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1.
Braz. j. med. biol. res ; 57: e12953, fev.2024. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1550149

ABSTRACT

Abstract Bone regeneration is crucial for repairing bone tissue following various injuries. Research techniques that enable the study of metabolic changes in bone tissue under different conditions are important for understanding bone repair and remodeling. This study used bone scintigraphy to evaluate osteogenesis secondary to osteotomy in a preclinical model of New Zealand rabbits. For this purpose, we conducted a longitudinal, prospective, case-control study in which scintigraphic variables were measured in both the right forearm (case-operated) and the left forearm (control - non-operated). The study sample consisted of 10 rabbits subjected to osteotomy, followed by a 12-week postoperative evaluation period, divided into six imaging stages at 1, 2, 3, 4, 8, and 12 weeks. We observed that the operated forearm showed significantly higher external radiation than the control side, using the pinhole collimator, denoting an increase in the biodistribution and tropism of the radiopharmaceutical to the operated forearm. Among the three evaluated time points, osteoblastic activity was highest in the second week and presented a significant decline in the 8th and 12th weeks, denoting regeneration and resolution of the surgical injury; the control forearm was also influenced by the inactivity imposed by the operated forearm. This fact was notably evidenced by the reduction in the metabolic activity of osteoblasts in the left forearm. Our study suggested that bone scintigraphy was sensitive enough to semi-quantitatively differentiate the metabolic activity of osteoblasts in the operated forearm in the three temporal landmarks evaluated in the study.

2.
J. appl. oral sci ; 32: e20230268, 2024. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1528889

ABSTRACT

Abstract Objective This retrospective study aimed to analyze the clinical efficacy of two regenerative surgical methods — Bio-Oss granules combined with barrier membranes and Bio-Oss Collagen alone — and to help clinicians achieve better periodontal regeneration outcomes in the specific periodontal condition. Methodology Patients who underwent periodontal regeneration surgery from January 2018 to April 2022 were retrospectively screened, and their clinical and radiographic outcomes at 6 months postoperatively were analyzed. The probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), gingival recession (GR), distance from the cemento-enamel junction to the bottom of the bone defect (CEJ-BD), and depth of intrabony defects (INFRA) were recorded before the operation (T0) and 6 months after it (T1), and subsequently compared. Results In total, 143 patients were included — 77 were placed in the Bio-Oss group and 66 were placed in the Bio-Oss Collagen group. All indicators, including PD and CAL at T1, showed significant differences compared to baseline, for both groups (P<0.001). PD reduction was greater in the group receiving the Bio-Oss Collagen treatment (P=0.042). Furthermore, in cases when the baseline PD range was 7-11 mm and the age range was 35-50 years, PD reduction was more significant for patients receiving the Bio-Oss Collagen treatment (P=0.031, 0.023). A linear regression analysis indicated that postoperative PD and CAL were positively correlated with baseline values, and that the efficacy tended to decrease with increasing age. Conclusion Both the use of Bio-Oss Collagen alone and the use of Bio-Oss granules combined with barrier membranes resulted in significant effects in the treatment of periodontal intrabony defects. The Bio-Oss Collagen treatment generated more improvements in PD than the Bio-Oss granules combined with barrier membranes, particularly within the baseline PD range of 7-11 mm and the 35-50 years age group. Additionally, age was the main factor influencing the effectiveness of regenerative surgery for intrabony defects: older individuals exhibited fewer improvements.

3.
Pesqui. bras. odontopediatria clín. integr ; 24: e220128, 2024. tab, graf
Article in English | LILACS, BBO | ID: biblio-1535006

ABSTRACT

ABSTRACT Objective: To assess the effects of cobalt chloride (CoCl2) as a hypoxia mimicking agent on human umbilical cord mesenchymal stem cells (hUCMSCs) expression of HIF-1α and mTOR for use in regenerative dentistry. Material and Methods: Human umbilical cord mesenchymal stem cells were isolated and then cultured. The characteristics of stemness were screened and confirmed by flow cytometry. The experiment was conducted on hypoxia (H) and normoxia (N) groups. Each group was divided and incubated into 24-, 48-, and 72-hours observations. Hypoxic treatment was performed using 100 µM CoCl2 on 5th passage cells in a conventional incubator (37°C; 5CO2). Then, immunofluorescence of HIF-1α and mTOR was done. Data was analyzed statistically using One-way ANOVA and Tukey's HSD. Results: Significant differences were found between normoxic and hypoxic groups on HIF-1α (p=0.015) and mTOR (p=0.000) expressions. The highest HIF-1α expression was found at 48 hours in the hypoxia group, while for mTOR at 24 hours in the hypoxia group. Conclusion: Hypoxia using cobalt chloride was able to increase human umbilical cord mesenchymal stem cells expression of HIF-1α and mTOR.


Subject(s)
Humans , Umbilical Cord/cytology , Chlorides/chemistry , Cobalt/chemistry , Mesenchymal Stem Cells/cytology , Hypoxia/pathology , Analysis of Variance , Flow Cytometry
4.
Biol. Res ; 572024.
Article in English | LILACS-Express | LILACS | ID: biblio-1550061

ABSTRACT

Background The monthly regeneration of human endometrial tissue is maintained by the presence of human endometrial mesenchymal stromal/stem cells (eMSC), a cell population co-expressing the perivascular markers CD140b and CD146. Endometrial regeneration is impaired in the presence of intrauterine adhesions, leading to infertility, recurrent pregnancy loss and placental abnormalities. Several types of somatic stem cells have been used to repair the damaged endometrium in animal models, reporting successful pregnancy. However, the ability of endometrial stem cells to repair the damaged endometrium remains unknown. Methods Electrocoagulation was applied to the left uterine horn of NOD/SCID mice causing endometrial injury. Human eMSC or PBS was then injected into the left injured horn while the right normal horn served as controls. Mice were sacrificed at different timepoints (Day 3, 7 and 14) and the endometrial morphological changes as well as the degree of endometrial injury and repair were observed by histological staining. Gene expression of various inflammatory markers was assessed using qPCR. The functionality of the repaired endometrium was evaluated by fertility test. Results Human eMSC successfully incorporated into the injured uterine horn, which displayed significant morphological restoration. Also, endometrium in the eMSC group showed better cell proliferation and glands formation than the PBS group. Although the number of blood vessels were similar between the two groups, gene expression of VEGF-α significantly increased in the eMSC group. Moreover, eMSC had a positive impact on the regeneration of both stromal and epithelial components of the mouse endometrium, indicated by significantly higher vimentin and CK19 protein expression. Reduced endometrial fibrosis and down-regulation of fibrosis markers were also observed in the eMSC group. The eMSC group had a significantly higher gene expression of anti-inflammatory factor Il-10 and lower mRNA level of pro-inflammatory factors Ifng and Il-2, indicating the role of eMSC in regulation of inflammatory reactions. The eMSC group showed higher implantation sites than the PBS group, suggesting better endometrial receptivity with the presence of newly emerged endometrial lining. Conclusions Our findings suggest eMSC improves regeneration of injured endometrium in mice.

5.
Braz. j. oral sci ; 23: e240338, 2024. ilus
Article in English | LILACS, BBO | ID: biblio-1537125

ABSTRACT

Demineralized freeze-dried bone allograft (DFDBA) contains bone morphogenetic proteins (BMPs), hence is osteoinductive. Autologous platelet concentrates exhibit a higher quantity of growth factors. Both these biomaterials aid in bone regeneration when placed in three-wall intrabony defects. However, their efficacy when used alone and in conjugation is not clear. Aim: To assess clinical and radiographic efficacy of injectable platelet-rich fibrin (i-PRF) with microsurgical access flap in the treatment of three-wall intrabony defects in chronic periodontitis patients. Methods: Thirty sites with three-wall intrabony defects were randomly assigned to control and test group by computer generated method. The test group obtained i-PRF mixed with DFDBA while the control group received only DFDBA. Clinical parameters such as site-specific Plaque index (PI), Radiographic intrabony defect depth (IBDD), modified- Sulcular bleeding index (mSBI), Clinical attachment level (CAL), and Probing pocket depth (PPD) were measured at baseline, three and six months. Results: Intragroup comparison within the control group and test group exhibited statistically highly significant variation of mean PI, mSBI, PPD, CAL, and IBDD score from baseline to 3 months and from 3-6 months (p<0.001). However, intergroup comparison demonstrated no statistically significant variation of mean IBDD at all 3 intervals (p>0.05). Conclusion: i-PRF combined with DFDBA enhanced the radiographic and clinical parameters as opposed to DFDBA alone. The role of i-PRF is promising in its capacity for easy obtainability and increased potential to aid in regeneration


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Bone Regeneration , Alveolar Bone Loss , Chronic Periodontitis , Allografts , Platelet-Rich Fibrin
6.
Journal of Prevention and Treatment for Stomatological Diseases ; (12): 155-160, 2024.
Article in Chinese | WPRIM | ID: wpr-1006382

ABSTRACT

@#A cemental tear is defined as an incomplete or complete detachment of the cementum along the dentino-cemental junction (CDJ) or the incremental line within the body of the cementum, which can also involve part of the root dentine adjacent to the cementum. The pathogenesis of cemental tears is not fully elucidated. From the literature review, possible predisposing factors were identified, including tooth type, sex, age, periodontitis, previous periodontal treatment or root canal treatment, history of dental trauma, and occlusal trauma or excessive occlusal force. The morphology of cemental tears can be either piece-shaped or U-shaped, which usually contributes to periodontal and periapical breakdown. Clinically, cemental tears have a unitary periodontal pocket and present with symptoms mimicking localized periodontitis, apical periodontitis, and vertical root fractures. Imaging examination is of great significance for the clinical diagnosis of cemental tears, which often manifest as thin ‘prickle-like’ radiopaque masses located longitudinally adjacent to the affected root surface. Exploratory surgery is needed in some cases. Although intraoperative cemental fragments and cemental lines on the root surface can assist in the diagnostic process, histopathology examination is the gold standard for the diagnosis of cemental tears. The treatment methods vary depending on the timing of the correct diagnosis and the clinical or radiological manifestations. With the development of regenerative biomaterials and the development of intentional replantation, an increasing number of affected teeth can survive for a long time. The aim of this review is to systematically describe the biological basis and predisposing factors, clinical features, radiographic and histological characteristics, diagnosis and clinical management of cemental tears, and treatment outcomes to help make a clear diagnosis and develop a personalized treatment plan.

7.
Journal of Prevention and Treatment for Stomatological Diseases ; (12): 81-88, 2024.
Article in Chinese | WPRIM | ID: wpr-1006352

ABSTRACT

@#The plasma matrix is a kind of autologous blood conduct. It has been widely used in maxillofacial tissue regeneration, skin cosmetology and some other fields. Recently, to preserve the dental pulp as well as the teeth, pulp regeneration therapy and apical surgery have become increasingly important as well as the applications of bioactive materials. As a kind of autologous bioactive material, the plasma matrix has some natural advantages as it is easy to obtain and malleable. The plasma matrix can be used in the following cases: ①pulp revascularization of young permanent teeth with open apical foramina that cannot stimulate apical bleeding; ② apical barrier surgery with bone defects and large area perforation repair with bone defects or root sidewall repair surgery; ③ apical surgeries of teeth with large area of apical lesions, with or without periodontal diseases. The plasma matrix is a product derived from our blood, and there are no obvious contraindications for its use. Several systematic reviews have shown that the plasma matrix can effectively promote the regenerative repair of dental pulp in patients with periapical diseases. However, the applications of plasma matrix are different because its characteristics are affected by different preparation methods. In addition, there is still a lack of long-term clinical researches on the plasma matrix, and the histological evidences are difficult to obtain, so a large number of in vitro and in vivo experimental studies are still needed. This article will describe the applications of different kinds of plasma matrix for dental pulp regeneration and bone tissue regeneration in apical surgeries to provide references for clinicians in indication selection and prognosis evaluation.

8.
Journal of Prevention and Treatment for Stomatological Diseases ; (12): 76-80, 2024.
Article in Chinese | WPRIM | ID: wpr-1003449

ABSTRACT

@#Periodontal ligament stem cells (PDLSCs) have the potential for multidirectional differentiation and are the preferred seed cells for periodontal tissue regeneration. In recent years, a large number of studies have confirmed that PDLSCs also possess broad immunomodulatory properties. Therefore, in-depth exploration of their specific molecular mechanisms is of great significance for the treatment of periodontitis. The aim of this paper is to summarize the research progress on the regulation of PDLSCs on various immune cells and the effect of the inflammatory environment on the immune characteristics of PDLSCs to provide an important theoretical basis for the allotransplantation of PDLSCs and improve the therapeutic effect of periodontal tissue regeneration. Studies have shown that PDLSCs possess a certain degree of immunosuppressive effect on both innate and acquired immune cells, and inflammatory stimulation may lead to the impairment of the immunoregulatory properties of PDLSCs. However, current studies are mainly limited to in vitro cell tests and lack in-depth studies on the immunomodulatory effects of PDLSCs in vivo. In vivo studies based on cell lineage tracing and conditional gene knockout technology may become the main directions for future research.

9.
Odontol.sanmarquina (Impr.) ; 26(4): e24640, oct.-dic. 2023.
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1551154

ABSTRACT

Objetivo: El propósito de este estudio fue observar el efecto del uso de L-PRF en defectos infraoseos de pacientes con periodontitis en estadios avanzados. Métodos: Se incluyeron 32 defectos infraoseos de 12 pacientes con diagnóstico de Periodontitis estadio III y IV (Workshop 2018). Se realizó raspaje a campo abierto con colocación de membrana de L-PRF. Se incluyeron defectos infraóseos de 1-2-3 paredes y cráter óseo. Se registró la profundidad de sondaje (PS), nivel de inserción clínica (NIC), índice de placa (IP) e índice de sangrado (IS). Se realizaron radiografías periapicale digitales antes de la cirugía y al cuarto mes para observar el llenado óseo. Resultados: De los 32 defectos el 75 % mostró disminución de la profundidad de sondaje (PS) y el 66 % mejoro el nivel de inserción clínica (NIC). Se realizó un análisis de correlación pre y posquirúrgico en PS: MV (p = 0,02), MP/L (p = 0,00), DP/L (p = 0,00) y V (p =0,00). El porcentaje de llenado óseo fue de 62,96 % (DS± 3,88). Conclusiones: La mayoría de los defectos infraóseos mostraron radiográficamente llenado óseo parcial o total con el uso de membranas L-PRF. Además, se mejoraron los parámetros clínicos de profundidad de sondaje y nivel de inserción clínica.


Objective: The purpose of this study was to observe the effect of L-PRF (Leuko- cyte-Platelet Rich Fibrin) usage in intraosseous defects in patients with advanced-stages of periodontitis. Methods: Thirty-two intraosseous defects in 12 patients diagnosed with stage III and IV periodontitis (Workshop 2018) were included in the study. Open flap debridement was performed with the placement of L-PRF membranes. Included defects consisted of 1-2-3 wall defects and osseous craters. Parameters such as probing depth (PD), clinical attachment level (CAL), plaque index (PI), and bleeding index (BI) were recorded. Digital periapical radiographs were taken before surgery and at the fourth month to assess bone fill. Results: Out of the 32 defects, 75% showed a reduction in probing depth (PD), and 66% showed improvement in clinical attachment level (CAL). Pre- and post-surgical correlation analysis was performed for PD: MV (p = 0.02), PI/L (p = 0.00), BI/L (p = 0.00), and CAL (p = 0.00). The percentage of bone fill was 62.96% (±3.88 SD). Conclusion: The majority of intraosseous defects exhibited partial or complete radiographic bone fill with the use of L-PRF membranes. Furthermore, clinical parameters such as probing depth and clinical attachment level improved.

10.
Rev. cir. traumatol. buco-maxilo-fac ; 23(2): 8-16, abr./jun 2023. ilus, tab
Article in English | LILACS, BBO | ID: biblio-1537341

ABSTRACT

Introduction: The intentionally exposed polypropylene (PP) membrane has been proposed for guided bone regeneration (GBR) of the alveo lar bone after extraction; however, there are biological limitations to this proposal. This study aimed to describe the effects of the PP membrane on neo-osteogenesis after tooth extraction, comparing to intentionally ex posed and primary soft tissue coverage techniques. Methodology: This clinical trial followed the TIDieR checklist and guide. Clinical and histo logical parameters of alveolar repair were compared between groups: 1 (control group), without regenerative procedure; 2, GBR; and 3, inten tionally exposed membrane. Results: Group 3 showed slight effect on the quality of new bone, compared to the control group. Although the GBR was underestimated by the early exposure of the membrane, alveo lar repair and newly formed bone were superior to the other groups. Poly propylene membrane intentionally exposed compromised the volume density of the immature and mineralized bone matrix, the osteoblast and osteocyte count, and stimulated the granulation tissue formation and local inflammatory infiltrate. Conclusions: Despite the exposure of the PP membrane in GBR, this technique improved the quality of new bone and alveolar repair compared to the surgical technique of intentional exposure and alveolus only sutured.


RESUMEN Introducción: La membrana de polipropileno (PP) intencionalmente expuesta ha sido propuesta para la regeneración ósea guiada (GBR) del hueso alveolar después de la extracción; sin embargo, existen limitaciones biológicas a esta propuesta. Este estudio tuvo como objetivo describir los efectos de la membrana de PP en la neo-osteogénesis después de la extracción del diente, en comparación con las técnicas de cobertura de tejido blando primarias y expuestas intencionalmente. Metodología: Este ensayo clínico siguió la lista de verificación y la guía TIDieR. Se compararon los parámetros clínicos e histológicos de la reparación alveolar entre los grupos: 1 (grupo control), sin procedimiento regenerativo; 2, GBR; y 3, membrana expuesta intencionalmente. Resultados: el grupo 3 mostró un ligero efecto sobre la calidad del hueso nuevo, en comparación con el grupo de control. Aunque la GBR fue subestimada por la exposición temprana de la membrana, la reparación alveolar y el hueso neoformado fueron superiores a los otros grupos. La membrana de polipropileno expuesta intencionalmente comprometió la densidad de volumen de la matriz ósea inmadura y mineralizada, el recuento de osteoblastos y osteocitos, y estimuló la formación de tejido de granulación y el infiltrado inflamatorio local. Conclusiones: A pesar de la exposición de la membrana de PP en GBR, esta técnica mejoró la calidad del hueso nuevo y la reparación alveolar en comparación con la técnica quirúrgica de exposición intencional y alvéolo solo suturado.


Introdução: A membrana de polipropileno (PP) intencionalmente exposta tem sido proposta para regeneração óssea guiada (ROG) do osso alveolar após exodontia; no entanto, existem limitações biológicas a esta proposta. Este estudo teve como objetivo descrever os efeitos da membrana de PP na neo-osteogênese após a extração dentária, comparando com as técnicas de exposição intencional e cobertura primária de tecidos moles. Metodologia: Este ensaio clínico seguiu a lista de verificação e o guia TIDieR. Parâmetros clínicos e histológicos do reparo alveolar foram comparados entre os grupos: 1 (grupo controle), sem procedimento regenerativo; 2, GBR; e 3, membrana intencionalmente exposta. Resultados: O Grupo 3 apresentou leve efeito na qualidade do novo osso, em comparação com o grupo controle. Embora o GBR tenha sido subestimado pela exposição precoce da membrana, o reparo alveolar e o osso neoformado foram superiores aos outros grupos. A exposição intencional da membrana de polipropileno comprometeu a densidade volumétrica da matriz óssea imatura e mineralizada, a contagem de osteoblastos e osteócitos e estimulou a formação de tecido de granulação e infiltrado inflamatório local. Conclusões: Apesar da exposição da membrana PP na ROG, esta técnica melhorou a qualidade do novo osso e da reparação alveolar em comparação com a técnica cirúrgica de exposição intencional e alvéolo apenas suturado.


Subject(s)
Humans , Polypropylenes , Bone Regeneration , Tooth Socket , Guided Tissue Regeneration , Alveolar Ridge Augmentation
11.
Rev. bras. ortop ; 58(5): 798-807, Sept.-Oct. 2023. tab, graf
Article in English | LILACS | ID: biblio-1529933

ABSTRACT

Abstract Objective To reproduce in an animal model the surgical technique of Masquelet used in the treatment of critical bone defects and to analyze the characteristics of the membrane formed around the bone cement. Methods A 10mm critical defect was created in the femoral shaft of 21 Sprague-Dawley rats. After resection of the central portion of the diaphysis, the defect was stabilized with a Kirschner wire introduced through the medullary canal and with the interposition of a bone cement spacer. After 2, 4, and 6 weeks of the surgical procedure, the animals were euthanized and evaluated on radiographs of the posterior limb regarding the size of the defect, alignment and stability of the osteosynthesis. The membranes formed around the spacer were subjected to histological analysis to assess thickness, connective tissue maturation and vascular density. Results Over time, the membranes initially made up of loose connective tissue were replaced by membranes represented by dense connective tissue, rich in thick collagen fibers. At six weeks, membrane thickness was greater (565 ± 208μm) than at four (186.9 ± 70.21μm, p = 0.0002) and two weeks (252.2 ± 55.1μm, p = 0.001). All membranes from the initial time showed foci of osteogenic differentiation that progressively reduced over time. Conclusion In addition to the structural and protective function of the membrane, its intrinsic biological characteristics can actively contribute to bone regeneration. The biological activity attributed by the presence of foci of osteogenesis confers to the membrane the potential of osteoinduction that favors the local conditions for the integration of the bone graft.


Resumo Objetivo Reproduzir em modelo animal a técnica cirúrgica de Masquelet utilizada no tratamento de defeitos ósseos críticos e analisar as características da membrana formada em torno do cimento ósseo. Métodos Um defeito crítico de 10mm foi realizado na diáfise femoral de 21 ratos Sprague-Dawley. Após a ressecção da porção central da diáfise o defeito foi estabilizado com fio de Kirschner introduzido pelo canal medular e com a interposição de espaçador de cimento ósseo. Após 2, 4, e 6 semanas do procedimento cirúrgico os animais foram eutanasiados e avaliados em radiografias do membro posterior quanto ao tamanho do defeito, o alinhamento e a estabilidade da osteossíntese. As membranas formadas em torno do espaçador foram submetidas a análise histológica para avaliação da espessura, da maturação do tecido conjuntivo e da densidade vascular. Resultados Ao longo do tempo as membranas inicialmente constituídas por tecido conjuntivo frouxo foram substituídas por membranas representadas por tecido conjuntivo denso, rico em fibras colágenas espessas. Com seis semanas a espessura das membranas foi maior (565 ± 208μm) do que com quatro (186,9 ± 70,21μm, p = 0,0002) e duas semanas (252,2 ± 55,1μm, p = 0,001). Todas as membranas do tempo inicial apresentaram focos de diferenciação osteogênica que reduziram progressivamente ao longo do tempo. Conclusão Além da função estrutural e protetora da membrana, suas características biológicas intrínsecas podem contribuir ativamente para a regeneração óssea. A atividade biológica atribuída pela presença de focos de osteogênese confere à membrana potencial de osteoindução que favorece as condições locais para a integração do enxerto ósseo.


Subject(s)
Animals , Bone Regeneration , Models, Animal
12.
Actual. osteol ; 19(2): 128-143, sept. 2023. ilus, tab
Article in Spanish | LILACS, UNISALUD, BINACIS | ID: biblio-1523882

ABSTRACT

El presente trabajo muestra la obtención de un material a partir de un polímero sintético (TerP) y otro natural, mediante entrecruzamiento físico y su caracterización fisicoquímica y biológica, con el fin de emplearlos para regeneración de tejido óseo. Las membranas fueron obtenidas por la técnica de evaporación del solvente y caracterizadas por espectroscopia FTIR, ensayos de hinchamiento, medidas de ángulo de contacto y microscopia electrónica de barrido (SEM). Se encontró que la compatibilidad entre los polímeros que la constituyen es estable a pH fisiológico y que, al incorporar mayor cantidad del TerP a la matriz, esta se vuelve más hidrofóbica y porosa. Además, teniendo en cuenta la aplicación prevista para dichos materiales, se realizaron estudios de biocompatibilidad y citotoxicidad con células progenitoras de médula ósea (CPMO) y células RAW264.7, respectivamente. Se evaluó la proliferación celular, la producción y liberación de óxido nítrico (NO) al medio de cultivo durante 24 y 48 horas y la expresión de citoquinas proinflamatorias IL-1ß y TNF-α de las células crecidas sobre los biomateriales variando la cantidad del polímero sintético. Se encontró mayor proliferación celular y menor producción de NO sobre las matrices que contienen menos proporción del TerP, además de poseer una mejor biocompatibilidad. Los resultados de este estudio muestran que el terpolímero obtenido y su combinación con un polímero natural es una estrategia muy interesante para obtener un biomaterial con posibles aplicaciones en medicina regenerativa y que podría extenderse a otros sistemas estructuralmente relacionados. (AU)


In the present work, the preparation of a biomaterial from a synthetic terpolymer (TerP) and a natural polymer, physically crosslinked, is shown. In order to evaluate the new material for bone tissue regeneration, physicochemical and biological characterizations were performed. The membranes were obtained by solvent casting and characterized using FTIR spectroscopy, swelling tests, contact angle measurements, and scanning electron microscopy (SEM). It was found that the compatibility between the polymers is stable at physiological pH and the incorporation of a higher amount of TerP into the matrix increases hydrophobicity and porosity.Furthermore, considering the intended application of these materials, studies of biocompatibility and cytotoxicity were conducted with Bone Marrow Progenitor Cells (BMPCs) and RAW264.7 cells, respectively. Cell proliferation, NO production and release into the culture medium for 24 and 48 hours, and proinflammatory cytokine expression of IL-1ß and TNF-α from cells grown on the biomaterials while varying the amount of the synthetic polymer were evaluated. Greater cell proliferation and lower NO production were found on matrices containing a lower proportion of TerP, in addition to better biocompatibility. The results of this study demonstrate that the obtained terpolymer and its combination with a natural polymer is a highly interesting strategy for biomaterial preparation with potential applications in regenerative medicine. This approach could be extended to other structurally related systems. (AU)


Subject(s)
Animals , Rats , Osteogenesis , Polymers/chemistry , Biocompatible Materials/chemical synthesis , Bone and Bones/chemistry , Bone Regeneration , Chitosan/chemistry , Polymers/toxicity , Biocompatible Materials/toxicity , Materials Testing , Cell Differentiation , Chromatography, Gel , Spectroscopy, Fourier Transform Infrared , Cell Culture Techniques , Nuclear Magnetic Resonance, Biomolecular , Chitosan/toxicity
13.
RFO UPF ; 27(1)08 ago. 2023. tab, ilus
Article in Portuguese | LILACS, BBO | ID: biblio-1511050

ABSTRACT

Objetivo: revisar a literatura sobre os diferentes tipos de derivados de plaquetas autólogas e o desempenho clínico do uso do sticky bone para aumento ósseo horizontal de rebordo. Materiais e métodos: Para realização dessa revisão foram realizadas buscas nas bases de dados PubMed, Google Scholar e Web of Science, utilizando os seguintes descritores: "platelet-rich fibrin" AND "sticky bone" OR "alveolar bone grafting" AND "sticky bone" OR "guided bone regeneration" AND "sticky bone" AND "alveolar ridge augmentation" OR "Alveolar ridge augmentation" AND "sticky bone". Foram incluídos artigos publicados em inglês, que abordavam conceitos relacionados aos agregados plaquetários e a regeneração óssea guiada para aumento ósseo horizontal de rebordo utilizando fibrina rica em plaquetas associada à enxertos ósseos (sticky bone). Resultados: Após avaliação dos estudos encontrados foram selecionados 11 artigos sobre o uso do sticky bone para aumento horizontal de rebordo. Para compor este trabalho foram selecionados também 14 estudos de revisão e artigos associados ao tema. Por ser de fácil aplicação e obtenção, muitos autores têm estudado as aplicações cirúrgicas do sticky bone e os resultados demonstram que o aumento horizontal do rebordo utilizando essa técnica pode ser realizado de forma previsível. Conclusão: apesar de haver estudos promissores sobre o uso do sticky bone, falta evidência na literatura sobre seu sucesso clínico. Assim, para compreender o potencial regenerativo desta técnica são necessários um maior número de estudos randomizados, com diferentes materiais de enxerto e protocolos padronizados de obtenção do sticky bone.(AU)


Objective: to review the literature on the different types of autologous platelet derivatives and the clinical performance of using sticky bone for horizontal bone ridge augmentation. Materials and methods: In order to conduct this review, it was conducted searches in the PubMed, Google Scholar, and Web of Science databases using the following descriptors: "platelet-rich fibrin" AND "sticky bone" OR "alveolar bone grafting" AND "sticky bone" OR "guided bone regeneration" AND "sticky bone" AND "alveolar ridge augmentation" OR "Alveolar ridge augmentation" AND "sticky bone". It included articles published in English that addressed concepts related to platelet aggregates and guided bone regeneration for horizontal bone augmentation using platelet-rich fibrin associated with bone grafts (sticky bone). Results: After evaluating the studies found, were selected 11 articles on the use of sticky bone for horizontal ridge augmentation. To compose this work, 14 review studies and articles associated with the topic were also selected. Due to its ease of application and availability, many authors have explored the surgical applications of sticky bone, and the results indicate that horizontal ridge augmentation using this technique can be predictably performed. Conclusion: while there are promising studies on the use of sticky bone, the literature lacks evidence regarding its clinical success. Therefore, to fully understand the regenerative potential of this technique, further randomized studies are needed, involving different graft materials and standardized protocols for obtaining sticky bone.(AU)


Subject(s)
Humans , Guided Tissue Regeneration/methods , Alveolar Ridge Augmentation/methods , Alveolar Bone Grafting/methods , Platelet-Rich Fibrin , Bone Regeneration/physiology
14.
Int. j. morphol ; 41(4): 1184-1190, ago. 2023. ilus, tab
Article in English | LILACS | ID: biblio-1514361

ABSTRACT

SUMMARY: Peripheral nerve damage is a significant clinical problem that can lead to severe complications in patients. Regarding the regeneration of peripheral nerves, it is crucial to use experimental animals' nerves and use different evaluation methods. Epineural or perineural suturing is the gold standard in treating sciatic nerve injury, but nerve repair is often unsuccessful. This study aimed to investigate the neuroregenerative effects of magnetotherapy and bioresonance in experimental animals with sciatic nerve damage. In this study, 24 female Wistar rats were divided into 7 groups (n=6) as follows: Group 1 (Control), Group 2 (Axonotmesis control), Group 3 (Anastomosis control), Group 4 (Axonotmesis + magnetotherapy), Group 5 (Anastomosis + magnetotherapy), Group 6 (Axonotmesis + bioresonance), Group 7 (Anastomosis + bioresonance). Magnetotherapy and bioresonance treatments were applied for 12 weeks. Behavioural tests and EMG tests were performed at the end of the 12th week. Then the rats were sacrificed, and a histopathological evaluation was made. The statistical significance level was taken as 5 % in the calculations, and the SPSS (IBM SPSS for Windows, ver.21) statistical package program was used for the calculations. Statistically significant results were obtained in animal behaviour tests, EMG, and pathology groups treated with magnetotherapy. There was no statistically significant difference in the groups treated with bioresonance treatment compared to the control groups. Muscle activity and nerve repair occurred in experimental animals with acute peripheral nerve damage due to 12 weeks of magnetotherapy, and further studies should support these results.


El daño a los nervios periféricos es un problema clínico importante que puede conducir a complicaciones graves en los pacientes. En cuanto a la regeneración de los nervios periféricos, es crucial utilizar los nervios de los animales de experimentación y diferentes métodos de evaluación. La sutura epineural o perineural es el gold estándar en el tratamiento de lesiones del nervio ciático, pero la reparación del nervio a menudo no tiene éxito. Este estudio tuvo como objetivo investigar los efectos neuroregenerativos de la magnetoterapia y la biorresonancia en animales de experimentación con daño del nervio ciático. En el estudio, 24 ratas hembras Wistar se dividieron en 7 grupos (n=6) de la siguiente manera: Grupo 1 (Control), Grupo 2 (Control de axonotmesis), Grupo 3 (Control de anastomosis), Grupo 4 (Axonotmesis + magnetoterapia), Grupo 5 (Anastomosis + magnetoterapia), Grupo 6 (Axonotmesis + biorresonancia), Grupo 7 (Anastomosis + biorresonancia). Se aplicaron durante 12 semanas tratamientos de magnetoterapia y biorresonancia. Las pruebas de comportamiento y las pruebas de EMG se realizaron al final de la semana 12. Luego se sacrificaron las ratas y se realizó una evaluación histopatológica. El nivel de significación estadística se tomó como 5 % en los cálculos, y se utilizó el programa de paquete estadístico SPSS (IBM SPSS para Windows, ver.21). Se obtuvieron resultados estadísticamente significativos en pruebas de comportamiento animal, EMG y grupos de patología tratados con magnetoterapia. No hubo diferencia estadísticamente significativa en los grupos con tratamiento de biorresonancia en comparación con los grupos controles. La actividad muscular y la reparación nerviosa, se produjeron en animales de experimentación con daño nervioso periférico agudo, debido a 12 semanas de magnetoterapia.Estudios adicionales deberían respaldar estos resultados.


Subject(s)
Animals , Female , Rats , Sciatic Nerve/injuries , Peripheral Nerve Injuries/therapy , Nerve Regeneration , Sciatic Nerve/physiology , Rats, Wistar , Electromyography , Magnetic Field Therapy , Peripheral Nerve Injuries/physiopathology , Bioresonance Therapy
15.
Rev. cuba. estomatol ; 60(2)jun. 2023.
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1530097

ABSTRACT

Introducción: La reconstrucción de defectos cutáneos nasales requiere del uso de procedimientos orientados a obtener la menor probabilidad de complicaciones posoperatorias en el menor período de tiempo posible. Novedosas técnicas utilizan los concentrados plaquetarios por sus propiedades moduladoras del dolor y el edema posoperatorio. Objetivo: Determinar el comportamiento del dolor y el edema posquirúrgico en la regeneración de defectos cutáneos nasales con el uso de la membrana de fibrina autóloga, rica en plaquetas y leucocitos. Método: Se realizó una investigación cuasiexperimental, con diseño antes-después, sin grupo control en el Servicio de Cirugía Maxilofacial del Hospital Universitario "Arnaldo Milián Castro" de la ciudad de Santa Clara, Villa Clara, Cuba, desde septiembre de 2015 a junio de 2019. La muestra seleccionada aleatoriamente fue de 46 pacientes. A partir de una autodonación de sangre del paciente se obtuvo una membrana de fibrina rica en plaquetas y leucocitos, la cual fue suturada en el defecto quirúrgico nasal. Resultados: La edad media fue 62,71 años y el 60,87 % de la muestra correspondió al sexo masculino. Se presentaron el dolor en el 23,91 % y el edema en el 28,26 % de la muestra estudiada. Conclusiones: Se encontraron escasas complicaciones posoperatorias como el dolor y el edema, las que se manifestaron predominantemente de intensidad leve. Existió asociación entre estas complicaciones y la edad, la cantidad de subunidades anatómicas afectadas, la diabetes mellitus y el tabaquismo.


Introduction: The reconstruction of nasal skin defects requires the use of procedures aimed at obtaining the lowest probability of postoperative complications in the shortest period of time possible. Novel techniques use platelet concentrates for their modulating properties of pain and postoperative edema. Objective: To determine the behavior of pain and post-surgical edema in the regeneration of nasal skin defects with the use of autologous platelet- and leukocyte-rich fibrin membrane. Method: A quasi-experimental research was carried out, with a before-after design, without a control group, in the Maxillofacial Surgery Service at Arnaldo Milián Castro University Hospital in Santa Clara, Villa Clara, Cuba, from September 2015 to June 2015. 2019. The randomly selected sample was 46 patients. A fibrin membrane rich in platelets and leukocytes was obtained from a patient's blood self-donation, which was sutured in the nasal surgical defect. Results: The mean age was 62.71 years and 60.87% of the sample was male. Pain was present in 23.91% and edema in 28.26% of the studied sample. Conclusions: Few postoperative complications such as pain and edema were found, showing to be mild predominantly. There was association between these complications and age, the number of affected anatomical subunits, diabetes mellitus and smoking habit.

16.
Rev. ADM ; 80(3): 165-170, mayo-jun. 2023. ilus
Article in Spanish | LILACS | ID: biblio-1518398

ABSTRACT

La pérdida ósea en el sector anterior, ya sea por un defecto horizontal, vertical o combinado, actualmente es un desafío, no sólo por la integración del implante, sino por la estética involucrada. Entre las técnicas de regeneración ósea que permiten solucionar estos defectos, cabe destacar la técnica de expansión de crestas. Se presenta el caso de una paciente de 58 años con reborde atrófico, que se sometió a la expansión de crestas con colocación simultánea de implantes en sector anterior, con xenoinjerto previo a técnica de expansión de crestas con piezoeléctrico, colocación simultánea de implantes Narrow Connection SLActive Straumann. Se logró ganancia ósea y estabilidad primaria de los implantes, sin complicaciones. En escenarios seleccionados, la técnica de expansión de crestas de manera predecible permite ganancia de hueso horizontal adecuada, el éxito de los implantes con tasa de supervivencia y mínimas complicaciones intra y postoperatorias (AU)


Bone loss in the anterior sector, both a horizontal, vertical or combined defect is a challenge today; not only for the integration of the implant but also the aesthetic involved. There are techniques of bone regeneration that help us to solve this type of defects, among them we should highlight the crest expansion technique. We present the case of a 58-year-old patient with atrophic flange, who underwent the expansion of crests with simultaneous placement of implants in the anterior sector, with xenograft prior to the piezoelectric crest expansion technique, Simultaneous placement of Narrow Connection SLActive Straumann implants, bone gain and primary stability of the implants were obtained, without complications. In selected scenarios, the crest expansion technique could be considered a predictable approach that demonstrates a high implant survival rate, adequate horizontal bone gain, and minimal intra- and postoperative complications (AU)


Subject(s)
Humans , Female , Middle Aged , Dental Implantation, Endosseous/methods , Alveolar Ridge Augmentation/methods , Osteotomy/methods , Piezosurgery/methods , Heterografts
17.
Braz. dent. j ; 34(3): 57-65, May-June 2023. graf
Article in English | LILACS-Express | LILACS, BBO | ID: biblio-1447608

ABSTRACT

Abstract The current literature on guided bone regeneration (GBR) and guided tissue regeneration (GTR) membrane contamination reports that the physicochemical characteristics of these biomaterials might influence affinity to bacteria, which appears to be a major drawback for the clinical outcome of the regenerative procedures. Thus, this study aimed to evaluate, in vitro, a multispecies biofilm adherence and passage of bacteria through different types of commercially available membranes for GTR/GBR. Four types of membranes were tested (n=12): LC) Lumina Coat®; JS) Jason®; BG) Biogide®; and LP) Lumina PTFE®. Aluminum foil (AL) simulated an impermeable barrier and was used as the control. The membranes were adapted to specific apparatus and challenged with a mixed bacterial culture composed of A. actinomycetemcomitans b, S. mutans, S. mitis, and A. israelii. After 2 h or 7 days, bacterial adhesion and passage of bacteria were evaluated through CFU counting, which was analyzed by two-way ANOVA e post hoc Tukey, at a 5% significance level. Representative areas of two membranes of each group were analyzed through scanning electron microscopy (SEM) to assess the morphology and organization of the biofilm over the membrane fibers. LC and LP presented similar values of adhered bacterial cells (p > 0.05), significantly inferior when compared to the other groups, in both time points (p < 0.05). All the tested groups were permeable to bacterial cells, with no significant difference between the trial period of 2 h and 7 days (p > 0.05). SEM analyses demonstrated that adhered bacteria number increased throughout the time points (2 h < 7 days). Commercially available biological membranes demonstrated intense bacterial adherence and passage of bacteria, which increased throughout the trial period.


Resumo O objetivo deste estudo foi avaliar, in vitro, a aderência do biofilme multiespécie e a passagem de bactérias através dos diferentes tipos de membranas disponíveis comercialmente para RTG/ROG. Quatro tipos de membranas foram testados (n=12): LC) Lumina Coat®; JS) Jason®; BG) Biogide®; e LP) Lumina PTFE®. Papel alumínio (AL) simulou uma barreira impermeável e foi usado como controle negativo. As membranas foram adaptadas à um aparato específico e desafiadas com uma cultura bacteriana mista composta de A. actinomycetemcomitans b, S. mutans, S. mitis, e A. israelii. Após 2 h ou 7 dias, a aderência e passagem bacteriana foi avaliada através da contagem de UFCs. Duas membranas de cada grupo foram analisadas através da microscopia eletrônica de varredura (MEV). LC e LP apresentaram valores semelhantes de células bacterianas aderidas (p < 0.05), significativamente inferiores quando comparados aos outros grupos, em ambos os períodos experimentais (p < 0.05). Desde a análise inicial, todos os grupos testados foram permeáveis às células bacterianas, sem diferença significativa entre o período experimental de 2 h e 7 dias (p > 0.05). As análises em MEV demonstraram que o número de bactérias aderidas aumentou com o tempo (2 h < 7 days). Membranas biológicas comercialmente disponíveis demonstraram intensa aderência bacteriana e passagem de bactérias, que aumentou durante os períodos experimentais.

18.
J. oral res. (Impresa) ; 12(1): 100-107, abr. 4, 2023. ilus
Article in English | LILACS | ID: biblio-1512550

ABSTRACT

Introduction: This case report analyzes the regeneration potential of advanced-platelet rich fibrin (A-PRF) in large bony lesions. Advanced-platelet rich fibrin provides various growth factors which aids in faster healing. Materials and Methods: Patient presented with peri-apical radiolucency. CBCT showed bony radiolucency in teeth 31, 32, 41, 42. A full mouth mucoperiosteal flap was raised and a cyst lining was enucleated. Apicoectomy was done with respect to 31, 32, 41, 42 along with and retrograde with a preparation of APRF clots were placed in the bony cavity. Results: Post-op CBCT at 6 months showed a significant difference in size and bone density of the lesion. Conclusions: Advanced-platelet rich fibrin has shown promising results in reducing the size of bony defect and periapical lesion in this case.


Introducción: Este caso clínico demuestra el potencial de regeneración de la fibrina rica en plaquetas avanzada (A-PRF) en lesiones óseas de gran tamaño. La fibrina rica en plaquetas avanzada proporciona varios factores de crecimiento que ayudan a una curación más rápida. Materiales y Métodos: El paciente se presentó con radiolucencia periapical. Tomografía computarizada de haz cónico mostró radiolucencia ósea en los dientes 31, 32, 41, 42. Se levantó un colgajo mucoperióstico de boca completa y se enucleó el revestimiento del quiste. Se realizó apicectomía con respecto a 31, 32, 41, 42, y se colocó una preparación de APRF se colocaron coágulos en la cavidad ósea. Resultados: La tomografía computarizada de haz cónico postoperatorio a los 6 meses mostró una diferencia significativa en el tamaño y la densidad ósea de la lesión. Conclusión: La fibrina rica en plaquetas avanzada ha mostrado resultados prometedores en la reducción del tamaño del defecto óseo y la lesión periapical en este caso.


Subject(s)
Humans , Female , Adult , Young Adult , Platelet-Rich Fibrin , Regenerative Endodontics/methods , Apicoectomy , Cysts/surgery , Cone-Beam Computed Tomography
19.
J. oral res. (Impresa) ; 12(1): 127-138, abr. 4, 2023. tab
Article in English | LILACS | ID: biblio-1516450

ABSTRACT

Introduction: The use of enamel matrix-derived proteins (EMD) has increased in recent years due to their tissue-inducing properties that support periodontal regeneration. This study is an overview of systematic reviews with FRISBEE methodology on the use of EMD alone or combined with autologous bone graft materials (BGM) in the treatment of intrabony defects. Materials and Methods: A systematic search in the Epistemonikos database was performed. RevMan 5.3 and GRADEpro were used for data analysis and presentation Results: Four systematic reviews and two clinical trials were identified. All studies analysed change in probing depth, clinical attachment level, gingival margin level and bone defect depth (all changes in favour of EMD+BGM groups: mean difference (MD): 0.37 mm more, MD: 0.7 mm more, MD: 0.3 mm less, MD: 0.75 more, respectively). Conclusions: Adding autologous bone graft to EMD to treat intrabony defects showed better results, but not a relevant clinical difference compared to the use of EMD alone.


Introducción: El uso de proteínas derivadas de la matriz del esmalte (EMD) ha aumentado en los últimos años debido a sus propiedades inductoras de tejidos que apoyan la regeneración periodontal. Este estudio es una revisión sistemática de revisiones sistemáticas utilizando metodología FRISBEE sobre el uso de EMD solo o combinado con materiales injerto óseo autólogo (BGM) en el tratamiento de defectos intraóseos. Materiales y Métodos: Se realizó una búsqueda sistemática en la base de datos Epistemonikos. Se utilizaron RevMan 5.3 y GRADEpro para el análisis y la presentación de los datos. Resultados: Se identificaron cuatro revisiones sistemáticas y dos ensayos clínicos. Todos los estudios analizaron el cambio en la profundidad de sondaje, el nivel de inserción clínica, el nivel del margen gingival y la profundidad del defecto óseo (todos los cambios a favor de los grupos EMD+BGM: MD: 0,37 mm más, media de diferencia (MD): 0,7 mm más, MD: 0,3 mm menos, MD: 0,75 más, respectivamente). Conclusión: La adición de injerto óseo autólogo a la EMD para tratar defectos intraóseos mostró mejores resultados, pero no una diferencia clínica relevante en comparación con el uso de la EMD sola.


Subject(s)
Humans , Alveolar Bone Loss/rehabilitation , Bone Transplantation/methods , Dental Enamel Proteins/therapeutic use , Periodontal Diseases , Transplantation, Autologous , Bone Regeneration
20.
J. oral res. (Impresa) ; 12(1): 152-167, abr. 4, 2023. tab, ilus
Article in English | LILACS | ID: biblio-1516525

ABSTRACT

Objective: The objective of the present systematic review and meta-analysis was to compare treatment with membrane associated with bone grafting and treatment exclusively with membrane in the approach of Class II furcation defects in mandibular molars. Materials and Methods: The Preferred Reporting Items for Systematic Reviews and Meta-analyses statement was followed. Searches were conducted in five databases (PubMed, Web of Science, Scopus, Ovid, and Lilacs), in Septem-ber 2021, without restriction regarding publication year or language. Studies comparing membranes associated with bone grafting and membranes exclusively in the treatment of Class II furcation lesions were included. Cross-sectional, case-control studies, and reviews were excluded. Study selection, data extraction, and risk of bias assessment (MINORS) were performed by two review authors. The certainty of the evidence (GRADE) was evaluated and meta-analysis was performed. Mean difference (MD) and 95% confidence interval (CI) were provided. Results: Four hundred eighty-six references were iden-tified and four studies were included. Greater reduction in probing depth [MD = 0.32 (CI = 0.09, 0.56)] and greater clinical attachment level gain [MD = 0.41 (CI = 0.24, 0.57)] were observed when membrane and bone grafting were used. The risk of bias of included studies was low. Conclusions: This present systematic review and meta-analysis demonstrated that treatment of Class II furcation defects in mandibular molars using membrane and bone grafing is significantly more efficacious than treatment with the exclusive use of membrane.


Objetivo: El objetivo de la presente revisión sistemática y metanálisis fue comparar el tratamiento con membrana asociado a injerto óseo y el tratamiento exclusivamente con membrana en el abordaje de lesiones de furca grado II en molares mandibulares. Materiales y Métodos: Se siguió la declaración de elementos de informe preferidos para revisiones sistemáticas y metanálisis (PRISMA). Las búsquedas se realizaron en cinco bases de datos (PubMed, Web of Science, Scopus, Ovid y Lilacs), en septiembre de 2021, sin restricción de año de publicación o idioma. Se incluyeron estudios que compararon membranas asociadas con injertos óseos y membranas exclusivamente en el tratamiento de lesiones de furca de grado II. Se excluyeron los estudios transversales, de casos y controles y las revisiones. Dos revisores realizaron la selección de estudios, la extracción de datos y la evaluación del riesgo de sesgo (MINORS). Se evaluó la certeza de la evidencia (GRADE) y se realizó un metanálisis. Se proporcionaron la diferencia de medias (DM) y el intervalo de confianza (IC) del 95%. Resultados: Se identificaron 486 referencias y se incluyeron cuatro estudios. Se observó una mayor reducción en la profundidad de sondaje [DM = 0,32 (IC = 0,09, 0,56)] y una mayor ganancia en el nivel de inserción clínica [DM = 0,41 (IC= 0,24, 0,57)] cuando se utilizaron injertos de membrana y hueso. El riesgo de sesgo de los estudios incluidos fue bajo. Conclusión: La presente revisión sistemática y metanálisis demostró que el tratamiento de los defectos de furca de grado II en molares mandibulares utilizando membrana e injertos de hueso es significativamente más eficaz que el tratamiento con el uso exclusivo de membrana.


Subject(s)
Humans , Bone Transplantation/methods , Furcation Defects/therapy , Periodontitis , Guided Tissue Regeneration , Membranes, Artificial
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