O reparo Ãsseo à um processo multifuncional com a participaÃÃo de vÃrios mediadores. Dentre os fÃrmacos que interferem nesse processo, destaca-se o Ranelato de EstrÃncio (RSr), o qual apresenta um mecanismo de aÃÃo dual, estimulando a neoformaÃÃo ao mesmo tempo que inibe a reabsorÃÃo Ãssea. Para avaliar a capacidade osteoindutiva, modelos que favorecem o estudo do potencial de reparo Ãsseo local tÃm sido utilizados, tais como o de induÃÃo de defeitos de tamanhos crÃticos (CSD) em calvÃrias de ratos. O objetivo deste estudo foi avaliar o RSr no reparo Ãsseo de defeitos crÃticos de 8 mm de diÃmetro induzidos em calvÃria de ratos. Para tanto, imediatamente apÃs a cirurgia, os CSD receberam uma Ãnica aplicaÃÃo de RSr (2,1 e 6,3 mg) ou nenhum tratamento (Controle). Grupos de animais foram sacrificados a 0 h e aos 15, 45, 90 e 120 dias apÃs a induÃÃo do CSD e calvÃrias foram processadas para anÃlise macroscÃpica, por meio de Tomografia Computadorizada tipo Cone Beam (TCCB), histolÃgica (HE) e imunohistoquÃmica para RANKL e OPG. Na anÃlise por TCCB, verificou-se que, no grupo RSr 6,3 mg, o RSr causou reduÃÃo significativa da Ãrea do CSD aos 90 dias (67,79  2,32 mmÂ) e 120 dias (62,28  4,17 mmÂ), quando comparadas Ãs calvÃrias recÃm-induzidas (0 h) (78,61  0,96 mmÂ) (p<0,05), mas nÃo em relaÃÃo ao grupo Controle apÃs 90 dias (74,2  2,73 mmÂ) e 120 dias (72,04  1,74 mmÂ) (p>0,05). Na anÃlise histolÃgica das calvÃrias dos animais do grupo Controle foram observadas alteraÃÃes histolÃgicas significantes relacionadas ao reparo Ãsseo como neoformaÃÃo Ãssea restrita Ãs bordas do CSD quando comparados aos animais do grupo normal em todos os perÃodos experimentais (p<0,05). Os animais do grupo RSr (2,1 mg) nÃo apresentaram alteraÃÃes histolÃgicas significantes quando comparados ao grupo Controle em todos os perÃodos experimentais (p>0,05) enquanto que, nos animais do grupo RSr (6,3 mg), foram observados aspectos histolÃgicos compatÃveis com reparo Ãsseo aos 90 dias e aos 120 dias como neoformaÃÃo Ãssea em borda e no centro do CSD com diferenÃas significativas quando comparados aos grupos Controle ou RSr 2,1 mg (p<0,05). Complementando esses resultados, as calvÃrias dos animais apÃs 120 dias da aplicaÃÃo local de RSr (6,3 mg) apresentaram intensa imunoexpressÃo para OPG e negativa para RANKL, enquanto que as calvÃrias do grupo Controle apresentaram imunoexpressÃo moderada apenas para RANKL. Assim, pode-se concluir que o tratamento local com RSr evidenciou seu papel osteoindutor favorecendo a reparaÃÃo Ãssea do CSD pela modulaÃÃo da via RANKL/RANK/OPG. / The bone repair is a multifunctional process involving various mediators. Among the many drugs that interfere with this process, we highlight the Strontium Ranelate (SrR), which has a dual mechanism of action, stimulating neoformation at the same time, which inhibits bone resorption. To evaluate the osteoinductive capacity, models of study that investigate the potential for bone repair site have been used, such as induction of critical size defects (CSD) in rat calvaria. The aim of this study was to evaluate bone healing induced by SrR in critical defects of 8 mm in diameter in rat calvaria. For this purpose, immediately after surgery, the CSD received a single application of SrR (2.1 and 6.3 mg) or no treatment (Control). Groups of animals were sacrificed at 0 h and at 15, 45, 90 and 120 days after induction of CSD and calvarial samples were removed and processed for analysis by macroscopic type Cone Beam Computed Tomography (CBCT), histological (HE) and immunohistochemical for RANKL and OPG. In CBCT analysis, it was found that induction of CSD group SrR 6.3 mg caused a significant reduction of the areas of CSD at 90 days (67.79  2.32 mmÂ) and at 120 days (62.28  4.17 mmÂ) compared to calvariae newly induced (0 h) (78.61 mm  0.96) (p<0.05) but not compared to Control groups at 90 days (74.2  2.73 mmÂ) and at 120 days (72.04 Â1.74 mmÂ) (p>0.05). We observed in the histological analysis of calvariae of Control groups significant changes related to bone repair when compared to normal group (p<0.05). The animals that received SrR (2.1 mg) showed no significant histological changes, compared to the Control groups in all experimental periods (p>0.05), while animals of SrR 6.3 mg group showed significantly histological features consistent with bone repair at 90 days and at 120 days as neoformation in edge and center of the CSD when compared to Control or SrR 2.1 mg groups (p<0.05). To complement these results, the calvariae of animals after 120 days of topical application of SrR (6.3 mg) showed intense immunostaining for OPG and RANKL negative, whereas the calvariae of Control groups showed moderate immunoreactivity only for RANKL. Thus, it can be concluded that the local treatment with SrR (6.3 mg) revealed its role favoring osteoinductive bone repair by modulating the CSD RANK/RANKL/OPG.

Thesis (M.S.)--University of Michigan, 1995. / Includes bibliographical references.

Indiana University-Purdue University Indianapolis (IUPUI) / Endodontic regeneration treatment of necrotic immature teeth has gained popularity in recent years. The approach suggests a biological alternative to induce a continuous root development. In this project, three in vitro experiments were conducted to investigate the effect of three medicaments used in endodontic regeneration on mechanical properties and chemical structure of radicular dentin. In the first experiment, we investigated longitudinally the effect of medicaments on the indentation properties of the root canal surface of immature teeth using a novel BioDent reference point indenter. A significant difference in the majority of indentation parameters between all groups was found after one-week and one-month application of medicaments (p<0.0001): triple antibiotic paste (TAP) > double antibiotic paste (DAP) > control > calcium hydroxide [Ca(OH)2]. The four-week exposure of dentin to TAP and DAP caused 43% and 31% increase in total indentation distance outcome, respectively. In the second experiment, we investigated longitudinally the effect of medicaments on the chemical structure of immature radicular dentin by measuring the phosphate/amide I ratios of dentin using Attenuated Total Reflection Fourier Transform Infrared Spectroscopy. Phosphate/amide I ratios were significantly different between the four groups after one week, two weeks and four week application of medicaments (p<0.0001): Ca(OH)2-treated dentin > untreated dentin > DAP-treated dentin > TAP-treated dentin. In the third experiment, we investigated longitudinally the effect of medicaments on root fracture resistance and microhardness of radicular dentin. For the microhardness, the two-way interaction between group and time was significant (p<0.001). TAP and DAP caused a significant and continuous decrease in dentin microhardness after one and three month application, respectively. The three-month intracanal application of Ca(OH)2 significantly increased the microhardness of root dentin. The time factor had a significant effect on fracture resistance (p<0.001). All medicaments caused significant decrease in fracture resistance ranging between 19%-30% after three month application compared to one week application. The three medicaments used in endodontic regeneration caused significant change in the chemical integrity of the superficial radicular dentin and significantly affected the indentation properties of the root canal surface. Furthermore, the three month intracanal application of medicaments significantly reduced the fracture resistance of roots.