rebecca; Witek, Lukasz; Coelho, Paulo G; Pippenger, Benjamin E; Shahdad, Shakeel
OBJECTIVE:The effectiveness of GBR procedures for the reconstruction of periodontal defects has been well documented. The objective of this investigation was to evaluate the degradation kinetics and biocompatibility of two resorbable collagen membranes in conjunction with a bovine xenograft material. MATERIALS AND METHODS/METHODS:Lower premolars and first molars were extracted from 18 male Yucatan minipigs. After 4 months of healing, standardized semi-saddle defects were created (12 mm × 8 mm × 8 mm [l˙̇ × W˙ × d]), with 10 mm between adjacent defects. The defects were filled with a bovine xenograft and covered with a either the bilayer collagen membrane (control) or the porcine pericardium-derived collagen membrane (test). Histological analysis was performed after 4, 8, and 12 weeks of healing and the amount of residual membrane evaluated. Non-inferiority was calculated using the Brunner-Langer mixed regression model. RESULTS:Histological analysis indicated the presence of residual membrane in both groups at all time points, with significant degradation noted in both groups at 12 weeks compared to 4 weeks (p = .017). No significant difference in ranked residual membrane scores between the control and test membranes was detected at any time point. CONCLUSIONS:The pericardium-derived membrane was shown to be statistically non-inferior to the control membrane with respect to resorption kinetics and barrier function when utilized for guided bone regeneration in semi-saddle defects in minipigs. Further evaluation is necessary in the clinical setting.
PMID: 33949796
ISSN: 2057-4347
CID: 4872312