Effect of hyperbaric oxygen therapy combined with autologous platelet concentrate applied in rabbit fibula fraction healing

array:24 ["pii" => "S1807593222016283" "issn" => "18075932" "doi" => "10.6061/clinics/2013(09)11" "estado" => "S300" "fechaPublicacion" => "2013-09-01" "aid" => "1628" "copyright" => "CLINICS" "copyrightAnyo" => "2013" "documento" => "article" "crossmark" => 0 "licencia" => "https://creativecommons.org/licenses/by-nc/3.0/" "subdocumento" => "fla" "cita" => "Clinics. 2013;68:1239-46" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "itemSiguiente" => array:19 [ "pii" => "S1807593222016295" "issn" => "18075932" "doi" => "10.6061/clinics/2013(09)12" "estado" => "S300" "fechaPublicacion" => "2013-09-01" "aid" => "1629" "copyright" => "CLINICS" "documento" => "article" "crossmark" => 0 "licencia" => "https://creativecommons.org/licenses/by-nc/3.0/" "subdocumento" => "fla" "cita" => "Clinics. 2013;68:1247-54" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "BASIC RESEARCH" "titulo" => "Effects of ovariectomy and resistance training on oxidative stress markers in the rat liver" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "1247" "paginaFinal" => "1254" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig4" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 425 "Ancho" => 677 "Tamanyo" => 32537 ] ] "descripcion" => array:1 [ "en" => "Levels of Vitamin E in liver homogenates 48h after the last session of the resistance training program in sham-operated sedentary (Sham-Sed), ovariectomized sedentary (Ovx-Sed), sham-operated resistance training, (Sham-Rt) and ovariectomized resistance training (Ovx-Rt). Values are presented as mean ± SDM; p ≤ 0.05. a statistically significant difference compared to Sham-Sed." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Maria Fernanda Cury Rodrigues, Uliana Sbeguen Stotzer, Mateus Moraes Domingos, Rafael Deminice, Gilberto Eiji Shiguemoto, Luciane Magri Tomaz, Nuno Manuel Frade de Sousa, Fabiano Candido Ferreira, Richard Diego Leite, Heloisa Sobreiro Selistre-de-Araújo, Alceu Afonso Jordão-Júnior, Vilmar Baldissera, Sérgio Eduardo de Andrade Perez" "autores" => array:13 [ 0 => array:2 [ "nombre" => "Maria Fernanda Cury" "apellidos" => "Rodrigues" ] 1 => array:2 [ "nombre" => "Uliana Sbeguen" "apellidos" => "Stotzer" ] 2 => array:2 [ "nombre" => "Mateus Moraes" "apellidos" => "Domingos" ] 3 => array:2 [ "nombre" => "Rafael" "apellidos" => "Deminice" ] 4 => array:2 [ "nombre" => "Gilberto Eiji" "apellidos" => "Shiguemoto" ] 5 => array:2 [ "nombre" => "Luciane Magri" "apellidos" => "Tomaz" ] 6 => array:2 [ "nombre" => "Nuno Manuel Frade" "apellidos" => "de Sousa" ] 7 => array:2 [ "nombre" => "Fabiano Candido" "apellidos" => "Ferreira" ] 8 => array:2 [ "nombre" => "Richard Diego" "apellidos" => "Leite" ] 9 => array:2 [ "nombre" => "Heloisa Sobreiro" "apellidos" => "Selistre-de-Araújo" ] 10 => array:2 [ "nombre" => "Alceu Afonso" "apellidos" => "Jordão-Júnior" ] 11 => array:2 [ "nombre" => "Vilmar" "apellidos" => "Baldissera" ] 12 => array:2 [ "nombre" => "Sérgio Eduardo" "apellidos" => "de Andrade Perez" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1807593222016295?idApp=UINPBA00004N" "url" => "/18075932/0000006800000009/v1_202212010704/S1807593222016295/v1_202212010704/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S1807593222016271" "issn" => "18075932" "doi" => "10.6061/clinics/2013(09)10" "estado" => "S300" "fechaPublicacion" => "2013-09-01" "aid" => "1627" "copyright" => "CLINICS" "documento" => "article" "crossmark" => 0 "licencia" => "https://creativecommons.org/licenses/by-nc/3.0/" "subdocumento" => "fla" "cita" => "Clinics. 2013;68:1231-8" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "BASIC RESEARCH" "titulo" => "Ulinastatin attenuates oxidation, inflammation and neural apoptosis in the cerebral cortex of adult rats with ventricular fibrillation after cardiopulmonary resuscitation" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "1231" "paginaFinal" => "1238" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig4" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 644 "Ancho" => 751 "Tamanyo" => 86006 ] ] "descripcion" => array:1 [ "en" => "UTI increased the number of Nissl-stained neurons and decreased the number of TUNEL-positive cells in the cortex. Nissl staining indicated that rat cortical cell numbers in the VF + PBS group were significantly lower than in the VF + PBS group 72 h after ROSC (A, B). There was a greater number of TUNEL-positive neurons (indicated by the white arrow) in rat cortices in the VF + PBS group than in the VF + UTI group 72 h after ROSC (C, D) (72 standard fields in the VF + PBS group and 126 standard fields in the VF+UTI group were analyzed). ∗ VF + PBS versus VF + UTI, p<0.05." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Chun Lin Hu, Jin Ming Xia, Jie Cai, Xin Li, Xiao Xing Liao, Hui Li, Hong Zhan, Gang Dai, Xiao Li Jing" "autores" => array:9 [ 0 => array:2 [ "nombre" => "Chun Lin" "apellidos" => "Hu" ] 1 => array:2 [ "nombre" => "Jin Ming" "apellidos" => "Xia" ] 2 => array:2 [ "nombre" => "Jie" "apellidos" => "Cai" ] 3 => array:2 [ "nombre" => "Xin" "apellidos" => "Li" ] 4 => array:2 [ "nombre" => "Xiao Xing" "apellidos" => "Liao" ] 5 => array:2 [ "nombre" => "Hui" "apellidos" => "Li" ] 6 => array:2 [ "nombre" => "Hong" "apellidos" => "Zhan" ] 7 => array:2 [ "nombre" => "Gang" "apellidos" => "Dai" ] 8 => array:2 [ "nombre" => "Xiao Li" "apellidos" => "Jing" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1807593222016271?idApp=UINPBA00004N" "url" => "/18075932/0000006800000009/v1_202212010704/S1807593222016271/v1_202212010704/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "BASIC RESEARCH" "titulo" => "Effect of hyperbaric oxygen therapy combined with autologous platelet concentrate applied in rabbit fibula fraction healing" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "1239" "paginaFinal" => "1246" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Paulo César Fagundes Neves, Simone de Campos Vieira Abib, Rogério Fagundes Neves, Oronzo Pircchio, Karen Ruggeri Saad, Paulo Fernandes Saad, Ricardo Santos Simões, Marcia Bento Moreira, Cristiano Frota de Souza Laurino" "autores" => array:9 [ 0 => array:4 [ "nombre" => "Paulo César Fagundes" "apellidos" => "Neves" "email" => array:2 [ 0 => "pauloc.fagundes@uol.com.br" 1 => "paulo.fagundes@univasf.edu.br" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "I" "identificador" => "aff1" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor1" ] ] ] 1 => array:3 [ "nombre" => "Simone" "apellidos" => "de Campos Vieira Abib" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "II" "identificador" => "aff2" ] ] ] 2 => array:3 [ "nombre" => "Rogério Fagundes" "apellidos" => "Neves" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "II" "identificador" => "aff2" ] ] ] 3 => array:3 [ "nombre" => "Oronzo" "apellidos" => "Pircchio" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "I" "identificador" => "aff1" ] ] ] 4 => array:3 [ "nombre" => "Karen Ruggeri" "apellidos" => "Saad" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "I" "identificador" => "aff1" ] ] ] 5 => array:3 [ "nombre" => "Paulo Fernandes" "apellidos" => "Saad" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "I" "identificador" => "aff1" ] ] ] 6 => array:3 [ "nombre" => "Ricardo Santos" "apellidos" => "Simões" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "II" "identificador" => "aff2" ] ] ] 7 => array:3 [ "nombre" => "Marcia Bento" "apellidos" => "Moreira" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "III" "identificador" => "aff3" ] ] ] 8 => array:3 [ "nombre" => "Cristiano Frota" "apellidos" => "de Souza Laurino" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "IV" "identificador" => "aff4" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Universidade Federal do Vale do São Francisco (UNIVASF), Colegiado de Medicina, Petrolina/PE, Brazil" "etiqueta" => "I" "identificador" => "aff1" ] 1 => array:3 [ "entidad" => "Universidade Federal de São Paulo (UNIFESP), Departamento de Cirurgia, São Paulo/SP, Brazil" "etiqueta" => "II" "identificador" => "aff2" ] 2 => array:3 [ "entidad" => "Universidade Federal do Vale do São Francisco (UNIVASF), Colegiado de Medicina Veterinária, Petrolina/PE, Brazil" "etiqueta" => "III" "identificador" => "aff3" ] 3 => array:3 [ "entidad" => "Sociedade Brasileira de Traumatologia Esportiva e Artroscopia, São Paulo/SP, Brazil" "etiqueta" => "IV" "identificador" => "aff4" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor1" "etiqueta" => "*" "correspondencia" => "Tel.: 55 87 2101–6865" ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig1" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 710 "Ancho" => 747 "Tamanyo" => 70605 ] ] "descripcion" => array:1 [ "en" => "Distribution of the average percentage of collagen (A), average number of osteoblasts (B) and osteocytes (C), and average lesion thickness (D), according to groups and euthanasia periods (subgroups)." ] ] ] "textoCompleto" => "INTRODUCTIONLoss of osseous continuity due to fracture is a disabling condition, even momentarily, that often deprives the individual of his or her social and professional lifestyle. Therefore, as a medical specialty, orthopedics has invested in studies that promote reduced bone healing time and, consequently, reduced time required to return to normal or almost normal function.Although most fractures do not present healing problems under normal conditions, in some situations, the poorly vascularized bone tissue does not respond adequately to treatment, resulting in delayed consolidation or non-consolidation (<a class="elsevierStyleCrossRef" href="#bib1">1</a>). Thus, developing new techniques to help the bone healing process and stimulate fracture consolidation is very important.Several studies have focused on reducing bone healing time using low-intensity pulsed ultrasound, low-energy lasers, electrical stimulation, and platelet-rich concentrates (<a class="elsevierStyleCrossRef" href="#bib2">2</a>).Platelet-rich concentrate (PRC) is an autologous concentration of platelets that releases growth factors. Platelets and the release of these proteins are essential for clot formation in the physiological process of tissue repair. A normal clot consists of 95% red blood cells, 4% platelets, and 1% white blood cells. However, an analysis of platelet-enriched clots reveals 95% platelets, 4% red blood cells, and 1% white blood cells (<a class="elsevierStyleCrossRef" href="#bib2">2</a>).Platelet-derived growth factor (PDGF) has defined periods of activity. PDGF is a major factor during the onset of tissue repair and acts directly on cell differentiation and angiogenesis. According to classic studies by Heldin & Westmark (<a class="elsevierStyleCrossRef" href="#bib3">3</a>), PDGF is the first growth factor that initiates repair by stimulating mitogenesis and increasing the local populations of mesenchymal stem cells and osteoprogenitor cells. At concentrations of 20 to 100 ng/ml, bone formation and alkaline phosphatase activity increase in the demineralized matrices of rats (<a class="elsevierStyleCrossRef" href="#bib4">4</a>).Transforming growth factor beta (TGF-β) is a cytokine synthesized in bone tissue and platelets that stimulates the proliferation of osteoblast precursor cells, promotes collagen synthesis, increases the number of cells that express the osteoblast genotype, increases osteoclast apoptosis, and activates endothelial cells for angiogenesis and chondroprogenitor cells in cartilage formation. However in vitro, TGF-β alone does not induce bone formation in an animal model (<a class="elsevierStyleCrossRef" href="#bib5">5</a>).Methods for obtaining platelet growth factors should consider the platelet concentrate rate, processing technique, concentration of secreted proteins, handling and application, and especially the clinical application (<a class="elsevierStyleCrossRef" href="#bib6">6</a>). Platelet-rich plasma (PRP) is undoubtedly the most widely used serum; however, its indiscriminate use has been criticized, and it is still not approved by the Food and Drug Administration (FDA) (<a class="elsevierStyleCrossRef" href="#bib7">7</a>).Autologous platelet concentrate (APC) is a platelet-rich concentrate (PRC) that is similar to PRP but has certain methodological advantages in terms of how it is obtained. In addition to being approved by the FDA (using the double-syringe method), APC can be withdrawn and used during a surgical procedure for fracture fixation and is easily processed in a few minutes, which is important because PDGF and TGF-β have half-lives of only a few minutes outside the vascular system (<a class="elsevierStyleCrossRef" href="#bib7">7</a>).The basic difference between PRP and APC is that PRP is an PRC, with a platelet concentration over 2 times greater than that of plasma. APC is a PRC that combines PRP with platelet-poor plasma (PPP); according to the manufacturer, APC contains 2 times the platelet concentration of blood plasma. According to studies by Graziane et al. (<a class="elsevierStyleCrossRef" href="#bib8">8</a>), this platelet concentration is sufficient to stimulate osteoblast proliferation in vitro. In addition, obtaining APC using the double-syringe method eliminates leukocytes, proteases, and hydrolases, which may be able to degrade APC (<a class="elsevierStyleCrossRef" href="#bib9">9</a>).Hyperbaric oxygen therapy (HBO) is another treatment that may have positive effects on the bone healing process.According to the Undersea and Hyperbaric Medical Society, HBO is defined as intermittently inhaling 100% oxygen inside a chamber at pressures greater than 1 atmosphere absolute (ATA). This therapy has been first-choice treatment for decompression sickness in divers since the 1920s; however, only since the 1950s has it been used to treat gas embolism, carbon monoxide poisoning, gangrene gas, compartment syndrome, soft tissue infection, osteomyelitis, and osteoradionecrosis (<a class="elsevierStyleCrossRef" href="#bib10">10</a>).The advantage of HBO is that it is a safe treatment. According to the literature, the complication rate is 1.83%, of which 94% are considered minor complications. The disadvantages of HBO include the high cost of the hyperbaric chamber and the technical training necessary, considering the number of circumstances under which it can be used with some level of evidence. However, the delayed consolidation or non-consolidation of fractures has significant financial impacts on society and represents a serious clinical challenge for which few treatment options are available. Various, often necessary surgical procedures are accompanied with patient morbidity and reduced quality of life (<a class="elsevierStyleCrossRef" href="#bib11">11</a>).This study was designed to test the hypothesis that many patients with fractures or delayed consolidations could benefit from APC, HBO, or a combination of both treatments because the literature indicates that the osteogenic action of growth factors depends directly on the tissue oxygen tension (<a class="elsevierStyleCrossRef" href="#bib12">12</a>).MATERIALS AND METHODSSampleThis study was approved by the Ethics Committee of Universidade Federal de São Paulo (0163/08). All animals were handled according to “The Ethical Principles of Animal Experiments of the International Union for the Protection of Animals” 11.794/2008 Act of October 8, 2008.A total of 128 6-8-month-old male New Zealand albino rabbits (Oryctolagus cuniculus), with an average weight of 3,000 grams, were subjected to an osteotomy of the right fibula after an adaptation period.After surgery, the animals were randomized into 4 groups of 32 rabbits according to the postsurgical treatment used, as follows:<ul class="elsevierStyleList" id="celist10"><li class="elsevierStyleListItem" id="celistitem10">•Control Group (CG) - animals subjected only to osteotomy of the right fibula, without further treatment</li><li class="elsevierStyleListItem" id="celistitem20">•APC Group (APCG) - animals subjected to osteotomy of the right fibula and treated with APC</li><li class="elsevierStyleListItem" id="celistitem30">•HBO Group (HBOG) - animals subjected to osteotomy of the right fibula and treated with consecutive daily HBO sessions, totaling 9 sessions</li><li class="elsevierStyleListItem" id="celistitem40">•APC and HBO group (APC+HBOG) - animals subjected to osteotomy of the right fibula and treated with APC, combined with consecutive daily HBO sessions, totaling 9 sessions</li></ul>Each group was further divided into 4 subgroups of 8 animals each, according to a pre-determined euthanasia time point at 2, 4, 6, and 8 weeks postoperatively.Operative procedureAll animals were food- and water-fasted for 6 hours pre-operatively and then weighed; all the fur was shaved at the leg region.Pre-anesthesia was induced with ketamine hydrochloride solution at a dose of 30 mg/kg, xylazine at a dose of 3 mg/kg, and tramadol hydrochloride at a dose of 5 mg/kg intramuscularly in the gluteal region.The animals were anesthetized with spinal anesthesia using 2% lidocaine without a vasoconstrictor at a dose of 0.5 mg/kg. Venoclysis of the right auricular vein was performed for the infusion of the necessary drugs. Antisepsis was then performed with polyvinylpyrrolidone, and the operative field was isolated with sterile field cloths, delimiting a restricted area for the surgery.Then, a 2-cm lateral longitudinal incision was made along the right leg and dissected by following the muscular planes and localization of the fibular diaphyseal region. A complete transverse osteotomy of the fibula was performed using a no. 15 scalpel blade at the proximal third of the tibial tuberosity.The surgery was completed by suturing the planes, aponeurosis, subcutaneous tissue, and skin with 4-0 nylon thread. Tramadol hydrochloride analgesic was administered at a dose of 2 mg/kg intramuscularly and maintained every 12 hours for 3 consecutive days, in combination with 4 intramuscular antibiotic treatments with benzathine penicillin and G potassium at doses of 20,000 IU/kg every 48 hours, in all animals.Immediately after the osteotomy of the fibula, the animals were randomized according to the pre-determined treatment groups under study and to their respective subgroups. The hind limb did not need to be immobilized because the distal portion of the fibula in rabbits exhibits fusion with the tibia.During the post-operative period, at the pre-determined time for each subgroup (2, 4, 6, or 8 weeks), the animals were anesthetized again according to the previous protocol, and the fibulae were resected, including the osseous callus, using a no. 15 scalpel blade. Euthanasia was induced during deep anesthesia with xylazine.Application of autologous platelet concentrateThis procedure was performed during the surgery. Before the surgical procedure, 2.5 ml of blood was withdrawn from the auricular vein using a 10-ml double-syringe (ACP-double syringe, Arthrex, Naples, FL, USA) containing 0.5 ml of acid citrate dextrose anticoagulant, and the syringe was gently agitated to ensure the adequate mixing of the blood with the anticoagulant. The syringe containing the anti-coagulated blood was then stored in a suitable tube and centrifuged (Rotofix 32A, Arthrex, USA) at 1500 RPM for 5 minutes to separate the red blood cells from the plasma.After centrifugation, the plasma was removed from the tube using the same syringe, while the internal syringe collected only the concentrate, leaving the red blood cells. Using this procedure, which was provided by the manufacturer, we obtained approximately 1.5 ml of concentrate, with a high concentration of autologous platelets enriched with growth factors.The platelet concentrate was applied directly to the fracture (osteotomy) in the proximal third of the rabbit fibula before closing the muscular fascia.Hyperbaric oxygen therapyHBO sessions were conducted using a veterinary hyperbaric chamber model (AN – 500, Sechrist, USA) with a 14-rabbit capacity (average weight of 2,500 grams each). The sessions were conducted daily, 8 animals at a time, and began on the first post-operative day for 90 minutes at 3 ATA (<a class="elsevierStyleCrossRef" href="#bib13">13</a>). We opted for 9 sessions in the HBO and APC+HBO groups because the growth factor acts primarily during the first 7 post-operative days (<a class="elsevierStyleCrossRef" href="#bib14">14</a>).The beginning of the session included a compression period. After 15 minutes, the chamber manometer indicated 2 atm of pressure; assuming that the manometer in the hyperbaric chamber measures the pressure difference between the chamber and the surrounding environment, the barometric pressure and environmental pressure (1 ATA) were added to convert the values into absolute atmospheres (ATA). Therefore, the pressure applied by the chamber was 3 ATA. This absolute pressure (3 ATA) was maintained for 60 minutes, followed by decompression for 15 minutes; thus, each session ended after 90 minutes.Histomorphometric analysisImmediately after the experiment, the proximal third of the fibula from each animal, containing the osseous callus region, was surgically removed and placed in 10% buffered formalin for 48 hours. After this period, the decalcification process was begun in ethylenediaminetetraacetic acid (EDTA); after 6 days, the pieces were dehydrated in increasing concentrations of ethyl alcohol, diaphanized in xylene, impregnated in histological paraffin, and embedded in paraffin.Paraffin blocks were cut with a Minot microtome (Leica, Model RM 2145) with semi-serial 4 ìm cuts. After drying for 6–8 hours in an oven at 60°C, some sections were stained with hematoxylin and eosin (HE), and others were stained with picrosirius red. The slides were observed under a light microscope (Carl Zeiss®) at 4 to 100×.To determine the concentration of bone cells (osteocytes, osteoblasts, and osteoclasts) in the fibula, an 1800×1600 μM rectangle was initially determined, drawn using a mouse, in two central regions adjacent to the healing bone; one was on the diaphysis side, and the other was on the epiphyseal side. Then, the cells were individually counted within the rectangles, excluding cells that touched the rectangles. For each animal, 6 slides were evaluated. We recorded the average number of cells counted in the rectangles for each animal.The thickness of the cartilage region within the remaining osseous callus was obtained at 3 points in each slide (6 slides for each animal) using a mouse. We recorded the average number of measurements in μM for each animal.Determining the percentages of collagenThe cuts stained with picrosirius red were used to determine the percentage of collagen formed. Initially, the sections were dewaxed in xylene and then hydrated in a decreasing ethanol gradient. Afterward, elastin was blocked with 0.2% phosphomolybdic acid for 10 minutes. The sections were washed in distilled water, immersed in a 0.1% sirius red solution, and dissolved in saturated aqueous picric acid for 90 minutes. Then, the sections were washed in 0.01 N HCl for 2 minutes. Later, the sections were dehydrated in an increasing ethanol gradient, cleared in xylene, and mounted with Entellan®.Photomicrographs of the picrosirius red-stained sections from the rabbit fibulae of different groups were taken under a polarized light microscope (Axiolab Standard 2.0, Carl Zeiss®) coupled to a high-resolution video camera (AxionCam, Carl Zeiss®) to identify the distribution of collagen fibers in the bone matrix. Then, the micrographs were analyzed on a computer with the Imagelab® program.Statistical analysisFor quantitative variables, descriptive statistics were calculated. Analysis of variance (ANOVA) and multiple comparisons by the Tukey test were used as inferential analyses to either confirm or refute the evidence found in the descriptive analysis.For all the results obtained via inferential analyses, a significance level of α = 5% was used. All statistical analyses were performed with the R program software, version 2.11.1.RESULTSInformation referring to the percentages of collagen, numbers of osteoblasts and osteocytes, and lesion thickness were important measurements assessed among groups and euthanasia time periods (subgroups). <a class="elsevierStyleCrossRef" href="#tbl1">Table 1</a> and <a class="elsevierStyleCrossRef" href="#fig1">Figure 1 (A – D)</a> summarize the behavior of these measurements according to the groups and euthanasia periods (subgroup).<elsevierMultimedia ident="tbl1"></elsevierMultimedia><elsevierMultimedia ident="fig1"></elsevierMultimedia><a class="elsevierStyleCrossRef" href="#tbl2">Table 2</a> shows the results of comparisons of the percentages of collagen, numbers of osteoblasts and osteocytes, and lesion thicknesses among groups and euthanasia periods. <a class="elsevierStyleCrossRef" href="#fig2">Figure 2 (A – H)</a> shows the HE slides from the groups and subgroups (2th and 6th weeks).<elsevierMultimedia ident="tbl2"></elsevierMultimedia><elsevierMultimedia ident="fig2"></elsevierMultimedia>DISCUSSIONThe results obtained from this experimental model indicate a higher rate of bone healing in response to APC combined with HBO. No previous study in the literature was found to have used this combination in an experimental study.Qualitative analysis highlighted the accelerated bone healing in the APC+HBOG compared with the CG during all weeks studied; additional data on the percentages of collagen and lesion thickness confirm this assessment. In 1983, a review article found that low oxygen tension reduced the action of autologous growth factors (<a class="elsevierStyleCrossRef" href="#bib12">12</a>). Similarly, the outcomes shown here suggest that the higher oxygen tension caused by HBO application could potentiate the effects of the growth factors offered by APC therapy on bone healing.Although there was no significant difference between the numbers of osteoblasts during any of the periods studied or between the number of osteocytes counted during the 2nd and 8th weeks, relative to the groups treated with APC and HBO combined, quantitative data on the average lesion thickness showed that the APCG, HBOG, and APC+HBOG were superior to the CG. The APC+HBOG was superior to the other groups across all periods, whereas the HBOG was superior to the APCG across all periods for this variable.The fact that PRC use (in this study, APC) led to a superior rate of bone healing compared with the CG corroborates the outcomes of other studies. Marx et al. (<a class="elsevierStyleCrossRef" href="#bib15">15</a>) performed the first and most convincing study using PRP combined with autogenous bone grafts. The authors evaluated the effect of PRP on the reconstruction of mandibular bone defects resulting from tumor removal. The authors stated that bone grafts with PRP showed more than double the maturity of the controls.Another study by Anitua produced excellent outcomes using autogenous bone grafts combined with PRP (<a class="elsevierStyleCrossRef" href="#bib16">16</a>). The authors observed a total alveolar bone regeneration in 8 of 10 patients who were treated with PRP and bone graft. Biopsies of the respective areas showed compact mature bone with normal morphology and well-organized trabecular regions, while the control patients showed connective tissue, mostly filled with alveoli, and no mature bone.However, some studies do not support the effect of PRC on the rate of bone healing. Recently, Broggini et al. (<a class="elsevierStyleCrossRef" href="#bib17">17</a>) evaluated bone repairs in the monocortical defects in the calvaria of 15 New Zealand rabbits. The authors concluded that PRP, alone or combined with an autogenous graft, did not lead to a higher rate of bone regeneration compared with basal clot during the initial healing.Currently, the literature is more concerned with quantifying the concentration of growth factors present in some of the most widely used PRCs, especially PRP. A study using this approach stated that the concentration of growth factors in PRP can reach up to 7 and 30 times the basal levels of TGF-β and PDGF, respectively, in a basal clot (<a class="elsevierStyleCrossRef" href="#bib18">18</a>). According to the manufacturer's data on the double-syringe method used in this study, APC can have up to 4 and 25 times the levels of TGF-β and PDGF, respectively. Although the concentrations of growth factors found in APC were lower than in PRP, this study demonstrated that this difference does not seem to be a disadvantage. However, it is important to note that functional and non-harmful amounts of these factors in tissue repair have not been well determined.Regarding our outcomes on the effect of HBO on the rate of bone healing, HBO increased the bone consolidation rate compared with the CG, which could be observed through the varying percentages of collagen during each week, the number of osteocytes during the 6th and 8th weeks, and the lesion thickness across all weeks.Our search for relevant publications led us to the observation that the first studies on the effects of HBO on bone healing date back to the 1960s. After almost 50 years, there are still few studies on this subject.In a Cochrane review study (<a class="elsevierStyleCrossRef" href="#bib19">19</a>), the authors concluded that there is insufficient evidence to support or refute HBO use for fracture treatment or as a therapy for non-consolidated fractures within an expected time. This conclusion was based on 9 potentially relevant articles among the 68 references identified. However, none of the articles met the review's inclusive criteria: any randomized or quasi-randomized studies that compared clinical results obtained with HBO use to those obtained without HBO use (no treatment).Although the literature did not include clinical results that met the methodology described above, our outcomes and the studies cited indicate that HBO is beneficial to the fracture healing process.In 1998, Ueng et al. (<a class="elsevierStyleCrossRef" href="#bib20">20</a>) studied bone mineral density and tensile strength in a rabbit tibial-lengthening model. The bone segments from HBO-treated animals had higher mineral densities and superior biomechanical properties compared with the control animals. Using the same experimental model, this group obtained similar findings, showing that HBO is also advantageous during the early stages of tibial fracture healing (<a class="elsevierStyleCrossRef" href="#bib21">21</a>).Chen et al. (<a class="elsevierStyleCrossRef" href="#bib22">22</a>) studied the effect of HBO in rabbits subjected to fusion of the vertebrae with a bone graft. According to these authors, the incidence of bone non-consolidation for this procedure in humans ranges from 6–35% of cases and 40–50% in rabbits. After 8 weeks, the HBO group showed a 100% consolidation of the fractures, which were identified radiologically and by torsional biomechanical tests.The vast majority of the studies combining HBO and bone repair refer to osteoradionecrosis treatment. Radiation therapy results in progressive obliterative endarteritis, which leads to ischemia and a pathological fracture of the bone with reduced healing ability (<a class="elsevierStyleCrossRef" href="#bib23">23</a>). Muhonen et al. (<a class="elsevierStyleCrossRef" href="#bib24">24</a>) evaluated the angiogenic and osteogenic responses after radiation and HBO in a rabbit mandibular distraction model. The authors concluded that the HBO group improved in the bone formation pattern.Most experimental studies have found a positive effect from HBO use in the fracture healing process. This effect may be directly associated with the increased formation of new vessels, which increases blood inflow and, thereby, bone formation. Wu et al. (<a class="elsevierStyleCrossRef" href="#bib25">25</a>) presented the outcomes of an in vitro study that investigated the effects of HBO on the proliferation and differentiation of human osteoblasts and concluded that HBO also stimulates initial cell proliferation and acts directly on osteogenic differentiation in osteoblasts.Jan et al. (<a class="elsevierStyleCrossRef" href="#bib26">26</a>) presented the results of a study that assessed the effect of HBO on a rabbit calvaria fracture model. After radiographic and histomorphometric evaluations of the lesion after 6 and 12 weeks, the authors concluded that bone regeneration was significantly improved in the group of HBO-treated animals. It is noteworthy that the type of lesion caused in this experiment was considered critical, and bone healing was unlikely to occur.Yeh et al. (<a class="elsevierStyleCrossRef" href="#bib27">27</a>) studied the effects of HBO on the neovascularization of the tendon-bone junction, on the behavior of collagen fibers within the graft, and on the incorporation process of the graft into the bone tunnel of rabbits subjected to knee arthroscopy for the reconstruction of the anterior cruciate ligament with a tendon graft. The graft is incorporated into the bone tunnel through callus formation and the posterior ossification of the tunnel (<a class="elsevierStyleCrossRef" href="#bib28">28</a>). In the HBO-treated animals, collagen fibers showed greater organization surrounding the graft and had an early mineralization of fibrocartilage compared with the control animals. The biomechanical test also indicated that HBO-treated animals exhibited greater resistance to the tensile strength of the graft at 18 weeks post-operation than the control animals.The benefits of HBO are related to its proven therapeutic safety and the possible use of the equipment to treat a wider range of diseases. Its disadvantages include the high cost of the equipment and the low level of scientific evidence for HBO use in treating these diseases (<a class="elsevierStyleCrossRef" href="#bib19">19</a>).However, in choosing a treatment method, one must consider many variables, such as the cost of the equipment, the specialized personnel, the methodological complexity, and the characteristics of the fracture to be treated. Although the mechanisms behind the actions of HBO and APC on bone repair may be different, the variables in this study showed only a few differences between the two methods of treatment. Although qualitative assessment highlights APC's superiority to HBO in relation to the consolidation rate, further studies should be conducted comparing the two therapies and their effects on bone healing.In this study, we observed that osteoblastic activity was high in the CG during the 4th and 6th weeks but was higher in all other groups during the 2nd week. We also observed that osteoblastic activity was higher in the APC group than in the HBO group during the 2nd and 4th weeks, while no difference was found between these groups in relation to the number of osteoblasts during the 6th and 8th weeks. These findings corroborate previous knowledge that osteoblastic actions are strongly associated with higher concentrations of growth factors. We wish to note that this action was stronger in the first weeks with APC treatment and that it was superior to treatment with HBO at this stage.Despite the differences observed in relation to the osteoblastic activity among the subgroups during the first experimental weeks, counting the number of osteocytes during the 8th week does not indicate the quantity of newly formed bone present in each subgroup, as advocated by other authors (<a class="elsevierStyleCrossRef" href="#bib29">29</a>). We believe that the number of osteocytes associated with qualitative analysis and other variables, such as lesion thickness and percentage of collagen, better suggest the quantity of newly formed bone. In this study, APC+HBO was superior in producing a greater quantity of new bone compared with the APC, HBO, and control treatments during the 8th week.The importance of this study lies in the possibility of combining these two treatments, the effects of which potentiate increased bone formation. Additional studies with other variables must be conducted to deepen our knowledge of the effects of each of these treatments on bone healing; further studies should examine the economic impact of these combinations.The analysis of these outcomes allows us to state that APC and HBO combined increased the rate of bone healing in this experimental model. In addition, the rate of bone repair in the groups treated with APC or HBO were similar, and both rates were higher than in the CG.AUTHOR CONTRIBUTIONSNeves PC, Abib SC, Neves RF, and Moreira MB conceived and designed the study. Neves PC, Neves RF, Pirchio O, Simoes RS, and Laurino CF conducted the experiments and performed the data analysis. Neves PC, Saad KR, and Saad PF performed the data analysis and wrote the manuscript. All authors approved the final version of the manuscript." "textoCompletoSecciones" => array:1 [ "secciones" => array:8 [ 0 => array:2 [ "identificador" => "xpalclavsec1581240" "titulo" => "KEYWORDS" ] 1 => array:2 [ "identificador" => "cesec10" "titulo" => "INTRODUCTION" ] 2 => array:3 [ "identificador" => "cesec20" "titulo" => "MATERIALS AND METHODS" "secciones" => array:7 [ 0 => array:2 [ "identificador" => "cesec30" "titulo" => "Sample" ] 1 => array:2 [ "identificador" => "cesec40" "titulo" => "Operative procedure" ] 2 => array:2 [ "identificador" => "cesec50" "titulo" => "Application of autologous platelet concentrate" ] 3 => array:2 [ "identificador" => "cesec60" "titulo" => "Hyperbaric oxygen therapy" ] 4 => array:2 [ "identificador" => "cesec70" "titulo" => "Histomorphometric analysis" ] 5 => array:2 [ "identificador" => "cesec80" "titulo" => "Determining the percentages of collagen" ] 6 => array:2 [ "identificador" => "cesec90" "titulo" => "Statistical analysis" ] ] ] 3 => array:2 [ "identificador" => "cesec100" "titulo" => "RESULTS" ] 4 => array:2 [ "identificador" => "cesec110" "titulo" => "DISCUSSION" ] 5 => array:2 [ "identificador" => "cesec120" "titulo" => "AUTHOR CONTRIBUTIONS" ] 6 => array:2 [ "identificador" => "xack638801" "titulo" => "ACKNOWLEDGMENTS" ] 7 => array:1 [ "titulo" => "REFERENCES" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2013-02-27" "fechaAceptado" => "2013-04-22" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "KEYWORDS" "identificador" => "xpalclavsec1581240" "palabras" => array:3 [ 0 => "Hyperbaric Oxygenation" 1 => "Platelet-rich Plasma" 2 => "Fibula, Fracture Consolidation" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:2 [ "resumen" => "OBJECTIVESThe purpose is to study the effects of hyperbaric oxygen therapy and autologous platelet concentrates in healing the fibula bone of rabbits after induced fractures. METHODSA total of 128 male New Zealand albino rabbits, between 6–8 months old, were subjected to a total osteotomy of the proximal portion of the right fibula. After surgery, the animals were divided into four groups (n = 32 each): control group, in which animals were subjected to osteotomy; autologous platelet concentrate group, in which animals were subjected to osteotomy and autologous platelet concentrate applied at the fracture site; hyperbaric oxygen group, in which animals were subjected to osteotomy and 9 consecutive daily hyperbaric oxygen therapy sessions; and autologous platelet concentrate and hyperbaric oxygen group, in which animals were subjected to osteotomy, autologous platelet concentrate applied at the fracture site, and 9 consecutive daily hyperbaric oxygen therapy sessions. Each group was divided into 4 subgroups according to a pre-determined euthanasia time points: 2, 4, 6, and 8 weeks postoperative. After euthanasia at a specific time point, the fibula containing the osseous callus was prepared histologically and stained with hematoxylin and eosin or picrosirius red. RESULTSAutologous platelet concentrates and hyperbaric oxygen therapy, applied together or separately, increased the rate of bone healing compared with the control group. CONCLUSIONHyperbaric oxygen therapy and autologous platelet concentrate combined increased the rate of bone healing in this experimental model." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "ceabs10" "titulo" => "OBJECTIVES" ] 1 => array:2 [ "identificador" => "ceabs20" "titulo" => "METHODS" ] 2 => array:2 [ "identificador" => "ceabs30" "titulo" => "RESULTS" ] 3 => array:2 [ "identificador" => "ceabs40" "titulo" => "CONCLUSION" ] ] ] ] "NotaPie" => array:1 [ 0 => array:1 [ "nota" => "No potential conflict of interest was reported." ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig1" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 710 "Ancho" => 747 "Tamanyo" => 70605 ] ] "descripcion" => array:1 [ "en" => "Distribution of the average percentage of collagen (A), average number of osteoblasts (B) and osteocytes (C), and average lesion thickness (D), according to groups and euthanasia periods (subgroups)." ] ] 1 => array:7 [ "identificador" => "fig2" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1040 "Ancho" => 695 "Tamanyo" => 224515 ] ] "descripcion" => array:1 [ "en" => "A) Photomicrograph of rabbit fibula of the CG showing the region of the lesion after 2 weeks. Note that there are many connective tissue cells (∗), blood vessels (V), and osteoblasts (arrows) (HE). B) Photomicrographs of the rabbit fibulae of the CG 6 weeks after the injury. Note the cartilaginous tissue and small regions of cartilage calcified into newly formed bone within the tissue (arrows) (HE). C) Photomicrograph of rabbit fibulae of the APCG 2 weeks after the injury (HE). D) Photomicrographs of the rabbit fibulae of the ACPG after 6 weeks showing the damaged areas. Note that the bone tissue contains numerous cavities (∗) (HE). E) Photomicrographs of the rabbit fibulae of the HBOG showing the region of the lesions after 2 weeks. Note the cartilaginous tissue (straight line) (HE). F) Photomicrographs of the rabbit fibulae of the HBOG showing the region of the lesion after 6 weeks (HE). G) Photomicrographs of the rabbit fibulae of the APC + HBOG after 2 weeks showing the region of the injury. Note that the site of the injury is filled with cartilage tissue (straight line) (HE). H) Photomicrographs of the rabbit fibulae of the APC + HBOG after 6 weeks showing the region of the injuries. Note the absence of injury and the bone tissue that formed (HE). HBOG was superior to the APCG across all periods for this variable." ] ] 2 => array:7 [ "identificador" => "tbl1" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "CG: Control Group; APCG: Autologous platelet concentrate Group; HBOG: Hyperbaric oxygen therapy Group; APC+HBOG: Autologous platelet concentrate plus Hyperbaric oxygen therapy Group." "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="justify" valign="top" scope="col">Group \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="top" scope="col">Euthanasia period (weeks) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="top" scope="col">No. of osteocytes \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="top" scope="col">No. of osteoblasts \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="top" scope="col">% of collagen \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="top" scope="col">Lesion thickness \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="justify" valign="top">CG \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">2 (n = 8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">0.13±0.35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">11.25±0.89 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">15.59±0.33 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">297.97±0.02 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">4 (n = 8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">10.38±0.52 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">6.38±0.52 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">30.26±0.27 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">192.30±0.10 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">6 (n = 8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">7.25±0.46 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">3.50±0.53 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">70.39±0.16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">98.34±0.18 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">8 (n = 8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">19.38±0.74 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">0.13±0.35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">80.83±0.28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">5.54±0.24 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="justify" valign="top">APCG \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">2 (n = 8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">1.00±0.00 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">13.63±0.52 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">15.58±0.29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">205.16±0.02 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">4 (n = 8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">11.25±0.71 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">4.38±0.52 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">50.50±0.31 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">165.76±0.28 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">6 (n = 8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">14.75±0.71 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">2.13±0.35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">81.76±0.28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">47.36±0.13 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">8 (n = 8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">20.00±0.76 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">0.38±0.52 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">92.86±0.55 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">3.43±0.28 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="justify" valign="top">HBOG \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">2 (n = 8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">1.25±0.46 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">12.38±0.52 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">19.81±0.15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">198.23±0.39 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">4 (n = 8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">10.75±0.46 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">2.25±0.46 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">45.78±0.24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">164.94±1.00 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">6 (n = 8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">16.00±0.53 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">1.25±0.46 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">83.24±0.42 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">34.99±0.41 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">8 (n = 8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">20.63±0.92 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">0.25±0.46 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">90.58±0.46 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">1.10±0.74 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="justify" valign="top">APC+HBOG \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">2 (n = 8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">1.38±0.52 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">12.75±0.89 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">20.91±0.18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">165.45±0.28 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">4 (n = 8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">14.75±0.71 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">2.00±0.00 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">65.38±0.35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">110.41±0.11 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">6 (n = 8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">20.00±0.93 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">0.38±0.52 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">95.06±0.26 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">24.62±0.46 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">8 (n = 8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">21.13±1.13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">0.00±0.00 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">98.00±0.39 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">0.25±0.46 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "Summary measurements (average ± standard deviation) of the percentage of collagen, number of osteoblasts and osteocytes, and lesion thickness, according to groups and euthanasia periods (subgroups)." ] ] 3 => array:7 [ "identificador" => "tbl2" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "W: Weeks; CG: Control Group; APCG: Autologous platelet concentrate Group; HBOG: Hyperbaric oxygen therapy Group; APC+HBOG: Autologous platelet concentrate plus Hyperbaric oxygen therapy Group." "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="justify" valign="top" scope="col">W \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="4" align="center" valign="top" scope="col">Comparisons between groups</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="justify" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="top" scope="col">% of collagen (p) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="top" scope="col">Lesion thickness (p) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="top" scope="col">No. of osteocytes (p) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="top" scope="col">No. of osteoblasts (p) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="justify" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">CG \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">CG>APCG>HBOG>APCG+HBOG (<0.001) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">CG = APCG = HBOG (>0.05) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">GC \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">APC+HBOG>CG (0.025) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">APC+HBOG>CG (<0.001) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">APC+HBOG = APCG = HBOG(>0.999) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">APC+HBOG = APCG, HBOG (>0.05) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="justify" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">CG \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">CG>APCG>HBOG>APC+HBOG(<0.001) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">CG = APCG = HBOG (>0.05) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">GC>HBOG>APCG (<0.001) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">APC+HBOG>CG, APCG, HBOG (<0.001) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">APC+HBOG \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">APC+HBOG = HBOG (>0.999) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="justify" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">CG \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">CG>APCG>HBOG>APCG+HBOG (<0.001) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">CG \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">CG>APCG, HBOG, APC+HBOG (<0.001) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">HBOG = APCG (0.077) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">APC+HBOG \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">APC+HBOG = HBOG (0.077) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="justify" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">CG \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">CG>APCG>HBOG>APCG+HBOG (<0.05) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">APCG = CG (0.885) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">CG = HBOG = APCG = APC+HBOG (>0.999) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">HBOG, APC+HBOG>CG (<0.05) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">HBOG = APCG = APC+HBOG (>0.05) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "Multiple comparisons of the average percentage of collagen, average number of osteoblasts and osteocytes, and average lesion thickness, according to groups and euthanasia periods (subgroups)." ] ] ] "bibliografia" => array:2 [ "titulo" => "REFERENCES" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "cebibsec10" "bibliografiaReferencia" => array:29 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Early experience and results of bone graft enriched with autologous platelet gel for recalcitrant nonunions of lower extremity" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => """ CC Chiang \n \t\t\t\t\t\t\t\t """ 1 => """ CY Su \n \t\t\t\t\t\t\t\t """ 2 => """ CK Huang \n \t\t\t\t\t\t\t\t """ 3 => """ WM Chen \n \t\t\t\t\t\t\t\t """ 4 => """ TH Chen \n \t\t\t\t\t\t\t\t """ 5 => """ YH Tzeng \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/01.ta.0000219937.51190.37" "Revista" => array:7 [ "tituloSerie" => "J Trauma" "fecha" => "2007" "volumen" => "63" "numero" => "3" "paginaInicial" => "655" "paginaFinal" => "661" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18073616" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib2" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The response of habbit patellar tendon after autologous blood injection" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => """ MA Taylor \n \t\t\t\t\t\t\t\t """ 1 => """ TL Norman \n \t\t\t\t\t\t\t\t """ 2 => """ NB Clovis \n \t\t\t\t\t\t\t\t """ 3 => """ JD Blaha \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/00005768-200201000-00012" "Revista" => array:7 [ "tituloSerie" => "Med Sci Sports Exerc" "fecha" => "2002" "volumen" => "34" "numero" => "1" "paginaInicial" => "70" "paginaFinal" => "73" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11782650" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib3" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "PDGF-like growth factors in autocrine stimulation of growth" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => """ CH Heldin \n \t\t\t\t\t\t\t\t """ 1 => """ B Westemark \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "J Cell Physiol Suppl" "fecha" => "1987" "paginaInicial" => "31" "paginaFinal" => "34" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib4" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Platelet delivery growth factor expression in normally healing human fractures" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => """ JG Andrew \n \t\t\t\t\t\t\t\t """ 1 => """ JA Hoyland \n \t\t\t\t\t\t\t\t """ 2 => """ AJ Freemont \n \t\t\t\t\t\t\t\t """ 3 => """ DL March \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/8756-3282(95)90191-4" "Revista" => array:6 [ "tituloSerie" => "Bone" "fecha" => "1995" "volumen" => "16" "paginaInicial" => "455" "paginaFinal" => 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BASIC RESEARCH

Paulo César Fagundes NevesI,

Corresponding author

pauloc.fagundes@uol.com.br
paulo.fagundes@univasf.edu.br

Tel.: 55 87 2101–6865

, Simone de Campos Vieira AbibII, Rogério Fagundes NevesII, Oronzo PircchioI, Karen Ruggeri SaadI, Paulo Fernandes SaadI, Ricardo Santos SimõesII, Marcia Bento MoreiraIII, Cristiano Frota de Souza LaurinoIV

I Universidade Federal do Vale do São Francisco (UNIVASF), Colegiado de Medicina, Petrolina/PE, Brazil

II Universidade Federal de São Paulo (UNIFESP), Departamento de Cirurgia, São Paulo/SP, Brazil

III Universidade Federal do Vale do São Francisco (UNIVASF), Colegiado de Medicina Veterinária, Petrolina/PE, Brazil

IV Sociedade Brasileira de Traumatologia Esportiva e Artroscopia, São Paulo/SP, Brazil

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="cesec10" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle60">INTRODUCTION</span><p id="para10" class="elsevierStylePara elsevierViewall">Loss of osseous continuity due to fracture is a disabling condition&#44; even momentarily&#44; that often deprives the individual of his or her social and professional lifestyle&#46; Therefore&#44; as a medical specialty&#44; orthopedics has invested in studies that promote reduced bone healing time and&#44; consequently&#44; reduced time required to return to normal or almost normal function&#46;</p><p id="para20" class="elsevierStylePara elsevierViewall">Although most fractures do not present healing problems under normal conditions&#44; in some situations&#44; the poorly vascularized bone tissue does not respond adequately to treatment&#44; resulting in delayed consolidation or non-consolidation &#40;<a class="elsevierStyleCrossRef" href="#bib1">1</a>&#41;&#46; Thus&#44; developing new techniques to help the bone healing process and stimulate fracture consolidation is very important&#46;</p><p id="para30" class="elsevierStylePara elsevierViewall">Several studies have focused on reducing bone healing time using low-intensity pulsed ultrasound&#44; low-energy lasers&#44; electrical stimulation&#44; and platelet-rich concentrates &#40;<a class="elsevierStyleCrossRef" href="#bib2">2</a>&#41;&#46;</p><p id="para40" class="elsevierStylePara elsevierViewall">Platelet-rich concentrate &#40;PRC&#41; is an autologous concentration of platelets that releases growth factors&#46; Platelets and the release of these proteins are essential for clot formation in the physiological process of tissue repair&#46; A normal clot consists of 95&#37; red blood cells&#44; 4&#37; platelets&#44; and 1&#37; white blood cells&#46; However&#44; an analysis of platelet-enriched clots reveals 95&#37; platelets&#44; 4&#37; red blood cells&#44; and 1&#37; white blood cells &#40;<a class="elsevierStyleCrossRef" href="#bib2">2</a>&#41;&#46;</p><p id="para50" class="elsevierStylePara elsevierViewall">Platelet-derived growth factor &#40;PDGF&#41; has defined periods of activity&#46; PDGF is a major factor during the onset of tissue repair and acts directly on cell differentiation and angiogenesis&#46; According to classic studies by Heldin &#38; Westmark &#40;<a class="elsevierStyleCrossRef" href="#bib3">3</a>&#41;&#44; PDGF is the first growth factor that initiates repair by stimulating mitogenesis and increasing the local populations of mesenchymal stem cells and osteoprogenitor cells&#46; At concentrations of 20 to 100 ng&#47;ml&#44; bone formation and alkaline phosphatase activity increase in the demineralized matrices of rats &#40;<a class="elsevierStyleCrossRef" href="#bib4">4</a>&#41;&#46;</p><p id="para60" class="elsevierStylePara elsevierViewall">Transforming growth factor beta &#40;TGF-&#946;&#41; is a cytokine synthesized in bone tissue and platelets that stimulates the proliferation of osteoblast precursor cells&#44; promotes collagen synthesis&#44; increases the number of cells that express the osteoblast genotype&#44; increases osteoclast apoptosis&#44; and activates endothelial cells for angiogenesis and chondroprogenitor cells in cartilage formation&#46; However <span class="elsevierStyleItalic">in vitro</span>&#44; TGF-&#946; alone does not induce bone formation in an animal model &#40;<a class="elsevierStyleCrossRef" href="#bib5">5</a>&#41;&#46;</p><p id="para70" class="elsevierStylePara elsevierViewall">Methods for obtaining platelet growth factors should consider the platelet concentrate rate&#44; processing technique&#44; concentration of secreted proteins&#44; handling and application&#44; and especially the clinical application &#40;<a class="elsevierStyleCrossRef" href="#bib6">6</a>&#41;&#46; Platelet-rich plasma &#40;PRP&#41; is undoubtedly the most widely used serum&#59; however&#44; its indiscriminate use has been criticized&#44; and it is still not approved by the Food and Drug Administration &#40;FDA&#41; &#40;<a class="elsevierStyleCrossRef" href="#bib7">7</a>&#41;&#46;</p><p id="para80" class="elsevierStylePara elsevierViewall">Autologous platelet concentrate &#40;APC&#41; is a platelet-rich concentrate &#40;PRC&#41; that is similar to PRP but has certain methodological advantages in terms of how it is obtained&#46; In addition to being approved by the FDA &#40;using the double-syringe method&#41;&#44; APC can be withdrawn and used during a surgical procedure for fracture fixation and is easily processed in a few minutes&#44; which is important because PDGF and TGF-&#946; have half-lives of only a few minutes outside the vascular system &#40;<a class="elsevierStyleCrossRef" href="#bib7">7</a>&#41;&#46;</p><p id="para90" class="elsevierStylePara elsevierViewall">The basic difference between PRP and APC is that PRP is an PRC&#44; with a platelet concentration over 2 times greater than that of plasma&#46; APC is a PRC that combines PRP with platelet-poor plasma &#40;PPP&#41;&#59; according to the manufacturer&#44; APC contains 2 times the platelet concentration of blood plasma&#46; According to studies by Graziane et al&#46; &#40;<a class="elsevierStyleCrossRef" href="#bib8">8</a>&#41;&#44; this platelet concentration is sufficient to stimulate osteoblast proliferation <span class="elsevierStyleItalic">in vitro</span>&#46; In addition&#44; obtaining APC using the double-syringe method eliminates leukocytes&#44; proteases&#44; and hydrolases&#44; which may be able to degrade APC &#40;<a class="elsevierStyleCrossRef" href="#bib9">9</a>&#41;&#46;</p><p id="para100" class="elsevierStylePara elsevierViewall">Hyperbaric oxygen therapy &#40;HBO&#41; is another treatment that may have positive effects on the bone healing process&#46;</p><p id="para110" class="elsevierStylePara elsevierViewall">According to the Undersea and Hyperbaric Medical Society&#44; HBO is defined as intermittently inhaling 100&#37; oxygen inside a chamber at pressures greater than 1 atmosphere absolute &#40;ATA&#41;&#46; This therapy has been first-choice treatment for decompression sickness in divers since the 1920s&#59; however&#44; only since the 1950s has it been used to treat gas embolism&#44; carbon monoxide poisoning&#44; gangrene gas&#44; compartment syndrome&#44; soft tissue infection&#44; osteomyelitis&#44; and osteoradionecrosis &#40;<a class="elsevierStyleCrossRef" href="#bib10">10</a>&#41;&#46;</p><p id="para120" class="elsevierStylePara elsevierViewall">The advantage of HBO is that it is a safe treatment&#46; According to the literature&#44; the complication rate is 1&#46;83&#37;&#44; of which 94&#37; are considered minor complications&#46; The disadvantages of HBO include the high cost of the hyperbaric chamber and the technical training necessary&#44; considering the number of circumstances under which it can be used with some level of evidence&#46; However&#44; the delayed consolidation or non-consolidation of fractures has significant financial impacts on society and represents a serious clinical challenge for which few treatment options are available&#46; Various&#44; often necessary surgical procedures are accompanied with patient morbidity and reduced quality of life &#40;<a class="elsevierStyleCrossRef" href="#bib11">11</a>&#41;&#46;</p><p id="para130" class="elsevierStylePara elsevierViewall">This study was designed to test the hypothesis that many patients with fractures or delayed consolidations could benefit from APC&#44; HBO&#44; or a combination of both treatments because the literature indicates that the osteogenic action of growth factors depends directly on the tissue oxygen tension &#40;<a class="elsevierStyleCrossRef" href="#bib12">12</a>&#41;&#46;</p></span><span id="cesec20" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle70">MATERIALS AND METHODS</span><span id="cesec30" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle80">Sample</span><p id="para140" class="elsevierStylePara elsevierViewall">This study was approved by the Ethics Committee of Universidade Federal de S&#227;o Paulo &#40;0163&#47;08&#41;&#46; All animals were handled according to &#8220;The Ethical Principles of Animal Experiments of the International Union for the Protection of Animals&#8221; 11&#46;794&#47;2008 Act of October 8&#44; 2008&#46;</p><p id="para150" class="elsevierStylePara elsevierViewall">A total of 128 6-8-month-old male New Zealand albino rabbits &#40;Oryctolagus cuniculus&#41;&#44; with an average weight of 3&#44;000 grams&#44; were subjected to an osteotomy of the right fibula after an adaptation period&#46;</p><p id="para160" class="elsevierStylePara elsevierViewall">After surgery&#44; the animals were randomized into 4 groups of 32 rabbits according to the postsurgical treatment used&#44; as follows&#58;<ul class="elsevierStyleList" id="celist10"><li class="elsevierStyleListItem" id="celistitem10"><span class="elsevierStyleLabel">&#8226;</span><p id="para170" class="elsevierStylePara elsevierViewall">Control Group &#40;CG&#41; - animals subjected only to osteotomy of the right fibula&#44; without further treatment</p></li><li class="elsevierStyleListItem" id="celistitem20"><span class="elsevierStyleLabel">&#8226;</span><p id="para180" class="elsevierStylePara elsevierViewall">APC Group &#40;APCG&#41; - animals subjected to osteotomy of the right fibula and treated with APC</p></li><li class="elsevierStyleListItem" id="celistitem30"><span class="elsevierStyleLabel">&#8226;</span><p id="para190" class="elsevierStylePara elsevierViewall">HBO Group &#40;HBOG&#41; - animals subjected to osteotomy of the right fibula and treated with consecutive daily HBO sessions&#44; totaling 9 sessions</p></li><li class="elsevierStyleListItem" id="celistitem40"><span class="elsevierStyleLabel">&#8226;</span><p id="para200" class="elsevierStylePara elsevierViewall">APC and HBO group &#40;APC&#43;HBOG&#41; - animals subjected to osteotomy of the right fibula and treated with APC&#44; combined with consecutive daily HBO sessions&#44; totaling 9 sessions</p></li></ul></p><p id="para210" class="elsevierStylePara elsevierViewall">Each group was further divided into 4 subgroups of 8 animals each&#44; according to a pre-determined euthanasia time point at 2&#44; 4&#44; 6&#44; and 8 weeks postoperatively&#46;</p></span><span id="cesec40" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle90">Operative procedure</span><p id="para220" class="elsevierStylePara elsevierViewall">All animals were food- and water-fasted for 6 hours pre-operatively and then weighed&#59; all the fur was shaved at the leg region&#46;</p><p id="para230" class="elsevierStylePara elsevierViewall">Pre-anesthesia was induced with ketamine hydrochloride solution at a dose of 30 mg&#47;kg&#44; xylazine at a dose of 3 mg&#47;kg&#44; and tramadol hydrochloride at a dose of 5 mg&#47;kg intramuscularly in the gluteal region&#46;</p><p id="para240" class="elsevierStylePara elsevierViewall">The animals were anesthetized with spinal anesthesia using 2&#37; lidocaine without a vasoconstrictor at a dose of 0&#46;5 mg&#47;kg&#46; Venoclysis of the right auricular vein was performed for the infusion of the necessary drugs&#46; Antisepsis was then performed with polyvinylpyrrolidone&#44; and the operative field was isolated with sterile field cloths&#44; delimiting a restricted area for the surgery&#46;</p><p id="para250" class="elsevierStylePara elsevierViewall">Then&#44; a 2-cm lateral longitudinal incision was made along the right leg and dissected by following the muscular planes and localization of the fibular diaphyseal region&#46; A complete transverse osteotomy of the fibula was performed using a no&#46; 15 scalpel blade at the proximal third of the tibial tuberosity&#46;</p><p id="para260" class="elsevierStylePara elsevierViewall">The surgery was completed by suturing the planes&#44; aponeurosis&#44; subcutaneous tissue&#44; and skin with 4-0 nylon thread&#46; Tramadol hydrochloride analgesic was administered at a dose of 2 mg&#47;kg intramuscularly and maintained every 12 hours for 3 consecutive days&#44; in combination with 4 intramuscular antibiotic treatments with benzathine penicillin and G potassium at doses of 20&#44;000 IU&#47;kg every 48 hours&#44; in all animals&#46;</p><p id="para270" class="elsevierStylePara elsevierViewall">Immediately after the osteotomy of the fibula&#44; the animals were randomized according to the pre-determined treatment groups under study and to their respective subgroups&#46; The hind limb did not need to be immobilized because the distal portion of the fibula in rabbits exhibits fusion with the tibia&#46;</p><p id="para280" class="elsevierStylePara elsevierViewall">During the post-operative period&#44; at the pre-determined time for each subgroup &#40;2&#44; 4&#44; 6&#44; or 8 weeks&#41;&#44; the animals were anesthetized again according to the previous protocol&#44; and the fibulae were resected&#44; including the osseous callus&#44; using a no&#46; 15 scalpel blade&#46; Euthanasia was induced during deep anesthesia with xylazine&#46;</p></span><span id="cesec50" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle100">Application of autologous platelet concentrate</span><p id="para290" class="elsevierStylePara elsevierViewall">This procedure was performed during the surgery&#46; Before the surgical procedure&#44; 2&#46;5 ml of blood was withdrawn from the auricular vein using a 10-ml double-syringe &#40;ACP-double syringe&#44; Arthrex&#44; Naples&#44; FL&#44; USA&#41; containing 0&#46;5 ml of acid citrate dextrose anticoagulant&#44; and the syringe was gently agitated to ensure the adequate mixing of the blood with the anticoagulant&#46; The syringe containing the anti-coagulated blood was then stored in a suitable tube and centrifuged &#40;Rotofix 32A&#44; Arthrex&#44; USA&#41; at 1500 RPM for 5 minutes to separate the red blood cells from the plasma&#46;</p><p id="para300" class="elsevierStylePara elsevierViewall">After centrifugation&#44; the plasma was removed from the tube using the same syringe&#44; while the internal syringe collected only the concentrate&#44; leaving the red blood cells&#46; Using this procedure&#44; which was provided by the manufacturer&#44; we obtained approximately 1&#46;5 ml of concentrate&#44; with a high concentration of autologous platelets enriched with growth factors&#46;</p><p id="para310" class="elsevierStylePara elsevierViewall">The platelet concentrate was applied directly to the fracture &#40;osteotomy&#41; in the proximal third of the rabbit fibula before closing the muscular fascia&#46;</p></span><span id="cesec60" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle110">Hyperbaric oxygen therapy</span><p id="para320" class="elsevierStylePara elsevierViewall">HBO sessions were conducted using a veterinary hyperbaric chamber model &#40;AN &#8211; 500&#44; Sechrist&#44; USA&#41; with a 14-rabbit capacity &#40;average weight of 2&#44;500 grams each&#41;&#46; The sessions were conducted daily&#44; 8 animals at a time&#44; and began on the first post-operative day for 90 minutes at 3 ATA &#40;<a class="elsevierStyleCrossRef" href="#bib13">13</a>&#41;&#46; We opted for 9 sessions in the HBO and APC&#43;HBO groups because the growth factor acts primarily during the first 7 post-operative days &#40;<a class="elsevierStyleCrossRef" href="#bib14">14</a>&#41;&#46;</p><p id="para330" class="elsevierStylePara elsevierViewall">The beginning of the session included a compression period&#46; After 15 minutes&#44; the chamber manometer indicated 2 atm of pressure&#59; assuming that the manometer in the hyperbaric chamber measures the pressure difference between the chamber and the surrounding environment&#44; the barometric pressure and environmental pressure &#40;1 ATA&#41; were added to convert the values into absolute atmospheres &#40;ATA&#41;&#46; Therefore&#44; the pressure applied by the chamber was 3 ATA&#46; This absolute pressure &#40;3 ATA&#41; was maintained for 60 minutes&#44; followed by decompression for 15 minutes&#59; thus&#44; each session ended after 90 minutes&#46;</p></span><span id="cesec70" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle120">Histomorphometric analysis</span><p id="para340" class="elsevierStylePara elsevierViewall">Immediately after the experiment&#44; the proximal third of the fibula from each animal&#44; containing the osseous callus region&#44; was surgically removed and placed in 10&#37; buffered formalin for 48 hours&#46; After this period&#44; the decalcification process was begun in ethylenediaminetetraacetic acid &#40;EDTA&#41;&#59; after 6 days&#44; the pieces were dehydrated in increasing concentrations of ethyl alcohol&#44; diaphanized in xylene&#44; impregnated in histological paraffin&#44; and embedded in paraffin&#46;</p><p id="para350" class="elsevierStylePara elsevierViewall">Paraffin blocks were cut with a Minot microtome &#40;Leica&#44; Model RM 2145&#41; with semi-serial 4 &#236;m cuts&#46; After drying for 6&#8211;8 hours in an oven at 60&#176;C&#44; some sections were stained with hematoxylin and eosin &#40;HE&#41;&#44; and others were stained with picrosirius red&#46; The slides were observed under a light microscope &#40;Carl Zeiss&#174;&#41; at 4 to 100&#215;&#46;</p><p id="para360" class="elsevierStylePara elsevierViewall">To determine the concentration of bone cells &#40;osteocytes&#44; osteoblasts&#44; and osteoclasts&#41; in the fibula&#44; an 1800&#215;1600 &#956;M rectangle was initially determined&#44; drawn using a mouse&#44; in two central regions adjacent to the healing bone&#59; one was on the diaphysis side&#44; and the other was on the epiphyseal side&#46; Then&#44; the cells were individually counted within the rectangles&#44; excluding cells that touched the rectangles&#46; For each animal&#44; 6 slides were evaluated&#46; We recorded the average number of cells counted in the rectangles for each animal&#46;</p><p id="para370" class="elsevierStylePara elsevierViewall">The thickness of the cartilage region within the remaining osseous callus was obtained at 3 points in each slide &#40;6 slides for each animal&#41; using a mouse&#46; We recorded the average number of measurements in &#956;M for each animal&#46;</p></span><span id="cesec80" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle130">Determining the percentages of collagen</span><p id="para380" class="elsevierStylePara elsevierViewall">The cuts stained with picrosirius red were used to determine the percentage of collagen formed&#46; Initially&#44; the sections were dewaxed in xylene and then hydrated in a decreasing ethanol gradient&#46; Afterward&#44; elastin was blocked with 0&#46;2&#37; phosphomolybdic acid for 10 minutes&#46; The sections were washed in distilled water&#44; immersed in a 0&#46;1&#37; sirius red solution&#44; and dissolved in saturated aqueous picric acid for 90 minutes&#46; Then&#44; the sections were washed in 0&#46;01 N HCl for 2 minutes&#46; Later&#44; the sections were dehydrated in an increasing ethanol gradient&#44; cleared in xylene&#44; and mounted with Entellan&#174;&#46;</p><p id="para390" class="elsevierStylePara elsevierViewall">Photomicrographs of the picrosirius red-stained sections from the rabbit fibulae of different groups were taken under a polarized light microscope &#40;Axiolab Standard 2&#46;0&#44; Carl Zeiss&#174;&#41; coupled to a high-resolution video camera &#40;AxionCam&#44; Carl Zeiss&#174;&#41; to identify the distribution of collagen fibers in the bone matrix&#46; Then&#44; the micrographs were analyzed on a computer with the Imagelab&#174; program&#46;</p></span><span id="cesec90" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle140">Statistical analysis</span><p id="para400" class="elsevierStylePara elsevierViewall">For quantitative variables&#44; descriptive statistics were calculated&#46; Analysis of variance &#40;ANOVA&#41; and multiple comparisons by the Tukey test were used as inferential analyses to either confirm or refute the evidence found in the descriptive analysis&#46;</p><p id="para410" class="elsevierStylePara elsevierViewall">For all the results obtained via inferential analyses&#44; a significance level of &#945; &#61; 5&#37; was used&#46; All statistical analyses were performed with the <span class="elsevierStyleItalic">R program software</span>&#44; version 2&#46;11&#46;1&#46;</p></span></span><span id="cesec100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle150">RESULTS</span><p id="para420" class="elsevierStylePara elsevierViewall">Information referring to the percentages of collagen&#44; numbers of osteoblasts and osteocytes&#44; and lesion thickness were important measurements assessed among groups and euthanasia time periods &#40;subgroups&#41;&#46; <a class="elsevierStyleCrossRef" href="#tbl1">Table 1</a> and <a class="elsevierStyleCrossRef" href="#fig1">Figure 1 &#40;A &#8211; D&#41;</a> summarize the behavior of these measurements according to the groups and euthanasia periods &#40;subgroup&#41;&#46;</p><elsevierMultimedia ident="tbl1"></elsevierMultimedia><elsevierMultimedia ident="fig1"></elsevierMultimedia><p id="para430" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl2">Table 2</a> shows the results of comparisons of the percentages of collagen&#44; numbers of osteoblasts and osteocytes&#44; and lesion thicknesses among groups and euthanasia periods&#46; <a class="elsevierStyleCrossRef" href="#fig2">Figure 2 &#40;A &#8211; H&#41;</a> shows the HE slides from the groups and subgroups &#40;2<span class="elsevierStyleSup">th</span> and 6<span class="elsevierStyleSup">th</span> weeks&#41;&#46;</p><elsevierMultimedia ident="tbl2"></elsevierMultimedia><elsevierMultimedia ident="fig2"></elsevierMultimedia></span><span id="cesec110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle160">DISCUSSION</span><p id="para440" class="elsevierStylePara elsevierViewall">The results obtained from this experimental model indicate a higher rate of bone healing in response to APC combined with HBO&#46; No previous study in the literature was found to have used this combination in an experimental study&#46;</p><p id="para450" class="elsevierStylePara elsevierViewall">Qualitative analysis highlighted the accelerated bone healing in the APC&#43;HBOG compared with the CG during all weeks studied&#59; additional data on the percentages of collagen and lesion thickness confirm this assessment&#46; In 1983&#44; a review article found that low oxygen tension reduced the action of autologous growth factors &#40;<a class="elsevierStyleCrossRef" href="#bib12">12</a>&#41;&#46; Similarly&#44; the outcomes shown here suggest that the higher oxygen tension caused by HBO application could potentiate the effects of the growth factors offered by APC therapy on bone healing&#46;</p><p id="para460" class="elsevierStylePara elsevierViewall">Although there was no significant difference between the numbers of osteoblasts during any of the periods studied or between the number of osteocytes counted during the 2<span class="elsevierStyleSup">nd</span> and 8<span class="elsevierStyleSup">th</span> weeks&#44; relative to the groups treated with APC and HBO combined&#44; quantitative data on the average lesion thickness showed that the APCG&#44; HBOG&#44; and APC&#43;HBOG were superior to the CG&#46; The APC&#43;HBOG was superior to the other groups across all periods&#44; whereas the HBOG was superior to the APCG across all periods for this variable&#46;</p><p id="para470" class="elsevierStylePara elsevierViewall">The fact that PRC use &#40;in this study&#44; APC&#41; led to a superior rate of bone healing compared with the CG corroborates the outcomes of other studies&#46; Marx et al&#46; &#40;<a class="elsevierStyleCrossRef" href="#bib15">15</a>&#41; performed the first and most convincing study using PRP combined with autogenous bone grafts&#46; The authors evaluated the effect of PRP on the reconstruction of mandibular bone defects resulting from tumor removal&#46; The authors stated that bone grafts with PRP showed more than double the maturity of the controls&#46;</p><p id="para480" class="elsevierStylePara elsevierViewall">Another study by Anitua produced excellent outcomes using autogenous bone grafts combined with PRP &#40;<a class="elsevierStyleCrossRef" href="#bib16">16</a>&#41;&#46; The authors observed a total alveolar bone regeneration in 8 of 10 patients who were treated with PRP and bone graft&#46; Biopsies of the respective areas showed compact mature bone with normal morphology and well-organized trabecular regions&#44; while the control patients showed connective tissue&#44; mostly filled with alveoli&#44; and no mature bone&#46;</p><p id="para490" class="elsevierStylePara elsevierViewall">However&#44; some studies do not support the effect of PRC on the rate of bone healing&#46; Recently&#44; Broggini et al&#46; &#40;<a class="elsevierStyleCrossRef" href="#bib17">17</a>&#41; evaluated bone repairs in the monocortical defects in the calvaria of 15 New Zealand rabbits&#46; The authors concluded that PRP&#44; alone or combined with an autogenous graft&#44; did not lead to a higher rate of bone regeneration compared with basal clot during the initial healing&#46;</p><p id="para500" class="elsevierStylePara elsevierViewall">Currently&#44; the literature is more concerned with quantifying the concentration of growth factors present in some of the most widely used PRCs&#44; especially PRP&#46; A study using this approach stated that the concentration of growth factors in PRP can reach up to 7 and 30 times the basal levels of TGF-&#946; and PDGF&#44; respectively&#44; in a basal clot &#40;<a class="elsevierStyleCrossRef" href="#bib18">18</a>&#41;&#46; According to the manufacturer&#39;s data on the double-syringe method used in this study&#44; APC can have up to 4 and 25 times the levels of TGF-&#946; and PDGF&#44; respectively&#46; Although the concentrations of growth factors found in APC were lower than in PRP&#44; this study demonstrated that this difference does not seem to be a disadvantage&#46; However&#44; it is important to note that functional and non-harmful amounts of these factors in tissue repair have not been well determined&#46;</p><p id="para510" class="elsevierStylePara elsevierViewall">Regarding our outcomes on the effect of HBO on the rate of bone healing&#44; HBO increased the bone consolidation rate compared with the CG&#44; which could be observed through the varying percentages of collagen during each week&#44; the number of osteocytes during the 6<span class="elsevierStyleSup">th</span> and 8<span class="elsevierStyleSup">th</span> weeks&#44; and the lesion thickness across all weeks&#46;</p><p id="para520" class="elsevierStylePara elsevierViewall">Our search for relevant publications led us to the observation that the first studies on the effects of HBO on bone healing date back to the 1960s&#46; After almost 50 years&#44; there are still few studies on this subject&#46;</p><p id="para530" class="elsevierStylePara elsevierViewall">In a Cochrane review study &#40;<a class="elsevierStyleCrossRef" href="#bib19">19</a>&#41;&#44; the authors concluded that there is insufficient evidence to support or refute HBO use for fracture treatment or as a therapy for non-consolidated fractures within an expected time&#46; This conclusion was based on 9 potentially relevant articles among the 68 references identified&#46; However&#44; none of the articles met the review&#39;s inclusive criteria&#58; any randomized or quasi-randomized studies that compared clinical results obtained with HBO use to those obtained without HBO use &#40;no treatment&#41;&#46;</p><p id="para540" class="elsevierStylePara elsevierViewall">Although the literature did not include clinical results that met the methodology described above&#44; our outcomes and the studies cited indicate that HBO is beneficial to the fracture healing process&#46;</p><p id="para550" class="elsevierStylePara elsevierViewall">In 1998&#44; Ueng et al&#46; &#40;<a class="elsevierStyleCrossRef" href="#bib20">20</a>&#41; studied bone mineral density and tensile strength in a rabbit tibial-lengthening model&#46; The bone segments from HBO-treated animals had higher mineral densities and superior biomechanical properties compared with the control animals&#46; Using the same experimental model&#44; this group obtained similar findings&#44; showing that HBO is also advantageous during the early stages of tibial fracture healing &#40;<a class="elsevierStyleCrossRef" href="#bib21">21</a>&#41;&#46;</p><p id="para560" class="elsevierStylePara elsevierViewall">Chen et al&#46; &#40;<a class="elsevierStyleCrossRef" href="#bib22">22</a>&#41; studied the effect of HBO in rabbits subjected to fusion of the vertebrae with a bone graft&#46; According to these authors&#44; the incidence of bone non-consolidation for this procedure in humans ranges from 6&#8211;35&#37; of cases and 40&#8211;50&#37; in rabbits&#46; After 8 weeks&#44; the HBO group showed a 100&#37; consolidation of the fractures&#44; which were identified radiologically and by torsional biomechanical tests&#46;</p><p id="para570" class="elsevierStylePara elsevierViewall">The vast majority of the studies combining HBO and bone repair refer to osteoradionecrosis treatment&#46; Radiation therapy results in progressive obliterative endarteritis&#44; which leads to ischemia and a pathological fracture of the bone with reduced healing ability &#40;<a class="elsevierStyleCrossRef" href="#bib23">23</a>&#41;&#46; Muhonen et al&#46; &#40;<a class="elsevierStyleCrossRef" href="#bib24">24</a>&#41; evaluated the angiogenic and osteogenic responses after radiation and HBO in a rabbit mandibular distraction model&#46; The authors concluded that the HBO group improved in the bone formation pattern&#46;</p><p id="para580" class="elsevierStylePara elsevierViewall">Most experimental studies have found a positive effect from HBO use in the fracture healing process&#46; This effect may be directly associated with the increased formation of new vessels&#44; which increases blood inflow and&#44; thereby&#44; bone formation&#46; Wu et al&#46; &#40;<a class="elsevierStyleCrossRef" href="#bib25">25</a>&#41; presented the outcomes of an <span class="elsevierStyleItalic">in vitro</span> study that investigated the effects of HBO on the proliferation and differentiation of human osteoblasts and concluded that HBO also stimulates initial cell proliferation and acts directly on osteogenic differentiation in osteoblasts&#46;</p><p id="para590" class="elsevierStylePara elsevierViewall">Jan et al&#46; &#40;<a class="elsevierStyleCrossRef" href="#bib26">26</a>&#41; presented the results of a study that assessed the effect of HBO on a rabbit calvaria fracture model&#46; After radiographic and histomorphometric evaluations of the lesion after 6 and 12 weeks&#44; the authors concluded that bone regeneration was significantly improved in the group of HBO-treated animals&#46; It is noteworthy that the type of lesion caused in this experiment was considered critical&#44; and bone healing was unlikely to occur&#46;</p><p id="para600" class="elsevierStylePara elsevierViewall">Yeh et al&#46; &#40;<a class="elsevierStyleCrossRef" href="#bib27">27</a>&#41; studied the effects of HBO on the neovascularization of the tendon-bone junction&#44; on the behavior of collagen fibers within the graft&#44; and on the incorporation process of the graft into the bone tunnel of rabbits subjected to knee arthroscopy for the reconstruction of the anterior cruciate ligament with a tendon graft&#46; The graft is incorporated into the bone tunnel through callus formation and the posterior ossification of the tunnel &#40;<a class="elsevierStyleCrossRef" href="#bib28">28</a>&#41;&#46; In the HBO-treated animals&#44; collagen fibers showed greater organization surrounding the graft and had an early mineralization of fibrocartilage compared with the control animals&#46; The biomechanical test also indicated that HBO-treated animals exhibited greater resistance to the tensile strength of the graft at 18 weeks post-operation than the control animals&#46;</p><p id="para610" class="elsevierStylePara elsevierViewall">The benefits of HBO are related to its proven therapeutic safety and the possible use of the equipment to treat a wider range of diseases&#46; Its disadvantages include the high cost of the equipment and the low level of scientific evidence for HBO use in treating these diseases &#40;<a class="elsevierStyleCrossRef" href="#bib19">19</a>&#41;&#46;</p><p id="para620" class="elsevierStylePara elsevierViewall">However&#44; in choosing a treatment method&#44; one must consider many variables&#44; such as the cost of the equipment&#44; the specialized personnel&#44; the methodological complexity&#44; and the characteristics of the fracture to be treated&#46; Although the mechanisms behind the actions of HBO and APC on bone repair may be different&#44; the variables in this study showed only a few differences between the two methods of treatment&#46; Although qualitative assessment highlights APC&#39;s superiority to HBO in relation to the consolidation rate&#44; further studies should be conducted comparing the two therapies and their effects on bone healing&#46;</p><p id="para630" class="elsevierStylePara elsevierViewall">In this study&#44; we observed that osteoblastic activity was high in the CG during the 4<span class="elsevierStyleSup">th</span> and 6<span class="elsevierStyleSup">th</span> weeks but was higher in all other groups during the 2<span class="elsevierStyleSup">nd</span> week&#46; We also observed that osteoblastic activity was higher in the APC group than in the HBO group during the 2<span class="elsevierStyleSup">nd</span> and 4<span class="elsevierStyleSup">th</span> weeks&#44; while no difference was found between these groups in relation to the number of osteoblasts during the 6<span class="elsevierStyleSup">th</span> and 8<span class="elsevierStyleSup">th</span> weeks&#46; These findings corroborate previous knowledge that osteoblastic actions are strongly associated with higher concentrations of growth factors&#46; We wish to note that this action was stronger in the first weeks with APC treatment and that it was superior to treatment with HBO at this stage&#46;</p><p id="para640" class="elsevierStylePara elsevierViewall">Despite the differences observed in relation to the osteoblastic activity among the subgroups during the first experimental weeks&#44; counting the number of osteocytes during the 8<span class="elsevierStyleSup">th</span> week does not indicate the quantity of newly formed bone present in each subgroup&#44; as advocated by other authors &#40;<a class="elsevierStyleCrossRef" href="#bib29">29</a>&#41;&#46; We believe that the number of osteocytes associated with qualitative analysis and other variables&#44; such as lesion thickness and percentage of collagen&#44; better suggest the quantity of newly formed bone&#46; In this study&#44; APC&#43;HBO was superior in producing a greater quantity of new bone compared with the APC&#44; HBO&#44; and control treatments during the 8<span class="elsevierStyleSup">th</span> week&#46;</p><p id="para650" class="elsevierStylePara elsevierViewall">The importance of this study lies in the possibility of combining these two treatments&#44; the effects of which potentiate increased bone formation&#46; Additional studies with other variables must be conducted to deepen our knowledge of the effects of each of these treatments on bone healing&#59; further studies should examine the economic impact of these combinations&#46;</p><p id="para660" class="elsevierStylePara elsevierViewall">The analysis of these outcomes allows us to state that APC and HBO combined increased the rate of bone healing in this experimental model&#46; In addition&#44; the rate of bone repair in the groups treated with APC or HBO were similar&#44; and both rates were higher than in the CG&#46;</p></span><span id="cesec120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle170">AUTHOR CONTRIBUTIONS</span><p id="para670" class="elsevierStylePara elsevierViewall">Neves PC&#44; Abib SC&#44; Neves RF&#44; and Moreira MB conceived and designed the study&#46; Neves PC&#44; Neves RF&#44; Pirchio O&#44; Simoes RS&#44; and Laurino CF conducted the experiments and performed the data analysis&#46; Neves PC&#44; Saad KR&#44; and Saad PF performed the data analysis and wrote the manuscript&#46; All authors approved the final version of the manuscript&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
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        0 => array:2 [
          "identificador" => "xpalclavsec1581240"
          "titulo" => "KEYWORDS"
        ]
        1 => array:2 [
          "identificador" => "cesec10"
          "titulo" => "INTRODUCTION"
        ]
        2 => array:3 [
          "identificador" => "cesec20"
          "titulo" => "MATERIALS AND METHODS"
          "secciones" => array:7 [
            0 => array:2 [
              "identificador" => "cesec30"
              "titulo" => "Sample"
            ]
            1 => array:2 [
              "identificador" => "cesec40"
              "titulo" => "Operative procedure"
            ]
            2 => array:2 [
              "identificador" => "cesec50"
              "titulo" => "Application of autologous platelet concentrate"
            ]
            3 => array:2 [
              "identificador" => "cesec60"
              "titulo" => "Hyperbaric oxygen therapy"
            ]
            4 => array:2 [
              "identificador" => "cesec70"
              "titulo" => "Histomorphometric analysis"
            ]
            5 => array:2 [
              "identificador" => "cesec80"
              "titulo" => "Determining the percentages of collagen"
            ]
            6 => array:2 [
              "identificador" => "cesec90"
              "titulo" => "Statistical analysis"
            ]
          ]
        ]
        3 => array:2 [
          "identificador" => "cesec100"
          "titulo" => "RESULTS"
        ]
        4 => array:2 [
          "identificador" => "cesec110"
          "titulo" => "DISCUSSION"
        ]
        5 => array:2 [
          "identificador" => "cesec120"
          "titulo" => "AUTHOR CONTRIBUTIONS"
        ]
        6 => array:2 [
          "identificador" => "xack638801"
          "titulo" => "ACKNOWLEDGMENTS"
        ]
        7 => array:1 [
          "titulo" => "REFERENCES"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2013-02-27"
    "fechaAceptado" => "2013-04-22"
    "PalabrasClave" => array:1 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "KEYWORDS"
          "identificador" => "xpalclavsec1581240"
          "palabras" => array:3 [
            0 => "Hyperbaric Oxygenation"
            1 => "Platelet-rich Plasma"
            2 => "Fibula&#44; Fracture Consolidation"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:1 [
      "en" => array:2 [
        "resumen" => "<span id="ceabs10" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle10">OBJECTIVES</span><p id="spara50" class="elsevierStyleSimplePara elsevierViewall">The purpose is to study the effects of hyperbaric oxygen therapy and autologous platelet concentrates in healing the fibula bone of rabbits after induced fractures&#46;</p></span> <span id="ceabs20" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle20">METHODS</span><p id="spara60" class="elsevierStyleSimplePara elsevierViewall">A total of 128 male New Zealand albino rabbits&#44; between 6&#8211;8 months old&#44; were subjected to a total osteotomy of the proximal portion of the right fibula&#46; After surgery&#44; the animals were divided into four groups &#40;n &#61; 32 each&#41;&#58; control group&#44; in which animals were subjected to osteotomy&#59; autologous platelet concentrate group&#44; in which animals were subjected to osteotomy and autologous platelet concentrate applied at the fracture site&#59; hyperbaric oxygen group&#44; in which animals were subjected to osteotomy and 9 consecutive daily hyperbaric oxygen therapy sessions&#59; and autologous platelet concentrate and hyperbaric oxygen group&#44; in which animals were subjected to osteotomy&#44; autologous platelet concentrate applied at the fracture site&#44; and 9 consecutive daily hyperbaric oxygen therapy sessions&#46; Each group was divided into 4 subgroups according to a pre-determined euthanasia time points&#58; 2&#44; 4&#44; 6&#44; and 8 weeks postoperative&#46; After euthanasia at a specific time point&#44; the fibula containing the osseous callus was prepared histologically and stained with hematoxylin and eosin or picrosirius red&#46;</p></span> <span id="ceabs30" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle30">RESULTS</span><p id="spara70" class="elsevierStyleSimplePara elsevierViewall">Autologous platelet concentrates and hyperbaric oxygen therapy&#44; applied together or separately&#44; increased the rate of bone healing compared with the control group&#46;</p></span> <span id="ceabs40" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle40">CONCLUSION</span><p id="spara80" class="elsevierStyleSimplePara elsevierViewall">Hyperbaric oxygen therapy and autologous platelet concentrate combined increased the rate of bone healing in this experimental model&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "ceabs10"
            "titulo" => "OBJECTIVES"
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          1 => array:2 [
            "identificador" => "ceabs20"
            "titulo" => "METHODS"
          ]
          2 => array:2 [
            "identificador" => "ceabs30"
            "titulo" => "RESULTS"
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          3 => array:2 [
            "identificador" => "ceabs40"
            "titulo" => "CONCLUSION"
          ]
        ]
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:1 [
        "nota" => "<p class="elsevierStyleNotepara" id="cenpara10">No potential conflict of interest was reported&#46;</p>"
      ]
    ]
    "multimedia" => array:4 [
      0 => array:7 [
        "identificador" => "fig1"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 710
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        "descripcion" => array:1 [
          "en" => "<p id="spara10" class="elsevierStyleSimplePara elsevierViewall">Distribution of the average percentage of collagen &#40;A&#41;&#44; average number of osteoblasts &#40;B&#41; and osteocytes &#40;C&#41;&#44; and average lesion thickness &#40;D&#41;&#44; according to groups and euthanasia periods &#40;subgroups&#41;&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig2"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
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            "Tamanyo" => 224515
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        "descripcion" => array:1 [
          "en" => "<p id="spara20" class="elsevierStyleSimplePara elsevierViewall">A&#41; Photomicrograph of rabbit fibula of the CG showing the region of the lesion after 2 weeks&#46; Note that there are many connective tissue cells &#40;&#8727;&#41;&#44; blood vessels &#40;V&#41;&#44; and osteoblasts &#40;arrows&#41; &#40;HE&#41;&#46; B&#41; Photomicrographs of the rabbit fibulae of the CG 6 weeks after the injury&#46; Note the cartilaginous tissue and small regions of cartilage calcified into newly formed bone within the tissue &#40;arrows&#41; &#40;HE&#41;&#46; C&#41; Photomicrograph of rabbit fibulae of the APCG 2 weeks after the injury &#40;HE&#41;&#46; D&#41; Photomicrographs of the rabbit fibulae of the ACPG after 6 weeks showing the damaged areas&#46; Note that the bone tissue contains numerous cavities &#40;&#8727;&#41; &#40;HE&#41;&#46; E&#41; Photomicrographs of the rabbit fibulae of the HBOG showing the region of the lesions after 2 weeks&#46; Note the cartilaginous tissue &#40;straight line&#41; &#40;HE&#41;&#46; F&#41; Photomicrographs of the rabbit fibulae of the HBOG showing the region of the lesion after 6 weeks &#40;HE&#41;&#46; G&#41; Photomicrographs of the rabbit fibulae of the APC &#43; HBOG after 2 weeks showing the region of the injury&#46; Note that the site of the injury is filled with cartilage tissue &#40;straight line&#41; &#40;HE&#41;&#46; H&#41; Photomicrographs of the rabbit fibulae of the APC &#43; HBOG after 6 weeks showing the region of the injuries&#46; Note the absence of injury and the bone tissue that formed &#40;HE&#41;&#46; HBOG was superior to the APCG across all periods for this variable&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "tbl1"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="TFN01t01" class="elsevierStyleSimplePara elsevierViewall">CG&#58; Control Group&#59; APCG&#58; Autologous platelet concentrate Group&#59; HBOG&#58; Hyperbaric oxygen therapy Group&#59; APC&#43;HBOG&#58; Autologous platelet concentrate plus Hyperbaric oxygen therapy Group&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="justify" valign="top" scope="col">Group&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">Euthanasia period &#40;weeks&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">No&#46; of osteocytes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">No&#46; of osteoblasts&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">&#37; of collagen&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">Lesion thickness&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="justify" valign="top">CG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">2 &#40;n &#61; 8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;13&#177;0&#46;35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">11&#46;25&#177;0&#46;89&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">15&#46;59&#177;0&#46;33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">297&#46;97&#177;0&#46;02&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="center" valign="top">4 &#40;n &#61; 8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">10&#46;38&#177;0&#46;52&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">6&#46;38&#177;0&#46;52&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">30&#46;26&#177;0&#46;27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">192&#46;30&#177;0&#46;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="center" valign="top">6 &#40;n &#61; 8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">7&#46;25&#177;0&#46;46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">3&#46;50&#177;0&#46;53&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">70&#46;39&#177;0&#46;16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">98&#46;34&#177;0&#46;18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " align="center" valign="top">8 &#40;n &#61; 8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">19&#46;38&#177;0&#46;74&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;13&#177;0&#46;35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="center" valign="top">80&#46;83&#177;0&#46;28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">5&#46;54&#177;0&#46;24&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="center" valign="top">2 &#40;n &#61; 8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="justify" valign="top">APC&#43;HBOG&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="center" valign="top">2 &#40;n &#61; 8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="center" valign="top">98&#46;00&#177;0&#46;39&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara30" class="elsevierStyleSimplePara elsevierViewall">Summary measurements &#40;average &#177; standard deviation&#41; of the percentage of collagen&#44; number of osteoblasts and osteocytes&#44; and lesion thickness&#44; according to groups and euthanasia periods &#40;subgroups&#41;&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "tbl2"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="TFN01t02" class="elsevierStyleSimplePara elsevierViewall">W&#58; Weeks&#59; CG&#58; Control Group&#59; APCG&#58; Autologous platelet concentrate Group&#59; HBOG&#58; Hyperbaric oxygen therapy Group&#59; APC&#43;HBOG&#58; Autologous platelet concentrate plus Hyperbaric oxygen therapy Group&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="justify" valign="top" scope="col">W&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="4" align="center" valign="top" scope="col">Comparisons between groups</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="justify" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">&#37; of collagen &#40;p&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">Lesion thickness &#40;p&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">No&#46; of osteocytes &#40;p&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">No&#46; of osteoblasts &#40;p&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="justify" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">CG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">CG&#62;APCG&#62;HBOG&#62;APCG&#43;HBOG &#40;&#60;0&#46;001&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">CG &#61; APCG &#61; HBOG &#40;&#62;0&#46;05&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">GC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">APC&#43;HBOG&#62;CG &#40;0&#46;025&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">APC&#43;HBOG&#62;CG &#40;&#60;0&#46;001&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">APC&#43;HBOG &#61; APCG &#61; HBOG&#40;&#62;0&#46;999&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">APC&#43;HBOG &#61; APCG&#44; HBOG &#40;&#62;0&#46;05&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="justify" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">CG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">CG&#62;APCG&#62;HBOG&#62;APC&#43;HBOG&#40;&#60;0&#46;001&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">CG &#61; APCG &#61; HBOG &#40;&#62;0&#46;05&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">GC&#62;HBOG&#62;APCG &#40;&#60;0&#46;001&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">APC&#43;HBOG&#62;CG&#44; APCG&#44; HBOG &#40;&#60;0&#46;001&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">APC&#43;HBOG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">APC&#43;HBOG &#61; HBOG &#40;&#62;0&#46;999&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="justify" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">CG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">CG&#62;APCG&#62;HBOG&#62;APCG&#43;HBOG &#40;&#60;0&#46;001&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">CG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">CG&#62;APCG&#44; HBOG&#44; APC&#43;HBOG &#40;&#60;0&#46;001&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">HBOG &#61; APCG &#40;0&#46;077&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">APC&#43;HBOG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">APC&#43;HBOG &#61; HBOG &#40;0&#46;077&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="justify" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">CG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">CG&#62;APCG&#62;HBOG&#62;APCG&#43;HBOG &#40;&#60;0&#46;05&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">APCG &#61; CG &#40;0&#46;885&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">CG &#61; HBOG &#61; APCG &#61; APC&#43;HBOG &#40;&#62;0&#46;999&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">HBOG&#44; APC&#43;HBOG&#62;CG &#40;&#60;0&#46;05&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">HBOG &#61; APCG &#61; APC&#43;HBOG &#40;&#62;0&#46;05&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara40" class="elsevierStyleSimplePara elsevierViewall">Multiple comparisons of the average percentage of collagen&#44; average number of osteoblasts and osteocytes&#44; and average lesion thickness&#44; according to groups and euthanasia periods &#40;subgroups&#41;&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "REFERENCES"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "cebibsec10"
          "bibliografiaReferencia" => array:29 [
            0 => array:3 [
              "identificador" => "bib1"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Early experience and results of bone graft enriched with autologous platelet gel for recalcitrant nonunions of lower extremity"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => """
                              CC Chiang \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              CY Su \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              CK Huang \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              WM Chen \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              TH Chen \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              YH Tzeng \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/01.ta.0000219937.51190.37"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Trauma"
                        "fecha" => "2007"
                        "volumen" => "63"
                        "numero" => "3"
                        "paginaInicial" => "655"
                        "paginaFinal" => "661"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18073616"
                            "web" => "Medline"
                          ]
                        ]
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        "titulo" => "ACKNOWLEDGMENTS"
        "texto" => "<p id="para680" class="elsevierStylePara elsevierViewall">This study was supported by the Funda&#231;&#227;o de Amparo &#224; Pesquisa do Estado de S&#227;o Paulo &#40;FAPESP &#35;104698&#41;&#46;</p>"
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Article information

ISSN: 18075932
Original language: English

DOI:10.6061/clinics/2013(09)11

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Year/Month	Html	Pdf	Total

2024 November	9	2	11
2024 October	48	29	77
2024 September	41	18	59
2024 August	42	24	66
2024 July	33	14	47
2024 June	28	14	42
2024 May	26	12	38
2024 April	32	12	44
2024 March	27	13	40
2024 February	21	17	38
2024 January	14	8	22
2023 December	13	16	29
2023 November	24	19	43
2023 October	25	30	55
2023 September	32	27	59
2023 August	35	9	44
2023 July	20	21	41
2023 June	27	7	34
2023 May	40	6	46
2023 April	32	1	33
2023 March	18	2	20
2023 February	15	1	16
2023 January	5	2	7
2022 December	48	4	52

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