Polydioxanone Enhances Bone Regeneration After Resection and Reconstruction of Rat Femur with rhBMP2.

The aim of this study was to assess the bone regeneration potential of a polydioxanone (PDO) scaffold together with recombinant human bone morphogenetic protein-2 (rhBMP-2) for the reconstruction of large bone defect. In total, 24 male rats (6 months old) were subjected to bilateral femoral stabilization using titanium plates to create a 2 mm gap, and reconstruction using rhBMP-2 (Infuse®; 3.25 µg). The bone defects were covered with PDO (PDO group), or with titanium mesh (Ti group). Animals were euthanized on days 14 and 60. Simultaneously, 16 rats received PDO and Ti in their dorsum for the purpose of biocompatibility analysis at 3, 5, 7, and 10 days postoperatively. X-ray densitometry showed a higher density in the PDO group on day 14. On day 60, coverage of the bone defect with PDO showed a larger quantity of newly formed bone than that found for the Ti group, a lower inflammatory infiltrate value, and a more significant number of blood vessels on day 14. By immunohistochemical assessment, runt-related transcription factor 2 (RUNX2) and osteocalcin (OCN) showed higher labeling on day 14 in the PDO group. On day 60, bone morphogenetic protein-2 (BMP-2) showed higher labeling in the PDO group, whereas Ti showed higher labeling for osteoprotegerin, nuclear factor kappa B ligand-activating receptor, RUNX2, and OCN. Furthermore, biocompatibility analysis showed a higher inflammatory response in the Ti group. The PDO scaffold enhanced bone regeneration when associated with rhBMP-2 in rat femur reconstruction. Impact statement Regeneration of segmental bone defects is a difficult task, and several techniques and materials have been used. Recent advances in the production of synthetic polymers, such as polydioxanone (PDO), produced by three-dimensional printing, have shown distinct characteristics that could improve tissue regeneration even in an important bone defect. The present preclinical study showed that PDO membranes used as scaffolds to carry recombinant human bone morphogenetic protein-2 (rhBMP-2) improved bone tissue regeneration by more than 8-fold when compared with titanium mesh, suggesting that PDO membranes could be a feasible and useful material for use in guided bone regeneration. (In English, viable is only used for living creatures capable of sustaining life.

Feasible low bone density condition for assessing bioactivity in ex-in vivo and in vivo studies.

OBJECTIVE: To choose a critical animal model for assessments of bone repair with implant installation by comparing senile rats (SENIL) to young ovariectomized rats (OXV). METHODOLOGY: For the ex-in vivo study, the femurs were precursors for bone marrow mesenchymal stem cells. Cellular responses were performed, including cell viability, gene expression of osteoblastic markers, bone sialoprotein immunolocalization, alkaline phosphatase activity, and mineralized matrix formation. For the in vivo study, the animals received implants in the region of the bilateral tibial metaphysis for histometric, microtomography, reverse torque, and confocal microscopy. RESULTS: Cell viability showed that the SENIL group had lower growth than OVX. Gene expression showed more critical responses for the SENIL group (p<0.05). The alkaline phosphatase activity obtained a lower expression in the SENIL group, as for the mineralization nodules (p<0.05). The in vivo histological parameters and biomechanical analysis showed lower data for the SENIL group. The confocal microscopy indicated the presence of a fragile bone in the SENIL group. The microtomography was similar between the groups. The histometry of the SENIL group showed the lowest values (p<0.05). CONCLUSION: In experimental studies with assessments of bone repair using implant installation, the senile model promotes the most critical bone condition, allowing a better investigation of the properties of biomaterials and topographic changes.

Feasible low bone density condition for assessing bioactivity in ex-in vivo and in vivo studies

Abstract Objective To choose a critical animal model for assessments of bone repair with implant installation by comparing senile rats (SENIL) to young ovariectomized rats (OXV). Methodology For the ex-in vivo study, the femurs were precursors for bone marrow mesenchymal stem cells. Cellular responses were performed, including cell viability, gene expression of osteoblastic markers, bone sialoprotein immunolocalization, alkaline phosphatase activity, and mineralized matrix formation. For the in vivo study, the animals received implants in the region of the bilateral tibial metaphysis for histometric, microtomography, reverse torque, and confocal microscopy. Results Cell viability showed that the SENIL group had lower growth than OVX. Gene expression showed more critical responses for the SENIL group (p<0.05). The alkaline phosphatase activity obtained a lower expression in the SENIL group, as for the mineralization nodules (p<0.05). The in vivo histological parameters and biomechanical analysis showed lower data for the SENIL group. The confocal microscopy indicated the presence of a fragile bone in the SENIL group. The microtomography was similar between the groups. The histometry of the SENIL group showed the lowest values (p<0.05). Conclusion In experimental studies with assessments of bone repair using implant installation, the senile model promotes the most critical bone condition, allowing a better investigation of the properties of biomaterials and topographic changes.

Análise do potencial do reparo ósseo através da reconstrução de ressecções segmentares por meio da associação de scaffolds de Polidioxanona ou malha de titânio e rhBMP-2: estudo in vivo / Bone potential analysis through segmental resection reconstruction using Polydioxanone or Titanium Mesh scaffolds and rhBMP-2: in vivo study

O objetivo deste trabalho foi analisar o potencial bioativo de um "scaffold" de Polidioxanona (PDO) com associação da rhBMP-2, nas reconstruções após simulação de ressecção óssea em fêmures de ratos. Para tanto, 24 ratos, machos, adultos, com 6 meses de idade, foram submetidos a ressecção e reconstrução dos fêmures bilateralmente. Inicialmente foi realizada a estabilização com fixação de placas e parafusos de titânio do sistema 1.5mm e em seguida a confecção de um "gap" de 2mm. A reconstrução foi realizada com rhBMP-2 (Infuse) carreada em esponja de colágeno (3,25 µg), tendo uma malha de titânio, para o grupo Titânio (n=24 fêmures) (grupo controle), atuando como um arcabouço. E para o grupo PDO (n=24 fêmures) (grupo teste), a reconstrução foi realizada também com a rhBMP-2 carreada em uma esponja de colágeno (3,25 µg), envolvido por um "scaffold" de PDO. Desses animais, 16 (2 por tempo) receberam em seu dorso, no plano subcutâneo, um fragmento do mesmo material testado em seu fêmur, para análise de biocompatibilidade, que foram removidos sob anestesia local, junto de fragmento do tecido subcutâneo adjacente, aos 3, 5, 7 e 10 dias para análise. Os animais foram submetidos à eutanásia (n=6 por grupo) nos períodos de 14 e 60 dias após a cirurgia de reconstrução tiveram seus órgãos de metabolização (cérebro, rim, fígado e músculo) removidos para análise anatomopatológica e seus fêmures também foram removidos, reduzidos, radiografados para análise da densitometria radiográfica posteriormente os fêmures passaram por descalcificação e em seguida todas as peças foram submetidas ao processamento para obtenção de lâminas com cortes de 5 µm de espessura, para avaliação histológica, com avaliação da área óssea neoformada e perfil inflamatório e para análise imunohistoquimica através das proteínas Runx2, OPG, RANKL, OCN e BMP2. Todos os dados quantitativos foram submetidos ao teste ANOVA-2 fatores e quando p< 0,05, o pós-teste Tukey foi realizado. Os resultados da densitometria radiográfica demonstraram maior densidade para o grupo PDO, especialmente no período de 14 dias (p< 0,05). Na análise histológica observou-se reparo mais favorável para o grupo PDO, especialmente aos 60 dias quando comparado ao Titânio, com diferença estatística significativa (p = 0.002) bem como menor infiltrado inflamatório e maior número de vasos sanguíneos aos 14 dias. Com relação as imunomarcações, BMP-2 não apresentou marcações para Titânio e dados expressivos para PDO, com diferença significativamente estatística aos 60 dias (p< 0.05). OPG e RANKL mostraram maior marcação para titânio, principalmente aos 60 dias (p< 0.05). Já Runx2 e OCN apresentaram resultados superiores para PDO aos 14 dias, entretanto, aos 60 dias titânio demonstrou maior expressão. A análise de biocompatibilidade mostrou maior processo inflamatório para o grupo titânio. Os órgãos de metabolização apresentaram aspectos de higidez dentro da normalidade para ambos grupos. Os resultados deste trabalho demonstram um padrão reparacional mais favorável à associação do "Scaffold" de PDO com a rhBMP-2, quando comparado a reconstrução com malha de titânio(AU)

The objective of this work was to analyze the bioactive potential of a Polydioxanone (PDO) scaffold with rhBMP-2 association, in reconstructions after simulating bone resection in rat femurs. Therefore, 24 male, adult rats, aged 6 months, underwent resection and reconstruction of the femurs bilaterally. Initially, stabilization was performed with fixation of titanium plates and screws of the 1.5mm system and then a 2mm gap was created. The reconstruction was performed with rhBMP-2 (Infuse) loaded in a collagen sponge (3.25 µg), with a titanium mesh, for the Titanium group (n=24 femurs) (control group), acting as a scaffold. And for the PDO group (n=24 femurs) (test group), the reconstruction was also performed with rhBMP-2 carried in a collagen sponge (3.25 µg), surrounded by a PDO scaffold. Of these animals, 16 (2 per time) received on their back, in the subcutaneous plane, a fragment of the same material tested in their femur, for biocompatibility analysis, which was removed under local anesthesia, together with a fragment of the adjacent subcutaneous tissue, at 3, 5, 7 and 10 days for analysis. The animals were euthanized (n=6 per group) in the periods of 14 and 60 days after the reconstruction surgery, had their metabolizing organs (brain, kidney, liver, and muscle) removed for anatomopathological analysis and their femurs were also removed, reduced, radiographed for analysis of radiographic densitometry later the femurs underwent decalcification and then all the pieces were submitted to processing to obtain 5 µm thick slices for histological evaluation, with the evaluation of the newly formed bone area and inflammatory profile and for immunohistochemical analysis through Runx2, OPG, RANKL, OCN, and BMP2 proteins. All quantitative data were submitted to the 2-way ANOVA test and when p< 0.05, the Tukey post-test was performed. The results of radiographic densitometry showed higher density for the PDO group, especially in the 14-day period (p< 0.05). In the histological analysis, a more favorable repair was observed for the PDO group, especially at 60 days when compared to Titanium, with a statistically significant difference (p = 0.002), as well as a lower inflammatory, infiltrate and a greater number of blood vessels at 14 days. Regarding immunostaining, BMP-2 did not show staining for Titanium and expressive data for PDO, with a statistically significant difference at 60 days (p< 0.05). OPG and RANKL showed higher staining for titanium, mainly at 60 days (p< 0.05). On the other hand, Runx2 and OCN showed superior results for PDO at 14 days, however, at 60 days titanium showed greater expression. The biocompatibility analysis showed a greater inflammatory process for the titanium group. The metabolizing organs presented aspects of health within the normal range for both groups. The results of this work demonstrate a more favorable repair pattern for the association of the PDO scaffold with rhBMP-2, when compared to reconstruction with titanium mesh(AU)

A triple-blind randomized clinical trial of different associations between dexamethasone and non-steroids anti-inflammatories for preemptive action in third molar extractions.

The aim of this study is to evaluate the preemptive analgesic effects of dexamethasone (DEX) alone or combined with non-steroidal anti-inflammatory drugs (NSAIDs) in third molar surgeries. The subjects were divided into five groups (n = 20 teeth/group); subjects received only 8 mg of dexamethasone 1 h before the surgical procedure (DEX group), or in combination with etodolac (DEX + ETO), ketorolac (DEX + KET), ibuprofen (DEX + IBU), loxoprofen (DEX + LOX). Paracetamol 750 mg was provided as the number of rescue analgesics (NRA). Salivary PGE2 expression was measured preoperatively and at 48 h. Edema and Maximum mouth opening (MMO) were measured postoperatively at 48 h and 7 days. A visual analog scale (VAS) was performed postoperatively at 6, 12, 24, 48, 72 h, and 7 days. Salivary expression of PGE2 showed a decrease only for the DEX group. Edema and MMO and NRA consumption showed no significant differences among the groups (P > 0.05). The VAS showed a significantly lower pain perception at 6 h after the surgery for the DEX + ETO and DEX + KET groups (P < 0.05). The combination of DEX and NSAIDS should be considered for preemptive acute postsurgical pain management in third molar surgery. In some drug associations such as dexamethasone 8 mg + NSAIDS (ETO and KET) in the pre-operative time, only a few rescue analgesics are necessary.

Titanium Allergy Caused by Dental Implants: A Systematic Literature Review and Case Report.

(1) Background: Hypersensitivity reactions to metals may arise in predisposed patients chronically exposed to metallic materials, including dental implants made of titanium alloys. The purpose of this article was to systematically review titanium allergy manifestations in patients treated with dental implants and report a clinical case; (2) Methods: A systematic electronic search was performed for articles published in the English language until July 2021. The following eligibility criteria were adopted: (1) Population: individuals undergoing titanium and/or titanium alloy implant-supported rehabilitations; (2) Exposure: peri-implant soft tissue reactions attributable to implant insertion; (3) Outcome: evidence of titanium allergy, diagnostic methods, and forms of resolution; (3) Results: The included studies, in summary, presented evidence that titanium should not be considered an inert material, being able to trigger allergic reactions, and may be responsible for implant failure. A 55-year-old male patient received 3 implants in the posterior region of the left mandible and presented an epulis-like lesion developed from the peri-implant mucosa. The immunohistochemical analysis of the biopsy specimen confirmed the initial diagnosis of allergic reaction to titanium; (4) Conclusions: Although the evidence is weak, and titanium allergy has a low incidence, hypersensitivity reactions should not be underestimated. A rapid and conclusive diagnosis is mandatory to prevent further complications.