Local effect of simvastatin combined with different osteoconductive biomaterials and collagen sponge on new bone formation in critical defects in rat calvaria

Abstract Purpose To evaluate the local effect of simvastatin (SVT) combined with deproteinized bovine bone (DBB) with hydroxyapatite/β-tricalcium phosphate biphasic ceramics (HA/TCP) and with collagen sponge (CS) on bone repair in critical size defects (CSDs) in rat calvaria. Methods Forty-two 5-mm diameter CSDs were made bilaterally in the calvaria of 18 rats. The animals were allocated according to the type of biomaterial and associations used to fill the CSD. After 8 weeks, the animals were euthanized, and their calvaria were evaluated for repaired tissue composition using histologic and histometric analyses. Results In the histometric analysis, the use of SVT showed to increase bone formation in the CSDs when combined with all the bone substitutes tested in this study (p<0.05). Greater bone formation was observed in the groups with SVT compared to the groups without SVT. Conclusions The use of SVT without the need for a vehicle and combined with a commercially available biomaterial may be a cheaper way to potentiate the formation of bone tissue without the need to produce new biomaterials. Therefore, SVT combined with DBB induced significantly greater new bone formation than did the other treatments.

Simvastatin and biphasic calcium phosphate affects bone formation in critical-sized rat calvarial defects

ABSTRACT PURPOSE: To investigate the effects of locally applied simvastatin plus biphasic calcium phosphate (BoneCeramic(r)) or collagen sponge on bone formation in critical-sized bone defects. METHODS: Thirty defects of 5mm in diameter were created bilaterally with a trephine bur in the calvariae of fifteen Wistar rats. The defects were divided into five groups: group 1 - control, no treatment; group 2 (BoneCeramic(r)); group 3 (BoneCeramic(r) + 0.1mg simvastatin); group 4 (collagen sponge); and group 5 (collagen sponge + 0.1mg simvastatin). After eight weeks the animals were euthanized and their calvariae were histologically processed. Hematoxylin and eosin-stained sections were subjected to histological and histomorphometrical analyses. The area of newly formed bone was calculated and compared between groups. RESULTS: The greater amount of a bone-like tissue was formed around the carrier in group 3 (BoneCeramic(r) + 0.1mg simvastatin) followed by group 2 (BoneCeramic(r)), and almost no bone was formed in the other groups. Group 3 was significantly different compared to group 2, and both groups were significantly different compared to the other groups. CONCLUSION: Simvastatin combined with BoneCeramic(r) induced significantly greater amounts of newly formed bone and has great potential for the healing of bone defects.

Entrevista com David L Cochran / An interview with David L. Cochran

Dr. David L. Cochran é graduado pela University of Virginia e recebeu os títulos de DDS, MS e PhD em Bioquímica pela Medical College of Virginia. Especializou-se em Periodontia pela Harvard School of Dental Medicine, onde também recebeu um segundo título de mestre. Recentemente, o Dr. Cochran recebeu o título de Doctor HonorisCausa pela University of Bern, na Suíça. Atualmente, é professor e chefe do Departamento de Periodontia na Faculdade de Odontologia da University of Texas Health Science Center, na cidade de San Antonio, nos Estados Unidos. Antes de assumir o cargo em San Antonio, era diretor do programa de pós-graduação em Periodontia naMedical College of Virginia. Dr. Cochran é membro de muitas organizações profissionais de Odontologia e diplomado pelo American Board of Periodontology. Além disso, é membro do American College of Dentistry e do International College of Dentistry.Dr. Cochran publicou inúmeros artigos científicos e resumos sobre vários tópicos relacionados à Periodontia, Bioquímica e Implantodontia. Recebeu prêmios nacionais e internacionais por suas pesquisas, e é um pesquisador clínico e científico ativo financiado tanto pela NIH-NIDCR (National Institutes of Health / National Institute of Dental and Craniofacial Research) quanto pela indústria privada...

Dr. David L. Cochran is a graduate of the University of Virginia and received hisDDS., MS. and PhD degrees in Biochemistry from the Medical College of Virginia (MCV). He was trained in Periodontology at the Harvard School of Dental Medicine where he also obtained a second Masters degree. He recently received an Honorary Doctorate from the University of Bern in Switzerland. Dr. Cochran is currently Professor and Chairman of the Department of Periodontics at The University of Texas Health Science Center at San Antonio, Dental School. Prior to his appointmentat San Antonio, Dr. Cochran was Director of Postgraduate Periodontics atMCV. Dr. Cochran is a member of many professional dental organizations and isa Diplomate of the American Board of Periodontology. He is a fellow of the American College of Dentistry and the International College of Dentistry. Dr. Cochran has published numerous scientific articles and abstracts on various periodontal, biochemistry, and implant topics. He has received awards for his research work at both the national and international levels. Dr. Cochran is an active basic science and clinical researcher who has received funding from both the NIH-NIDCR andprivate industry...

Behavioural and cognitive effects of simvastatin dose used in stimulation of bone regeneration in rats

To analyze the effects of simvastatin (SVT) in the locomotion, anxiety and memory of rats, as a reflection of the administration of a minimum dose capable of stimulating bone regeneration in defects in the calvariae. METHODS: Surgical procedures were performed in 15 female Wistar rats, 2-month old, to insert the grafting material regenerator (Bone-ceramic(r)) and/or SVT, followed by behavioural and cognitive assessments in the 7th, 30th and 60th days post surgery. RESULTS: The SVT locally applied with the goal of bone regeneration in defects created in rat calvariae does not interfere with locomotion, anxiety levels and/or memories of rats, except for the first week following surgery, when an anxiolytic effect was observed, as a result of a possible central action. CONCLUSION: Failure to provoke any response within 30 and 60 days post surgical procedures suggests that SVT may constitute a good choice in stimulating bone regeneration without affecting the long term neural functions.

Efeito de superfícies de implantes nano-estruturadas na expressão de genes de osteoblastos e no contato osso-implante in vivo / Effect of nanostructured implant surfaces on osteoblast related gene expression and bone-implant contact in vivo

As tendências atuais na terapia com implantes odontológicostêm incluído o uso de implantes com superfícies modificadasutilizando nanotecnologia. Ciência que permite a construçãode novos materiais e dispositivos pela manipulação de átomosindividuais e moléculas (escala menor do que 100nm). O objetivodeste trabalho foi avaliar o papel das modificações em escalananométrica de superfícies de implantes osseointegradospara melhorar o processo de osseointegração. Nanotecnologiaoferece a engenheiros e profissionais da área de biologia e saúdenovos meios para entender e otimizar funções e respostasespecíficas de células. As várias técnicas utilizadas para adicionarcaracterísticas nanométricas às superfícies de implantesosseointegrados são descritas neste trabalho. Vários trabalhostem apresentado os efeitos da nanotecnologia na modulaçãode etapas fundamentais do processo de osseointegração. Asvantagens e desvantagens da utilização da nanotecnologia nasuperfície de implantes também são discutidas nesse trabalho.Posteriormente, em uma série de experimentos in vitro e in vivo,foi possível avaliar o efeito específico destas modificações emdois diferentes modelos. Como efeitos observados da aplicaçãode nanoestruturas à superfície dos implantes osseointegradosfoi possível verificar-se uma melhor e mais rápida resposta deosseointegração destes materiais, atuando efetivamente na cascatade diferenciação de osteoblastos.

Current trends in clinical dental implant therapy include useof endosseous dental implant surfaces embellished with nanoscaletopographies. Nanotechnology deals with materials withat least one significant dimension less than 100nm. The goal ofthis study was to consider the role of nanoscale topographic modificationof titanium substrates for the purpose of improvingosseointegration. Nanotechnology offers engineers and biologistsnew ways of interacting with relevant biological processes.Moreover, nanotechnology has provided means of understandingand achieving cell specific functions. The various techniquesthat can impart nanoscale topographic features to titaniumendosseous implants are described. Existing data supportingthe role of nanotopography suggests that critical steps in osseointegrationcan be modulated by nanoscale modification ofthe implant surface. Important distinctions between nanoscaleand micron-scale modification of the implant surface are presentlyconsidered. The advantages and disadvantages of nanoscalemodification of the dental implant surface are discussed.Finally, available data concerning the current dental implantsurfaces that utilize nanotopography in clinical dentistry aredescribed. Nanoscale modification of titanium endosseous implantsurfaces can alter cellular and tissue responses that maybenefit osseointegration and dental implant therapy. In a seriesof in vitro and in vivo experiments it was possible to evaluatethe effect of this modifications in different study designs. Theadvantages of the use of nanocues added to the surface of theosseointegrated dental implants allowed to a better and fasterosseointegration response of these materials, by acting on thedifferentiation of the osteoblasts.

Avaliação do comportamento de células mesenquimais humanas sobre superfícies de implantes dentários / Evaluation of differentiation and mineralization of human mesenchymal cells plated on dental implant surfaces

O objetivo deste estudo foi avaliar uma superfície de implante dentário compatível biologicamente e que aumente a resposta celular de osteoblastos de maneira a estimular o processo de diferenciação do tecido ósseo. Neste estudo foram utilizados discos de titânio comercialmente puro (cpTi) grau IV (6,0 mm x 1,0 mm) divididos em três grupos. Estes discos foram somente usinados (grupo U) ou usinados e subsequentemente tratados com ataque ácido (grupo Ac) ou usinado, jateamento e ataque ácido (grupo J/Ac). Células mesenquimais humanas indiferenciadas foram cultivadas sobre os discos e diferenciadas em osteoblastos. Os níveis de expressão de genes relacionados à diferenciação do tecido ósseo (Fostatase Alcalina-ALP; Sialoproteína Óssea-BSP; e Runx2) foram avaliados após sete e 21 dias através de PCR-tempo real (o gene GAPDH foi utilizado como controle endógeno). Após 35 dias avaliou-se a formação de nódulos de mineralização corados com Alizarin Red S. Observou-se um aumento relativo nos níveis de expressão dos genes ALP, BSP e Runx2 para a superfície com J/Ac quando comparada com as superfícies U e Ac. Após 21 dias a expressão de ALP estava 80 vezes maior na superfície J/Ac e o aumento no nível de BSP foi de 25 vezes. Após 35 dias a área mineralizada foi de 18%, 71% e 80%, para as superfícies U, Ac e J/Ac, respectivamente. Estes resultados sugerem que o jateamento da superfície previamente ao ataque ácido permitiu um maior nível de expressão de genes relacionados à cascata de diferenciação do tecido ósseo e formação de nódulos de mineralização in vitro, podendo levar a uma maior e melhor resposta de osseointegração destas superfícies.

Novel implant surfaces have been developed to improve/accelerate the osseointegration process. The mechanism by which implant surface improves osteoblast response at endosseous titanium implants is not fully understood. One of the mechanisms is related to induction of expression of bone-tissue specific genes inducing cells to differentiate into osteoblasts. The aim of this study was to evaluate a biologically compatible implant surface that can improve osteoblast responses and leads to a faster osseointegration. Commercially pure grade IV titanium disks (6.0x1.0mm) were machined (U) or machined acid etching (Ac) or sandblasted/acid etching (J/Ac), and divided into three groups. Human Mesenchymal Stem Cells were plated onto the disks and differentiated into osteoblasts. The expression levels of osteoblast-specific genes were evaluated by Real Time PCR to measure the mRNA levels of alkaline phosphatase (ALP), bone sialoprotein (BSP), and Runx2 after 7 and 21 days. The housekeeping gene GAPDH was used as a control. At 35 days, mineralization nodules were evaluated by Alizarin Red S staining. After 21 days, the expression levels of ALP for J/Ac and BSP were upregulated 80-fold and 25-fold, respectively. After 35 days, the mineralized area U, Ac and J/Ac was 18%, 71%, and 80%, for, respectively. The results demonstrated that a sandblasted/acid etched surface can affect adherent cell-bone specific gene expression, leading to a higher expression of osteoblast-specific genes and an increased in vitro mineralization response.

Influência do uso de Tropicamida a 1 por cento na espessura corneana central / Influence of the pupil dilating on the corneal pachymetry

Objetivo: Verificar se existe variação da espessura corneana com a midríase após instilação de Tropicamida a 1 por cento. Local: Clínica de Olhos da Santa Casa de Misericórdia de Belo Horizonte. Métodos: Medidas paquimétricas foram realizadas em 70 olhos de 36 pacientes antes e 30 minutos após a midríase com Tropicamida a 1 por cento. Em cada olho foram realizadas três medidas centrais utilizando o paquímetro ultra-sônico TopconP. G. H. Resultados: A média da espessura corneana encontrada antes da mídriase foi de 527,50mm no olho direito (OD) e 531,15mm no olho esquerdo (OE); após a midríase, 531,57mm e 531,71mm, respectivamente. Não houve diferenças estatisticamente significativas entre a espessura corneana antes a após a mídriase (p+0,083). Conclusão: A mídriase por tropicamida a 1por cento não interfere, estatisticamente, na medida paquimétrica corneana.