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1.
Aesthetic Plast Surg ; 48(9): 1825-1830, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38123846

RESUMO

BACKGROUND: Alopecia is defined as partial or complete hair loss. The most common form is androgenetic alopecia, which occurs in both men and women. Despite the nonsurgical options available for treatment, the only permanent solution is hair transplantation. Hair loss has been shown to have significant psychological consequences associated with loss of self-confidence, poor self-image and difficulties in social functioning. We aim to examine the effect of hair transplantation on quality of life and psychosocial functioning. METHODS: Forty-eight patients with androgenetic alopecia were enrolled in this two-center prospective study and underwent hair transplantation by the Follicular Unit Extraction method. Different questionnaires were used to assess their quality of life and other psychosocial parameters before and after hair transplantation. RESULTS: According to SF-36 Physical and Mental Health Score patients showed significant improvement in life quality after hair transplantation. Diener's Life Satisfaction Scale (DASS-21) revealed increased life satisfaction after the procedure. Stress and anxiety DASS-21 subscales showed significantly reduced results; while, the DASS-21 depression scale and MSPSS were not significantly changed. CONCLUSION: Taken together, quality of life and psychosocial functioning increased after hair transplantation. Structured abstract is required. Please provide.I insert name of paragraphs within abstract as follows: background, methods, results, conclusion Level of Evidence II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Assuntos
Alopecia , Cabelo , Qualidade de Vida , Humanos , Feminino , Masculino , Alopecia/cirurgia , Alopecia/psicologia , Adulto , Estudos Prospectivos , Pessoa de Meia-Idade , Cabelo/transplante , Inquéritos e Questionários , Resultado do Tratamento , Adulto Jovem , Satisfação do Paciente/estatística & dados numéricos , Estudos de Coortes
2.
Int J Mol Sci ; 24(14)2023 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-37511437

RESUMO

The calcium-sensing receptor (CaSR) plays a crucial role in maintaining the balance of calcium in the body. Altered signaling through the CaSR has been linked to the development of various tumors, such as colorectal and breast tumors. This retrospective study enrolled 79 patients who underwent surgical removal of invasive breast carcinoma of no special type (NST) to explore the expression of the CaSR in breast cancer. The patients were categorized based on age, tumor size, hormone receptor status, HER2 status, Ki-67 proliferation index, tumor grade, and TNM staging. Immunohistochemistry was conducted on core needle biopsy samples to assess CaSR expression. The results revealed a positive correlation between CaSR expression and tumor size, regardless of the tumor surrogate subtype (p = 0.001). The expression of ER exhibited a negative correlation with CaSR expression (p = 0.033). In contrast, a positive correlation was observed between CaSR expression and the presence of HER2 receptors (p = 0.002). Increased CaSR expression was significantly associated with lymph node involvement and the presence of distant metastasis (p = 0.001 and p = 0.038, respectively). CaSR values were significantly higher in the patients with increased Ki-67 (p = 0.042). Collectively, higher CaSR expression in breast cancer could suggest a poor prognosis and treatment outcome regardless of the breast cancer subtype.


Assuntos
Neoplasias da Mama , Receptores de Detecção de Cálcio , Feminino , Humanos , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Receptor ErbB-2/metabolismo , Receptores de Detecção de Cálcio/genética , Receptores de Progesterona/metabolismo , Estudos Retrospectivos
3.
Medicina (Kaunas) ; 59(3)2023 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-36984563

RESUMO

Background and Objectives: Bone fractures contribute significantly to the global disease and disability burden and are associated with a high and escalating incidence and tremendous economic consequences. The increasingly challenging climate of orthopaedic training and practice re-echoes the established potential of leveraging computer-based reality technologies to support patient-specific simulations for procedural teaching and surgical precision. Unfortunately, despite the recognised potential of virtual reality technologies in orthopaedic surgery, its adoption and integration, particularly in fracture procedures, have lagged behind other surgical specialities. We aimed to review the available virtual reality systems adapted for orthopaedic trauma procedures. Materials and Methods: We performed an extensive literature search in Medline (PubMed), Science Direct, SpringerLink, and Google Scholar and presented a narrative synthesis of the state of the art on virtual reality systems for bone trauma procedures. Results: We categorised existing simulation modalities into those for fracture fixation techniques, drilling procedures, and prosthetic design and implantation and described the important technical features, as well as their clinical validity and applications. Conclusions: Over the past decade, an increasing number of high- and low-fidelity virtual reality systems for bone trauma procedures have been introduced, demonstrating important benefits with regard to improving procedural teaching and learning, preoperative planning and rehearsal, intraoperative precision and efficiency, and postoperative outcomes. However, further technical developments in line with industry benchmarks and metrics are needed in addition to more standardised and rigorous clinical validation.


Assuntos
Ortopedia , Realidade Virtual , Humanos , Simulação por Computador , Ortopedia/educação , Interface Usuário-Computador , Fixação de Fratura
4.
Diagnostics (Basel) ; 13(4)2023 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-36832182

RESUMO

This study aimed to evaluate the performance of multiparametric breast magnetic resonance imaging (mpMRI) for predicting response to neoadjuvant chemotherapy (NAC) in patients with luminal B subtype breast cancer. The prospective study included thirty-five patients treated with NAC for both early and locally advanced breast cancer of the luminal B subtype at the University Hospital Centre Zagreb between January 2015 and December 2018. All patients underwent breast mpMRI before and after two cycles of NAC. Evaluation of mpMRI examinations included analysis of both morphological (shape, margins, and pattern of enhancement) and kinetic characteristics (initial signal increase and post-initial behavior of the time-signal intensity curve), which were additionally interpreted with a Göttingen score (GS). Histopathological analysis of surgical specimens included grading the tumor response based on the residual cancer burden (RCB) grading system and revealed 29 NAC responders (RCB-0 (pCR), I, II) and 6 NAC non-responders (RCB-III). Changes in GS were compared with RCB classes. A lack of GS decrease after the second cycle of NAC is associated with RCB class and non-responders to NAC.

5.
Diagnostics (Basel) ; 12(9)2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36140495

RESUMO

We aimed to determine diagnostic accuracy of CT-guided bone lesion biopsy for the confirmation of bone metastases in patients with breast cancer and assessment of hormone receptor status in metastatic tissue. A total of 56 female patients with breast cancer that underwent CT-guided biopsy of suspected bone metastasis were enrolled in this retrospective study. Three different techniques were employed to obtain samples from various sites of skeleton. Collectively, 11 true negative and 3 false negative findings were revealed. The sensitivity of CT-guided biopsy for diagnosing bone metastases was 93.6%, specificity was 100% and accuracy was 94.8%. Discordance in progesterone receptor status and complete concordance in estrogen receptor status was observed. Based on our single-center experience, bone metastasis biopsy should be routinely performed in patients with breast cancer and suspicious bone lesions, due to the impact on further treatment.

6.
Int J Mol Med ; 47(4)2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33649802

RESUMO

The relationship between hemochromatosis and diabetes has been well established, as excessive iron deposition has been reported to result in impaired function of the endocrine and exocrine pancreas. Therefore, the objective of the present study was to analyze the effects of iron accumulation on the pancreata and glucose homeostasis in a bone morphogenetic protein 6­knockout (Bmp6­/­) mouse model of hemochromatosis. The sera and pancreatic tissues of wild­type (WT) and Bmp6­/­ mice (age, 3 and 10 months) were subjected to biochemical and histological analyses. In addition, 18F­fluorodeoxyglucose biodistribution was evaluated in the liver, muscle, heart, kidney and adipose tissue of both animal groups. The results demonstrated that 3­month­old Bmp6­/­ mice exhibited iron accumulation preferentially in the exocrine pancreas, with no signs of pancreatic injury or fibrosis. No changes were observed in the glucose metabolism, as pancreatic islet diameter, insulin and glucagon secretion, blood glucose levels and glucose uptake in the liver, muscle and adipose tissue remained comparable with those in the WT mice. Aging Bmp6­/­ mice presented with progressive iron deposits in the exocrine pancreas, leading to pancreatic degeneration and injury that was characterized by acinar atrophy, fibrosis and the infiltration of inflammatory cells. However, the aging mice exhibited unaltered blood glucose levels and islet structure, normal insulin secretion and moderately increased α­cell mass compared with those in the age­matched WT mice. Additionally, iron overload and pancreatic damage were not observed in the aging WT mice. These results supported a pathogenic role of iron overload in aging Bmp6­/­ mice leading to iron­induced exocrine pancreatic deficiency, whereas the endocrine pancreas retained normal function.


Assuntos
Células Acinares/patologia , Proteína Morfogenética Óssea 6/genética , Diabetes Mellitus/patologia , Hemocromatose/patologia , Sobrecarga de Ferro/patologia , Animais , Glicemia/análise , Modelos Animais de Doenças , Fibrose/patologia , Fluordesoxiglucose F18/farmacocinética , Glucose/metabolismo , Ferro/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pâncreas/lesões , Pâncreas/patologia , Tomografia por Emissão de Pósitrons
7.
Int Orthop ; 45(4): 1043-1047, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32613301

RESUMO

PURPOSE: It was demonstrated that about 6% of patients with a ruptured Achilles tendon experience the rupture of contralateral tendon in the future; the aim of this study was to estimate the risk for rupture of contralateral tendon in patients who underwent surgical reconstruction of ruptured Achilles tendon by using subjective questionnaires and shear-wave elastography. METHODS: Twenty-four patients who underwent surgical repair of the ruptured Achilles tendon and twelve age-matched healthy controls were examined with ultrasound SWE. Functional outcomes were assessed with American Orthopedic Foot and Ankle Society (AOFAS) scoring system and subjective rating system which we introduced and validated. RESULTS: The elasticity of injured tendon was markedly decreased (by 42%) compared to the contralateral tendon of the patient, as expected. Both AOFAS score and our novel subjective assessment scale positively correlate with ultrasound SWE values in ruptured Achilles tendons. The elasticity of contralateral Achilles tendons in patients was 23% lower than among healthy individuals. CONCLUSION: Irrespective of the lack of difference in the subjective feeling assessed by AOFAS, the contralateral tendon in the patients with reconstructed Achilles tendon has significantly lower stiffness than healthy individuals. Therefore, contralateral tendons in patients who suffered from rupture are more prone to future ruptures.


Assuntos
Tendão do Calcâneo , Técnicas de Imagem por Elasticidade , Traumatismos dos Tendões , Tendão do Calcâneo/diagnóstico por imagem , Tendão do Calcâneo/cirurgia , Humanos , Ruptura/diagnóstico por imagem , Ruptura/cirurgia , Traumatismos dos Tendões/diagnóstico por imagem , Traumatismos dos Tendões/epidemiologia , Ultrassonografia
8.
Acta Diabetol ; 56(3): 365-371, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30539233

RESUMO

AIMS: Bone morphogenetic proteins (BMPs) are involved in the development and homeostasis of multiple organs and tissues. There has been a significant focus on understanding the role of BMPs in pancreatic ß-cell dysfunction associated with type 2 diabetes (T2D). Our objective was to investigate the relationship between BMP6 and glucose homeostasis. METHODS: Ob/ob mice were treated with BMP6 for 6 days and analyzed for insulin release, body weight, lipid parameters and glucose tolerance. Quantitative real-time PCR, chromatin immunoprecipitation and glucose output assays were used to assess BMP6 effect on gluconeogenesis in rat hepatoma H4IIE cells. Specificity of BMP6 receptors was characterized by the utilization of various receptor Fc fusion proteins in luciferase reporter gene and glucose output assays in INS1 and H4IIE cells. RESULTS: Treatment of ob/ob mice with BMP6 for 6 days resulted in a reduction of circulating glucose and lipid levels, followed by a significantly elevated plasma insulin level in a dose-dependent manner. In addition, BMP6 improved the glucose excursion during an oral glucose tolerance test, lowering the total glycemic response by 21%. In rat H4IIE hepatoma cells, BMP6 inhibited gluconeogenesis and glucose output via downregulation the PepCK expression. Moreover, BMP6 inhibited glucose production regardless of the presence of cAMP, antagonizing its glycogenolytic effect. BMP6 acted on pancreatic and liver cells utilizing Alk3, Alk6 and ActRIIA serine/threonine kinase receptors. CONCLUSIONS: Collectively, we demonstrate that BMP6 improves glycaemia in T2D mice and regulates glucose metabolism in hepatocytes representing an exciting prospect for future treatments of diabetes.


Assuntos
Proteína Morfogenética Óssea 6/farmacologia , Diabetes Mellitus Experimental/metabolismo , Glucose/metabolismo , Homeostase/efeitos dos fármacos , Animais , Glicemia/genética , Glicemia/metabolismo , Proteína Morfogenética Óssea 6/fisiologia , Células CHO , Células Cultivadas , Cricetinae , Cricetulus , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Homeostase/genética , Insulina/metabolismo , Masculino , Camundongos , Camundongos Obesos , Ratos , Proteínas Recombinantes/farmacologia
9.
Acta Dermatovenerol Croat ; 25(2): 142-144, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28871929

RESUMO

Generalized psoriasis and renal function disorder were previously described in sporadic adult cases, revealing a new entity - psoriatic nephropathy. So far there have been only two cases describing this association in children. We present and discuss a case of 10-year-old girl with the unique biopsy findings of double glomerulonephritis associated with the simultaneous onset of generalized psoriasis.


Assuntos
Glomerulonefrite/complicações , Glomerulonefrite/patologia , Psoríase/complicações , Psoríase/patologia , Criança , Feminino , Humanos
10.
Ann Anat ; 203: 69-76, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25843780

RESUMO

The human sphenoid sinus is an extremely variable cavity and an important landmark in hypophyseal surgery. The aim of this study was to investigate the relationship between the sphenoid sinus type, size, extent of pneumatization and occurrence of protrusions of the adjacent neurovascular structures. A total of 51 randomly selected skulls (≥20 years of age, 33 male; 102 sinuses) were analyzed using cone beam computed tomography to estimate pneumatization extension beyond the body of the sphenoid (planum sphenoidale, pterygoid process, greater wings, clivus, dorsum sellae) and protrusions of the maxillary, mandibular, optic or pterygoid nerve or the internal carotid artery. Difference in pneumatization type between the left and the right-sided sinus was observed in 45% of the skulls. Conchal pneumatization was registered in 2%, presellar in 24%, sellar in 41% and postsellar in 33% of total sinuses. Presellar sinuses frequently pneumatized planum sphenoidale and sporadically other structures, and were characterized by sporadic optic nerve protrusions. Sellar and particularly postsellar sinuses were characterized by simultaneous pneumatization extensions and neurovascular protrusions. In the case of postsellar-type sinuses, the probability of these multiple interactions was not affected by their actual size, while it increased with the increasing sinus dimensions in the case of sellar-type sinuses. A more detailed analysis indicated that increasing sinus height, length or width increased the probability of interactions and pneumatization of particular surrounding structures. Data suggest that the sphenoid sinus pneumatization type and dimensions might be used to estimate the risks of iatrogenic injury during transsphenoidal surgical procedures.


Assuntos
Seio Esfenoidal/anatomia & histologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Vasos Sanguíneos/anatomia & histologia , Tomografia Computadorizada de Feixe Cônico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nervo Óptico/anatomia & histologia , Sela Túrcica/anatomia & histologia , Crânio/anatomia & histologia , Osso Esfenoide/anatomia & histologia , Seio Esfenoidal/irrigação sanguínea , Seio Esfenoidal/inervação , População Branca , Adulto Jovem
11.
Growth Factors ; 33(3): 200-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26190421

RESUMO

Type III transforming growth factor (TGFß) receptor (TGFßrIII) modulates TGFß superfamily signaling. Its tumor tissue expression is downregulated in human breast cancer. We determined (indirect ELISA) plasma levels of the soluble receptor (sTGFßrIII) in 47 women with breast cancer (AJCC stages 0-IIB) (cases) pre-surgery and over two months after the surgery, and in 36 healthy women (controls). Plasma sTBFßrIII was lower in cases than in the controls (age-adjusted difference -29.7 ng/mL, p < 0.001), and discriminated between disease and health (sensitivity and specificity 100% at 16.6 ng/mL). With adjustment for age, AJCC stage, lymph node involvement, HER2 and hormone receptor status, higher pre-surgery sTBFßrIII was associated with better progression-free survival (HR = 0.68, 95%CI 0.49-0.89, p = 0.004). An increasing trend in plasma sTBFßrIII was observed over 2 months after the surgery (0.6% increase/day, p < 0.001), consistently across the patient subsets. Data suggest a high potential of plasma sTBFßrIII as a novel diagnostic and prognostic biomarker in breast cancer.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/mortalidade , Proteoglicanas/sangue , Receptor ErbB-2/metabolismo , Receptores de Fatores de Crescimento Transformadores beta/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/terapia , Intervalo Livre de Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Humanos , Metástase Linfática/patologia , Pessoa de Meia-Idade , Proteoglicanas/genética , Receptores de Fatores de Crescimento Transformadores beta/genética , Transdução de Sinais/genética
12.
Int Orthop ; 39(5): 1005-11, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25772279

RESUMO

Segmental bone defect management is among the most demanding issues in orthopaedics and there is a great medical need for establishing an appropriate treatment option. Tissue transfer, including bone autografts or free flaps, depending on the size of the bone deficiency, is currently the "gold standard" for treatment of such defects. Osteogenic cells in combination with adequate growth factors and a suitable scaffold, from the aspect of osteoinductivity, osteoconductivity and mechanical stability, are mandatory to successfully restore a bone defect as determined in the "diamond concept". Our current knowledge on this topic is limited and mostly based on retrospective studies, case reports and a few small randomised clinical trials due to the lack of large and accurately designed randomised clinical trials using novel approaches to regenerative orthopaedics. However, preclinical research on different animal models for critical size defects is abundant, showing emerging candidate cells and cytokines for defect rebridgement. In this article we provide an overview on existing clinical studies and promising preclinical experiments that utilised osteogenic cells, growth factors and biomaterials, as well as their combination for repair of segmental bone defects.


Assuntos
Substitutos Ósseos , Transplante Ósseo , Osso e Ossos , Retalhos de Tecido Biológico , Engenharia Tecidual , Animais , Autoenxertos , Doenças Ósseas/cirurgia , Transplante Ósseo/métodos , Citocinas/fisiologia , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Transplante de Células-Tronco , Cicatrização/fisiologia
13.
Int Orthop ; 38(9): 1979-85, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25030962

RESUMO

PURPOSE: Bone morphogenetic protein (BMP)-2 and -7 are used in patients with long-bone fractures, nonunions and spinal fusions. It is unknown whether their potential systemic bioavailability following local bone administration might affect skeletal metabolism. To answer this question, we examined effects of systemically administered BMP-2 and -7 on bone in a newly developed rat model with a low level of calciotropic hormones. METHODS: Removal of thyroid and parathyroid glands (TPTx) in rats resulted in a decreased level of calciotropic hormones and subsequent bone loss assessed by micro computed tomography (micro-CT) and measurement of serum bone formation and resorption markers, including osteocalcin, C-telopeptide, osteoprotegerin and receptor activator of nuclear factor kappa-B ligand. Results were complemented with in vitro studies on osteoblast and osteoclast activity by both BMP-2 and -7. The doses used were calculated from published pharmacodynamic studies and bioavailability results from preclinical BMP-2 and -7 studies. RESULTS: TPTx resulted in bone loss, which was restored by systemic administration of 10-70 µg/kg of BMP-2 and 10-250 µg/kg of BMP-7. BMP-2 showed a higher capacity for enhancing trabecular microarchitecture, whereas BMP-7 augmented trabecular thickness. In vitro experiments revealed that BMP-2 and -7 when uncoupled increased the number and activity of both osteoblasts and osteoclasts. CONCLUSIONS: Surprisingly, both BMP-2 and -7 showed an increased bone volume in an in vivo environment of low calciotropic hormones. Locally administered BMP-2 and -7 from bone devices might become partially available in circulation but will not mediate systemic bone loss.


Assuntos
Proteína Morfogenética Óssea 2/farmacologia , Proteína Morfogenética Óssea 7/farmacologia , Remodelação Óssea/efeitos dos fármacos , Reabsorção Óssea , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Animais , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Técnicas In Vitro , Modelos Animais , Osteoblastos/efeitos dos fármacos , Osteoblastos/patologia , Osteoclastos/efeitos dos fármacos , Osteoclastos/patologia , Osteogênese/efeitos dos fármacos , Osteoprotegerina/metabolismo , Ligante RANK/metabolismo , Ratos , Ratos Sprague-Dawley
14.
Int Orthop ; 38(3): 635-47, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24352822

RESUMO

PURPOSE: The purpose of this study was to revise the clinical use of commercial BMP2 (Infuse) and BMP7 (Osigraft) based bone devices and explore the mechanism of action and efficacy of low BMP6 doses in a novel whole blood biocompatible device OSTEOGROW. METHODS: Complications from the clinical use of BMP2 and BMP7 have been systemically reviewed in light of their role in bone remodeling. BMP6 function has been assessed in Bmp6-/- mice by µCT and skeletal histology, and has also been examined in mesenchymal stem cells (MSC), hematopoietic stem cells (HSC) and osteoclasts. Safety and efficacy of OSTEOGROW have been assessed in rats and rabbits. RESULTS: Clinical use issues of BMP2 and BMP7 have been ascribed to the limited understanding of their role in bone remodeling at the time of device development for clinical trials. BMP2 and BMP7 in bone devices significantly promote bone resorption leading to osteolysis at the endosteal surfaces, while in parallel stimulating exuberant bone formation in surrounding tissues. Unbound BMP2 and BMP7 in bone devices precipitate on the bovine collagen and cause inflammation and swelling. OSTEOGROW required small amounts of BMP6, applied in a biocompatible blood coagulum carrier, for stimulating differentiation of MSCs and accelerated healing of critical size bone defects in animals, without bone resorption and inflammation. BMP6 decreased the number of osteoclasts derived from HSC, while BMP2 and BMP7 increased their number. CONCLUSIONS: Current issues and challenges with commercial bone devices may be resolved by using novel BMP6 biocompatible device OSTEOGROW, which will be clinically tested in metaphyseal bone fractures, compartments where BMP2 and BMP7 have not been effective.


Assuntos
Proteína Morfogenética Óssea 6/farmacologia , Proteína Morfogenética Óssea 6/uso terapêutico , Sistemas de Liberação de Medicamentos , Fraturas Ósseas/tratamento farmacológico , Osteogênese/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Animais , Materiais Biocompatíveis/administração & dosagem , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/uso terapêutico , Proteína Morfogenética Óssea 2/farmacologia , Proteína Morfogenética Óssea 2/uso terapêutico , Proteína Morfogenética Óssea 6/administração & dosagem , Proteína Morfogenética Óssea 7/farmacologia , Proteína Morfogenética Óssea 7/uso terapêutico , Relação Dose-Resposta a Droga , Fraturas Ósseas/fisiopatologia , Camundongos , Camundongos Knockout , Modelos Animais , Osteogênese/fisiologia , Coelhos , Ratos , Cicatrização/fisiologia
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