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1.
Arch Oral Biol ; 162: 105962, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38569446

ABSTRACT

OBJECTIVE: This study assessed the impact of an anti-sclerostin monoclonal antibody (Scl-Ab)-based osteoporosis drug on the post-extraction alveolar repair of ovariectomized rats. DESIGN: Fifteen female rats were randomly distributed into three groups: CTR (healthy animals), OST (osteoporosis induced by ovariectomy), and OST+Scl-Ab (osteoporosis induction followed by Scl-Ab treatment). Ovariectomy or sham surgery was performed 30 days before baseline, and Scl-Ab or a vehicle was administered accordingly in the groups. After seven days, all rats underwent the first lower molar extraction and were euthanized 15 days later. Computed microtomography, histological analysis, and collagen content measurement were performed on post-extraction sockets and intact mandibular and maxillary bone areas. RESULTS: Microtomographic analyses of the sockets and mandibles did not reveal significant differences between groups on bone morphometric parameters (p > 0.05), while maxillary bone analyses resulted in better maintenance of bone architecture in OST+Scl-Ab, compared to OST (p < 0.05). Descriptive histological analysis and polarization microscopy indicated better post-extraction socket repair characteristics and collagen content in OST+Scl-Ab compared to OST (p < 0.05). CONCLUSIONS: Scl-Ab-based medication did not accelerate alveolar bone formation but exhibited better post-extraction repair characteristics, and collagen content compared to ovariectomized animals only.


Subject(s)
Bone Morphogenetic Proteins , Osteoporosis , Rats , Female , Animals , Rats, Sprague-Dawley , Genetic Markers , Antibodies, Monoclonal/pharmacology , Collagen
2.
Clin Oral Investig ; 28(1): 89, 2024 Jan 13.
Article in English | MEDLINE | ID: mdl-38217802

ABSTRACT

OBJECTIVE: To evaluate the osseointegration of implants with hydrophobic (HFB) and hydrophilic (HFL) surfaces in a murine model of high-dose bisphosphonates (BPs). MATERIALS AND METHODS: Sixty-four rats were randomly allocated into four groups: control group with HFB implants (CG-HFB), control group with HFL implants (CG-HFL), BP group with HFB implants (BP-HFB), and BP group with HFL implants (BP-HFL). Animals were euthanized after 15 and 45 days (n=8). The dependent variables assessed were the removal torque (biomechanical analysis), the bone volume around the implants (%BV/TV) (microtomographic analysis), the bone-implant contact (%BIC), the bone between the threads (%BBT) (histomorphometric analysis), and the expression of bone metabolism markers (immunohistochemistry analysis). RESULTS: The CG-HFL and BP-HFL groups presented higher removal torque than the CG-HFB and BP-HFB implants. The %BIC of the CG-HFL surfaces was slightly higher than that of the CG-HFB implants. The BP-HFB and BP-HFL groups presented a higher %BIC than that of the CG-HFB and CG-HFL groups (p<0.001). BP therapy also increased the %BBT at both implant surfaces. Higher levels of ALP were observed in the matrix region of bone tissue on the HFL surfaces than on the HFB surfaces. CONCLUSION: Both surfaces enable osseointegration in rats under BP therapy. CLINICAL RELEVANCE: The study demonstrates that hydrophobic (HFB) and hydrophilic (HFL) implant surfaces can promote osseointegration in rats undergoing bisphosphonate therapy. The HFL surfaces exhibited improved biomechanical performance, higher bone-implant contact, and increased bone volume, suggesting their potential clinical relevance for implant success in individuals on bisphosphonate treatment.


Subject(s)
Dental Implants , Rats , Mice , Animals , Osteogenesis , Diphosphonates/pharmacology , Disease Models, Animal , Surface Properties , Titanium/chemistry , Osseointegration
3.
Clin Implant Dent Relat Res ; 25(5): 919-928, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37309706

ABSTRACT

OBJECTIVE: The aim of the present study was to evaluate the effect of obesity on the osseointegration of implants with hydrophobic and hydrophilic surfaces. MATERIALS AND METHODS: Sixty-four male rats were distributed among four experimental groups: H-HB (Healthy/Hydrophobic): healthy animals with hydrophobic implants; H-HL (Healthy/Hydrophilic): healthy animals with hydrophilic implants; O-HB (Obese/Hydrophobic): animals with induced obesity and hydrophobic implants; O-HL (Obese/Hydrophilic): animals with induced obesity and hydrophilic implants. One hundred and twenty-eight implants were installed in the tibiae of the animals bilaterally (64 on the left tibiae and 64 on the right one) after 75 days of a specific diet (standard or high-fat diet) and euthanasia was performed in the experimental periods of 15 and 45 days after implant placement. Bone formation was assessed by biomechanical analysis (on the left tibiae of each animal), and microtomographic and histomorphometric analyses (on the right tibiae of each animal). Statistical analysis was performed using the Shapiro-Wilk test for normality and ANOVA followed by Tukey test to observe whether there was a significant difference between groups (p < 0.05); the t-test was used to compare the animals' body weight. RESULTS: The biomechanical analysis showed an increase in the removal torque value of animals after 45 days in comparison to after 15 days, with the exception of O-HB groups. The microtomographic analysis demonstrated no significant differences in the mineralized bone tissue volume between the groups. In the histomorphometric analysis, the H-HL/45 day group/period demonstrated higher bone-implant contact, in comparison to H-HL/15 days and the O-HL/45 day group/period showed an increase in bone area between the implant threads, in comparison to O-HL/15 days. CONCLUSION: In conclusion, obesity does not interfere with the osseointegration of hydrophobic and hydrophilic implants.


Subject(s)
Dental Implants , Osseointegration , Male , Rats , Animals , Tibia/surgery , Implants, Experimental , Obesity/complications , Surface Properties , Titanium/chemistry , Torque
4.
Periodontol 2000 ; 93(1): 139-152, 2023 Oct.
Article in English | MEDLINE | ID: mdl-38194350

ABSTRACT

The possibilities for oral bone regeneration procedures vary depending on the type of bone defect to be treated, which in turn dictate the type of graft to be used. Atrophic alveolar ridges are non-contained defects and pose a challenging defect morphology for bone regeneration/augmentation. Successful results are regularly obtained with the use of particulate grafts in combination with barrier membranes. In cases of very narrow ridges with need of larger amount of bone augmentation, block grafts are often used. Fresh-frozen allogeneic bone block grafts have been proposed as an alternative to autogenous (AT) bone blocks. Based on a systematic appraisal of pre-clinical in vivo studies and clinical trials including a direct comparison of fresh-frozen bone (FFB) blocks versus AT bone blocks it can be concluded that a FFB block graft: (a) cannot be considered as a reliable replacement of a AT bone block, and (b) should only be considered in cases where the amount of necessary augmentation-in a lateral direction-is relatively limited, so that the main portion of the body of the implant lies within the inner (i.e., the vital) aspect of the block.


Subject(s)
Alveolar Ridge Augmentation , Hematopoietic Stem Cell Transplantation , Humans , Alveolar Process/surgery , Bone Regeneration , Bone Transplantation
5.
J Proteomics ; 263: 104616, 2022 07 15.
Article in English | MEDLINE | ID: mdl-35595054

ABSTRACT

The prevalence of obesity has increased significantly worldwide. Therefore, this study aimed to evaluate the influence of obesity on the proteomic profile of periodontal ligament (PDL) tissues of rat first maxillary molars (1 M) submitted to orthodontic tooth movement (OTM). Ten Holtzman rats were distributed into two groups (n = 5): the M group (OTM), and the OM group (obesity induction plus OTM). Obesity was induced by a high-fat diet for the entire experimental periods After that period, the animals were euthanized and the hemimaxillae removed and processed for laser capture microdissection of the PDL tissues of the 1 M. Peptide extracts were obtained and analyzed by LC-MS/MS. Data are available via ProteomeXchange with identifier PXD033647. Out of the 109 proteins with differential abundance, 49 were identified in the OM group, including Vinculin, Cathepsin D, and Osteopontin, which were selected for in situ localization by immunohistochemistry analysis (IHC). Overall, Gene Ontology (GO) analysis indicated that enriched proteins were related to the GO component cellular category. IHC validated the trends for selected proteins. Our study highlights the differences in the PDL proteome profiling of healthy and obese subjects undergoing OTM. These findings may provide valuable information needed to better understand the mechanisms involved in tissue remodeling in obese patients submitted to orthodontic treatment. SIGNIFICANCE: The prevalence of obesity is increasing worldwide. Emerging findings in the field of dentistry suggest that obesity influences the tissues around the teeth, especially those in the periodontal ligament. Therefore, evaluation of the effect of obesity on periodontal tissues remodeling during orthodontic tooth movement is a relevant research topic. To our knowledge, this is the first study to evaluate proteomic changes in periodontal ligament tissue in response to the association between orthodontic tooth movement and obesity. Our study identified a novel protein profile associated with obesity by using laser microdissection and proteomic analysis, providing new information to increase understanding of the mechanisms involved in obese patients undergoing orthodontic treatment which can lead to a more personalized orthodontic treatment approach.


Subject(s)
Obesity , Periodontal Ligament , Proteome , Tooth Movement Techniques , Animals , Biomechanical Phenomena/physiology , Chromatography, Liquid , Humans , Obesity/metabolism , Osteoclasts , Periodontal Ligament/metabolism , Proteomics/methods , Rats , Rats, Sprague-Dawley , Tandem Mass Spectrometry
6.
J Periodontal Res ; 57(3): 545-557, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35246839

ABSTRACT

BACKGROUND AND OBJECTIVES: Many studies have been conducted to better understand the molecular mechanism involved with periodontitis progression. There has been growing interest in the potential impact of obesity on periodontitis onset and progression, but the mechanisms involved remain to be elucidated. The present study was designed to determine the impact of obesity on experimentally induced periodontitis in rats and identify novel pathways involved. METHODS: Sixteen Holtzman rats were distributed into two groups (n = 8): ligature-induced periodontitis (P) and obesity plus ligature-induced periodontitis (OP). Obesity was induced by a high-fat diet for 70 days, whereas periodontitis was induced for 20 days, with a cotton thread placed around the upper first molars bilaterally. Alveolar bone loss was measured by microtomographic analysis and histologically by histometry on the hemimaxillae. The protein composition of the periodontal ligament was evaluated by proteomic analysis. RESULTS: Data analysis (body weight, adipose tissue weight, and blood test) confirmed obesity induction, whereas bone loss was confirmed by micro-CT and histologic analyses. Proteome analysis from the periodontal ligament tissues (PDL) identified 819 proteins, 53 exclusive to the P group, 28 exclusive to the OP group, and 738 commonly expressed. Validation was performed by immunohistochemistry for selected proteins (spondin1, vinculin, and TRAP). CONCLUSION: Histologically, it was found that obesity did not significantly affect bone loss resulting from periodontitis. However, the present study's findings indicated that obesity affects the proteome of PDL submitted to experimental periodontitis, allowing for identifying potential targets for personalized approaches.


Subject(s)
Alveolar Bone Loss , Periodontitis , Alveolar Bone Loss/pathology , Animals , Obesity/complications , Periodontal Ligament/metabolism , Periodontitis/metabolism , Proteome , Proteomics , Rats , Rats, Wistar
7.
Braz Oral Res ; 35(Supp 2): e101, 2021.
Article in English | MEDLINE | ID: mdl-34586215

ABSTRACT

When periodontal disease is diagnosed, it is difficult to predict the clinical response of treatment of a tooth over time because the result of treatment is affected by several factors and will depend on the maintenance and support of periodontal treatment. Rehabilitation with removable dental prostheses, fixed prostheses, and dental implants makes it possible to restore the function and esthetics of patients with tooth loss due to periodontal disease. The predictive factors of tooth loss in periodontitis patients should be assessed by dentists to inform their clinical decision-making during dental treatment planning. This will provide detailed individualized information and level of risk of patients considered suitable for dental rehabilitation. Therefore, the aim of this article was to review the subject of "Impact of tooth loss due to periodontal disease on the prognosis of rehabilitation" and the effect of fixed, removable, and implant-supported prostheses in periodontal patients.


Subject(s)
Dental Implants , Periodontal Diseases , Tooth Loss , Dental Implants/adverse effects , Dental Prosthesis, Implant-Supported , Humans , Periodontal Diseases/complications , Prognosis , Tooth Loss/etiology
8.
J Tissue Eng Regen Med ; 15(8): 722-731, 2021 08.
Article in English | MEDLINE | ID: mdl-34038031

ABSTRACT

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


Subject(s)
Bone Regeneration , Guided Tissue Regeneration , Histones/pharmacology , Intercellular Signaling Peptides and Proteins/pharmacology , Tissue Scaffolds , Animals , Cells, Cultured , Rats , Scattering, Small Angle , X-Ray Diffraction
9.
Am J Orthod Dentofacial Orthop ; 159(4): 480-490, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33563505

ABSTRACT

INTRODUCTION: Orthodontic movement triggers a sequence of cellular and molecular events that may be affected by different systemic conditions. This study evaluated the effect of obesity on rat periodontal tissue remodeling induced by mechanical orthodontic force. METHODS: Thirty-two Holtzman rats were distributed into 4 groups: control, obesity induction (O), orthodontic movement (M), and obesity induction and orthodontic movement (OM). Obesity was induced by a high-fat diet for 90 days. After 15 days of orthodontic movement, the animals were killed. Obesity induction was confirmed by animal body weight, adipose tissue weight, and serologic analysis. Periodontal tissue remodeling was evaluated using microcomputed tomography and histologic analysis. The gene expression of adipokines and cytokines in gingival tissues was evaluated. RESULTS: An increase in body and adipose tissue weight was observed in the obesity induction groups. The O group presented an increase in lipids and blood glucose. The OM group showed a decrease in bone volume fraction and bone mineral density compared with all other groups and a tendency for more rapid tooth movement than the M group. The OM group showed a higher quantity of inflammatory cells and higher Mmp1 expression than the O group. The O and OM groups showed higher Nampt expression than the control group and lower Nampt expression than the M group. CONCLUSIONS: Obesity modulates periodontal tissue remodeling during orthodontic movement and results in more inflammation and bone loss than in nonobese animals.


Subject(s)
Obesity , Tooth Movement Techniques , Animals , Bone Remodeling , Gingiva , Periodontal Ligament , Rats , Rats, Sprague-Dawley , X-Ray Microtomography
10.
Braz. oral res. (Online) ; 35(supl.2): e101, 2021.
Article in English | LILACS-Express | LILACS, BBO - Dentistry | ID: biblio-1339467

ABSTRACT

Abstract When periodontal disease is diagnosed, it is difficult to predict the clinical response of treatment of a tooth over time because the result of treatment is affected by several factors and will depend on the maintenance and support of periodontal treatment. Rehabilitation with removable dental prostheses, fixed prostheses, and dental implants makes it possible to restore the function and esthetics of patients with tooth loss due to periodontal disease. The predictive factors of tooth loss in periodontitis patients should be assessed by dentists to inform their clinical decision-making during dental treatment planning. This will provide detailed individualized information and level of risk of patients considered suitable for dental rehabilitation. Therefore, the aim of this article was to review the subject of "Impact of tooth loss due to periodontal disease on the prognosis of rehabilitation" and the effect of fixed, removable, and implant-supported prostheses in periodontal patients.

11.
Rev. odontol. UNESP (Online) ; 50: e20210055, 2021. tab
Article in Portuguese | LILACS, BBO - Dentistry | ID: biblio-1357369

ABSTRACT

Introdução Toda má oclusão apresenta origem multifatorial, e dentre os fatores que a desencadeiam estão os hábitos. O surgimento de um hábito pode estar relacionado com o emocional, o fisiológico ou com o aprendizado condicionado do indivíduo. Objetivo Analisar as relações entre hábitos e más oclusões associado a problemas respiratórios em escolares de 5 anos. Material e método Foi realizado um estudo transversal com uma amostra de 753 crianças pertencentes à rede municipal de ensino da cidade de Araraquara, SP. Foram realizados exames clínicos para avaliação da má oclusão (Foster & Hamilton), além de aplicado questionários aos pais para avaliação de condição socioeconômica e demográfica, qualidade de vida relacionada à saúde bucal (ECOHIS) e hábitos. A análise dos dados foi feita pela análise bivariada por teste qui-quadrado seguida de modelo de regressão logística múltipla considerando nível de significância de 5%. Resultado A prevalência de crianças com problemas respiratórios e/ou alergias foi de 46,9%, com má oclusão foi de 58,7% e com algum tipo de hábito oral deletério foi de 12,0%. Apresentaram mais chance de ter problemas respiratórios e/ou alergias crianças do sexo masculino (1,40 vezes mais) e crianças com algum hábito oral deletério (1,95 vezes mais). Conclusão Observou-se que apresentaram maior chance de problemas respiratórios e/ou alergias as crianças do sexo masculino, crianças com algum hábito oral deletério e que apresentavam bruxismo.


Introduction All malocclusion has a multifactorial origin, and among the factors that trigger it are the habits. The appearance of a habit can be related to the emotional, physiological or conditioned learning of the individual. Objective Evaluate the relationship between habits and malocclusions associated with respiratory problems in 5-year-old students. Material and method A cross-sectional study were carried out with a sample of 753 children belonging to the municipal education network of the city of Araraquara-SP. Clinical exams were performed for malocclusion evaluation (Foster & Hamilton), applying questionnaires to the parents for evaluation of socioeconomic and demographic condition, oral health related quality of life (ECOHIS) and habits. Data analysis was performed by bivariate analysis using chi-square test followed by multiple logistic regression model considering 5% significance level. Result The prevalence of children with respiratory problems and/or allergies was 46.9%, with malocclusion was 58.7% and with some type of deleterious oral habit was 12.0%. Male children were 1.40 times more likely to present respiratory problems or allergies and children with some deleterious oral habits were 1.95 times more likely to present respiratory problems or allergies. Conclusion It was observed that male children, children that presented deleterious oral habits, and children with bruxism are more likely to have respiratory problems and/or allergies.


Subject(s)
Child, Preschool , Bruxism , Child, Preschool , Oral Health , Dental Arch/abnormalities , Data Analysis , Habits , Hypersensitivity , Malocclusion
12.
Case Rep Dent ; 2020: 7234310, 2020.
Article in English | MEDLINE | ID: mdl-32181022

ABSTRACT

This case report is aimed at describing a flapless, minimally invasive clinical crown lengthening with an osteotomy performed using a piezoelectric ultrasound. A female patient complained about the amount of gum that was exposed when she smiled, which caused aesthetic discomfort. After a clinical examination, it was confirmed that the patient had excessive gum exposure in the upper arch of the dental region for teeth 14 to 24 when she smiled. The tomographic exam showed that bone tissue was at the level of the enamel-cementum junction, and gingival tissue covered a part of the anatomic crown. Virtual analysis using digital smile design (DSD) demonstrated that enlarging the clinical crowns would provide better aesthetics. The excess gingival tissue was removed from the gingival margin region with the aid of a mockup without interference to the interdental papillae. Then, osteotomy was performed using piezoelectric ultrasound until there was a 2.5 mm distance from the top of the bone crest to the new gingival margin. In the postoperative period, good repositioning of the gingival margin, absence of postoperative complications, and rapid healing of the gingival tissue were verified. After 6 months, a good aesthetic outcome was observed with stability in the level of the periodontal tissues obtained via the crown-lengthening technique. It can be concluded that the minimally invasive clinical crown-lengthening technique was effective in repositioning the gingival margin with no postoperative complications.

13.
Rev. odontol. UNESP (Online) ; 48: e20190108, 2019. graf, ilus
Article in Portuguese | LILACS, BBO - Dentistry | ID: biblio-1099188

ABSTRACT

Resumo Introdução A quantidade e qualidade óssea na implantodontia é um fator de alta relevância quando se tem por objetivo instalar implantes e reabilitar pacientes. No entanto, essa disponibilidade é comprometida na maioria dos casos, havendo a necessidade da busca de novos biomateriais, membranas e substâncias para uma regeneração mais favorável. Objetivo: O objetivo deste estudo foi avaliar a resposta da neoformação óssea em defeitos críticos em calvárias de ratos utilizando scaffolds de fibras de blenda polimérica a partir de poli (ácido láctico-co-glicólico) e poli-isopreno (Cellprene®). O projeto foi aprovado pelo Comitê de Ética em Experimentação Animal. Material e método Neste estudo, foram utilizados 36 ratos (Rattus Norvegicus), variação albinus, Holtzman, adultos. Os animais foram submetidos à tricotomia na região da calota craniana e à confecção de defeitos ósseos circulares bilaterais com 5 mm de diâmetro. Os animais foram divididos em três grupos: GC - defeito sem colocação de biomaterial; GCol - scaffolds de colágeno (Bio-Gide, da empresa Geistlich Pharma Ag - Biomaterials); GPoli - scaffolds de fibras de blenda polimérica a partir de poli (ácido láctico-co-glicólico - Cellprene®). Cada grupo foi avaliado em quatro períodos experimentais (7, 15, 30 e 60 dias). Após esses períodos, os animais foram sacrificados, e as peças passaram por tramitação laboratorial de rotina e inclusão em parafina. Foram obtidos cortes semisseriados e corados pela técnica de hematoxilina e eosina para análise histométrica e histológica. Foi executada análise histométrica para avaliar a composição do tecido ósseo reparado (% osso). Os dados obtidos foram analisados estatisticamente com nível de significância de 95%. Resultado Foi verificado que o GCol apresentou maior preenchimento do defeito nos períodos de 30 e 60 dias em comparação aos GC e GPoli. Conclusão Os scaffolds de fibras de blenda polimérica a partir de poli (ácido láctico-co-glicólico) e poli-isopreno (Cellprene®) não apresentaram vantagens quando utilizados em defeitos críticos.


Abstract Introduction The bone quantity and quality in implant dentistry is a highly relevant factor when it aims the use of implants and rehabilitation in patients. However, this availability is compromised in most cases, with the need to research new biomaterials, membranes and substances for more favorable regeneration. Objective: The aim of this study was to evaluate the response of bone neoformation in critical defects in rat calvaries using polymeric blend fiber scaffolds from Poly (Lactic-Co-Glycolic Acid) and Polyisoprene (Cellprene®). The project was approved by the Animal Experimentation Ethics Committee. Material and method In this study 36 rats (Rattus Norvegicus), variation albinus, Holtzman, adults were used. The animals had trichotomy in the region of the skull and the confection of bilateral circular bone defects with a diameter of 5 mm. The animals were divided into 3 groups: Group GC - defect without biomaterial placement, Group GCol - collagen scaffolds (Bio-Gide, from Geistlich Pharma Ag - Biomaterials), Group GPoli - polymeric blend fiber scaffolds from Poly (Lactic-Co-Glycolic Acid)-Polyisoprene. Each group was evaluated in 4 experimental periods (7, 15, 30 and 60 days). After these periods the animals were sacrificed and the pieces underwent routine laboratory procedures and paraffin embedding. Semi-serial sections were obtained and stained by hematoxylin and eosin technique for histometric and histological analysis. Histometric analysis was performed to evaluate the composition of repaired bone tissue (% Bone). The data obtained were statistically analyzed with a significance level of 95%. Result It was found that the GCol group presented greater defect filling in the 30 and 60 days periods compared to the GC and GPoli groups. Conclusion Polymer blend fiber scaffolds from Poly (Lactic-Co-Glycolic Acid) and Polyisoprene (Cellprene®) did not have advantages when used in critical defects.


Subject(s)
Animals , Rats , Bone Regeneration , Bone Substitutes , Polylactic Acid-Polyglycolic Acid Copolymer/therapeutic use , Polyprenols/therapeutic use
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