A scoping review of graphene-based biomaterials for in vivo bone tissue engineering.

The growing demand for more efficient materials for medical applications brought together two previously distinct fields: medicine and engineering. Regenerative medicine has evolved with the engineering contributions to improve materials and devices for medical use. In this regard, graphene is one of the most promising materials for bone tissue engineering and its potential for bone repair has been studied by several research groups. The aim of this study is to conduct a scoping review including articles published in the last 12 years (from 2010 to 2022) that have used graphene and its derivatives (graphene oxide and reduced graphene) in preclinical studies for bone tissue regeneration, searching in PubMed/MEDLINE, Embase, Web of Science, Cochrane Central, and clinicaltrials.gov (to confirm no study has started with clinical trial). Boolean searches were performed using the defined key words "bone" and "graphene", and manuscript abstracts were uploaded to Rayyan, a web-tool for systematic and scoping reviews. This scoping review was conducted based on Joanna Briggs Institute Manual for Scoping Reviews and the report follows the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses - Extension for Scoping Reviews (PRISMA-ScR) statement. After the search protocol and application of the inclusion criteria, 77 studies were selected and evaluated by five blinded researchers. Most of the selected studies used composite materials associated with graphene and its derivatives to natural and synthetic polymers, bioglass, and others. Although a variety of graphene materials were analyzed in these studies, they all concluded that graphene, its derivatives, and its composites improve bone repair processes by increasing osteoconductivity, osteoinductivity, new bone formation, and angiogenesis. Thus, this systematic review opens up new opportunities for the development of novel strategies for bone tissue engineering with graphene.

IRF6 is a risk factor for nonsyndromic cleft lip in the Brazilian population.

Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is a complex disorder with a worldwide incidence estimated at 1:700. Among the putative susceptibility loci, the IRF6 gene and a region at 8q24.21 have been corroborated in different populations. To test the role of IRF6 in NSCL/P predisposition in the Brazilian population, we conducted a structured association study with the SNPs rs642961 and rs590223, respectively, located at 5' and 3' of the IRF6 gene and not in strong linkage disequilibrium (LD), in patients from five different Brazilian locations. We also evaluated the effect of these SNPs in IRF6 expression in mesenchymal stem cells (MSC). We observed association between rs642961 and cleft lip only (CLO) (P=0.009; odds ratio (OR) for AA genotype=1.83 [95% Confidence interval (CI), 0.64-5.31]; OR for AG genotype=1.72 [95% CI, 1.03-2.84]). This association seems to be driven by the affected patients from Barbalha, a location which presents the highest heritability estimate (H2=0.85), and the A allele at rs642961 is acting through a dominant model. No association was detected for the SNP rs590223. We did not find any correlation between expression levels and genotypes of the two loci, and it is possible that these SNPs have a functional role in some specific period of embryogenesis.

Tissue Engineering and Cell Therapy for Cartilage Repair: Preclinical Evaluation Methods.

A chondral injury is a limiting disease that can affect the quality of life and be an economic burden due to the cost of immediate treatment and loss in work productivity. If left untreated, such an injury may progress to osteoarthritis, a degenerative and debilitating joint disease characterized by pain and functional impairment. Mesenchymal stromal cells (MSCs), which have immune-modulatory properties and the ability to differentiate into chondroblasts and osteoblasts, are a predictable source for the treatment of cartilage injuries. This article presents tools to evaluate cartilage restoration by tissue engineering and cell therapy treatment in a translational and preclinical large animal model. In this controlled experimental study with 14 miniature pigs, a scaffold-free tissue engineering construct (TEC) derived from dental pulp and synovial MSCs for cartilage therapy was tested. Total thickness cartilage defects were performed in both posterior knees. The defect was left empty in one of the knees, and the other received the TEC. The tissue repair was morphologically assessed by magnetic resonance imaging (MRI) using the three-dimensional double echo steady-state (3D-DESS) sequence, and compositional assessment was carried out based on the T2 mapping technique. The osteochondral specimens were fixed for histopathology, decalcified, subjected to standard histological processing, sectioned, and stained with hematoxylin and eosin. The sections stained for immunohistochemical detection of collagen types were digested with pepsin and chondroitinase and incubated with antibodies against them. The mechanical evaluation involved analysis of Young's modulus of the cartilage samples based on the indentation and maximum compression test. In addition, a finite element model was used to simulate and characterize properties of the osteochondral block. At 6 months after surgery, there were no complications with the animals and the MRI, histological, immunohistochemical, and biomechanical evaluations proved to be effective and qualified to differentiate good quality chondral repair from inadequate repair tissue. The proposed methods were feasible and capable to properly evaluate the defect filled with TEC containing stromal cells after 6 months of follow-up in a large animal model for articular cartilage restoration. Impact Statement Articular chondral injuries are prevalent and represent an economic burden due to the cost of treatment. The engineering of cartilage tissue can promote the repair of chondral injuries and is dependent on selecting appropriate cells and biocompatible frameworks. In this article, methods for evaluation of a scaffold-free cell delivery system made from mesenchymal stromal cells were present in a translational study that allows further clinical safety and efficacy trials.

Genetic contribution for non-syndromic cleft lip with or without cleft palate (NS CL/P) in different regions of Brazil and implications for association studies.

Non-syndromic cleft lip with or without cleft palate (NS CL/P) is a complex disease in which heritability estimates vary widely depending on the population studied. To evaluate the importance of genetic contribution to NS CL/P in the Brazilian population, we conducted a study with 1,042 families from five different locations (Santarém, Fortaleza, Barbalha, Maceió, and Rio de Janeiro). We also evaluated the role of consanguinity and ethnic background. The proportion of familial cases varied significantly across locations, with the highest values found in Santarém (44%) and the lowest in Maceió (23%). Heritability estimates showed a higher genetic contribution to NS CL/P in Barbalha (85%), followed by Santarém (71%), Rio de Janeiro (70%), Fortaleza (64%), and Maceió (45%). Ancestry was not correlated with the occurrence of NS CL/P or with the variability in heritability. Only in Rio de Janeiro was the coefficient of inbreeding significantly larger in NS CL/P families than in the local population. Recurrence risk for the total sample was approximately 1.5-1.6%, varying according to the location studied (0.6-0.7% in Maceió to 2.2-2.8% in Barbalha). Our findings show that the degree of genetic contribution to NS CL/P varies according to the geographic region studied, and this difference cannot be attributed to consanguinity or ancestry. These findings suggest that Barbalha is a promising region for genetic studies. The data presented here will be useful in interpreting results from molecular analyses and show that care must be taken when pooling samples from different populations for association studies.

Case Report: A Severe SARS-CoV-2 Infection in a Teenager With Angelman Syndrome.

Teenagers generally present mild to no symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In the present report, we present the case of a 14-year-old boy with Angelman syndrome (AS) who presented with severe COVID-19 symptoms. He spent 20 days in the ICU with elevated inflammatory biomarkers (C-reactive protein and D-dimer) and increased peaks of neutrophil-to-lymphocyte ratio, which is uncommon for teenagers diagnosed with COVID-19. Although he showed physiological instability, he was able to produce neutralizing antibodies, suggesting a functional immune response. The literature concerning the immune response to infections in patients with AS is still poor, and to our knowledge, this was the first report of a patient with AS diagnosed with COVID-19. As such, the present study may alert other patients with AS or other rare diseases that they lack a competent immune response and could suffer severe consequences of SARS-CoV-2 infection.

Human fallopian tube: a new source of multipotent adult mesenchymal stem cells discarded in surgical procedures.

BACKGROUND: The possibility of using stem cells for regenerative medicine has opened a new field of investigation. The search for sources to obtain multipotent stem cells from discarded tissues or through non-invasive procedures is of great interest. It has been shown that mesenchymal stem cells (MSCs) obtained from umbilical cords, dental pulp and adipose tissue, which are all biological discards, are able to differentiate into muscle, fat, bone and cartilage cell lineages. The aim of this study was to isolate, expand, characterize and assess the differentiation potential of MSCs from human fallopian tubes (hFTs). METHODS: Lineages of hFTs were expanded, had their karyotype analyzed, were characterized by flow cytometry and underwent in vitro adipogenic, chondrogenic, osteogenic, and myogenic differentiation. RESULTS: Here we show for the first time that hFTs, which are discarded after some gynecological procedures, are a rich additional source of MSCs, which we designated as human tube MSCs (htMSCs). CONCLUSION: Human tube MSCs can be easily isolated, expanded in vitro, present a mesenchymal profile and are able to differentiate into muscle, fat, cartilage and bone in vitro.

Is There a Noninvasive Source of MSCs Isolated with GMP Methods with Better Osteogenic Potential?

BACKGROUND: A new trend in the treatment for alveolar clefts in patients with cleft lip and palate involves the use of bone tissue engineering strategies to reduce or eliminate the morbidity associated with autologous bone grafting. The use of mesenchymal stem cells-autologous cells obtained from tissues such as bone marrow and fat-combined with various biomaterials has been proposed as a viable option for use in cleft patients. However, invasive procedures are necessary to obtain the mesenchymal stem cells from these two sources. To eliminate donor site morbidity, noninvasive stem cell sources such as the umbilical cord, orbicularis oris muscle, and deciduous dental pulp have been studied for use in alveolar cleft bone tissue engineering. In this study, we evaluate the osteogenic potential of these various stem cell types. METHODS: Ten cellular strains obtained from each different source (umbilical cord, orbicularis oris muscle, or deciduous dental pulp) were induced to osteogenic differentiation in vitro, and the bone matrix deposition of each primary culture was quantified. To evaluate whether greater osteogenic potential of the established mesenchymal stem cell strains was associated with an increase in the expression profile of neural crest genes, real-time qPCR was performed on the following genes: SRY-box 9, SRY-box 10, nerve growth factor receptor, transcription factor AP-2 alpha, and paired box 3. RESULTS: The mesenchymal stem cells obtained from deciduous dental pulp and orbicularis oris muscle demonstrated increased osteogenic potential with significantly more extracellular bone matrix deposition when compared to primary cultures obtained from the umbilical cord after twenty-one days in culture (p = 0.007 and p = 0.005, respectively). The paired box 3 gene was more highly expressed in the MSCs obtained from deciduous dental pulp and orbicularis oris muscle than in those obtained from the umbilical cord. CONCLUSION: These results suggest that deciduous dental pulp and orbicularis oris muscle stem cells demonstrate superior osteogenic differentiation potential relative to umbilical cord-derived stem cells and that this increased potential is related to their neural crest origins. Based on these observations, and the distinct translational advantage of incorporating stem cells from noninvasive tissue sources into tissue engineering protocols, greater study of these specific cell lines in the setting of alveolar cleft repair is indicated.

Stem cell proliferation under low intensity laser irradiation: a preliminary study.

BACKGROUND AND OBJECTIVES: Phototherapy with low intensity laser irradiation has shown to be effective in promoting the proliferation of different cells. The aim of this in vitro study was to evaluate the potential effect of laser phototherapy (660 nm) on human dental pulp stem cell (hDPSC) proliferation. STUDY DESIGN/MATERIALS AND METHODS: The hDPSC cell strain was used. Cells cultured under nutritional deficit (10% FBS) were either irradiated or not (control) using two different power settings (20 mW/6 seconds to 40 mW/3 seconds), with an InGaAIP diode laser. The cell growth was indirectly assessed by measuring the cell mitochondrial activity through the MTT reduction-based cytotoxicity assay. RESULTS: The group irradiated with the 20 mW setting presented significantly higher MTT activity at 72 hours than the other two groups (negative control--10% FBS--and lased 40 mW with 3 seconds exposure time). After 24 hours of the first irradiation, cultures grown under nutritional deficit (10% FBS) and irradiated presented significantly higher viable cells than the non-irradiated cultures grown under the same nutritional conditions. CONCLUSIONS: Under the conditions of this study it was possible to conclude that the cell strain hDPSC responds positively to laser phototherapy by improving the cell growth when cultured under nutritional deficit conditions. Thus, the association of laser phototherapy and hDPSC cells could be of importance for future tissue engineering and regenerative medicine. Moreover, it opens the possibility of using laser phototherapy for improving the cell growth of other types of stem cells.

Low Power Laser Therapy: A Strategy to Promote the Osteogenic Differentiation of Deciduous Dental Pulp Stem Cells from Cleft Lip and Palate Patients.

Dental pulp stem cells (DPSCs) can undergo several types of differentiation, including osteogenic differentiation. One osteogenesis-inducing factor that has been previously described is in vitro low-power laser irradiation of cells. Laser irradiation promotes the acceleration of bone matrix mineralization of the cell strain. However, no consensus exists regarding the dose and treatment time. We used DPSC strains from cleft lip and palate patients because new bone tissue engineering strategies have used DPSCs in preclinical and clinical trials for the rehabilitation of alveolar bone clefts. Optimizing bone tissue engineering techniques for cleft and lip palate patients by applying low-power laser therapy (LPLT) to DPSCs obtained from these patients can help improve current strategies to quickly close large alveolar clefts. The aim of this study was to investigate the effects of LPLT at different energy densities in DPSC strains obtained from cleft lip and palate patients during in vitro osteogenic differentiation. Ten DPSC strains were obtained from cleft lip and palate patients and then used in the following study groups: group 1: control, the strains underwent osteogenic differentiation for 21 days; and groups 2, 3, and 4: the strains were irradiated each day with a low-power red laser (660 nm) (5, 10, and 20 J) during 21 days of osteogenic differentiation. Using Bonferroni's test, a statistically significant difference in the mean values was found between the irradiated groups (2, 3, and 4) and the control group (p < 0.001). However, no significant difference in osteogenic potential was found among the irradiated groups. Our findings showed that the osteogenic potential of DPSCs increases with red laser irradiation at 5, 10, and 20 J, and this treatment could be considered a new approach for preconditioning these cells to be used in bone tissue engineering.

Idiopathic hypertrophic osteopathy in a cat.

This report describes the first case of idiopathic hypertrophic osteopathy (HO) in a cat. No causes for the bone pathology were found following evaluation of the physical and laboratory examinations (complete blood count, albumin, creatinine, urea, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase and gamma-glutamyltransferase and urinalysis), and after histopathological evaluation of organs at necropsy. Based on the radiographic, clinical and anatomopathological findings, idiopathic HO was diagnosed.

Fat grafts supplemented with adipose-derived stromal cells in the rehabilitation of patients with craniofacial microsomia.

BACKGROUND: Although first reports of the clinical use of adipose-derived stromal cells suggest that this approach may be feasible and effective for soft-tissue augmentation, there is a lack of randomized, controlled clinical trials in the literature. Thus, this study aimed to investigate whether a faster protocol for isolation of adipose-derived stromal cells and their use in combination with fat tissue improve the long-term retention of the grafts in patients with craniofacial microsomia. METHODS: Patients with craniofacial microsomia (n = 14) were grafted either with supplementation of adipose-derived stromal cells (experimental group) or without supplementation of adipose-derived stromal cells (control group). The number of viable cells isolated before and after the supplementation of the grafts was calculated, and these cells were examined for mesenchymal cell surface markers using flow cytometry. Computed tomography was performed to assess both hemifaces preoperatively and at 6 months postoperatively. RESULTS: The average number of viable cells isolated before and after the supplementation of the grafts was 5.6 × 10 and 9.9 × 10 cells/ml of fat tissue (p = 0.015). Flow cytometric analysis revealed that the adipose-derived stromal cells were positive for mesenchymal cell markers (>95 percent for CD73 and CD105). Surviving fat volume at 6 months was 88 percent for the experimental group and 54 percent for the control group (p = 0.003). CONCLUSION: These results suggest that this strategy for isolation and supplementation of adipose-derived stromal cells is effective, safe, and superior to conventional lipoinjection for facial recontouring in patients with craniofacial microsomia. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Human fallopian tube mesenchymal stromal cells enhance bone regeneration in a xenotransplanted model.

We have recently reported that human fallopian tubes, which are discarded during surgical procedures of women submitted to sterilization or hysterectomies, are a rich source of human fallopian tube mesenchymal stromal cells (htMSCs). It has been previously shown that human mesenchymal stromal cells may be useful in enhancing the speed of bone regeneration. This prompted us to investigate whether htMSCs might be useful for the treatment of osteoporosis or other bone diseases, since they present a pronounced capacity for osteogenic differentiation in vitro. Based on this prior knowledge, our aim was to evaluate, in vivo, the osteogenic capacity of htMSCs to regenerate bone through an already described xenotransplantation model: nonimmunosuppressed (NIS) rats with cranial defects. htMSCs were obtained from five 30-50 years old healthy women and characterized by flow cytometry and for their multipotenciality in vitro capacity (osteogenic, chondrogenic and adipogenic differentiations). Two symmetric full-thickness cranial defects on each parietal region of seven NIS rats were performed. The left side (LS) of six animals was covered with CellCeram (Scaffdex)-a bioabsorbable ceramic composite scaffold that contains 60% hydroxyapatite and 40% ß-tricalciumphosphate-only, and the right side (RS) with the CellCeram and htMSCs (10(6) cells/scaffold). The animals were euthanized at 30, 60 and 90 days postoperatively and cranial tissue samples were taken for histological analysis. After 90 days we observed neobone formation in both sides. However, in animals euthanized 30 and 60 days after the procedure, a mature bone was observed only on the side with htMSCs. PCR and immunofluorescence analysis confirmed the presence of human DNA and thus that human cells were not rejected, which further supports the imunomodulatory property of htMSCs. In conclusion, htMSCs can be used successfully to enhance bone regeneration in vivo, opening a new field for future treatments of osteoporosis and bone reconstruction.

Mesenchymal stem cells derived from canine umbilical cord vein--a novel source for cell therapy studies.

The canine model provides a large animal system to evaluate many treatment modalities using stem cells (SCs). However, only bone marrow (BM) protocols have been widely used in dogs for preclinical approaches. BM donation consists of an invasive procedure and the number and differentiation potential of its mesenchymal stem cells (MSCs) decline with age. More recently, umbilical cord was introduced as an alternative source to BM since it is obtained from a sample that is routinely discarded. Here, we describe the isolation of MSCs from canine umbilical cord vein (cUCV). These cells can be obtained from every cord received and grow successfully in culture. Their multipotent plasticity was demonstrated by their capacity to differentiate in adipocytic, chondrocytic, and osteocytic lineages. Furthermore, our results open possibilities to use cUCV cells in preclinical trials for many well-characterized canine model conditions homologs to human diseases.

Alveolar osseous defect in rat for cell therapy: preliminary report.

PURPOSE: To study were to reproduce an alveolar bone defect model in Wistar rats to be used for testing the efficacy of stem cell therapies. Additionally, we also aimed to determine the osteogenesis process of this osseous defect in the 1 month period post-surgery. METHODS: The animals were randomly divided into two groups of 7 animals each. A gingivobuccal incision was made, and a bone defect of 28 mm(2) of area was performed in the alveolar region. Animals were killed at 2 weeks after surgery (n=7) and 4 weeks after surgery (n=7). RESULTS: The average area of the alveolar defect at time point of 2 weeks was 22.27 +/- 1.31 mm(2) and the average area of alveolar defect at time point of 4 weeks was 9.03 +/- 1.17 mm(2). The average amount of bone formation at time point of 2 weeks was 5.73 +/- 1.31 mm(2) and the average amount of bone formation at time point of 4 weeks was 19 +/- 1.17 mm(2). Statistically significant differences between the amount of bone formation at 2 weeks and 4 weeks after surgery were seen (p=0.003). CONCLUSION: The highest rate of ossification occurred mostly from 2 to 4 weeks after surgery. This observation suggests that 4 weeks after the bone defect creation should be a satisfactory timing to assess the potential of bone inductive stem cells to accelerate bone regeneration in Wistar rats.

Reconstruction of large cranial defects in nonimmunosuppressed experimental design with human dental pulp stem cells.

The main aim of this study is to evaluate the capacity of human dental pulp stem cells (hDPSC), isolated from deciduous teeth, to reconstruct large-sized cranial bone defects in nonimmunosuppressed (NIS) rats. To our knowledge, these cells were not used before in similar experiments. We performed two symmetric full-thickness cranial defects (5 x 8 mm) on each parietal region of eight NIS rats. In six of them, the left side was supplied with collagen membrane only and the right side (RS) with collagen membrane and hDPSC. In two rats, the RS had collagen membrane only and nothing was added at the left side (controls). Cells were used after in vitro characterization as mesenchymal cells. Animals were euthanized at 7, 20, 30, 60, and 120 days postoperatively and cranial tissue samples were taken from the defects for histologic analysis. Analysis of the presence of human cells in the new bone was confirmed by molecular analysis. The hDPSC lineage was positive for the four mesenchymal cell markers tested and showed osteogenic, adipogenic, and myogenic in vitro differentiation. We observed bone formation 1 month after surgery in both sides, but a more mature bone was present in the RS. Human DNA was polymerase chain reaction-amplified only at the RS, indicating that this new bone had human cells. The use of hDPSC in NIS rats did not cause any graft rejection. Our findings suggest that hDPSC is an additional cell resource for correcting large cranial defects in rats and constitutes a promising model for reconstruction of human large cranial defects in craniofacial surgery.

Apert p.Ser252Trp mutation in FGFR2 alters osteogenic potential and gene expression of cranial periosteal cells.

Apert syndrome (AS), a severe form of craniosynostosis, is caused by dominant gain-of-function mutations in FGFR2. Because the periosteum contribution to AS cranial pathophysiology is unknown, we tested the osteogenic potential of AS periosteal cells (p.Ser252Trp mutation) and observed that these cells are more committed toward the osteoblast lineage. To delineate the gene expression profile involved in this abnormal behavior, we performed a global gene expression analysis of coronal suture periosteal cells from seven AS patients (p.Ser252Trp), and matched controls. We identified 263 genes with significantly altered expression in AS samples (118 upregulated, 145 downregulated; SNR >or= |0.4|, P

RAB23 mutations in Carpenter syndrome imply an unexpected role for hedgehog signaling in cranial-suture development and obesity.

Carpenter syndrome is a pleiotropic disorder with autosomal recessive inheritance, the cardinal features of which include craniosynostosis, polysyndactyly, obesity, and cardiac defects. Using homozygosity mapping, we found linkage to chromosome 6p12.1-q12 and, in 15 independent families, identified five different mutations (four truncating and one missense) in RAB23, which encodes a member of the RAB guanosine triphosphatase (GTPase) family of vesicle transport proteins and acts as a negative regulator of hedgehog (HH) signaling. In 10 patients, the disease was caused by homozygosity for the same nonsense mutation, L145X, that resides on a common haplotype, indicative of a founder effect in patients of northern European descent. Surprisingly, nonsense mutations of Rab23 in open brain mice cause recessive embryonic lethality with neural-tube defects, suggesting a species difference in the requirement for RAB23 during early development. The discovery of RAB23 mutations in patients with Carpenter syndrome implicates HH signaling in cranial-suture biogenesis--an unexpected finding, given that craniosynostosis is not usually associated with mutations of other HH-pathway components--and provides a new molecular target for studies of obesity.

Alveolar osseous defect in rat for cell therapy: preliminary report / Defeito ósseo alveolar em ratos para terapia celular: estudo preliminar

PURPOSE: To study were to reproduce an alveolar bone defect model in Wistar rats to be used for testing the efficacy of stem cell therapies. Additionally, we also aimed to determine the osteogenesis process of this osseous defect in the 1 month period post-surgery. METHODS: The animals were randomly divided into two groups of 7 animals each. A gingivobuccal incision was made, and a bone defect of 28 mm² of area was performed in the alveolar region. Animals were killed at 2 weeks after surgery (n=7) and 4 weeks after surgery (n=7). RESULTS: The average area of the alveolar defect at time point of 2 weeks was 22.27 ± 1.31 mm² and the average area of alveolar defect at time point of 4 weeks was 9.03 ± 1.17 mm². The average amount of bone formation at time point of 2 weeks was 5.73 ± 1.31 mm² and the average amount of bone formation at time point of 4 weeks was 19 ± 1.17 mm². Statistically significant differences between the amount of bone formation at 2 weeks and 4 weeks after surgery were seen (p=0.003). CONCLUSION: The highest rate of ossification occurred mostly from 2 to 4 weeks after surgery. This observation suggests that 4 weeks after the bone defect creation should be a satisfactory timing to assess the potential of bone inductive stem cells to accelerate bone regeneration in Wistar rats.

OBJETIVO: Reproduzir um novo modelo de defeito ósseo alveolar em ratos Wistar que será utilizado para terapia genética e estudos com células tronco. Adicionalmente, outro objetivo do presente estudo foi determinar o pico de regeneração óssea do defeito criado na região alveolar do modelo experimental. MÉTODOS: Os animais foram aleatoriamente divididos em dois grupos de sete animais. Através de uma incisão gengivobucal foi criado um defeito ósseo medindo 28 mm² de área na região alveolar dos ratos. Os ratos foram sacrificados após duas semanas (n=7) e quatro semanas (n=7) da cirurgia. RESULTADOS: A área média do defeito alveolar após duas semanas de cirurgia foi de 22.27 ± 1.31 mm² e a área média do defeito alveolar após quatro semanas de cirurgia foi de 9.03 ± 1.17 mm². A taxa de formação óssea foi de 5.73 ± 1.31 mm² após duas semanas de cirurgia e de 19 ± 1.17 mm² após quatro semanas de cirurgia. Foi observada diferença estatisticamente significante na taxa de formação óssea entre o grupo dos animais sacrificados com duas e quatro semanas (p=0.003). CONCLUSÃO: Este estudo demonstrou que a maior taxa de regeneração óssea ocorreu no período entre duas e quatro semanas após a cirurgia de criação do defeito ósseo alveolar, portanto esta observação sugere que o período de tempo de quatro semanas será suficiente para avaliar a capacidade de células tronco em regenerar osso em ratos Wistar com defeito ósseo alveolar.

A contribuição de fatores genéticos e ambientais para a ocorrência das fissuras lábio-palatinas não-sindrômicas é a mesma em diferentes regiões do país? / Is the contribuition of genetics and environmental factors to the occurence of non syndromic cleft lip with or without cleft palate the same in different regions of the country?

Fissura labial com ou sem fissura de palato (FL/P) não-sindrômica, uma das malformações congênita mais prevalentes, é determinda por um modelo de herança multifuncionale, portanto, fatores genéticos e ambientais contribuem para a ocorrência desta malformação. O presente estudo avaliou se os fatores de predisposição as FL/Ps são semelhantes em três regiões do Brasil (Santarém-PA; Fortaleza e Barbalha-CE), por meio de estimativas das proporções de casos familiais, bem como da taxa de consagüinidade entre os pais de afetados por FL/P. Ainda, avaliamos se a distribuição dos tipos de FL/Ps difere nestas 3 regiões. Um total de 460 casos foi avaliado durante missões da Operação Sorriso realizadas em 2007-2008. Não observamos diferenças bos subtipos de fissuras nas 3 regiões. Contudo, verificamos que a proporção de casos familiares e da taxa de consagüinidade foi significantemente maior entre os pais dos fissurados averiguados em Santarém e Fortaleza do que na população geral. Estes resultados corroboram que a consagüinidade é um fator de risco para a ocorrência das FL/Ps e sugerem que os fatores de predisposição, ambientais ou genéticos para Fl/P são diferentes na população de Santarém A confirmação destes resultados um uma amostra maior poderá fornecer subsídios para o estabelecimento de futuras políticas de prevenção das FL/Ps nas diferentes regiões do Brasil.