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Background: The versatile combination of emdogain or enamel matrix derivative (EMD), recombinant human platelet-derived growth factor-BB (rhPDGF-BB), and demineralized freeze-dried bone allograft (DFDBA) has not been utilized in the treatment of intrabony defects yet. Aim: The present study attempted to investigate the efficacy of a combination of simple, uncomplicated nature of modified minimally invasive surgical technique (M-MIST) with EMD, rhPDGF-BB, and DFDBA in the surgical management of intrabony defects and to assess the possible favorable effects for a period of 6 months. Patients and Methods: Thirty healthy subjects were included in the present double-blind, randomized controlled, two-arm parallel study. The test group was treated with M-MIST by using rhPDGF-BB, EMD, and DFDBA, and the control group was treated with M-MIST by using rhPDGF-BB and EMD. Results: Differences between the mean values of primary clinical parameters including relative attachment level, probing depth, and gingival recession at baseline and those at 6 months after surgery were statistically significant in both groups. Inter-group comparison for clinical attachment level gain, probing depth reduction, and change in the position of gingival margin revealed no statistically significant differences. Inter-group comparison revealed significant differences in linear bone growth (LBG) and percentage bone fill (% BF) but no significant differences in the residual defect depth and change in the alveolar crest position. Conclusion: The additional use of DFDBA provides superior benefits in terms of LBG and % BF in intrabony defects. This improvement might be attributed to the use of an osteoinductive scaffold.
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Pérdida de Hueso Alveolar , Humanos , Becaplermina/uso terapéutico , Pérdida de Hueso Alveolar/cirugía , Resultado del Tratamiento , Pérdida de la Inserción Periodontal/cirugíaRESUMEN
Charcot neuroarthropathy has traditionally been treated using both nonsurgical and surgical strategies. Recently, orthobiologics have been used to promote arthrodesis in Charcot reconstructions, obviating the need for bone graft in some cases. Recombinant human platelet-derived growth factor BB homodimer (rhPDGF-BB) in combination with beta-tricalcium phosphate scaffold (ß-TCP) is a bone graft substitute shown to have comparable efficacy to autograft in incidence of foot and ankle fusion. This multicenter, consecutive case series analyzed patients undergoing Charcot reconstructions utilizing rhPDGF-BB/ß-TCP for joint fusion. In this cohort, 98 patients (62.24% male) with a mean age of 62.82 ± 10.28 years (range 40-87) had a fusion incidence of 217 of 223 joints (97.31%) with a mean time to fusion of 13.09 ± 4.87 weeks (range 6-30). There were 6 nonunions in the patient population. Fusion was defined as ≥50% osseous bridging based on computed tomography and/or radiographic consolidation, in addition to clinical findings. With an overall complication rate of 26.53% (26/98), adverse events occurring in more than 1 patient limb included hardware failures (nâ¯=â¯7, 7.14%), infection (nâ¯=â¯4, 4.08%), wound dehiscence (nâ¯=â¯4, 4.08%), amputation (nâ¯=â¯3, 3.06%), and death (nâ¯=â¯2, 2.04%). There were no adverse events related to the grafting material. From this review, we found rhPDGF-BB/ß-TCP to be a safe and effective graft material that can be considered a viable alternative to autograft, even in high-risk patients such as those with Charcot neuroarthropathy.
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Artrodesis , Fosfatos de Calcio , Becaplermina , Preescolar , Femenino , Humanos , Lactante , Masculino , Estudios Multicéntricos como Asunto , Proteínas Proto-Oncogénicas c-sis , Estudios RetrospectivosRESUMEN
To investigate the mechanism of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) and human adipose-derived stem cells (hADSCs) in the treatment of Achilles tendinitis. Biomechanical indices of stiffness, stress, and maximum load-to-failure were detected by biomechanical test. mRNA and protein levels of miR-363, p-PI3K/AKT, tendon-related genes Collagen I, Scleraxis (Scx), and Tenascin C (TNC) were measured by qRT-PCR and western blot. The proliferation of hADSCs was accessed by MTT assay. Biomechanical indices of stiffness, stress, and maximum load-to-failure, and mRNA and protein levels of tendon-related genes could be improved by rhPDGF-BB or hADSCs alone, and could be further improved by rhPDGF-BB + hADSCs. rhPDGF-BB and hADSCs downregulated the expression of miR-363 and upregulated the levels of p-PI3K/Akt, and rhPDGF-BB + hADSCs further strengthened these effects. In addition, rhPDGF-BB promoted the proliferation of hADSCs in vitro and upregulated the expression of tendon-related genes. miR-363 mimic downregulated the levels of p-PI3K/Akt, miR-363 inhibitor upregulated the levels of p-PI3K/Akt, and miR-363 mimic and PI3K/Akt pathway inhibitor LY294002 reversed the positive effect of rhPDGF-BB on the proliferation of hADSCs, which suggested that rhPDGF-BB promoted the proliferation of hADSCs via miR-363/PI3K/Akt pathway. Biomechanical indices and tendon-related genes could be improved by rhPDGF-BB and hADSCs. Moreover, rhPDGF-BB promoted the proliferation of hADSCs via miR-363/PI3K/Akt pathway, indicating that rhPDGF-BB combined with ADSCs could treat Achilles tendinitis via miR-363/PI3K/Akt pathway.
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Tendón Calcáneo , Tejido Adiposo/metabolismo , Proteínas Proto-Oncogénicas c-sis/farmacología , Trasplante de Células Madre , Células Madre/metabolismo , Tendinopatía/terapia , Tejido Adiposo/patología , Animales , Becaplermina , Modelos Animales de Enfermedad , Xenoinjertos , Humanos , Ratas , Ratas Sprague-Dawley , Células Madre/patología , Tendinopatía/metabolismo , Tendinopatía/patologíaRESUMEN
OBJECTIVES: Improvement in localized bone regeneration is needed to avoid the use of autogenous tissue. For that purpose, the use biologic mediators was proposed. The aim was to test whether or not one of two biologic mediators, recombinant human bone morphogenetic protein-2 (rhBMP-2) or recombinant platelet-derived growth factor (rhPDGF-BB), is superior to the other and to control groups for localized bone regeneration. MATERIALS AND METHODS: Four cylinders (height: 5 mm; diameter: 7 mm) were screwed on the parietal and frontal bones at the cranium in 12 rabbits. The cylinders either received (i) deproteinized bovine bone mineral (DBBM) mixed rhBMP-2 (DBBM/BMP-2), (ii) DBBM mixed with rhPDGF-BB (DBBM/PDGF), (iii) DBBM (DBBM), and (iv) empty control (control). Rabbits were euthanized at 2 and 8 weeks (n = 6, respectively). Conventional histomorphometric and micro-CT analyses were performed. Parametric linear mixed models were applied for the analyses with Bonferroni correction for the multiple group comparisons. RESULTS: The area of bone regeneration (histology; AAHisto ) at 2 weeks peaked for DBBM (41.91%) with statistically significantly greater values compared to DBBM/PDGF and the control group (P < 0.05). At 8 weeks, mean AAHisto values were 96.29% (DBBM/BMP-2), 46.37% (DBBM/PDFG), 39.66% (DBBM), and 35.98% (control) (DBBM/BMP-2 vs. all groups (P < 0.05)). At 8 weeks, bone regeneration was greatest for DBBM/BMP-2 (35.62%) with statistically significant differences compared to all other groups (P < 0.05). The area of bone regeneration (micro-CT; AAm-CT ) at 2 weeks amounted to 43.87% (DBBM/BMP-2), 42.81% (DBBM/PDFG), 48.71% (DBBM), and 0.96% (control). The control group demonstrated statistically significantly less AAm-CT compared to all groups (P < 0.05). At 8 weeks, mean AAm-CT values were 63.65% (DBBM/BMP-2), 50.21% (DBBM/PDFG), 44.81% (DBBM), and 4.57% (control) (P > 0.05). CONCLUSIONS: The use of rhBMP-2 significantly enhanced bone regeneration compared to all other groups including the group with rhPDGF-BB.
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Proteína Morfogenética Ósea 2/farmacología , Regeneración Ósea/efectos de los fármacos , Proteínas Proto-Oncogénicas c-sis/farmacología , Animales , Becaplermina , Hueso Frontal/diagnóstico por imagen , Hueso Frontal/crecimiento & desarrollo , Hueso Frontal/patología , Hueso Frontal/cirugía , Hueso Parietal/diagnóstico por imagen , Hueso Parietal/crecimiento & desarrollo , Hueso Parietal/patología , Hueso Parietal/cirugía , Conejos , Proteínas Recombinantes , Microtomografía por Rayos XRESUMEN
Nanotube morphology has been previously applied to improve osseointegration in osteoporosis, but the osteogenic capability of the technique requires further improvements. This study aimed to investigate the effects of vacuum extraction on the loading of rhPDGF-BB on nanotube arrays as well as its effects on the osseointegration of ovariectomized (OVX) rats. More rhPDGF-BB protein particles aggregated on the nanotube surface and into the nanotube after vacuum extraction for 10 min. The immobilized protein could be slowly released for at least 14 days and still kept its biological activity. In vitro, the immobilized rhPDGF-BB enhanced cell adhesion, proliferation and osteogenic differentiation. In vivo, more rhPDGF-BB immobilized on the nanotube surface also promoted the osseointegration. These results suggest that the enhanced immobilization of rhPDGF-BB on nanotube arrays can potentially be used in the future as an implant surface modification strategy in dental and orthopedic applications in osteoporotic patients. FROM THE CLINICAL EDITOR: This study presents convincing evidence that enhanced immobilization of recombinant human PDGF-BB protein particles on nanotubes lead to improved osteogenic differentiation in an experimental system. When used as a surface modification strategy for dental or orthopedic implants, this method was able to promote osseointegration even in an osteoporotic animal model, raising the likelihood for potential future clinical applications.
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Nanotubos/química , Oseointegración/efectos de los fármacos , Proteínas Proto-Oncogénicas c-sis/química , Proteínas Proto-Oncogénicas c-sis/farmacología , Vacio , Animales , Becaplermina , Femenino , Ovariectomía , RatasRESUMEN
Bone morphogenetic protein (BMP) and platelet-derived growth factor (PDGF) are known to regulate/stimulate osteogenesis, playing vital roles in bone homeostasis, rendering them strong candidates for osteoporosis treatment. We evaluated the effects of recombinant human BMP-7 (rhBMP7) and PDGF-BB (rhPDGF-BB) in an oophorectomy-induced osteoporosis rat model. Forty Sprague Dawley rats underwent oophorectomy surgery; treatments commenced on the 100th day post-surgery when all animals exhibited signs of osteoporosis. These peptide growth factors were administered intraocularly (iv) once or twice a week and the animals were monitored for a total of five weeks. Two weeks after the conclusion of the treatments, the animals were euthanized and tissues were collected for assessment of alkaline phosphatase, X-ray, micro-CT, and histology. The results indicate that the most promising treatments were 20 µg/kg rhPDGF-BB + 30 µg/kg rhBMP-7 twice a week and 30 µg/kg BMP-7 twice a week, showing significant increases of 15% (p < 0.05) and 13% (p < 0.05) in bone volume fraction and 21% (p < 0.05) and 23% (p < 0.05) in trabecular number, respectively. In conclusion, rhPDGF-BB and rhBMP-7 have demonstrated the ability to increase bone volume and density in this osteoporotic animal model, establishing them as potential candidates for osteoporosis treatment.
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Proteína Morfogenética Ósea 7 , Osteoporosis , Humanos , Ratas , Animales , Becaplermina/farmacología , Proteínas Proto-Oncogénicas c-sis/farmacología , Proteínas Proto-Oncogénicas c-sis/uso terapéutico , Proteína Morfogenética Ósea 7/farmacología , Proteína Morfogenética Ósea 7/uso terapéutico , Ratas Sprague-Dawley , Proteínas Recombinantes/farmacología , Proteínas Recombinantes/uso terapéutico , Proteínas Morfogenéticas Óseas , Osteoporosis/tratamiento farmacológico , Proteína Morfogenética Ósea 2RESUMEN
PURPOSE: The purpose of this study was to investigate if the addition of biologic agents to a particulate bone graft enhances horizontal ridge augmentation outcomes in terms of bone dimensions, bone density, and successful implant placement. MATERIALS AND METHODS: A retrospective chart review was done to assess the clinical and radiographic outcomes in 52 horizontal ridge augmentation sites in 43 patients. Information was gathered regarding surgical technique, type of graft material, biologic agents used (PRP or rhPDGF-BB), method of space maintenance, and achieved alveolar ridge width and bone density changes as quantified on CBCT scans. RESULTS: The use of tenting screws, a resorbable membrane, and a combination of particulate allogenic and xenogenic bone graft material provided an average horizontal bone gain of 3.6 mm in the 52 augmented sites. There was no statistically significant difference observed in the amount of horizontal bone gain between sites treated with the addition of biologic agents (n = 21), or with a particulate bone graft alone (n = 31). A marginally statistically significant difference was found in the density of the grafted bone with the addition of biologics (p value = .0653). CONCLUSION: The addition of biologic agents to the graft materials did not have a significant effect on the amount of horizontal bone gain or successful implant placement; however, it marginally enhanced the bone density of the grafted area.
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Aumento de la Cresta Alveolar , Productos Biológicos , Factores Biológicos , Implantación Dental Endoósea , Humanos , Estudios RetrospectivosRESUMEN
BACKGROUND CONTEXT: While the clinical effectiveness of recombinant human Platelet Derived Growth Factor-B chain homodimer combined with collagen and ß-tricalcium phosphate (rhPDGF-BB + collagen/ß-TCP) treatment for indications involving hindfoot and ankle is well-established, it is not approved for use in spinal interbody fusion, and the use of autograft remains the gold standard. PURPOSE: The purpose of this study was to compare the effects of rhPDGF-BB + collagen/ß-TCP treatment on lumbar spine interbody fusion in an ovine model to those of autograft bone and collagen/ß-TCP treatments using biomechanical, radiographic, and histological assessment techniques. STUDY DESIGN: Thirty-two skeletally mature Columbian Rambouillet sheep were used to evaluate the safety and effectiveness of rhPDGF-BB + collagen/ß-TCP matrix in a lumbar spinal fusion model. Interbody polyetheretherketone (PEEK) cages contained either autograft, rhPDGF-BB + collagen/ß-TCP, collagen/ß-TCP matrix, or left empty. METHODS: Animals were sacrificed 8- or 16-weeks post-surgery. Spinal fusion was evaluated via post-sacrifice biomechanical, micro-computed tomography (µCT), and histological analysis. Outcomes were statistically compared using a two-way analysis of variance (ANOVA) with an alpha value of 0.05 and a Tukey post-hoc test. RESULTS: There were no statistically significant differences between groups within treatment timepoints for flexion-extension, lateral bending, or axial rotation range of motion, neutral zone, neutral zone stiffness, or elastic zone stiffness. µCT bone volume fraction was significantly greater between treatment groups independent of timepoint where Autograft and rhPDGF-BB + collagen/ß-TCP treatments demonstrated significantly greater bone volume fraction as compared to collagen/ß-TCP (P = .026 and P = .038, respectively) and Empty cage treatments (P = .002 and P = .003, respectively). µCT mean bone density fraction was most improved in rhPDGF-BB + collagen/ß-TCP specimens at the 8 week and 16-week timepoints as compared to all other treatment groups. There were no statistically significant differences in histomorphometric measurements of bone, soft tissue, or empty space between rhPDGF-BB + collagen/ß-TCP and autograft treatments. CONCLUSIONS: The results of this study indicate that the use of rhPDGF-BB combined with collagen/ß-TCP promotes spinal fusion comparable to that of autograft bone. CLINICAL SIGNIFICANCE: The data indicate that rhPDGF-BB combined with collagen/ß-TCP promotes spinal fusion comparably to autograft bone treatment and may offer a viable alternative in large animal spinal fusion. Future prospective clinical studies are necessary to fully understand the role of rhPDGF-BB combined with collagen/ß-TCP in human spinal fusion healing.
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BACKGROUND: Joint arthrodesis often employs autograft to promote union; graft harvesting can lead to perioperative morbidity. A Canadian randomized controlled trial (RCT) demonstrated that recombinant human platelet-derived growth factor BB homodimer (rhPDGF-BB) combined with beta-tricalcium phosphate (ß-TCP)-collagen was a safe, effective alternative to autograft. This multicenter North American RCT compared the safety and efficacy of rhPDGF-BB/ß-TCP-collagen with autograft for ankle and hindfoot fusion. Subclassification using propensity scores (PS) incorporated patients from previous trials for enhanced statistical power for noninferiority testing and broader review of treatments. METHODS: Patients requiring ankle or hindfoot arthrodesis and supplemental bone graft were treated with rhPDGF-BB/ß-TCP-collagen (n = 69) or autograft (n = 35). Outcomes included joint fusion on computed tomography (24 weeks), clinical healing status, visual analog scale (VAS) pain, Short-Form 12 (SF-12), American Orthopaedic Foot & Ankle Society (AOFAS) Ankle-Hindfoot Scale, and Foot Function Index (FFI) scores over 52 weeks. PS methodology addressed potential selection bias arising from pooling data among these patients and 2 previous RCTs with similar inclusion criteria, surgical techniques, graft harvest techniques, and outcomes. All 132 rhPDGF-BB/ß-TCP-collagen-treated patients and 167 of 189 candidate autograft-treated controls were selected for comparison by an independent statistician blinded to outcomes. RESULTS: In the PS subclassification, 68.1% treatment patients and 68.4% controls achieved >50% osseous bridging at fusion sites. Clinical healing status was achieved in 84.8% of treated patients and 90.7% of controls at 52 weeks. Clinical, functional, and quality of life results demonstrated noninferiority of rhPDGF-BB/ß-TCP-collagen to autograft. Safety-related outcomes were equivalent. CONCLUSION: PS subclassification analysis of 3 RCTs demonstrated that rhPDGF-BB/ß-TCP-collagen was as effective as autograft for ankle and hindfoot fusions, with less pain and morbidity than treatment with autograft. LEVEL OF EVIDENCE: Level I, prospective randomized study.
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Articulación del Tobillo/cirugía , Artrodesis , Becaplermina/uso terapéutico , Materiales Biocompatibles/uso terapéutico , Fosfatos de Calcio/uso terapéutico , Colágeno/uso terapéutico , Adulto , Anciano , Autoinjertos , Canadá , Terapia Combinada , Evaluación de la Discapacidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Proteínas Recombinantes/uso terapéutico , Estados UnidosRESUMEN
BACKGROUND: The presence of insufficient bone volume remains a major clinical problem for dental implant placement to restore oral function. Tissue engineering provides a promising approach for inducing bone regeneration and enhancing osseointegration in dental implants. PURPOSE: The tissue-engineered bone consisting of recombinant human platelet-derived growth factor (rhPDGF-BB), bone marrow stem cells (BMSCs), and beta-tricalcium phosphate (ß-TCP) particles was validated for the first time in a preclinical large animal canine model in terms of its ability to promote new bone formation around the implants, as well as osseointegration between the tissue-engineered bone and dental implants. MATERIALS AND METHODS: Proliferation and osteogenic differentiation of canine BMSCs treated with rhPDGF-BB were evaluated with an MTT, alkaline phosphatase (ALP) activity, Alizarin Red staining, and real-time quantitative PCR (RT-qPCR) analysis of osteogenic genes. The therapeutic potential of tissue-engineered bone consisting of rhPDGF-BB/BMSCs/ß-TCP in bone repair was evaluated in mesial-implant defects of immediate postextraction implants in the canine mandible. RESULTS: rhPDGF-BB treatment significantly increased proliferation and osteogenic differentiation of canine BMSCs. Furthermore, the tissue-engineered bone consisting of rhPDGF-BB/BMSCs/ß-TCP significantly enhanced bone formation and osseointegration. CONCLUSION: This study provides important evidence that supports the potential application of rhPDGF-BB/BMSCs/ß-TCP tissue-engineered bone in immediate implantation for oral function restoration.
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Regeneración Ósea , Fosfatos de Calcio , Implantes Dentales , Factor de Crecimiento Derivado de Plaquetas , Células Madre , Animales , Perros , Humanos , Mandíbula , Oseointegración , OsteogénesisRESUMEN
Nonunion remains the most impactful complication following ankle and hindfoot arthrodesis. Historically, surgeons have relied on autologous bone graft (ABG) to combat nonunion risk. Although effective, ABG remains limited in quantity, varies in quality, and can be associated with harvest site pain and morbidity. Use of alternative bone-stimulating agents, however, avoids harvesting an autograft, and provides a more predictable dose-response efficacy. This article highlights findings from basic science, animal, and human clinical research that led to the approval of Augment Bone Graft. We present an adaptation of the surgical techniques described for investigators participating in the pivotal trial.
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Conservadores de la Densidad Ósea/uso terapéutico , Fosfatos de Calcio/farmacología , Curación de Fractura/efectos de los fármacos , Fracturas no Consolidadas/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-sis/uso terapéutico , Animales , Tobillo/cirugía , Artrodesis , Becaplermina , Conservadores de la Densidad Ósea/farmacología , Trasplante Óseo , Fosfatos de Calcio/uso terapéutico , Pie/cirugía , Curación de Fractura/fisiología , Fracturas no Consolidadas/cirugía , Humanos , Proteínas Proto-Oncogénicas c-sis/farmacología , Ratas , Cicatrización de Heridas/efectos de los fármacos , Cicatrización de Heridas/fisiologíaRESUMEN
Regenerative endodontic treatment has provided a treatment option that aims to allow root maturation. The present report describes the regenerative endodontic treatment of a necrotic, immature molar by using recombinant human platelet-derived growth factor (rhPDGF-BB) and shows the continued root maturation in the tooth with arrested root development. A regenerative endodontic procedure that used a growth factor was performed for a necrotic molar with arrested root formation in a 20-year-old patient. Thorough disinfection by using mechanical instrumentation and copious irrigation of antimicrobial agents as well as intracanal medication with calcium hydroxide was performed throughout the first 2 appointments. At the third appointment, the root canals were irrigated with an antimicrobial solution and 17% EDTA, and bleeding was evoked by passing sterile paper points beyond the apex in each canal. Small pieces of a collagen membrane saturated with rhPDGF-BB solution from GEM 21S were packed into each canal. Mineral trioxide aggregate was placed, and Cavit and composite resin were used to restore the tooth. Complete root maturation and resolution of a periapical radiolucency were observed at the 15-month follow-up. The present report presents a regenerative endodontic procedure that uses rhPDGF-BB for a necrotic molar with arrested root development. The finding of continued root development in the present case suggests that regenerative endodontic treatment may be able to resume the root maturation process in teeth with arrested root formation. Further clinical studies are required to investigate the efficacy of rhPDGF-BB in regenerative endodontic treatment.
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Diente Molar/patología , Factor de Crecimiento Derivado de Plaquetas/uso terapéutico , Raíz del Diente/crecimiento & desarrollo , Humanos , Masculino , Necrosis/terapia , Proteínas Recombinantes/uso terapéutico , Adulto JovenRESUMEN
BACKGROUND: Ankle and hindfoot arthrodesis is often supplemented with autograft to promote bony union. Autograft harvest can lead to increased perioperative morbidity. Purified recombinant human platelet-derived growth factor BB homodimer (rhPDGF-BB) has stimulated bone formation in mandibular defects and hindfoot fusion. This randomized controlled trial evaluated the efficacy and safety of rhPDGF-BB combined with an injectable, osteoconductive beta-tricalcium phosphate (ß-TCP)-collagen matrix versus autograft in ankle and hindfoot fusions. METHODS: Seventy-five patients requiring ankle or hindfoot fusion were randomized 5:1 for rhPDGF-BB/ß-TCP-collagen (treatment, n = 63) or autograft (control, n = 12). Prospective analysis included 142 autograft control subjects from another clinical trial with identical study protocols. Standardized operative and postoperative protocols were used. Patients underwent standard internal fixation augmented with autograft or 0.3 mg/mL rhPDGF-BB/ß-TCP-collagen. Radiologic, clinical, and quality-of-life outcomes were assessed over 52 weeks. Primary outcome was joint fusion (50% or more osseous bridging on computed tomography) at 24 weeks. Secondary outcomes included radiographs, clinical healing status, visual analog scale pain score, American Orthopaedic Foot & Ankle Society Ankle-Hindfoot Scale score, Foot Function Index score, and Short Form-12 score. Noninferiority P values were calculated. RESULTS: Complete fusion of all involved joints at 24 weeks as indicated by computed tomography was achieved in 53 of 63 (84%) rhPDGF-BB/ß-TCP-collagen-treated patients and 100 of 154 (65%) autograft-treated patients (P < .001). Mean time to fusion was 14.3 ± 8.9 weeks for rhPDGF-BB/ß-TCP-collagen patients versus 19.7 ± 11.5 weeks for autograft patients (P < .01). Clinical success at 52 weeks was achieved in 57 of 63 (91%) rhPDGF-BB/ß-TCP-collagen patients and 120 of 154 (78%) autograft patients (P < .001). Safety-related outcomes were equivalent. Autograft controls had 2 bone graft harvest infections. CONCLUSIONS: Application of rhPDGF-BB/ß-TCP-collagen was a safe, effective alternative to autograft for ankle and hindfoot fusions, eliminating the pain and morbidity associated with autograft harvesting. LEVEL OF EVIDENCE: Level I, prospective randomized study.
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Articulación del Tobillo/cirugía , Artrodesis/métodos , Regeneración Ósea/efectos de los fármacos , Fosfatos de Calcio/uso terapéutico , Colágeno Tipo I/uso terapéutico , Pie/cirugía , Proteínas Proto-Oncogénicas c-sis/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Inductores de la Angiogénesis/uso terapéutico , Articulación del Tobillo/diagnóstico por imagen , Becaplermina , Materiales Biocompatibles/uso terapéutico , Trasplante Óseo , Quimioterapia Combinada , Femenino , Pie/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Tomografía Computarizada por Rayos X , Trasplante Autólogo , Adulto JovenRESUMEN
This article discusses nonclinical and clinical data regarding the safety of recombinant human platelet-derived growth factor-BB as a component of the Augment(®) Bone Graft (Augment). Augment is a bone graft substitute intended to be used as an alternative to autologous bone graft in the fusion of hindfoot and ankle joints. Nonclinical studies included assessment of the pharmacokinetic profile of intravenously administered recombinant human platelet-derived growth factor-BB in rat and dog, effects of intravenous administration of recombinant human platelet-derived growth factor-BB in a reproductive and development toxicity study in rats, and chronic toxicity and carcinogenicity of Augment in a 12-month implantation model. These studies showed that systemic exposure was brief and clearance was rapid. No signs of toxicity, carcinogenicity, or tumor promotion were observed even with doses far exceeding the maximum clinical dose. Results of clinical trials (605 participants) and commercial use of recombinant human platelet-derived growth factor-BB containing products indicate that these products are not associated with increased incidence of adverse events or cancer. The safety data presented provide evidence that recombinant human platelet-derived growth factor-BB is a safe therapeutic when used in combination products as a single administration during surgical procedures for bone repair and fusion. There is no evidence associating use of recombinant human platelet-derived growth factor-BB in Augment with chronic toxicity, carcinogenicity, or tumor promotion.
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PURPOSE: This study was to investigate the effects of recombinant human platelet-derived growth factor (rhPDGF-BB) and heparin to titanium surfaces for enhancement of osteoblastic functions and inhibition of inflammation activity. MATERIALS AND METHODS: The anodized titanium discs, not coated with any material, were used as a control group. In heparinized- Ti group, dopamine was anchored to the surface of Ti substrates, and coated with heparin. In PDGF-Ti group, rhPDGF-BB was immobilized onto heparinized Ti surface. The surface morphologies were investigated by the scanning electron microscope in each group. The release kinetics of rhPDGF-BB were analyzed, and cytotoxicity tests for each group were conducted. The biocompatibilities were characterized by measuring cell proliferation, alkaline phosphatase activity, and calcium deposition using MG-63 cells. Statistical comparisons were carried out by one-way ANOVA tests. Differences were considered statistically significant at (*)P<.05 and (**)P<.001. RESULTS: The combination of rhPDGF-BB and heparin stimulated alkaline phosphatase activity and OCN mRNA expression in osteoblastic cells ((*)P<.05 and (**)P<.001). MG-63 cells grown on PDGF-Ti had significantly higher amounts of calcium deposition than those grown on anodized Ti ((**)P<.001). Heparinized Ti was more anti-inflammatory compared to anodized Ti, when exposed to lipopolysaccharide using the transcript levels of TNF-α and IL-6 of proinflammatory cytokine ((*)P<.05 and (**)P<.001). CONCLUSION: The result of this study demonstrated that the incorporation of rhPDGF-BB and heparin onto Ti surface enhanced osteoblastic functions and inhibited inflammation.
RESUMEN
OBJECTIVE: The present study is aimed to test minimum threshold rhPDGF-BB concentration required to obtain greater root surface biocompatibility and most suitable condition for fibroblast cell attachment and growth in chronic periodontitis. MATERIAL AND METHOD: Proximal surfaces of twenty selected periodontitis teeth were prepared and divided into four groups (ten specimens/each): - I: untreated diseased (control); II: scaling & root planning (SRP); III: SRP then rhPDGF-BB application (50ng/ml); IV: SRP then rhPDGF-BB application (25ng/ml). Fibroblasts were pooled on root specimens, then specimens were incubated. Results of both cell count and shape were assessed by SEM and evaluated repeatedly within a representative standard area. RESULTS: Group II: showed a comparable negative effect, since no significant differences found.Group III: showed a significant positive effect, higher than both groups I & II but lower than group IV. Group IV: demonstrated the best results for cell quantity & quality, where it had favorable significant differences when compared to all others. CONCLUSION: rhPDGF-BB with 25ng/ml concentration showed a more positive effect in getting higher fibroblast cell count & more healthy cell shape than rhPDGF-BB (50ng/ml). A promising role of rhPDGF-BB (25ng/ml) as good modulating agent for fibroblast cell attachment in chronic periodontitis may be suggested.
OBJETIVO: O presente estudo objetivou testar o limite de concentração rhPDGF-BB requerido para obter maior biocompatibilidade com a superfície da raiz e a condição mais adequada para a inserção das células fibroblásticas e crescimento na periodontite crônica . MATERIAL E MÉTODO: Superfícies proximais de 20 dentes com periodontite selecionados foram preparados e divididos em quatro grupos (dez espécimes em cada grupo). I: dentes não tratados (controle): II: curetagem e alisamento radicular; III. aplicação de SRP seguido de rhPDGF (40ng/ml); aplicação de IV: SRP seguido de rh PDGF-BB. Os fibroblastos foram semeados em espécimes radiculares, seguindo-se incubação dos espécimes. Os resultados da contagem celular e forma foram observados pela SEM e avaliados repetidamente dentre de área padrão representativa. RESULTADOS: O Grupo II demonstrou um efeito negativo comparativamente, uma vez que não ocorreram diferenças significativas. O Grupo III mostrou um efeito positivo significativo, maior do que ambos grupos I e II, porém menor do que o Grupo IV. O Grupo IV mostrou o melhor resultado para a quantidade e qualidade celular, onde apresentou diferenças favoráveis quando comparados com todos os outros. CONCLUSÃO: rhPDGF-BB com 25 ng/ml de concentração demonstrou efeito mais positivo na contagem de fibroblastos e as células apresentaram forma mais sadia do que no rhPDGFBB com 50ng/ml. Sugere-se que o rhPDGF-BB apresenta boas possibilidades como um bom agente modulador para inserção de fibroblastos na periodontite crônica.