RESUMO
BACKGROUND: This study aimed to compare the histomorphometric and histological bone response to laser-sintered implants followed by resorbable-blasting media (RBM) process relative to standard machined/RBM surface treated implants. MATERIAL AND METHODS: Six male sheep (n=6) received 2 Ti-6Al-4V implants (1 per surface) in each side of the mandible for 6 weeks in vivo. The histomorphometric parameters bone-implant contact (BIC) and bone area fraction occupancy (BAFO) were evaluated. RESULTS: Optical interferometry revealed higher Sa and Sq values for the laser-sintered/RBM surface in relation to standard/RBM implants. No significant differences in BIC were observed between the two groups (p>0.2), but significantly higher BAFO was observed for standard/RBM implants (p<0.01). CONCLUSIONS: The present study demonstrated that both surfaces were biocompatible and osseoconductive, and the combination of laser sintering and RBM has no advantage over the standard machined implants with subsequent RBM.
Assuntos
Implantação Dentária Endóssea , Implantes Dentários , Animais , Lasers , Masculino , Osseointegração , Ovinos , Propriedades de SuperfícieRESUMO
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.
Assuntos
Substitutos Ósseos , Animais , Regeneração Óssea , Substitutos Ósseos/farmacologia , Transplante Ósseo , Bovinos , Minerais , Coelhos , Crânio/cirurgiaRESUMO
PURPOSE: We investigated safety, tolerability, pharmacokinetics, and antitumor activity of the protein tyrosine kinase 7 (PTK7)-targeted, auristatin-based antibody-drug conjugate (ADC) PF-06647020/cofetuzumab pelidotin (NCT02222922). PATIENTS AND METHODS: Patients received PF-06647020 intravenously every 3 weeks at 0.2-3.7 mg/kg or every 2 weeks at 2.1-3.2 mg/kg, in sequential dose escalation, following a modified toxicity probability interval method. In dose expansion, pretreated patients with advanced, platinum-resistant ovarian cancer, non-small cell lung cancer (NSCLC), or triple-negative breast cancer (TNBC) received PF-06647020 2.8 mg/kg every 3 weeks. RESULTS: The most common, treatment-related adverse events for PF-06647020 administered every 3 weeks were nausea, alopecia, fatigue, headache, neutropenia, and vomiting (45%-25%); 25% of patients had grade ≥ 3 neutropenia. Two patients experienced dose-limiting toxicities (grade 3 headache and fatigue) at the highest every 3 weeks dose evaluated. The recommended phase II dose was 2.8 mg/kg every 3 weeks. The overall safety profile observed with PF-06647020 administered every 2 weeks was similar to that of the every 3 weeks regimen. Systemic exposure for the ADC and total antibody generally increased in a dose-proportional manner. Antitumor activity was observed in treated patients with overall objective response rates of 27% in ovarian cancer (n = 63), 19% in NSCLC (n = 31), and 21% in TNBC (n = 29). Responders tended to have moderate or high PTK7 tumor expression by IHC. CONCLUSIONS: This PTK7-targeted ADC demonstrated therapeutic activity in previously treated patients with ovarian cancer, NSCLC, and TNBC at a dose range of 2.1-3.2 mg/kg, supporting further clinical evaluation to refine dose, schedule, and predictive tissue biomarker testing in patients with advanced malignancies.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma Epitelial do Ovário , Imunoconjugados , Neoplasias Pulmonares , Neoplasias Ovarianas , Neoplasias de Mama Triplo Negativas , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/patologia , Moléculas de Adesão Celular/antagonistas & inibidores , Imunoconjugados/farmacologia , Imunoconjugados/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
This study investigated the effects of osseodensification drilling on the stability and osseointegration of machine-cut and acid-etched endosteal implants in low-density bone. Twelve sheep received six implants inserted into the ilium, bilaterally (n = 36 acid-etched, and n = 36 as-machined). Individual animals received three implants of each surface, placed via different surgical techniques: (1) subtractive regular-drilling (R): 2.0 mm pilot, 3.2 and 3.8 mm twist drills); (2) osseodensification clockwise-drilling (CW): Densah Bur (Versah, Jackson, MI) 2.0 mm pilot, 2.8, and 3.8 mm multifluted tapered burs; and (3) osseodensification counterclockwise-drilling (CCW) Densah Bur 2.0 mm pilot, 2.8 mm, and 3.8 mm multifluted tapered burs. Insertion torque was higher in the CCW and CW-drilling compared to the R-drilling (p < 0.001). Bone-to-implant contact (BIC) was significantly higher for CW (p = 0.024) and CCW-drilling (p = 0.006) compared to the R-drilling technique. For CCW-osseodensification-drilling, no statistical difference between the acid-etched and machine-cut implants at both time points was observed for BIC and BAFO (bone-area-fraction-occupancy). Resorbed bone and bone forming precursors, preosteoblasts, were observed at 3-weeks. At 12-weeks, new bone formation was observed in all groups extending to the trabecular region. In low-density bone, endosteal implants inserted via osseodensification-drilling presented higher stability and no osseointegration impairments compared to subtractive regular-drilling technique, regardless of evaluation time or implant surface. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 615-623, 2019.
Assuntos
Interface Osso-Implante , Osso Esponjoso/metabolismo , Implantes Experimentais , Osseointegração , Osteoblastos/metabolismo , Animais , Osso Esponjoso/patologia , Masculino , Osteoblastos/patologia , OvinosRESUMO
Injuries to the extremities often require resection of necrotic hard tissue. For large-bone defects, autogenous bone grafting is ideal but, similar to all grafting procedures, is subject to limitations. Synthetic biomaterial-driven engineered healing offers an alternative approach. This work focuses on three-dimensional (3D) printing technology of solid-free form fabrication, more specifically robocasting/direct write. The research hypothesizes that a bioactive calcium-phosphate scaffold may successfully regenerate extensive bony defects in vivo and that newly regenerated bone will demonstrate mechanical properties similar to native bone as healing time elapses. Robocasting technology was used in designing and printing customizable scaffolds, composed of 100% beta tri-calcium phosphate (ß-TCP), which were used to repair critical sized long-bone defects. Following full thickness segmental defects (~11 mm × full thickness) in the radial diaphysis in New Zealand white rabbits, a custom 3D-printed, 100% ß-TCP, scaffold was implanted or left empty (negative control) and allowed to heal over 8, 12, and 24 weeks. Scaffolds and bone, en bloc, were subjected to micro-CT and histological analysis for quantification of bone, scaffold and soft tissue expressed as a function of volume percentage. Additionally, biomechanical testing at two different regions, (a) bone in the scaffold and (b) in native radial bone (control), was conducted to assess the newly regenerated bone for reduced elastic modulus (Er ) and hardness (H) using nanoindentation. Histological analysis showed no signs of any adverse immune response while revealing progressive remodelling of bone within the scaffold along with gradual decrease in 3D-scaffold volume over time. Micro-CT images indicated directional bone ingrowth, with an increase in bone formation over time. Reduced elastic modulus (Er ) data for the newly regenerated bone presented statistically homogenous values analogous to native bone at the three time points, whereas hardness (H) values were equivalent to the native radial bone only at 24 weeks. The negative control samples showed limited healing at 8 weeks. Custom engineered ß-TCP scaffolds are biocompatible, resorbable, and can directionally regenerate and remodel bone in a segmental long-bone defect in a rabbit model. Custom designs and fabrication of ß-TCP scaffolds for use in other bone defect models warrant further investigation.
Assuntos
Materiais Biocompatíveis/farmacologia , Osso e Ossos/patologia , Impressão Tridimensional , Alicerces Teciduais/química , Cicatrização , Animais , Osso e Ossos/diagnóstico por imagem , Varredura Diferencial de Calorimetria , Nanotecnologia , Coelhos , Espectroscopia de Infravermelho com Transformada de Fourier , Termogravimetria , Microtomografia por Raio-XRESUMO
PURPOSE: The present study hypothesized that different bone healing patterns through initial stages of osseointegration would be observed when three distinct commercially available implant systems (Nobel Groovy, Implacil, and Zimmer TSV) were used, leading to significant variations in histometric levels of total bone and new bone formation during the osseointegration process. MATERIALS AND METHODS: A total of 48 implants were placed bilaterally on the tibias of eight beagle dogs and allowed to heal for 2 and 6 weeks. Following euthanasia, nondecalcified specimens were processed for morphologic and histometric evaluation. Bone-to-implant contact (BIC) and new bone area fraction occupancy (BAFO) analyses for native and new bone were performed along the whole perimeter of each implant and separately for the cortical and trabecular bone regions. RESULTS: Morphologic evaluation of cortical bone presented different healing patterns and osseointegration levels for different implant systems as time elapsed in vivo. Interfacial remodeling was the chief healing pattern in Zimmer implants, while a combination of interfacial remodeling and healing chambers was observed in Nobel and Implacil implants. When trabecular bone was evaluated, similar bone healing patterns were observed between systems despite different levels of osseointegration observed as a function of implantation time, implant system, and native and/or new bone BIC and BAFO. CONCLUSION: Different implant systems led to different healing patterns during early stages of osseointegration. Such variation in pattern was more noticeable in the cortical regions compared to the trabecular regions. The variation in bone healing pattern did significantly influence overall indicators of native and new BIC and BAFO during the osseointegration process. The postulated hypothesis was accepted.
RESUMO
A bone drilling concept, namely osseodensification, has been introduced for the placement of endosteal implants to increase primary stability through densification of the osteotomy walls. This study investigated the effect of osseodensification on the initial stability and early osseointegration of conical and parallel walled endosteal implants in low density bone. Five male sheep were used. Three implants were inserted in the ilium, bilaterally, totaling 30 implants (n=15 conical, and n=15 parallel). Each animal received 3 implants of each type, inserted into bone sites prepared as follows: (i) regular-drilling (R: 2mm pilot, 3.2mm, and 3.8mm twist drills), (ii) clockwise osseodensification (CW), and (iii) counterclockwise (CCW) osseodensification drilling with Densah Bur (Versah, Jackson, MI, USA): 2.0mm pilot, 2.8mm, and 3.8mm multi-fluted burs. Insertion torque as a function of implant type and drilling technique, revealed higher values for osseodensification relative to R-drilling, regardless of implant macrogeometry. A significantly higher bone-to-implant contact (BIC) for both osseodensification techniques (p<0.05) was observed compared to R-drilling. There was no statistical difference in BIC as a function of implant type (p=0.58), nor in bone-area-fraction occupancy (BAFO) as a function of drilling technique (p=0.22), but there were higher levels of BAFO for parallel than conic implants (p=0.001). Six weeks after surgery, new bone formation along with remodeling sites was observed for all groups. Bone chips in proximity with the implants were seldom observed in the R-drilling group, but commonly observed in the CW, and more frequently under the CCW osseodensification technique. In low-density bone, endosteal implants present higher insertion torque levels when placed in osseodensification drilling sites, with no osseointegration impairment compared to standard subtractive drilling methods.
Assuntos
Densidade Óssea , Ílio/fisiologia , Osseointegração , Próteses e Implantes , Animais , Interface Osso-Implante , Masculino , Osteotomia , Ovinos , TorqueRESUMO
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: Two implant surface roughness profiles (acid etched, machined) in CP titanium (type II) alloy implants were boronized by solid-state diffusion until 10-15 µm 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 vivobone healing warrant further investigation
No disponible
Assuntos
Animais , Masculino , Osseointegração/fisiologia , Compostos de Boro/química , Titânio/química , Prótese Ancorada no Osso , Boro/química , Ovinos , Osseointegração/efeitos dos fármacos , Quadril/cirurgia , Microscopia Eletrônica de Varredura , Propriedades de Superfície , Reprodutibilidade dos Testes , Fatores de TempoRESUMO
BACKGROUND: This study aimed to compare the histomorphometric and histological bone response to laser-sintered implants followed by resorbable-blasting media (RBM) process relative to standard machined/RBM surface treated implants. MATERIAL AND METHODS: Six male sheep (n=6) received 2 Ti-6Al-4V implants (1 per surface) in each side of the mandible for 6 weeks in vivo. The histomorphometric parameters bone-implant contact (BIC) and bone area fraction occupancy (BAFO) were evaluated. RESULTS: Optical interferometry revealed higher Sa and Sq values for the laser-sintered/RBM surface in relation to standard/RBM implants. No significant differences in BIC were observed between the two groups (p > 0.2), but significantly higher BAFO was observed for standard/RBM implants (p < 0.01). CONCLUSIONS: The present study demonstrated that both surfaces were biocompatible and osseoconductive, and the combination of laser sintering and RBM has no advantage over the standard machined implants with subsequent RBM