Primary sensory afferent outgrowth within the developing longitudinal pathway of the spinal cord is important for intrasegmental and intersegmental communication that underlies coordination and development of reflexes and contributes to sensory perception. The endogenous mechanisms that regulate primary sensory afferent extension are the primary focus of this dissertation. This dissertation tested the hypothesis that primary sensory afferent extension in the longitudinal pathway is regulated by sphingosine 1-phosphate type 1 receptor (S1P1R) and tyrosine kinase receptor B (TrkB) through a brain derived neurotrophic factor (BDNF) related mechanism. To test this hypothesis we used embryonic day five (E5) chicken embryos, as this is the developmental time point when sensory afferents are growing along the longitudinal axis of the spinal cord but have not yet turned ventrally to make connections with the grey matter of the spinal cord. Chicken embryos were removed from their in ovo environment to allow for labeling of primary afferent neurons in the thoracic 3/4 (T3/4) dorsal root ganglia (DRG). Tissue was then put into culture with or without various pharmacological agents and subsequently assayed for length of growth of the labeled primary afferent axons along the longitudinal axis of the spinal cord. Results showed both BDNF and fingolimod-p, an S1P1R agonist known to increase BDNF mRNA and protein production/secretion in cortical neurons, increased primary axon extension along the longitudinal pathway. Further, fingolimod-p increased BDNF mRNA production in DRG in this system. Conversely, inhibition of BDNF or S1PRs attenuated primary afferent axon extension along the longitudinal pathway. We found BDNF signaling to be required for fingolimod-p's effects as addition of αBDNF attenuated the effects of fingolimod-p on axon outgrowth. TrkB, the high affinity receptor for BDNF, is expressed in chicken DRG during embryonic development. We hypothesized that TrkB activation by BDNF regulates DRG axon extension in the longitudinal pathway through the PLC-γ signaling pathway. We found inhibition of TrkB and/or PLC-γ signaling pathway attenuated DRG axon extension with or without BDNF stimulation. Additional pathways associated with TrkB activation: mitogen activated kinase (MAPK) and phosphoinositide 3-kinase (PI3K) appeared to either have no effect on DRG axon extension or were involved in DRG axon extension through a mechanism that is not related to TrkB. Collectively, these studies suggest an endogenous mechanism for the regulation of DRG axon outgrowth within the longitudinal pathway. With this mechanism, DRG axon outgrowth may be enhanced or attenuated following manipulation of S1P1R, BDNF and/or TrkB. Further, these findings suggest an action through BDNF on CNS axons as a potential therapeutic effect of fingolimod-p, a treatment for relapsing remitting forms of Multiple Sclerosis

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

This thesis explores a selection of the ways in which an era of high mineral commodity prices - commonly dubbed the 'super-cycle' of the 2000s - is reshaping the map of global commodity markets. It pursues this agenda through three research aims: (1) to recast the relationship between geophysical resource supply, prices, and markets; (2) to examine some of the institutions that channel and benefit from resource wealth; and (3) to 'open the black box' of the commodity price formation process. The thesis pursues this agenda through four substantive papers, each with its own set of research objectives and findings, and primarily uses the example of phosphate as a vehicle for discussion. The first half of the thesis focuses on the production side of commodity markets. It begins by exploring the multidimensional nature of the concept of resource scarcity, both in its geophysical and socioeconomic aspects, by interrogating a prominent inherited conception of natural resource scarcity: 'peak' natural resources, specifically peak phosphorus discourses (chapter 3). The thesis then carries on the research agenda suggested by this initial study by conducting a field research-based case study of the little-known Moroccan state-owned phosphate mining and fertilizer company, OCP Group (chapter 4). It explores the particular type of principal-agent problem in generating and distributing national resource wealth that national extractive companies (NECs) such as OCP face. The second substantive half of the thesis is concerned with global commodity trading and price formation. It constructs an 'anatomy' of global phosphate markets in order to shed light on the phosphate price formation process (chapter 5). Based on this investigation, the thesis argues that despite the opacity of the processes by which phosphate is priced, an apparent lack of a 'benchmark' or reference price is not necessarily as problematic as market theorists might assume. Finally, the thesis takes a macro-level perspective of the relationship between finance and physical commodity trade by examining the role of financial trading in the governance of commodity markets (chapter 6). Overall the thesis distils the following findings. To begin with, a deeper and more nuanced understanding of the concept of resource scarcity puts short-term price movements as indicators of resource availability into perspective while revealing an unforeseen degree of complexity, as well as certain 'blind spots', in the geopolitical and institutional aspects of resource supply and trading. Second, the power of two particular, less-researched types of institutions that channel and benefit from resource wealth - names, national extractive companies and financial investors - is both less great and different in nature than is commonly assumed. Third, for institutional as well as geographic reasons that are specific to different types of commodities, the commodity price formation process is even further from the joint ideals of market transparency and liquidity than is commonly assumed. Finally, insofar as commodity production and trade can be conceived as part of the 'real economy', it cannot succumb to what is widely feared as the hegemony of 'financial logic'.

Phosphate (Pi) deficiency is a global problem for food production. Plants have evolved complex mechanisms to adapt to low Pi. We focused on the initial aspects of adaptation to low Pi - perception and immediate-early responses to changes in external Pi. To examine whether a labile repressor controls expression of the high affinity Pi transporter, Pht1;1, we performed electrophoretic mobility shift assays (EMSA) but observed only weak protein-DNA binding activity using extracts from Arabidopsis suspension cultures or seedlings. The regulatory role of different regions in Pht1;1 promoter was dissected by promoter deletion analysis, using uidA as a reporter. We identified two domains important for regulation: sequences between -1898 bp and - 932 bp are important for induction of Pht1;1 in low Pi; the intron in the 5’UTR impacts Pht1;1 expression in the young part of both primary and lateral root apices. A complementary approach to identify repressors of Pi starvation responses was pursued: We identified ZAT18, a putative transcription factor, as a candidate repressor. ZAT18 contains an EAR motif, a repressor domain in plants; the expression of ZAT18 responds to Pi starvation. Using transgenic lines with promoter::ZAT18-VENUS constructs, we studied its expression, localization and abundance in different levels of Pi availability: ZAT18 is mainly expressed in the nucleus of Arabidopsis root hair cells. Its accumulation was induced by 4 day Pi starvation. We also performed a microarray analysis to examine global gene expression levels during Pi starvation and rapid recovery. Our data indicated that 258 genes were induced and 188 genes were suppressed during Pi starvation. For most of these genes, responses were reversed after 4 hour Pi recovery. Further study of these genes will help to define targets of the early Pi starvation-signalling pathway.

In der vorliegenden Arbeit wurden Untersuchungen an Rückständen von thermisch abgebauten, flammgeschützten Polymeren vorgenommen, mit dem Ziel, die Struktur und den Phasenbestand der eingebauten Flammschutzmittel und der Polymere sowie deren Wechselwirkungen als Funktion der Temperatur und umgebenden Atmosphäre (N2 und Luft) zu charakterisieren. Ein wichtiges Werkzeug, das Informationen über den amorphen Zustand der Abbauprodukte und deren thermisch bedingte Phasenumwandlungen in andere amorphe oder kristalline Strukturen sowie Aussagen über die Nahordnungen der betrachteten Kernspinsorte liefert, stellt in dieser Arbeit der Einsatz der Festkörper-NMR-Spektroskopie dar. Hierbei sind neben Einzelimpuls- (SP), rotor-synchronisierte Spin-Echo- (RSE) und Kreuzpolarisationstechniken (CP) auch REDOR- (Rotational echo double resonance) und TRAPDOR- (Transfer of population in double resonance) Messungen zur Anwendung gekommen. Zusätzlich konnten aus den 11B- und 31P-NMR-Experimenten quantitative Aussagen über den relativen Borat- und Phosphor bzw. Phosphat-Anteil im festen Rückstand getroffen werden, wobei insbesondere für die 31P-Kerne eine quantitative Erfassung der kristallinen und amorphen Phosphatphasen durchgeführt wurde. Im ersten System wurden die Flammschutzmittel roter Phosphor (Prot) und Mg(OH)2 in HIPS kombiniert. Aus den Ergebnissen umfangreicher NMR-Experimente konnte abgeleitet werden, dass der größte Teil des eingesetzten Prot hauptsächlich in amorphen (Mg-Ortho-, -Di-, -Ketten- und Ringphosphaten) und weniger in kristallinen Phosphatphasen verbleibt. Zudem konnte für den Parameter der Temperatur und aus der Verfügbarkeit von Sauerstoff (N2-Atmosphäre/Luft) einen deutlicher Einfluss auf den Abbauprozess und die Bildung der Phosphatphasen (kristallin/amorph) nachgewiesen werden. Aus dem Vergleich der Ergebnisse der Temperversuche mit den Ergebnissen der Verbrennungsversuche im Cone Calorimeter konnte ein anaerober Abbauweg bestätigt werden. In einem zweiten System wurden die thermischen Reaktionen zwischen den Flammschutzadditiven BDP und Zinkborat sowie ihren Einfluss auf den thermischen Abbau eines PC/ABS-Blends untersucht. Der thermisch belastete Rückstand wird unabhängig von der Atmosphäre von amorphen Phosphatgruppen dominiert. Dabei konnten die während der Temperprozesse gebildeten Verbindungen α Zn3(PO4)2 und BPO4 als Folge einer Festphasenreaktion zwischen den eingesetzten Flammschutzadditiven identifiziert werden, wobei das α Zn3(PO4)2/BPO4 Verhältnis als Indikator für einen aeroben bzw. anaeroben Abbauprozess dient, der für die Feuerrückstände eindeutig einen anaeroben Abbau liefert. / This study aims at the structural characterisation of embedded flame retardants and polymers. Analysis includes determination of the phase contents as well as description of their mutual interactions as a function of their thermal history in different atmospheres (air and nitrogen). Solid-state NMR spectroscopy is the most important tool applied in this thesis. This technique enables structural information about the amorphous state of the decomposed products, determination of the thermal and thermo-oxidative conversion in different amorphous and crystalline structures, and predictions about the short-range order of the observed nuclei. In this context measurements of single pulse (SP), rotor-synchronised spin echo (RSE) and cross polarisation (CP) experiments, as well as REDOR (Rotational echo double resonance) and TRAPDOR- (Transfer of population in double resonance) have been conducted. Additionally, 11B SP and 31P RSE experiments have been used to study quantitatively the borate and both phosphorus and phosphate contents in the solid residues. Particular emphasis was put on quantifying crystalline and non-crystalline phosphate phases. The first system consists of a combination of the flame retardants red phosphorus (Pred) and Mg(OH)2 in HIPS. From the results of extensive NMR experiments it was deduced that most of inserted red phosphorus remains in amorphous phosphates phases (ortho, pyro, and chain/ring phosphates) besides some crystalline phosphate phases. Decomposition characteristics such as temperature and the availability of oxygen (N2 atmosphere/air) show a significant influence on the decomposition process and the formation of phosphate phases (crystalline/amorphous). By comparing the results of the annealing processes to the results of the cone calorimeter measurements an anaerobic decomposition way was confirmed. In a second system, thermal reactions between the two flame retardants BDP and zinc borate as well their influence on the thermal decomposition of a PC/ABS blend were investigated. The thermally residues are independently of the atmosphere dominated by amorphous phosphate units. During the thermal decomposition the formation of α-Zn3(PO4)2 and BPO4 could be identified as solid reaction products of the inserted flame retardants. In addition, the α Zn3(PO4)2/BPO4 ratio served as an indicator of aerobic or anaerobic decomposition processes, proving an anaerobic decomposition mechanism for the fire residues.

Thesis advisor: Thomas N. Seyfried / Thesis advisor: Charles Hoffman / Bis(monoacylglycero)phosphate, BMP, is a negatively charged glycerol-phospholipid with an unusual sn-1;sn-1’ structural configuration. BMP is primarily enriched in endosomal/lysosomal membranes. BMP is thought to play a role in glycosphingolipid degradation and cholesterol transport. It constitutes only about 1-2% of the total phospholipids in most mammalian cells, but is abundant in lung alveolar macrophages where it can comprise up to 16% of the total phospholipids. BMP also accumulates in tissues of humans and animals with lysosomal storage disorders. However, little information is available on BMP levels in gangliosidosis brain tissue. In this work, I found that total BMP content was significantly greater in cells of macrophage/microglial origin than in cells of macroglial origin (astrocyte, oligodendrocyte progenitor), whether normal or tumorigenic. I also observed that BMP in brain was significantly greater in humans and in animals (mice, cats, American black bears) with either GM1 or GM2 ganglioside storage diseases, than in brains of normal subjects. Since BMP is associated with macrophages, I also analyzed the BMP levels in relation to disease-associated inflammation in gangliosidoses. I found that BMP levels were increased due to accumulation of primary storage material gangliosides, rather than an outcome of disease-associated inflammation. In addition, in this thesis I also explored the effect of new ketogenic diet formula from Solace Nutrition (KetoGen) on the growth and metastatic spread of the VM-M3 tumor. Most current drug therapies for cancer are toxic and only marginally effective in providing long-term management. Respiratory insufficiency with compensatory aerobic fermentation (Warburg effect) is the hallmark biochemical phenotype of nearly all neoplastic cells within tumors. Calorie restriction, which lowers blood glucose and elevates ketone bodies, is known to reduce tumor growth to a certain extent, however it does not reduce systemic metastasis. Tumor bearing VM mice were fed either a standard lab chow diet in unrestricted amounts (SD-UR), a standard lab chow restricted to obtain an 18% reduction in body weight (SD-R), or the KetoGen diet restricted (KG-R) to match the body weights of the SD-R group. Tumor size was significantly smaller and organ metastasis was significantly less in the KG-R group than in the SD-UR or SD-R groups. Even though blood glucose was reduced similarly in both the SD-R and KG-R groups, blood ketones were 3-fold higher in the KG-R group than in the SD-R group. These results show that VM-M3 tumor growth and systemic metastasis were managed better with the restricted KetoGen KD than with calorie restriction of a high carbohydrate standard diet. As all human and mouse tumors cells suffer from respiratory insufficiency, my findings suggest that the restricted KetoGen diet should be an effective non-toxic therapy against tumor growth and systemic metastatic cancer. / Thesis (PhD) — Boston College, 2015. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Biology.

Compostos de fósforo insolúveis em água, como os do tipo Fe - K - P podem ser formados em fertilizantes fosfatados totalmente acidulados (FFTA). Em superfosfatos dois dos mais comuns são os compostos Fe3KH8(PO4)6.6H2O (H8) e Fe3KH14(PO4)8.4H2O (H14). Elevadas quantidades de rocha fosfática são descartadas a fim de garantir que FFTA apresentem na fração citrato neutro de amônio (CNA) + água, 90% de P2O5 solúvel em CNA, como prevê a legislação brasileira de fertilizantes. Experimentos anteriores mostraram que os FFTA não necessitam, obrigatoriamente, conter alta solubilidade em água. Estudos anteriores indicaram que rochas fosfáticas poderão ser melhores utilizadas conhecendo-se a performance agronômica das impurezas insolúveis em água. Para adicionar informações a este assunto, os compostos H8 e H14 foram sintetizados em condições de laboratório. Os precipitados foram analisados através de análise química elementar, difratometria de raios-x, microscopia eletrônica de varredura e espectrometria de energia dispersiva (EED). As análises efetuadas confirmaram a correta precipitação de ambos compostos. Um experimento de hidrólise foi conduzido usando soluções de NaCl 0,01; 0,05 e 0,1 mol L -1 com pH variando de 3,0 a 7,5. Amostras do H8, H14 e de FR de Catalão foram agitadas utilizando-se as soluções até pH de equilíbrio. O pH da solução foi ajustado adicionando-se NaOH ou HCl. Depois de atingido o pH de equilíbrio, as soluções foram filtradas, e as concentrações de P, Fe, K, S, Na e Cl determinadas analiticamente e utilizado o programa MINTEQ para calcular a atividade dos íons ortofosfato (H2PO4 - e HPO4 2- ). Os precipitados que ficaram retidos no papel de filtro foram analisados analiticamente e submetidos a raios-x e EED. As quantidades de H8 e H14 sintetizadas foram suficientes para o estudo de hidrólise. Os resultados indicaram que a porcentagem de P liberada dos compostos do tipo Fe - K - P aumentava com o aumento do pH. Quantidades mais elevadas de P foram liberadas do composto H14 quando comparado ao H8. Também, a atividade dos íons ortofosfato foi mais elevada para o H14 quando comparado ao H8. Observou-se uma tendência a elevação da atividade dos íons ortofosfato com a diminuição da força iônica para ambos compostos. Para o H8 ocorreu um aumento da atividade com o aumento do pH para NaCl 0,01 mol L -1 . Para o H14 a tendência foi o aumento da atividade até pH 5,0 para NaCl 0,05 e 0,1 mol L -1 e pH 6,0 para NaCl 0,01 mol L -1 . Após estes valores a atividade tendeu a diminuir devido provavelmente à formação do par NaHPO4 - . As análises químicas, raios-x e EED dos precipitados oriundos do estudo de hidrólise mostraram que os resultados de composição e raios-x são similares ao do composto H8, atestando novamente baixa porcentagem de liberação de P deste composto. Para o composto H14 verificou-se a formação de um novo composto, possivelmente estrengita amorfa. Os dados obtidos neste estudo indicam que elevadas quantidades de P liberado de compostos do tipo Fe - K - P a solução não significam necessariamente elevada atividade. Os resultados confirmam que o composto H14 pode apresentar melhor eficiência agronômica do que o H8. / Water-insoluble P compounds, as of the type Fe-K-P, can be formed in totally acidulated phosphate fertilizers (TAPF). In superphosphates two of the most common are the Fe3KH8(PO4)6.6H2O (H8) and the Fe3KH14(PO4)8.4H2O (H14). High amounts of phosphate rock (PR) are discarded in order to produce APF with about 90% of P2O5 neutral ammonium citrate (NAC) soluble fraction in the available P fraction (NAC + H2O), as indicated by the brazilian fertilizer legislation. Previous experimental data have shown that TAPF do not necessarily need to always contain high water solubility. Studies have indicated that PR will be better utilized by accessing the agronomic performance of water-insoluble P impurities. To add information related to this topic H8 and H14 compounds were synthesized at laboratory conditions. The precipitates were exposed to elemental chemical analysis, x-ray, scanning electron microscope and energy-dispersive spectroscopy (EDS). All chemical plus instrumental analysis confirmed the correct precipitation of both compounds. A hydrolysis experiment was conducted using 0,01; 0,05 and 0,1 mol L -1 NaCl solution with pH ranging from 3 to 7.5. Sub samples of the H8, the H14 and a PR from Catalão were agitated with each solution until certain equilibrium was achieved. Solution pH was adjusted by adding NaOH or HCl. After equilibrium the solutions were filtered, the concentrations of P, Fe, K, S, Na and Cl determined and the software MINTEQ used to calculate the activity of the orthophosphate ions (H2PO4 - and HPO4 2- ). The precipitate remaining in the filter paper was also analyzed for the same elements and submitted to x-ray and EDS. The amounts of H8 and H14 synthesized were enough for the hydrolysis study. The results indicated that the amount of P released from both Fe-K-P compounds increased in higher solution pH. More P was released from the H14 than the H8 compound. Also, the activity for the orthophosphate ions was higher for the H14 than for the H8 compound. There was a trend to obtain higher activity of the ions orthophosphate with lower ionic strength for both compounds. For the H8 it was obtained higher activity as the solution pH increased when the ionic strength was of 0,01 mol L -1 NaCl. For the H14 the trend was for the activity to increase until pH 5 for the 0,05 and 0,1 mol L -1 NaCl solution and until pH 6 for the 0,01 mol L -1 . After these values the activity tended to decrease most likely due to the formation of the NaHPO4 - ionic par. The elemental chemical composition, x-ray and EDS of the precipitates after the hydrolysis study showed composition and x-ray results similar to the H8 compound attesting low hydrolysis in this situation. For the H14 compound it was found the formation of a new compound, most likely an amorphous strengite. Data obtained in this study indicate that higher amounts of P released from compounds of the type Fe-K-P as the solution pH increases does not necessarily mean higher activity. The results confirm that the H14 compound should be of higher agronomic effectiveness than the H8.

A radioterapia interna seletiva é uma alternativa para o tratamento de alguns tipos de cânceres como o carcinoma hepatocelular (CHC), ou câncer de fígado primário. Neste tratamento, microesferas de vidro ou polimérica contendo em sua estrutura radionuclídeos emissores de partículas β- são introduzidas no fígado por meio da artéria hepática e migram, preferencialmente, para regiões hipervascularizadas, que são características da presença de tecido canceroso. Neste trabalho, foram propostos o desenvolvimento de vidros fosfato contendo hólmio para produção de microesferas e sua aplicação em radioterapia interna seletiva no Brasil. O vidro desenvolvido apresentou durabilidade química adequada, densidade de 2,7(3)g/cm3, alta estabilidade térmica e as impurezas encontradas não inviabilizam o tratamento. As microesferas foram produzidas pelos métodos da chama e da queda gravitacional e foram caracterizadas por diversas técnicas em que se observaram forma, granulometria, atividade e biocompatibilidade apropriados para o tratamento pretendido. Propõe-se que as microesferas possam ser submetidas a testes in vivo. / The selective internal radiotherapy is an alternative for some kinds of cancer as the hepatocellular carcinoma (HCC) or primary liver cancer treatment. In this treatment, glass or polymer microspheres containing radionuclides inside their structure are introduced in the liver through hepatic artery and trapped at the arterioles that feed the tumor. In this work, the development of phosphate glasses containing holmium for production of microspheres and their application in Brazil are proposed. The developed glasses presented suitable chemical durability, density of 2,7(3) g/cm3, high thermal stability and the impurities contained therein do not preclude the treatment. The microspheres were produced by the flame method and the gravitational fall method, and were characterized by means of several techniques to evaluate shape, average particle size, activity and biocompatibility suitable for selective internal radiotherapy. Based in the main results, the submission to in vivo tests is proposed.

Um dos grandes desafios para o tratamento de defeitos ósseos extensos na região bucomaxilofacial têm sido o desenvolvimento de um biomaterial substituto ósseo ao enxerto autógeno. No presente trabalho avaliou-se a formação óssea e a biodegrabilidade do osso desproteinizado bovino Bio-Oss® e do seu similar GenOx Inorg® e da cerâmica bifásica GenPhos® XP no processo de reparo de defeitos ósseos cranianos em coelhos, comparativamente ao osso autógeno (controle positivo) e coágulo sanguíneo (controle negativo). Foram realizados cirurgicamente defeitos bilaterais de 8-mm de diâmetro nos ossos parietais de 39 coelhos. A seguir os defeitos foram preenchidos aleatoriamente com 0,1cm3 de material ou coágulo conforme cada grupo de tratamento. Após os períodos de 4, 8 e 24 semanas os crânios foram coletados, analisados no microtomógrafo e processados histologicamente. O percentual de volume do defeito ocupado pelo material e osso neoformado foi avaliado pela microtomografia e histomorfometria, enquanto que, para a medula óssea, tegumento e tecido conjuntivo, apenas pela análise histomorfométrica. Os resultados quantitativos obtidos foram comparados estatisticamente pela ANOVA a dois critérios (período e tratamento) e teste de Tukey com p<0,05. A intensidade da associação linear dos dados microtomográficos e histomorfométricos avaliada pelo coeficiente de correlação de Pearson, mostraram correlação moderada a forte. Nos períodos iniciais de reparo (30 e 60 dias), os defeitos tratados com Bio-Oss®, GenOx® Inorg e GenPhos® XP apresentaram manutenção do volume do material enxertado (Vvi médio de 34% ) e formação óssea menor e mais imatura em relação grupo autógeno (Vvi = 22% vs. 32% no grupo autógeno). No período mais tardio (180 dias) a quantidade de formação óssea foi estatisticamente similar nos grupos Bio-Oss® (Vvi = 27%), GenOx® Inorg (Vvi = 26%) e GenPhos® XP (Vvi = 20%) porém, o GenOx® Inorg promoveu a formação de um tecido ósseo mais organizado e com maior acúmulo de biomaterial+osso+medula óssea (Vvi = 67,9%) comparado ao GenPhos® XP (Vvi =58,9%) e Bio Oss (Vvi = 55,6%) mas, inferior ao do enxerto autógeno (Vvi = 78%). Os resultados aqui obtidos permitem concluir que o osso autógeno promove rápida formação e maturação óssea, porém não consegue promover o reestabelecimento completo da díploe removida cirurgicamente. Os materiais BioOss, GenOx® Inorg e GenPhos® XP são excelentes materiais osteocondutores levando a formação óssea em toda extensão do defeito, sendo o GenOx® Inorg o que apresenta menor grau de reabsorção e maior e melhor preenchimento do defeito. / One major challenge for treatment of critical size defects in maxillofacial region has been the development of a substitute biomaterial to the autogenous bone grafts. In present study we evaluated the bone formation and biodegradability of deproteinized bovine bone Bio-Oss® and GenOx® Inorg, and biphasic calcium phosphate GenPhos XP® during bone repair process in rabbits cranial defects compared to autogenous bone (positive control) and blood clot (negative control). In parietal bone of 39 rabbits were made bilateral 8-mm diameter defects, which were filled randomly with 0,1cm3 material or clot as each treatment group. After periods of 4, 8 and 24 weeks skulls of animals were collected, analyzed the MicroCT scanner and histologically processed. The percentage of defect volume occupied by biomaterial and new-formed bone were assessed by histomorphometry and microtomography, while the bone marrow, connective tissue and tegument only by first analysis. The quantitative data were compared by two-way ANOVA analysis (time and treatment) and Tukey\'s test at p <0.05. The intensity of the linear association of MicroCT and morphometric data evaluated by the Pearson correlation coefficient, showed moderate to strong correlation. In the early repair periods (30 and 60 days), the defects treated with Bio- Oss, GenOx® Inorg and GenPhos® XP showed maintenance of the graft material volume (average Vvi of 34%) and lower and more immature bone compared autograft group (Vvi = 22% vs. 32% in the autograft group). In the later period (180 days) the amount of bone formation was statistically similar to the groups Bio-Oss® (Vvi = 27 %), GenOx® Inorg (Vvi = 26%) and GenPhos® XP (Vvi = 20%) however, the bone formation in GenOx® Inorg was more organized and with greater accumulation of particles + bone tissue + bone marrow (Vvi = 67.9%), when compared to GenPhos® XP (Vvi = 58.9%) and Bio-Oss® (Vvi = 55.6%) but lower than the autograft (Vvi = 78%). It was concluded that the autogenous bone promotes rapid bone formation and maturation, but cannot promote the complete reestablishment of diploe surgically removed. The Bio-Oss®, GenOx® Inorg and GenPhos® XP are excellent osteoconductive materials leading to bone formation in the full extent of the defects, and the GenOx® Inorg showing less absorption promotes more and better defect filling.