Desenvolvimento, caracterização e desempenho biológico de um novo biomaterial de liberação controlada à base de carbonato de lítio aplicado ao reparo ósseo / Development, characterization and biological performance of a new biomaterial of controlled release based on lithium carbonate applied to bone repair

Neste trabalho desenhou-se bases de desenvolvimento, caracterização e avaliação dos aspectos biológicos relacionados ao Sistema BoneLithium, idealizado a partir da associação de partículas de carbonato de lítio dispersas em matriz gel de carbopol®, com capacidade de atuar como um sistema liberador de fármacos. Metodologicamente este estudo se dividiu em quatro partes: Na primeira delas, o objetivo central foi o desenvolvimento e a caracterização do biomaterial através da manipulação farmacológica. Na segunda etapa, avaliou-se a reação tecidual em subcutâneo de ratos, na terceira a influência das partículas de lítio liberadas pelo Sistema BoneLithium no reparo ósseo através de modelos experimentais utilizando coelhos, e por ultimo, a capacidade de cicatrização de defeitos ósseos criados cirurgicamente em calvária de ratos, tratados com o biomaterial e diferentes opções de enxertos ósseos com o objetivo de comparar a eficiência do Sistema BoneLithium aos protocolos pré-existentes. Experimentalmente, avaliou-se a reação tecidual onde se utilizou 15 ratos machos divididos aleatatoriamente em 5 grupos onde implantouse no subcutâneo tubos de butterfly contendo o biomaterial por períodos de preservação recomendados pela norma ADA 10993 para teste de reação tecidual. Os resultados demonstram que o Sistema BoneLithium apresenta reação tecidual normal. Para a avaliação do comportamento biológico do Sistema BoneLithium foram utilizados coelhos brancos adultos da raça New Zealand nos quais defeitos ósseos bilaterais de 1 cm de diâmetro foram confeccionados cirurgicamente na calvária e foram Tratados com o Sistema Bone Lithium do (lado Direito) e somente o Gel de Carbopol (lado esquerdo)/Coágulo sanguíneo (controle). A Histomorfometria demonstrou comportamento favorável ao reparo ósseo e adicionalmente através de Microtomografia Computadorizada (CT SKYSCAN), foi possível constatar diferenças significativas considerando p> 0.05 (ANOVA, Tukey) para o processo de reparo ósseo. A avaliação da performance do Sistema BoneLithium utilizando ratos Wistar nos quais foram criados defeitos críticos no centro da calvária e tratados com diferentes modalidades de enxertos ósseos (controle, autógeno, osso de banco (Unioss®, Marília Brasil), Bio-Oss® e associações com o Sistema BoneLithium. A histomorfometria mostrou diferenças significativas considerando p> 0.05 (ANOVA, Tukey) para avaliação de tecido conjuntivo pré-osteogênico e tecido ósseo neoformado, e quando avaliado qualitativamente por tomografia computadorizada de feixe cônico (I cat Cone Beam FOV 0.05 Xoran Tecnology, LLC, EUA e E-vol, CDT, Brasil), observaram-se áreas de neoformação óssea compatíveis com hiperdensidade óssea em toda a extensão do defeito quando apuradas em analises de paridade em escala Hounsfield. Dessa forma, conclui-se que no contexto deste estudo é possível concluir que Sistema BoneLithium representa uma alternativa com potencial viabilidade clínica e necessita seguimento de aplicação em novas metodologias.(AU)

In this work, bases for the development, characterization and evaluation of the biological aspects related to the BoneLithium System were designed, based on the association of lithium carbonate particles dispersed in carbopol® gel matrix, capable of acting as a drug-releasing system. Methodologically this study was divided in four parts: In the first one, the central objective was the development and characterization of the biomaterial through the pharmacological manipulation. In the second step, the tissue reaction was evaluated in subcutaneous of rats, in the third the influence of the lithium particles released by BoneLithium System in the bone repair through experimental models using rabbits, and finally, the capacity of healing of bone defects created surgically in Calvaria of rats, treated with the biomaterial and different options of bone grafts with the objective to compare the efficiency of the BoneLithium System to the preexisting protocols. Experimentally, the tissue reaction was evaluated in which 15 male rats were randomly divided into 5 groups, where butterfly tubes containing the biomaterial were implanted in the subcutaneous tubes for preservation periods recommended by the ADA 10993 standard for biocompatibility test. The results demonstrate that the BoneLithium System is tissue reaction positive. To evaluate the biological behavior of the BoneLithium System, adult New Zealand white rabbits were used in which bilateral bone defects of 1 cm in diameter were surgically made on calvaria and treated with the Bone Lithium System (right side) and only Gel Of Carbopol (left side) / blood clot (control). Histomorphometry showed a favorable behavior to bone repair and, in addition, through Computerized Microtomography (CT SKYSCAN), it was possible to verify significant differences considering p> 0.05 (ANOVA, Tukey) for the bone repair process. The evaluation of the performance of the BoneLithium System using Wistar rats in which critical defects were created at the calvarial center and treated with different bone graft modalities (control, autogenous, bone bank (Unioss®, Marília Brazil), Bio-Oss® and associations (ANOVA, Tukey) for evaluation of pre osteogenic connective tissue and neoformed bone tissue, and when assessed qualitatively by cone beam computed tomography (I cat - Cone Beam - FOV 0.05 - Xoran Tecnology, LLC, USA and E-vol, CDT, Brazil), areas of bone neoformation compatible with bone hyperdensity throughout the extent of the defect were ascertained in Hounsfield scale parity analyzes, It is concluded that in the context of this study it is possible to conclude that the BoneLithium System represents an alternative with potential clinical feasibility And requires follow-up of application in new methodologies.(AU)

Evaluation and Comparison of the Transverse Strength of Two Heat Cure Denture Base Resins Repaired with Auto Polymerizing Resin by Wetting with Methyl Methacrylate (MMA) at Different Time Intervals - An In vitro Study.

Aims: Fracture of dentures is a common clinical finding in daily prosthodontic practice, resulting in great inconvenience to both the patient and the dentist. A satisfactory repair should be costeffective, simple to perform, and quick. This study evaluated and compared the transverse strength of two heat cure denture base resins repaired with auto polymerizing resin by wetting with methyl methacrylate (MMA) at different time intervals. Materials and Methods: Stellon and Trevalon denture base materials were used in the study. A total of 200 heat cure acrylic resin specimens (100 specimens each of Stellon and Trevalon acrylic material) with the dimensions of (65 mm x 10 mm x 3 mm) were prepared. The specimens were divided with 10 specimens for each of the test groups (n =10). The test groups were designated as Group A through J. Repair gap of 2 mm was prepared in the centre of the specimen. The repair surface of the specimens were wetted with MMA at different time intervals (1, 2, 3, 4, 5, 10, 15 and 30 minutes) and repaired by using auto polymerizing resin. The transverse strength of the repaired specimens was tested by a 3 point bending test. All data was statistically analyzed with one-way ANOVA, differences within the groups were analyzed by independent sample t -test. Results: The results showed that the significant difference between the specimens wetted with MMA at different time intervals. A gradual increase was shown in the mean transverse strength of repaired specimens wetted from 1 minute to 5 minutes in Stellon and from 1 minute to 10 minutes in Trevalon. Conclusion: Wetting the repair surfaces with MMA for a period of more than 5 minutes and 10 minutes in case of Stellon and Trevalon respectively increases the incidence of adhesive failure in the repaired specimens.

Linear Focal Elastosis Following Striae Distensae: Further Evidence of Keloidal Repair Process in the Pathogenesis of Linear Focal Elastosis

Linear focal elastosis (LFE) is a rare dermal elastosis characterized by hypertrophic yellowish linear plaques and increased abnormal elastic tissues in the lumbosacral area. Although the pathogenesis of this disorder remains unknown, it may be associated with keloidal repair process (KRP) of elastic tissues in striae distensae (SD), because there have been some reported cases of LFE accompanied by SD. We herein report a 14-year-old boy with LFE following SD in the lumbar region. Our case supports the hypothesis of KRP in the pathogenesis of LFE. Immunohistochemical study for transforming growth factor-beta (TGF-beta) was negative. Therefore, we assume that the pathogenesis of KRP in LFE is different from that of keloid development, which is the TGF-beta signaling pathway.

In Vitro Effects of Ascorbic Acid on the Repair Process of the Fetal Rat Femur Damaged by Cyclophosphamide / 대한정형외과학회잡지

After bone damage of the fetal rat femurs induced by administrating cyclophosphamide(CP),(1/8 LD50) to the pregnant rat on 13th day of gestation, the effects of serum and ascorbic acid on the repair process of the bone during organ culture were studied, histologically and scanning electron microscopically. CP-damaged fetal femurs harvested at 20 days of gestation were cultured fro 2, 5 and 7 days in the waymouth media(WM) with or without fetal bovine serum(FBS) and ascorbic acid, and were observed with light microscope and JSM-35C scanning electron microscope. The results were as follows:1. CP-damaged bone tissue cultured in WM with 10% FBS showed relatively enhanced activities in the differentiation of chondrocytes and ossificstion as compared to that cultured in WM. 2. CP-damaged bone tissue cultured in WM with 10% FBS and 100µg/ml ascorbic acid, showed increase in the length of the bone marrow cavity, and active formation of new osteoid and collagen bundles. 3. The bone tissues cultured in WM with 10% FBS and 400µg/ml ascorbic acid revealed active deposition of bone matrix, thickening of periosteum and marked elongation of the bone marrow cavity. 4. Bone trabeculae of CP-damaged femurs cultured for 2 days in WM showed poor cell proliferation and insignificant bone matix formation. 5. The number of new cells and the amount of the collagen fibrils increased on the bone trabeculae of the bone cultured in WM with 10% FBS as compared to that cultured in WM and this increase was enhanced as the culture time progressed. 6. A remarkable increase was noted in the number of cells and collagen fibrils in the bone tissues cultured in WM with 10% FBS and ascorbic acid than in those cultured in WM with 10% FBS. 7. The number of the spherules formed by cellular component with collagen fibrils is more numerous than that formed by calcospherites associated with collagen fibrils.