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Assessing osseointegration of metallic implants with boronized surface treatment

Witek, L; Tovar, N; Lopez, C-D; Morcos, J; Bowers, M; Petrova, R-S; Coelho, P-G
BACKGROUND:Modification of endosteal implants through surface treatments have been investigated to improve osseointegration. Boronization has demonstrated favorable mechanical properties, but limited studies have assessed translational, in vivo outcomes. This study investigated the effect of implant surface boronization on bone healing. MATERIAL AND METHODS/METHODS:Two implant surface roughness profiles (acid etched, machined) in CP titanium (type II) alloy implants were boronized by solid-state diffusion until 10-15µm boron coating was achieved. The surface-treated implants were placed bilaterally into 5 adult sheep ilia for three and six weeks. Four implant groups were tested: boronized machined (BM), boronized acid-etched (BAA), control machined (CM), and control acid-etched (CAA). Osseointegration was quantified by calculating bone to implant contact (BIC) and bone area fraction occupancy (BAFO). RESULTS:Both implant types treated with boronization had BIC values not statistically different from machined control implants at t=3 weeks, and significantly less than acid-etched control (p<0.02). BAFO values were not statistically different for all 3-week groups except machined control (significantly less at p <0.02). BAFO had a significant downward trend from 3 to 6 weeks in both boronized implant types (p<0.03) while both control implant types had significant increases in BIC and BAFO from 3 to 6 weeks. CONCLUSIONS:Non-decalcified histology depicted intramembranous-like healing/remodeling in bone for controls, but an absence of this dynamic process in bone for boronized implants. These findings are inconsistent with in vitro work describing bone regenerative properties of elemental Boron and suggests that effects of boron on in vivo bone healing warrant further investigation.
PMID: 32271322
ISSN: 1698-6946
CID: 4379132

Aging resistance of an experimental zirconia-toughened alumina composite for large span dental prostheses: Optical and mechanical characterization

Benalcázar Jalkh, E B; Bergamo, E T P; Monteiro, K N; Cesar, P F; Genova, L A; Lopes, A C O; Lisboa Filho, P N; Coelho, P G; Santos, C F; Bortolin, F; Piza, M M T; Bonfante, E A
PURPOSE/OBJECTIVE:To synthesize a zirconia-toughened alumina (ZTA) composite with 85% alumina matrix reinforced by 15% zirconia and to characterize its optical and mechanical properties before and after artificial aging, to be compared with a conventional dental zirconia (3Y-TZP). MATERIAL AND METHODS/METHODS:After syntheses, ZTA and 3Y-TZP powders were uniaxially and isostatically pressed. Green-body samples were sintered and polished to obtain 80 disc-shaped specimens per group (12 × 1 mm, ISO 6872:2015). The crystalline content and microstructure were characterized by X-ray diffraction (XRD) and scanning electron microscope (SEM). Optical properties were determined by the calculation of contrast ratio (CR) and translucency parameter (TP) using reflectance data. Mechanical properties were assessed by Vickers hardness, fracture toughness and biaxial flexural strength test (BFS). All analyses were conducted before and after artificial aging (20h, 134 °C, 0.22 MPa). Optical parameters and microhardness differences were evaluated through repeated-measures analysis of variance (p < 0.05). BFS data were analyzed using Weibull statistics (95% CI). RESULTS:The synthesis of the experimental ZTA composite was successful, with 98% of theoretical density, as shown in the SEM images. XRD patterns revealed typical zirconia and alumina crystalline phases. ZTA optical properties parameters showed no effect of aging, with a high CR and low TP values denoting a high masking-ability. 3Y-TZP presented lower masking-ability and aging significantly affected its optical properties. ZTA Vickers hardness, fracture toughness and Weibull parameters, including characteristic stress and Weibull modulus were not influenced by aging, while 3Y-TZP presented a significant decrease in characteristic stress and increase in fracture toughness after aging. The ZTA probability of survival for missions of 300 and 500 MPa was estimated at ~99% validating its use for 3-unit posterior fixed dental prostheses (FDP), and no different from conventional 3Y-TZP. At high-stress mission (800 MPa) a significant decrease in probability of survival was observed for aged 3Y-TZP (84%) and for immediate and aged ZTA (73 and 82% respectively). CONCLUSION/CONCLUSIONS:The ZTA composite presented a dense microstructure, with preservation of the crystalline content, optical and mechanical properties after artificial aging, which encourages future research to validate its potential use for large span FDP.
PMID: 32174417
ISSN: 1878-0180
CID: 4350412

Bone Tissue Engineering in the Growing Calvaria Using Dipyridamole-Coated, Three-Dimensionally-Printed Bioceramic Scaffolds: Construct Optimization and Effects on Cranial Suture Patency

Maliha, Samantha G; Lopez, Christopher D; Coelho, Paulo G; Witek, Lukasz; Cox, Madison; Meskin, Alan; Rusi, Sejndi; Torroni, Andrea; Cronstein, Bruce N; Flores, Roberto L
BACKGROUND:Three-dimensionally-printed bioceramic scaffolds composed of β-tricalcium phosphate delivering the osteogenic agent dipyridamole can heal critically sized calvarial defects in skeletally mature translational models. However, this construct has yet to be applied to growing craniofacial models. In this study, the authors implanted three-dimensionally-printed bioceramic/dipyridamole scaffolds in a growing calvaria animal model and evaluated bone growth as a function of geometric scaffold design and dipyridamole concentration. Potential adverse effects on the growing suture were also evaluated. METHODS:Bilateral calvarial defects (10 mm) were created in 5-week-old (approximately 1.1 kg) New Zealand White rabbits (n = 16 analyzed). Three-dimensionally-printed bioceramic scaffolds were constructed in quadrant form composed of varying pore dimensions (220, 330, and 500 μm). Each scaffold was coated with collagen and soaked in varying concentrations of dipyridamole (100, 1000, and 10,000 μM). Controls consisted of empty defects. Animals were killed 8 weeks postoperatively. Calvariae were analyzed using micro-computed tomography, three-dimensional reconstruction, and nondecalcified histologic sectioning. RESULTS:Scaffold-induced bone growth was statistically greater than bone growth in empty defects (p = 0.02). Large scaffold pores, 500 μm, coated in 1000 μM dipyridamole yielded the most bone growth and lowest degree of scaffold presence within the defect. Histology showed vascularized woven and lamellar bone along with initial formation of vascular canals within the scaffold lattice. Micro-computed tomographic and histologic analysis revealed patent calvarial sutures without evidence of ectopic bone formation across all dipyridamole concentrations. CONCLUSION/CONCLUSIONS:The authors present an effective pediatric bone tissue-engineering scaffold design and dipyridamole concentration that is effective in augmentation of calvarial bone generation while preserving cranial suture patency.
PMID: 31985634
ISSN: 1529-4242
CID: 4293882

The effect of platelet-rich fibrin exudate addition to porous poly(lactic-co-glycolic acid) scaffold in bone healing: An in vivo study

Witek, Lukasz; Tian, Han; Tovar, Nick; Torroni, Andrea; Neiva, Rodrigo; Gil, Luiz F; Coelho, Paulo G
Bone grafting procedures have been widely utilized as the current state-of-the-art for bone regeneration, with autogenous bone graft being the gold-standard bone reconstructive option. However, the use of autografts may be limited by secondary donor-site comorbidities, a finite amount of donor supply, increased operating time, and healthcare cost impact. Synthetic materials, or alloplasts, such as the polymeric material, poly(lactic-co-glycolic acid) (PLGA) has previously been utilized as a transient scaffold to support healing of bone defects with the potential to locally delivery osteogenic additives. In this study a novel procedure was adopted to incorporate both the dissolved contents and mechanical components of leukocyte- and platelet-rich fibrin (L-PRF) into an PLGA scaffold through a two-step method: (a) extraction of the L-PRF membrane transudate with subsequent immersion of the PLGA scaffold in transudate followed by (b) delivering a fibrin gel as a low-viscosity component that subsequently polymerizes into a highly viscous, gel-like biological material within the pores of the PLGA scaffold. Two, ~0.40 cm3 , submandibular defects (n = 24) were created per side using rotary instrumentation under continuous irrigation in six sheep. Each site received a PLGA scaffold (Intra-Lock R&D, Boca Raton, FL), with one positive control (without L-PRF exudate addition [nL-PRF]), and one experimental (augmented with PLGA/L-PRF Blocks [L-PRF]). Animals were euthanized 6 weeks postoperatively and mandibles retrieved, en bloc, for histological analysis. Histomorphometric evaluation for bone regeneration was evaluated as bone area fraction occupancy (BAFO) within the region of interest of the cortical bone (with specific image analysis software) and data presented as mean values with the corresponding 95% confidence interval values. Qualitative evaluation of nondecalcified histologic sections revealed extensive bone formation for both groups, with substantially more bone regeneration for the L-PRF induced group relative nL-PRF group. Quantitative BAFO within the defect as function of the effect of L-PRF exudate on bone regeneration, demonstrated significantly (p = .018) higher values for the L-PRF group (38.26% ± 8.5%) relative to the nL-PRF group (~28% ± 4.0%). This in vivo study indicated that L-PRF exudate has an impact on the regeneration of bone when incorporated with the PLGA scaffold in a large translational model. Further studies are warranted in order to evaluate the L-PRF exudate added, as well as exploring the preparation methods, in order to facilitate bone regeneration.
PMID: 31429195
ISSN: 1552-4981
CID: 4046432

3D Printing and Adenosine Receptor Activation for Craniomaxillofacial Regeneration

Chapter by: Lopez, Christopher D; Witek, Lukasz; Flores, Roberto L; Torroni, Andrea; Rodriguez, Eduardo D; Cronstein, Bruce N; Coelho, Paulo G
in: Regenerative strategies for maxillary and mandibular reconstruction : a practical guide by Melville, James C; et al [Eds]
Cham, Switzerland : Springer, [2019]
pp. 255-267
ISBN: 9783319936673
CID: 5457522

Synergistic Effects of Implant Macrogeometry and Surface Physicochemical Modifications on Osseointegration: An In Vivo Experimental Study in Sheep

Bergamo, Edmara T P; de Oliveira, Paula G F P; Jimbo, Ryo; Neiva, Rodrigo; Tovar, Nick; Witek, Lukasz; Gil, Luiz F; Bonfante, Estevam Augusto; Coelho, Paulo Guilherme
This study evaluates the influence of two surface physicochemical modifications on osseointegration parameters of a healing chamber implant design. We examine dental implants with internal and external trapezoidal threads that have the following surface modifications: dual acid etching (DAE) and nano-hydroxyapatite (HA) coating over DAE surface (Nano). We installed implants in the right ilium of sheep and conducted histologic/metric analyses after 3 and 12 wk in vivo. We quantified the percentage of bone-to-implant contact (%BIC) and bone area fraction occupancy (%BAFO) within implant threads. Histologic micrographs indicate early bone formation within the healing chambers of implants with Nano surface relative to DAE surface. Histomorphometric analysis demonstrates there to be no significant differences in %BIC between 3 and 12 wk (p = 0.298). Compared to DAE, Nano shows more bone formation in contact with implant, regardless of time (p < 0.025). We observe > %BAFO at 12 wk relative to 3 wk, which differs significantly for Nano (p < 0.038). Implant surface treatment affects the amounts of bone formation within healing chambers, with Nano significantly outperforming DAE at 12 wk (p < 0.025). Nano presents a synergistic effect with implant design, improving osseointegration parameters.
PMID: 32749134
ISSN: 1940-4379
CID: 4557202

Histological Analysis of an Implant Retrieved from a β-Tricalcium Phosphate Graft after 4 Years: A Case Study

Daher, Shadi; Leary, Joseph; Ewers, Rolf; Coelho, Paulo G; Bonfante, Estevam Augusto
We describe the retrieval of a dental implant device that had been successfully osseointegrated for more than 4 years. After obtaining an informed patient consent, the device was retrieved for retreatment purposes from its position in a β-tricalcium phosphate (β-TCP) grafted sinus floor. The sinus floor augmentation, using β-TCP, had been performed in conjunction with the original implant placement, which in turn enabled the histological evaluation of specific regions of interest that were comprised of either grafted or native bone. Radiographs documented the rehabilitated area before and after grafting. The osteogenic events that occurred during the 4-yr-period depict the interplay of implant, synthetic graft material, and native bone in a dynamic process of osteogenesis, ongoing bone maturation, and remodeling that led to the development of haversian-like bone morphology. Two distinct areas were observed histologically, wherein osteointegration occurred uneventfully in both native bone and areas of grafted bone. Of particular interest was the presence of multiple remodeling sites of lamellar bone that could be seen between the plateaus-healing chambers-in which bone eventually evolved into a haversian cortical-like configuration.
PMID: 32464022
ISSN: 1940-4379
CID: 4473802

Practice-Based Clinical Evaluation of Dental Implants Placed with Immediate or Delayed Loading Protocols: One-Year Follow-Up

Lopes, Adolfo Coelho de Oliveira; Coelho, Paulo Guilherme; de Carvalho, Paulo Sérgio Perri de Carvalho; Bonjardim, Leonardo Rigoldi; Neppelenbroek, Karin Hermana; Jalkh, Ernesto Byron Benalcazar; Zahoui, Abbas; Bonfante, Estevam Augusto
We evaluate bone remodeling and prostheses survival of immediately provisionalized with occlusal loading and delayed loading (DL) single implants placed in the posterior region after 1-yr follow-up in dental practices. Included in the study are patients selected to receive one regular implant (4 × 10 mm) for single tooth replacement in healed ridge sockets in the mandible and maxilla. Implants are immediately loaded or delayed functionally loaded with metal ceramic crowns, depending on peak insertion torque value. All implants are clinically and radiographically evaluated at T1, immediately postoperatively; T2, 60 d; T3, 180 d; and T4, 360 d. Measurements between implant platform and top of alveolar bone crest at distal and mesial areas are performed using periapical radiographs. Data are statistically evaluated through two-way repeated measures of analysis of variance following post hoc comparisons using the Tukey test (p < 0.05). Ten specialists working in ten different practices treat 36 patients who receive one implant each with internal conical connection (hybrid implant system, 4 × 10 mm) (Emfils; Itu, Brazil). Results show that bone-level alterations in immediate (IM; 0.56 mm; confidence interval [CI]: ± 0.21 mm) and delayed (0.65 mm; CI: ± 0.19 mm) groups are not significantly different (p = 0.515) during the course of the 1-yr observation period. In both groups, statistically significant progressive bone-level remodeling occurs through the evaluated follow-up time points (p < 0.047). All prostheses are rated "alpha," presenting 100% success at 1-yr follow-up. The loading method does not influence bone-remodeling levels around IM or DL at the posterior region after 1-yr follow-up. No prostheses complications are reported.
PMID: 32464023
ISSN: 1940-4379
CID: 4466002

Tissue-engineered alloplastic scaffolds for reconstruction of alveolar defects

Chapter by: Witek, Lukasz; Colon, Ricardo Rodriguez; Wang, Maxime M.; Torroni, Andrea; Young, Simon; Melville, James; Lopez, Christopher D.; Flores, Roberto L.; Cronstein, Bruce N.; Coelho, Paulo G.
in: Handbook of Tissue Engineering Scaffolds: Volume One by
[S.l.] : Elsevier, 2019
pp. 505-520
ISBN: 9780081025642
CID: 4394182

Effect of cell therapy with osteoblasts differentiated from bone marrow or adipose tissue stromal cells on bone repair

Freitas, Gileade P; Lopes, Helena B; P Souza, Alann T; F P Oliveira, Paula G; G Almeida, Adriana L; Coelho, Paulo G; Ferreira, Fernanda U; Covas, Dimas T; Beloti, Marcio M; Rosa, Adalberto L
Aim: The aim of this study was to investigate the effect of local injection of osteoblasts differentiated from bone marrow (BM-OB) or adipose tissue (AT-OB) mesenchymal stromal cells on bone tissue formation. Materials & methods: Defects were created in rat calvaria and injected with BM-OB or AT-OB and phosphate-buffered saline without cells were injected as control. Bone formation was evaluated 4 weeks postinjection. Results: Injection of BM-OB or AT-OB resulted in higher bone formation than that obtained with control. The bone tissue induced by cell injections exhibited similar mechanical properties as those of pristine calvarial bone, and its molecular cues suggested the occurrence of a remodeling process. Conclusion: Results of this study demonstrated that cell therapy with osteoblasts induced significant bone formation that exhibited the same quality as that of pre-existent bone.
PMID: 31960753
ISSN: 1746-076x
CID: 4273742