Exploring calcium-free alternatives in endochondral bone repair tested on In vivo trials - A review.

Bone repair via endochondral ossification is a complex process for the critical size reparation of bone defects. Tissue engineering strategies are being developed as alternative treatments to autografts or allografts. Most approaches to bone regeneration involve the use of calcium composites. However, exploring calcium-free alternatives in endochondral bone repair has emerged as a promising way to contribute to bone healing. By analyzing researches from the last ten years, this review identifies the potential benefits of such alternatives compared to traditional calcium-based approaches. Understanding the impact of calcium-free alternatives on endochondral bone repair can have profound implications for orthopedic and regenerative medicine. This review evaluates the efficacy of calcium-free alternatives in endochondral bone repair through in vivo trials. The findings may guide future research to develop innovative strategies to improve endochondral bone repair without relying on calcium. Exploring alternative approaches may lead to the discovery of novel therapies that improve bone healing outcomes.

Micro-Computed Tomography Analysis of Peri-Implant Bone Defects Exposed to a Peri-Implantitis Microcosm, with and without Bone Substitute, in a Rabbit Model: A Pilot Study.

Peri-implantitis is an inflammatory condition characterized by inflammation in the peri-implant connective tissue and a progressive loss of supporting bone; it is commonly associated with the presence of biofilms on the surface of the implant, which is an important factor in the development and progression of the disease. The objective of this study was to evaluate, using micro-CT, the bone regeneration of surgically created peri-implant defects exposed to a microcosm of peri-implantitis. Twenty-three adult New Zealand white rabbits were included in the study. Bone defects of 7 mm diameter were created in both tibiae, and a cap-shaped titanium device was placed in the center, counter-implanted with a peri-implantitis microcosm. The bone defects received a bone substitute and/or a resorbable synthetic PLGA membrane, according to random distribution. Euthanasia was performed 15 and 30 days postoperatively. Micro-CT was performed on all samples to quantify bone regeneration parameters. Bone regeneration of critical defects occurred in all experimental groups, with a significantly greater increase in cases that received bone graft treatment (p < 0.0001), in all measured parameters, at 15 and 30 days. No significant differences were observed in the different bone neoformation parameters between the groups that did not receive bone grafts (p > 0.05). In this experimental model, the presence of peri-implantitis microcosms was not a determining factor in the bone volume parameter, both in the groups that received regenerative treatment and in those that did not.

Safety and efficacy of a novel retrograde route for femoral bone graft harvesting by Reamer-Irrigator-Aspirator: a pilot study on 24 patients.

BACKGROUND: The Reamer-Irrigator-Aspirator system was initially developed to reduce fat embolism and thermic necrosis during reamed intramedullary nail fixation of femoral shaft fractures. Currently, this system is used in extended applications including accessing large volume of autologous bone graft, as alternative for iliac crest harvesting. Antegrade femoral bone graft harvesting using the Reamer-Irrigator-Aspirator system is considered the standard technique. The aim of our study is to evaluate the efficacy (bone graft volume) and the complications (blood loss, postoperative pain, and incidence of iatrogenic fractures) of the Reamer-Irrigator-Aspirator system through the retrograde femoral route in a series of patients with post-traumatic bone defects or nonunions. METHODS: A non-controlled single center retrospective observational cohort study was conducted in a level1 trauma center to evaluate all patients who were treated using the RIA system. Between November 2015 and May 2019, 24 patients (8 women and 16 men; mean age: 41 years [range 27-55 years]) with bone defects or nonunions underwent bone graft harvesting using the Reamer-Irrigator-Aspirator system through retrograde femoral route. Postoperative pain, complications, and bone graft volume were analyzed. Inclusion criteria was patients older than 18 years with a diagnosis of post-traumatic bone defect or associated tibial or femoral nonunion, with minimum 6-months follow, treated using the RIA. We hypothesized that the retrograde route of the RIA system is a safe and efficacious method for bone harvesting. RESULTS: The average volume of collected graft was 45 cc (range 30-60 cc). In 83% of the cases, bone grafting was sufficient, while in 17% it was necessary to add iliac crest bone graft to completely fill the bone defect. A mean drop in postoperative hemoglobin of 4.1 g / dL (range 0.5-6.0 g / dL) was evidenced. In 4 cases (33%), a unit of packed red blood cells was required. Regarding postoperative pain, visual analogue scale after 3 months postoperatively was 1.6 in average. After 6 months, the value has decreased to 0.4. There were no perioperative or postoperative complications at 6-month follow-up. CONCLUSION: In this limited case series, large volumes of bone graft were harvested using the retrograde route of the RIA system and there were no intra-/ postoperative complications observed at 6-month follow-up. Therefore this novel technique appears safe and efficacious. However, it's important to highlight that future prospective controlled studies are necessary to validate the insights from this pilot study.

Evaluation of tissue in repair with natural latex and / or hyaluronic acid in surgical bone defects

Abstract This study evaluated the bone repair in surgical defects of rats treated with hyaluronic acid (HA) associated or not with Hevea brasiliensis fraction protein (F-1). Bone defect were created in 15 albino Wistar rats divided into 3 groups (n=5): Control group (1) - blood clot; HA group (2) - 0.5% hyaluronic acid; HAF1 group (3) - 0.1% F-1 protein fraction dissolved in 0.5% hyaluronic acid. After 4 weeks, the animals were euthanized and the bone repair was evaluated through histomorphometric analysis, zymography and immunohistochemistry. The neoformed bone area did not show a significant difference (p = 0.757), but there was a tendency for bone trabeculation to increase in the groups HA and HAF1. For immunohistochemically analysis, there was a difference in vascular endothelial growth factor (VEGF) labeling (p = 0.023), being higher in the groups HA and HAF1 than the control group. No significant difference in bone sialoprotein (BSP) (p = 0.681), osteocalcin (p = 0.954), however, significant difference in platelet endothelial cell adhesion molecule-1 (CD-31) (p = 0.040), with HAF1 group being significantly lower than the control. For zymographic analysis, there was no significant difference for metalloproteinase-2 (MMP-2) (p = 0.068), but there was a tendency to increase MMP-2 in the HA group. Despite the influence on angiogenic factors and the apparent tendency for greater trabeculation in the HA and HAF1 groups, there was no significant difference in the area of ​​newly formed bone tissue in the analyzed period.

Resumo Este estudo avaliou o reparo ósseo em defeitos cirúrgicos de ratos tratados com ácido hialurônico (AH) associado ou não à fração proteica de Hevea brasiliensis (F-1). Foram criados defeitos ósseos em 15 ratos albinos Wistar divididos em 3 grupos (n = 5): Grupo controle (1) - coágulo sanguíneo; Grupo HA (2) - ácido hialurônico 0,5%; Grupo HAF1 (3) - fração proteica F-1 0,1% dissolvida em ácido hialurônico a 0,5%. Após 4 semanas, os animais foram submetidos à eutanásia e o reparo ósseo avaliado por meio de análise histomorfométrica, zimografia e imunohistoquímica. A área óssea neoformada não apresentou diferença significativa (p = 0,757), mas houve tendência de aumento da trabeculação óssea nos grupos HA e HAF1. Para a análise imunoistoquímica, houve diferença na marcação do fator de crescimento endotelial vascular (VEGF) (p = 0,023), sendo maior nos grupos HA e HAF1 do que no grupo controle. Nenhuma diferença significativa na sialoproteína óssea (BSP) (p = 0,681), osteocalcina (p = 0,954), no entanto, diferenças significativas foram encontradas para a molécula de adesão de células endoteliais plaquetárias-1 (CD-31) (p = 0,040), com o grupo HAF1 sendo significativamente inferior ao controle. Para a análise zimográfica, não houve diferença significativa para metaloproteinase-2 (MMP-2) (p = 0,068), mas houve tendência de aumento da MMP-2 no grupo HA. Apesar da influência sobre os fatores angiogênicos e da aparente tendência de maior trabeculação nos grupos HA e HAF1, não houve diferença significativa na área de tecido ósseo neoformado no período analisado.

Bone Regeneration in an Extreme Dental Clinical Condition.

Here, the authors present the clinical case of a 45-year-old woman with a diagnosis of a chronic periodontal abscess of the tooth #8. After atraumatic dental extraction and bone regeneration with the use of platelet-rich fibrin and bone graft, the area showed excellent bone regeneration with adequate stability of the soft tissue, even 4 months after the surgery.

Bone Defects in Revision Total Knee Arthroplasty.

The increase in the number of revision total knee arthroplasty surgeries has been observed in recent years, worldwide, for several causes. In the United States, a 601% increase in the number of total knee arthroplasties, between 2005 and 2030, is estimated. Among the enormous challenges of this complex surgery, the adequate treatment of bone defects is essential to obtain satisfactory and lasting results. The adequate treatment of bone defects aims to build a stable and lasting support platform for the implantation of the definitive prosthetic components and, if possible, with the reconstruction of bone stock. Concomitantly, it allows the correct alignment of the prosthetic and limb components, as well as restoring the height of the joint interline and, thus, restoring the tension of soft parts and load distribution to the host bone, generating a joint reconstruction with good function, stable, and painless. There are several options for the management of these bone defects, among them: bone cement with or without reinforcement with screws, modular metallic augmentations, impacted bone graft, structural homologous graft and, more recently, metal metaphyseal cones, and metaphyseal sleeves. The objective of the present article was to gather classic information and innovations about the main aspects related to the treatment of bone defects during revision surgeries for total knee arthroplasty.

In vivo effectiveness of hybrid membranes with osteogenic growth peptide for bone regeneration.

Guided bone regeneration (GBR) technique helps to restore bone tissue through cellular selectivity principle. Currently no osteoinductive membrane exists on the market. Osteogenic growth peptide (OGP) acts as a hematopoietic stimulator. This association could improve the quality of bone formation, benefiting more than 2.2 million patients annually. The objective of this work was to develop membranes from ureasil-polyether materials containing OGP. The membranes were characterized by differential scanning calorimetry (DSC) and small angle X-ray scattering (SAXS). OGP was synthesized by the solid phase method. Sterilization results using gamma radiation at 24 kGy did not change the structure of the material, as confirmed by DSC. The SAXS technique revealed the structural homogeneity of the matrix. OGP was incorporated in 66.25 × 10-10  mol and release results showed that the ureasil-PPO400/PEO500 and ureasil-PPO400/PEO1900 membranes released 7% and 21%, respectively, after 48 h. In vivo results demonstrated that the amount and quality of bone tissue formed in the bone defects in the presence of ureasil-polyether membranes with OGP were similar to commercial collagen material with BMP. The results allow us to conclude that membranes with OGP have characteristics that make them potential candidates for the GBR.

Bone Defects in Revision Total Knee Arthroplasty / Falhas ósseas nas revisões de artroplastia total do joelho

Abstract The increase in the number of revision total knee arthroplasty surgeries has been observed in recent years, worldwide, for several causes. In the United States, a 601% increase in the number of total knee arthroplasties, between 2005 and 2030, is estimated. Among the enormous challenges of this complex surgery, the adequate treatment of bone defects is essential to obtain satisfactory and lasting results. The adequate treatment of bone defects aims to build a stable and lasting support platform for the implantation of the definitive prosthetic components and, if possible, with the reconstruction of bone stock. Concomitantly, it allows the correct alignment of the prosthetic and limb components, as well as restoring the height of the joint interline and, thus, restoring the tension of soft parts and load distribution to the host bone, generating a joint reconstruction with good function, stable, and painless. There are several options for the management of these bone defects, among them: bone cement with or without reinforcement with screws, modular metallic augmentations, impacted bone graft, structural homologous graft and, more recently, metal metaphyseal cones, and metaphyseal sleeves. The objective of the present article was to gather classic information and innovations about the main aspects related to the treatment of bone defects during revision surgeries for total knee arthroplasty.

Resumo O aumento do número de cirurgias de revisão de artroplastia total do joelho tem sido observado nos últimos anos, em todo o mundo, por diversas causas. Nos Estados Unidos, é estimado um aumento de 601% no número de artroplastias totais do joelho entre 2005 e 2030. Dentre os enormes desafios dessa cirurgia complexa, o adequado tratamento dos defeitos ósseos é essencial para a obtenção de resultados satisfatórios e duradouros. O adequado tratamento dos defeitos ósseos objetiva construir uma plataforma de suporte estável e duradoura para a implantação dos componentes protéticos definitivos e, se possível, com recomposição do estoque ósseo. Concomitantemente, possibilita o correto alinhamento dos componentes protéticos e do membro, assim como permite restabelecer a altura da interlinha articular e, dessa forma, restaurar a tensão de partes moles e distribuição de carga ao osso hospedeiro, gerando uma reconstrução articular com boa função, estável e indolor. Diversas são as opções para manejo dessas falhas ósseas, entre elas: cimento ósseo com ou sem reforço com parafusos, aumentos metálicos modulares, enxerto ósseo impactado, enxerto estrutural homólogo e, mais recentemente, cones metafisários de metal trabecular e sleeve metafisário. O objetivo do presente artigo foi reunir informações clássicas e inovações dos principais aspectos relativos ao tratamento das falhas ósseas durante as cirurgias de revisão de artroplastia total do joelho.

Characterization and Biological Performance of Marine Sponge Collagen

Abstract This study characterized the morphological aspects of marine collagen - spongin (SPG) extract from marine sponges, as well as, evaluating its in vitro and in vivo biological performance. Aplysina fulva marine sponge was used for the SPG extraction. It was investigated the physicochemical and morphological properties of SPG by using scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction and compared to PMMA and bovine collagen. Additionally, the SPG cytotoxicity and its influence on cell proliferation, through in vitro tests. Moreover, the in vivo biological response was investigated using an experimental model of tibial bone defect. The results demonstrated that SPG presented an irregular granular aspect, with a composition of OH, C=O, NH, CN and an amorphous profile. Also, in vitro viability results for the L929 and MC3T3 cell lines cultured with SPG extracts demonstrated normal growth in comparison to controls, except for MC3T3 viability at day 3. For in vivo analysis, using tibial bone defects in rats, SPG treated animals presented an increased rate of material resorption and higher granulation and bone formation deposition in the region of the defect, mainly after 45 days. As a conclusion, SPG was successfully extracted. The in vitro and in vivo studies pointed out that SPG samples produced an increase in L929 and MC3T3 viability and improved the performance in tibial bone defects. It can be concluded that SPG can be used as a bone graft for bone regeneration.

Graft application and dexamethasone treatment influences new bone formation in rat tibial bone defects / Aplicación de injerto y tratamiento con dexametasona influyen en la formación de hueso nuevo en los defectos en la tibia de rata

SUMMARY: The objective of this study were bone defect complications that occur due to traumas or infections. Bone grafts are required to provide support, fill gaps and improve biological repair in skeletal damage. Dexamethasone plays role in calcium signaling modulation and used in diseases. Aim of this study was to evaluate osteonectin and osteopontin expressions in new bone development after dexamethasone application on tibial bone defects. Rats were divided into defect, defect+graft and defect+graft+dexamethasone treated groups. Tibial bone defect created, and rats were kept immobile for 28 days. Alloplastic material was placed in defect area in second and group third groups. 2.5 mg/kg Dex and normal saline were injected to dexamethasone and defect groups twice a week for 56 days. Inflammation and congestion were increased in defect and defect+graft groups. Defect+graft+dexamethasone group; increased number of osteoblast and osteocyte cells, dense bone matrix, formation of new bone trabeculae was observed. Defect+graft group; osteonectin expression in graft regions, osteoblast cells, some connective tissue cells and fibers were seen whereas in defect+graft+dexamethasone group; osteopontin expression in osteoblast and osteocyte cells of new bone trabeculae were observed. Dexamethasone may lead to formation of new bone trabeculae into the graft material resulting in increased osteoconduction and osteoinductive effect for differentiation of osteon.

RESUMEN: Los defectos óseos son complicaciones que ocurren debido a traumas o infecciones. Se requieren injertos óseos para proporcionar apoyo, llenar los espacios y mejorar la reparación biológica en el hueso dañado. La dexametasona desempeña un papel importante en la modulación de la señalización del calcio y se usa en enfermedades. El objetivo de este estudio fue evaluar las expresiones de osteonectina y osteopontina en el desarrollo óseo después de la aplicación de dexametasona en defectos óseos tibiales. Las ratas se dividieron en grupos: defecto, defecto + injerto y defecto + injerto + grupos tratados con dexametasona. Se creó un defecto óseo tibial, y las ratas se mantuvieron inmóviles durante 28 días. El material aloplástico se colocó en el área del defecto en el segundo y tercer grupo. Se inyectaron 2,5 mg / kg de dexametasona y solución salina normal a grupos de defectos dos veces por semana durante 56 días. La inflamación y la congestión aumentaron en los grupos de defectos y defectos + injerto; En el grupo defecto + injerto + grupo tratado con dexametasona se observó un aumento en el número de osteoblastos y osteocitos, de matriz ósea densa y en la formación de nuevas trabéculas óseas. En el grupo defecto + grupo de injerto se observó la expresión de osteonectina en las áreas de injerto, osteoblastos, algunas células y fibras de tejido conectivo, mientras que en el grupo defecto + injerto + dexametasona se observó la expresión de osteopontina en osteoblastos y osteocitos y formación de nuevas trabéculas óseas . En conclusión la dexametasona puede conducir a la formación de nuevas trabéculas óseas en el material de injerto, lo que resulta en un aumento de la osteoconducción y un efecto osteoinductivo para la diferenciación del osteón.

Concentration-dependent effects of latex F1-protein fraction incorporated into deproteinized bovine bone and biphasic calcium phosphate on the repair of critical-size bone defects.

F1-protein fraction (F1) is a natural bioactive compound extracted from the rubber tree, Hevea brasiliensis, and has been recently studied for its therapeutic potential in wound healing. In this study, we investigated the concentration-dependent effects of F1 (0.01%, 0.025%, 0.05%, and 0.1%) incorporated into deproteinized bovine bone (DBB) and porous biphasic calcium phosphate (pBCP), on the repair of rat calvarial critical-size bone defects (CSBD). The defects were analyzed by 3D-microtomography and 2D-histomorphometry at 12 weeks postsurgery. The binding efficiency of F1 to pBCP (96.3 ± 1.4%) was higher than that to DBB (67.7 ± 3.3%). In vivo analysis showed a higher bone volume (BV) gain in all defects treated with DBB (except in 0.1% of F1) and pBCP (except in 0.05% and 0.1% of F1) compared to the CSBD without treatment/control group (9.96 ± 2.8 mm3 ). DBB plus 0.025% F1 promoted the highest BV gain (29.7 ± 2.2 mm3 , p < .0001) compared to DBB without F1 and DBB plus 0.01% and 0.1% of F1. In the pBCP group, incorporation of F1 did not promote bone gain when compared to pBCP without F1 (15.9 ± 4.2 mm3 , p > .05). Additionally, a small BV occurred in defects treated with pBCP plus 0.1% F1 (10.4 ± 1.4 mm3, p < .05). In conclusion, F1 showed a higher bone formation potential in combination with DBB than with pBCP, in a concentration-dependent manner. Incorporation of 0.25% F1 into DBB showed the best results with respect to bone formation/repair in CSBD. These results suggest that DBB plus 0.25% F1 can be used as a promising bioactive material for application in bone tissue engineering.

Reparo de defeitos ósseos críticos usando hidroxiapatita sintética ou bovina com ou sem fração mononuclear da medula óssea: análise histomorfométrica e imuno-histoquímica / Repair of critical size bone defects using synthetic or bovine hydroxyapatite with or without bone marrow mononuclear fraction: histomorphometric and immunohistochemical analysis

O presente trabalho teve como objetivo avaliar a regeneração óssea de defeitos ósseos críticos na calvária de ratos com a utilização de enxerto xenógeno Bio-Oss Small ( Bio-Oss® Geistlich Pharma AG, Wolhusen, Suíça) e hidroxiapatita sintética, (Alobone poros Osseocon Biomateriais Ltda., Rio de Janeiro/RJ, Brasil ) puros e enriquecidos com a fração mononuclear medular de célula tronco. Material e métodos: quarenta ratos adultos jovens machos, Sprague Dawley, com doze semanas distribuídos em cinco grupos com oito animais, sendo assim denominados: grupo controle, grupo 1, grupo 2, grupo 3, e grupo 4. Além dos quarenta ratos adultos jovens, mais oito ratos adultos jovens machos, Sprague Dawley, com doze semanas foram utilizados como doadores de medula óssea. Os cinco grupos foram submetidos a defeitos ósseos críticos com trefina de 8 (oito) milímetros de diâmetro, na região temporoparietal. No grupo controle não teve a colocação de biomaterial, no grupo 1 os defeitos críticos foram preenchidos por hidroxiapatita sintética ,0.10 gramas, (Alobone poros Osseocon Biomateriais Ltda., Rio de Janeiro/RJ, Brasil), no grupo 2 foram preenchidos com hidroxiapatita bovina,0,10 gramas, Bio-Oss Small (Bio-Oss® Geistlich Pharma AG, Wolhusen, Suíça), no grupo 3 os defeitos críticos foram preenchidos por hidroxiapatita sintética,0,10 gramas, (Alobone poros Osseocon Biomateriais Ltda, Rio de Janeiro/RJ, Brasil) enriquecida com 300 µl da fração mononuclear medular de células tronco na concentração de 1 x 10 6, obtida dos animais doadores de medula, e no grupo 4 os defeitos críticos foram preenchidos por hidroxiapatita bovina, 0,10 gramas, Bio-Oss Small (Bio-Oss® Geistlich Pharma AG, Wolhusen, Suíça) também enriquecida com 300 µl da fração mononuclear medular de células tronco na concentração de 1 x 10 6, obtida dos animais doadores de medula Após oito semanas, os cinco grupos tiveram todos os animais eutanasiados, por intermédio de overdose anestésica de Pentobarbital (180 mg/ kg intraperitoneal). Os grupos, foram submetidos a análises histomorfométrica, preparados corados com tricrômico de Masson, e técnicas imuno-histoquímica de VEGF e Osteopontina. Não existiu diferença estatisticamente significativa entre os grupos 1, 2, 3 e 4, porém existiu entre o grupo controle e os demais grupos que receberam tratamento para regeneração dos defeitos ósseos críticos.

The present study aimed to evaluate the bone regeneration of critical bone defects in the calvaria of rats using xenogenous grafts, Bio-Oss Small (Bio-Oss® Geistlich Pharma AG, Wolhusen, Switzerland) and synthetic hypooxypatite, (Alobone poros Osseocon Biomateriais Ltda., Rio de Janeiro / RJ, Brazil) pure or enriched with the medullary mononuclear fraction of stem cells, in the material and methods: forty young adult male rats, Sprague Dawley, were used, with twelve weeks distributed in five groups with eight animals, being thus named: control group, group 1, group 2, group 3, and group 4. In addition to the forty young adult rats, eight more animals were used as bone marrow donors. The Five groups were submitted to critical size bone defects with 8 (eight) millimeter diameter trephine, in the temporoparietal region. In the control group there was no biomaterial placement, in group 1 the critical size bone defects were filled with synthetic hydroxyapatite, 0,10 grams, (Alobone poros Osseocon Biomateriais Ltda., Rio de Janeiro / RJ, Brazil), in group 2 they were filled with bovine hydroxyapatite,0,10gramas, Bio-Oss Small (Bio-Oss® Geistlich Pharma AG, Wolhusen, Switzerland), in group 3 the critical size bone defects were filled with synthetic hydroxyapatite,0,10 grams, (Alobone poros Osseocon Biomateriais Ltda., Rio de Janeiro / RJ, Brazil) enriched with 300 µl of BMMF containing 1x106 cells, obtained from bone marrow donors animals, and in group 4 the critical size bone defects were filled with bovine hydroxyapatite, 0,10 grams Bio-Oss Small (Bio-Oss® Geistlich Pharma AG, Wolhusen, Switzerland) enriched with 300 µl of BMMF containing 1x106 cells, obtained from bone marrow donors animals. After eight weeks, all five of animals were euthanized by Pentobarbital anesthetic overdose (180 mg / kg intraperitoneal). The groups were submitted to histomorphometric analysis, using Masson's trichrome Stain, and immunohistochemical techniques of VEGF and Osteopontin. There was no statistically significant difference among groups 1, 2, 3 and 4, but it did exist with the control group and the other groups that received treatment for the regeneration of critical bone defects.

The osteoclast, a target cell for microorganisms.

Bone is a highly adaptive tissue with regenerative properties that is subject to numerous diseases. Infection is one of the causes of altered bone homeostasis. Bone infection happens subsequently to bone surgery or to systemic spreading of microorganisms. In addition to osteoblasts, osteoclasts (OCs) also constitute cell targets for pathogens. OCs are multinucleated cells that have the exclusive ability to resorb bone mineral tissue. However, the OC is much more than a bone eater. Beyond its role in the control of bone turnover, the OC is an immune cell that produces and senses inflammatory cytokines, ingests microorganisms and presents antigens. Today, increasing evidence shows that several pathogens use OC as a host cell to grow, generating debilitating bone defects. In this review, we exhaustively inventory the bacteria and viruses that infect OC and report the present knowledge in this topic. We point out that most of the microorganisms enhance the bone resorption activity of OC. We notice that pathogen interactions with the OC require further investigation, in particular to validate the OC as a host cell in vivo and to identify the cellular mechanisms involved in altered bone resorption. Thus, we conclude that the OC is a new cell target for pathogens; this new research area paves the way for new therapeutic strategies in the infections causing bone defects.

Proteína morfogénica ósea en cirugía maxilofacial. Revisión bibliográfica / Bone morphogenic protein in maxillofacial surgery. Bibliographic review

El propósito de esta revisión es presentar una visión concreta de las proteínas morfogenéticas óseas, su potencial de inducir osteogénesis y la aplicación en los procesos regenerativos. Las investigaciones acerca de los iniciadores moleculares de diferenciación ósea y cartilaginosa han identificado un grupo entero de proteínas morfogenéticas óseas que ejercen efecto regulador. La proteína morfogenética ósea (BMP) es endógena, presenta propiedades osteoinductivas, osteoconductivas y osteogénicas, y ha mostrado efectos significativos en la promoción de la formación ósea, por lo cual es una buena alternativa en reconstrucción. El uso de BMP se ha descrito en la reconstrucción de los defectos óseos de origen traumático y patológico, incluyendo: fisura nasoalveolar, aumento del reborde alveolar, elevación del seno maxilar, injerto de alvéolo postextracción y cirugía peri-implantaria.

The purpose of this review is to present a concrete vision about bone morphogenetic proteins, their potential in the induction of osteogenesis and their application in regenerative processes. Research on the molecular primers of bone and cartilage differentiation has identified an entire group of bone morphogenetic proteins that exert a regulatory effect. The bone morphogenetic protein (BMP) is an endogenous protein, has osteoinductive, osteoconductive and osteogenic properties, has shown significant effects in the promotion of bone formation, being a good alternative in reconstruction. The use of BMP has been described in the reconstruction of bone defects of traumatic and pathological origin, including nasoalveolar fissure, increased alveolar ridge, maxillary sinus elevation, post-extraction alveolar graft, and perimplant surgery

Photobiomodulation on critical bone defects of rat calvaria: a systematic review.

Bone defects following trauma represent a high impact on the quality of life of millions of people around the world. The aim of this study was to review photobiomodulation (PBM) action in the treatment of bone critical defects in rat calvaria, related to evaluation of the current protocols applied. One hundred and forty-seven articles related to the subject were found by searching the main databases (Pubmed, Lilacs, Web of Science, and Scopus) considering the period of publication until the year 2017, and only 14 corresponded the inclusion criteria established for this systematic review. The main parameters of the PBM were expressed in Table 1. In addition, it was possible to observe the use of two different wavelengths (red and infrared), which are considered therapeutic. Most of the evaluated articles presented positive results that describe a greater amount of neoformed bone, an increase in collagen synthesis, and a contribution to microvascular reestablishment. However, two studies report no effect on the repair process when the PBM was used. In addition, we observed considerable variations between the values of power, fluence, and total energy, which make it difficult to compare the results presented between the selected studies. It was possible to conclude that the infrared laser was more effective in positively stimulating the bone repair process of critical defects. Furthermore, a discrepancy was found in the parameter values used, which made it difficult to choose the best protocol for the treatment of this type of lesion.

Osteogenesis induced by a three-dimensional bioimplant composed of demineralised bone matrix, collagen, hydroxyapatite, and bone marrow-derived cells in massive bone defects: An experimental study.

Treatment of massive bone defects is one of the most difficult problems to solve in orthopedics. At present, there is no consensus on the best way to resolve these problems. The aim of our study was to evaluate the effect of a three-dimensional bioimplant over massive bone defects, and to analyse if it improves the speed and quality of integration in recipient bone compared to allograft treatment. Fifteen female lambs with massive bone defects, surgically created in their tibias, were randomly divided into three groups of five lambs each: Group I -treated with the bioimplant; Group 2 -treated with the bioimplant plus nucleated cells of autologous bone marrow; Group 3 -treated with a frozen allograft. Radiographs were taken post-treatment at weeks 1, 6, and 12. Animals were euthanized to obtain the studied bone segment for morphological analyses. TREATMENT: with bioimplants vs. bioimplant plus bone marrow nucleated cells (BMNCs) showed a notorious osteogenic effect, but with greater osteoid synthesis and cellularity in the latter. These results suggest that combined treatment with bioimplants and BMNCs have an additive effect on massive bone defects in lambs. These experimental results could be applied to repair damaged human bone.

Autologous bone graft in the treatment of post-traumatic bone defects: a systematic review and meta-analysis.

BACKGROUND: This meta-analysis aimed to determine the bone union rate of bone defects treated with the different autologous bone graft techniques. METHODS: The PubMed and the Cochrane Library databases were searched using the terms: 'fracture' AND ('bone loss' OR 'defect' OR 'defects') AND 'bone graft', restricted to English language, to human species, and to a publication period from January 1999 to November 2014. Data were extracted by one of the reviewers and then checked by the second. A quality of evidence score and a methodology score were used. Heterogeneity was assessed. A random effects model approach was used to combine estimates. RESULTS: Out of 376 selected studies only 34 met the inclusion criteria. The summary pooled union rate was 91 % (95 % CI: 87-95 %) while union rate after additional procedures raised to 98 % (95 % CI 96-99 %). No association between union rate and bone defect size was found. (Univariable regression model: vascularized: P = 0.677; non-vascularized: 0.202. Multivariable regression model: vascularized: P = 0.381; non-vascularized: P = 0.226). Vascularized graft was associated with a lower risk of infection after surgery when compared to non-vascularized graft (95 % CI 0.03 to 0.23, p < 0.001). CONCLUSION: The results of this meta-analysis demonstrate the effectiveness of autologous graft for bone defects. Furthermore, from the available clinical evidence bone defect size does not seem to have an impact on bone union when treated with autologous bone graft techniques.

The effect of dietary supplements on healing of alloplastic bone grafted defects in rat tibia / Efecto de los suplementos dietarios sobre la cicatrización de defectos injertados con hueso aloplástico en la tibia de ratas

The aim of this investigation was to evaluate the potential effects of the systemically delivered combination of calcium, zinc and vit-d supplementation of the locally applied alloplastic bone graft. 28 male Wistar albino rats were used in this study. In each animal, bone defects (10 mm length ¥ 3 mm width ¥ 2 mm depth) were created in the tibias. The animals were divided into four groups. In Group 1 (Control Group) rats were fed with standard rat diet. In Group 2 (Calcium Group) rats received calcium carbonate (15 mg/kg body weight) suspended in saline. In Group 3 (Calcium/Zinc Group) rats received calcium carbonate (15 mg/kg body weight) and zinc sulfate (4 mg/kg body weight) suspended in saline. In Group 4 (Calcium/Vitamin D Group) rats received calcium carbonate (15 mg/kg body weight) and Vitamin D (500 IU/kg body weight) suspended in olive oil. Histopathological analysis of samples was performed to evaluate the process of osteoblastic activity, matrix formation, trabecular bone formation and myeloid tissue in bone defects. Total amounts of osteoblastic activity, matrix formation, trabecular bone formation and myeloid yissue in Ca Group (p= 0.002), Ca/Zinc Group (p= 0.002), and Ca/Vit.D Group (p= 0.001) were significantly higher than in Control Group. The total amounts of Ca/Vit.D Group were significantly different than Control Group and Ca Group. The results of the present study indicated that the oral calcium carbonate supplementation combination with zinc may have systemic effects on accelerating bone regeneration in alloplastic bone grafted tibial defects. Further human studies involving long-term follow up and different type of bone grafts should be conducted.

El objetivo de esta investigación fue evaluar los efectos potenciales de la combinación sistémica de calcio, zinc y vitamina D como suplemento de la aplicación local de un injerto óseo aloplástico. Fueron utilizadas 28 ratas Wistar albinas (machos). En cada animal, se crearon defectos óseos en las tibias (cuyas medidas fueron: 10 mm de longitud x 3 mm de ancho x 2 mm de profundidad). Los animales fueron divididos en cuatro grupos. En el Grupo 1 (control) las ratas fueron alimentadas con una dieta estándar. En el Grupo 2 (grupo de calcio) las ratas recibieron carbonato de calcio (15 mg/kg de peso corporal) suspendido en solución salina. En el Grupo 3 (grupo de calcio/zinc) las ratas recibieron carbonato de calcio (15 mg/kg de peso corporal) y sulfato de zinc (4 mg/kg de peso corporal) suspendido en solución salina. El Grupo 4 (calcio/vitamina D) recibió carbonato de calcio (15 mg/kg de peso corporal) y vitamina D (500 UI/kg de peso corporal) suspendidos en aceite de oliva. Se realizó un análisis histopatológico de las muestras para evaluar el proceso de actividad osteoblástica, formación de la matriz, hueso trabecular y tejido mieloide en defectos óseos. Las cantidades totales de actividad osteoblástica, formación de matriz, de hueso trabecular y tejido mieloide en los grupos Calcio (p= 0,002), Calcio/Zinc (p= 0,002), y Calcio/Vitamina D (p= 0,001) fueron significativamente mayores que en el grupo de control. Las cantidades totales de Calcio/Vitamina D Grupo fueron significativamente diferentes de los grupos Control y Calcio. Los resultados del presente estudio indican que lacombinación de suplementos de carbonato de calcio por vía oral con zinc puede tener efectos sistémicos sobre la aceleración de la regeneración ósea en defectos tibiales con injertos aloplásticos. Deben llevarse a cabo otros estudios en humanos, que involucren un largo plazo de seguimiento y también diferentes tipos de injertos óseos.

Treatment of circumferential defects with osseoconductive xenografts of different porosities: a histological, histometric, resonance frequency analysis, and micro-CT study in dogs.

BACKGROUND: Finding the most effective method of minimizing the gap effect in alveolar crest remodeling constitutes a clinical challenge for immediate implant technique. PURPOSE: To evaluate the effectiveness of osseoconductive xenografts with different porosities in the crestal bone region, with and without guided bone regeneration, over immediate implant installation. MATERIALS AND METHODS: Five bone defects (6 mm in diameter/4 mm depth) were prepared on one side of the mandibles of twelve dogs. Implants of 3.3 × 10 mm were installed on the mesial side of each defect, providing a 2.7-mm distal gap. Defects were randomly filled with autogenous bone, coagulum, a deproteinized bovine bone mineral (DBBM) block, a DBBM sponge, or DBBM granules. The same procedures were performed on the opposite side after 8 weeks. Collagen membranes were used to cover the defects on half of the sides. The animals were sacrificed after 8 weeks. The outcomes were evaluated by histology, histomorphometric analysis, resonance frequency analysis, and micro-CT analysis. RESULTS: The histomorphometry showed the DBBM sponge to provide similar bone formation to autogenous bone at 8 weeks without a membrane. The coagulum rendered better bone formation at 16 weeks (membrane) (p < .05). The DBBM block exhibited the poorest results between treatments (8 and 16 weeks, with or without membrane). Micro-CT analysis revealed increasing bone surface values in sites with DBBM granules, followed by the DBBM sponge (8 weeks without membrane) and autogenous bone at 8 weeks with membrane (p < .05). Porosity analysis of the biomaterials showed the highest number, volume, and surface area of closed pores in DBBM granules. The DBBM block presented the highest volume of open pores, open porosity, and total porosity. CONCLUSIONS: The high-porosity block (DBBM block) failed to provide greater bone repair within the defect. Biomaterials with lower porosity (DBBM sponge and granules) showed similar or higher bone formation when compared with autogenous bone.

Tomografia computadorizada por feixe cônico para identificação de defeitos ósseos peri-implantares quimicamente simulados em costelas bovinas frescas / Cone beam computed tomography for identification of peri-implant bone loss chemically simulated in fresh bovine ribs

O objetivo deste estudo foi avaliar a acurácia, sensibilidade, especificidade e concordância inter e intra-observador dos exames radiográficos: radiografia periapical digital indireta (RP) por meio de placas de fósforo e tomografia computadorizada por feixe cônico (TCFC) na detecção de defeitos ósseos peri-implantares quimicamente simulados com Ácido Perclórico a 70%. 80 implantes foram instalados em blocos de costela bovina. Os implantes foram divididos em 2 grupos (grupo controle e grupo teste), em seguida o grupo teste foi dividido em 2 subgrupos (G1 e G2). O grupo G1 foi exposto a 4h de ácido causando defeitos de aproximadamente 3-4 mm de profundidade e largura <=1 mm, enquanto o grupo G2 foi exposto a 12h . Posteriormente, as amostras foram submetidas a um sistema de Radiografia digital indireta por meio de placa de fósforo (CS 7600) e a dois diferentes tomógrafos, utilizando variados protocolos (iCAT Next Generation e 3D Accuitomo 170). Os observadores avaliaram as imagens em um programa de visualização independente (OsiriX MD) utilizando a ferramenta a 3D-RMP que permite explorar cortes axiais, coronais, sagitais, parassagitais e circunferenciais simultaneamente. Nas amostras avaliadas por radiografia periapical, os valores da ASC encontrados nas amostras com defeitos ósseo menores variaram entre 0,442 a 0,534; no iCAT Next Generantion, variaram entre 0,645 a 0.828 em dois protocolos diferente. No 3D Accuitomo 170, variaram entre 0.563 a 0.904, em protocolos diferentes. No grupo com defeito ósseos maiores os resultados foram superiores. Na radiografia periapical, os valores encontrados variaram entre 0,652 a 0,771; no iCAT Next Generation, variaram entre 0,708 a 0,946 em dois protocolos diferentes e no 3D Accuitomo 170, entre 0.628 a 0.962 em 4 protocolos diferentes...

The aim of this study was to test the accuracy, sensitivity, specificity, inter and intra-observer and area AZ values of two radiographic examinations: digital periapical radiographs and cone beam computed tomography (CBCT) in the detection of two sizes of peri-implant bone defects chemically simulated with Perchloric Acid 70%. PR and CBCT were performed in 80 dental implants installed in blocks of bovine rib. An indirect digital radiography system using smart phosphor plates (CS 7600) and two different CBCT scanners, using different protocols (iCAT Next Generation 3D Accuitomo 170) were evaluated. Observers evaluated the images in a separate DICOM viewer (OsiriX MD) using the 3D-RMP tool. This tool allows the visualization of axial, coronal, sagittal, cross-section and circumferential images. In samples evaluated by periapical radiography, the AZ values found in the samples with smaller bone defects ranged from 0.442 to 0.534; in iCAT Next Generantion, ranged from 0.645 to 0.828 in two different protocols. In the group with larger bone defect results were superior. In periapical, the values found ranged from 0.652 to 0.771; iCAT the Next Generation ranged from 0.708 to 0.946 in two different protocols and 3D Accuitomo 170, 0.628-0.962 in 4 different protocols...