Orientadora: Daniele Botticelli / Banca: Idelmo Rangel Garcia Junior / Banca: Francisley Ávila Souza / Banca: Ronaldo Célio Mariano / Banca: Adolfo Embacher Filho / Resumo: Este trabalho teve por objetivo avaliar o tecido ósseo periimplantar formado após o enxerto sinusal com hidroxiapatita e beta-tricálcio fosfato (HA + -TCP), nas apresentações em grânulos e em pasta, concomitante à instalação de implantes em coelhos. Trinta e quatro seios maxilares de coelhos foram enxertados com HA + -TCP, sendo metade do grupo grânulos e metade do grupo pasta. Concomitantemente, foi realizada a instalação de implantes. Aos 7 e 40 dias pós-operatórios, realizou-se a eutanásia dos animais, e as amostras foram preparadas para as análises tomográfica, microtomográfica, histológica (coloração por hematoxilina e eosina - HE), imunoistoquímica (marcação de fator de transcrição Runt-2 - RUNX2 -, fator de crescimento endotelial vascular - VEGF -, osteocalcina - OCN - e fosfatase ácida resistente ao tartarato - TRAP) e de torque de remoção dos implantes. Na tomografia, foi observada a manutenção da integridade da membrana sinusal, sem extravasamento de material, nos dois grupos e períodos. Parâmetros morfométricos de volume ósseo, porcentagem do volume ósseo e número de trabéculas foram significativamente superiores para o grupo pasta do que para o grupo grânulos aos 7 dias, enquanto que a porosidade foi maior para o grupo grânulos nesse mesmo período. Aos 40 dias, não houve diferença significativa entre os grupos para a maioria dos parâmetros microtomográficos estudados. Nos cortes histológicos corados por HE, observou-se que em ambos os grupos ocorreu a formação d... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: This work aimed to evaluate the peri-implant bone tissue after maxillary sinus grafting with hydroxyapatite and beta-tricalcium phosphate (HA + -TCP), in granular and paste formulations, concomitant with implant placement in rabbits. Thirty four rabbit maxillary sinuses were grafted with HA + -TCP, being half of the granular group and half of the paste group. Concomitantly, the implant placement was performed. At 7 and 40 postoperative days, animals were euthanized, and the samples were prepared for tomographic, microtomographic, histological (hematoxylin and eosin staining), immunohistochemical (Runt-related transcription factor 2 - RUNX2, vascular endothelial growth factor - VEGF -, osteocalcin - OCN - and tartrate-resistant acid phosphatase - TRAP - staining) and implant torque removal analyses. In computed tomography, the maintenance of sinus membrane integrity, with no material extravasation, was observed in both groups and periods. Morphometric parameters of bone volume, percentage of bone volume and trabecular number were significantly higher for paste than granular group at day 7, while the porosity was higher for granular group in this period. At day 40, there were no significant differences between both groups for the majority of the microtomographic parameters studied. In the HE-stained histological sections, it was observed that bone healing around implant threads occurred for both groups at day 40, enhancing osseointegration. Similar positive immunostainings we... (Complete abstract click electronic access below) / Doutor

Objetivo: o objetivo deste ensaio clínico controlado aleatorizado foi avaliar o uso de um substituto ósseo sintético associado a uma membrana de colágeno absorvível na preservação da crista óssea alveolar após extração dentária, por meio de análises clínica e tomográfica em humanos. Metodologia: Quatorze pacientes foram selecionados, cada um apresentando ao menos dois dentes anteriores maxilares indicados para extração: no Grupo Teste (GT), o alvéolo pós-exodontia foi preenchido pelo substituto ósseo sintético Reprobone, e no Grupo Controle (GC) houve o preenchimento do alvéolo apenas por coágulo. Em ambos os grupos os alvéolos foram cobertos por uma membrana absorvível de colágeno (BioMend), que por sua vez foi recoberta por um retalho mucoperióstico fechado oclusivamente. Tomografias computadorizadas do tipo Cone Beam foram realizadas no pós-operatório imediato e após 6 meses do procedimento cirúrgico, e as alterações dimensionais horizontais e verticais das cristas ósseas foram quantificadas. Para a análise estatística intragrupo utilizou-se o teste t pareado; para avaliações intergupo, teste t não pareado. Em todas as comparações foi adotado um nível de significância de 5%. Resultados: A Medida Vertical Vestibular reabsorveu 1,5 mm (ou 21,3%) da medida inicial no Grupo Teste (p<0,05) e 1,8 mm (ou 25,8%) no Grupo Controle (p<0,05). A Medida Vertical Palatina diminuiu 0,3 mm em ambos os grupos (p>0,05). A Altura Máxima reduziu 0,5 mm ou 7,9% no grupo com Reprobone e BioMend quando comparada ao baseline (p>0.05), e 1,1 mm ou 14,8% no grupo com BioMend apenas (p<0,05), sendo esta diferença intergrupo estatisticamente significante (p<0,05). A Medida Horizontal Apical diminuiu 0,2 mm no GT, o equivalente a 2,9% (p>0,05), enquanto que no GC diminuiu 0,5 mm ou 7,3% (p<0,05), não havendo diferença estatisticamente significante entre os grupos. A Medida Horizontal Cervical (MHC) perdeu 0,5 mm ou 7,2% no GT e 1,4 mm ou 15,1 % no GC: a análise intragrupo apontou diferença estatística entre os dados iniciais e após 6 meses para este parâmetro (p<0,05), em ambos os grupos, e também foi encontrada diferença estatisticamente significante na avaliação entre grupos para a MHC. Conclusão: Os resultados obtidos demonstraram que o uso do Reprobone associado à Biomend apresentou benefícios e melhores resultados na manutenção vertical e horizontal do rebordo alveolar em comparação ao uso apenas da membrana colágena. / Objective: The aim of this randomized controlled clinical trial was to evaluate the use of a synthetic bone substitute associated with an absorbable collagen membrane in preserving the alveolar crest after tooth extraction, through clinical and tomography analysis in humans. Methods: Fourteen patients were selected, each featuring at least two front teeth jaws indicated for extraction: in Test Group (TG), the post-extraction sockets were filled by the synthetic bone substitute ReproBone, and the control group (CG) was filling the alveoli only by clot. In both groups, the wells were covered with a resorbable collagen membrane (BioMend), which in turn was covered with a mucoperiosteal flap closed occlusally. CT Cone Beam type were performed in the immediate postoperative period and after 6 months of surgery, and the horizontal and vertical dimensional changes of the bone crests were quantified. For intra-group statistical analysis used the paired t test; to intergupo reviews, unpaired t test. In all comparisons was adopted a 5% significance level. Results: Vestibular Vertical Measure reabsorbed 1.5 mm (or 21.3%) of the original measure in the test group (p <0.05) and 1.8 mm (or 25.8%) in the control group (p <0 , 05). The Measured Vertical Palatine 0.3 mm decreased in both groups (p> 0.05). The Maximum Height reduced 0.5 mm or 7.9% for the ReproBone and BioMend compared to baseline (p> 0.05), and 1.1 mm or 14.8% for the BioMend only (p <0.05 ), statistically significant intergroup difference (p <0.05). Measure the horizontal apical decreased by 0.2 mm WG, equivalent to 2.9% (p> 0.05), whereas the CG 0.5 mm or decreased by 7.3% (p <0.05), not statistically significant difference between groups. The Horizontal Cervical Measure (MHC) lost 0.5 mm or 7.2% in GT and 1.4 mm or 15.1% of CG: the intra-group analysis showed statistical difference between the initial data and after 6 months for this parameter (p <0.05) in both groups, and was also a statistically significant difference between groups in the evaluation for the MHC. Conclusion: The results showed that the use of ReproBone associated with BioMend presented benefits and better results in vertical and horizontal maintenance of alveolar ridge compared to using only the collagen membrane.

O objetivo principal deste trabalho consiste na incorporação de substâncias de interesse biológico (fármacos) em filmes de látex natural (NRL). Assim, estudou-se a liberação destes, visando no futuro usar estes filmes como membrana oclusiva e como sistema de liberação controlada (SLC) de substâncias para aplicações odontológicas e ortopédicas, que envolvem a cicatrização óssea guiada. Estudamos o comportamento do SLC utilizando albumina de soro bovina (BSA) como modelo de proteína e o metronidazol (MTZ) como modelo de antibiótico. Diferentes tratamentos térmicos foram aplicados durante a confecção dos filmes a fim de gerar diferentes porosidades e com isso estudar-se a taxa de liberação destes fármacos. A taxa de liberação dos fármacos foi monitorada e quantificada utilizando o método de Lowry e o método UVVIS. Microscopia Eletrônica de Varredura (MEV) e a Microscopia de Força Atômica (AFM) determinaram a morfologia do SLC. Em outro parte deste trabalho desenvolvemos um sistema para liberação do óxido nítrico (NO) agregando-se o complexo (FeDETC) ao NRL, pois esta substância atua como spin trapp para este radical. A taxa de liberação do NO pelo sistema NRL-FeDETC-NO foi caracterizada pela Ressonância Paramagnética Eletrônica (EPR). A escolha destas substâncias para este estudo deve-se pelo fato que auxiliam no processo de regeneração óssea (MTZ e NO). Entretanto, a BSA foi utilizada porque possui peso molecular da mesma magnitude e é mais barata que as proteínas morfogenéticas ósseas (BMP). As BMP´s são excelentes estimuladores do crescimento ósseo. / In this work, we have tested Natural Rubber Latex (NRL) as an occlusive membrane for GBR with promising results. One possible way to accelerate bone regeneration would be to incorporate proteins bone morphogenetic protein (BMPs) in NRL. BMPs have strong bone-inductive activity. However since bone healing takes place in weeks to months, it is important that BMPs are released in these time scales. Instead of using BMPs, in our study we used BSA that has similar molecular weight however is less expensive. Moreover, we also employed the metronidazole (MTZ) and nitric oxide (NO) as drug delivery model. MTZ is a used antibiotic for treatment of infections in the skin, fabrics and bones. Initially, we study the BSA delivery system behavior and MTZ delivery system using different thermal treatments during the membranes polymerization. The thermal treatments control the size of the pores of the SLC and release rate of the BSA and MTZ. These membranes were characterized by Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM), as well as the Lowry Method to measure the BSA release. Finally, we propose a NO delivery system made of a spin trap (iron(II)-diethyldithiocarbamate complex, FeDETC) encapsulated in a NRL matrix. NO is an early mediator of the increase in bone formation. NO delivery system presents high stability by Electron Paramagnetic Resonance. The results indicate that natural rubber latex could be used in the future as an active membrane for accelerated bone healing.

Made available in DSpace on 2014-06-11T19:30:59Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-07-02Bitstream added on 2014-06-13T19:40:33Z : No. of bitstreams: 1 monteiro_asf_dr_sjc.pdf: 1275364 bytes, checksum: bfdaa8d7f731a5d896cca9e24553ed29 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O propósito deste trabalho foi avaliar o efeito do plasma rico em plaquetas associados ou não ao enxerto ósseo autógeno no processo de reparação óssea em defeitos cirúrgicos confeccionados na tíbia de coelhos. Nesta pesquisa foram utilizados 25 coelhos adultos, nos quais foram realizados 2 defeitos em cada tíbia, divididos nos seguintes grupos de acordo com o tratamento: controle (C - defeito preenchido somente por coágulo sangüíneo), autógeno (A - defeito + enxerto), PRP (PRP = defeito + PRP) e autógeno + PRP (PRPA - defeito + enxerto + PRP). Todos os defeitos foram recobertos com uma barreira de PTFE e decorridos 15, 30 e 60 dias, 5 animais foram sacrificados por período, sendo as peças contendo os defeitos processadas para análises histológica e histomorfométrica. Outros 5 animais foram sacrificados aos 30 e 60 dias e submetidos à análise das propriedades biomecânicas e todos os espécimes foram submetidos ao exame radiográfico para análise da densidade óptica. Os resultados biomecânicos, radiográficos e histomorfométricos mostraram maior resistência, densidade óptica e maior formação óssea nos grupos A e PRPA quando comparados com os grupos C e PRP. Os resultados obtidos possibilitaram concluir que não houve uma melhora nos parâmetros radiográficos, mecânicos e na neoformação óssea quando o PRP foi usado isoladamente ou associado ao enxerto ósseo autógeno. / The aim of this study was to evaluate the effect of platelet rich plasma associated or not to autogenous bone graft in bone repair process of tibia rabbits surgical defects. In this research 25 adult rabbits were used, 2 defects were accomplished in each tibia, divided into groups: control (C = bone defect only filled out by blood coagulum), autogenous (A = bone defect + autogenous graft), PRP (PRP = bone defect + PRP) and autogenous + PRP (PRPA = bone defect + autogenous graft + PRP). All of the defects were covered with a PTFE barrier and after 15, 30 and 60 days there were elapsed. Five animals were sacrificed by period, being the pieces containing the defects processed for histological and histomorphometric analysis. Other 5 animals were sacrificed to the 30 and 60 days and submitted to biomechanics analysis and all of the specimens were submitted to the radiographic examination of the optical density. The biomechanic, radiographic and histomorphometric results showed larger resistance, optical density and better bone formation in the groups A and PRPA when compared with the groups C and PRP. This study demonstrated that there was not an improvement in the radiographic, mechanics, and bone formation parameters when PRP was used separately or associated to the autogenous bone graft.

Orientador: Horácio Faig Leite / Banca: Vanessa Ávila Sarmento Silveira / Banca: Luiz Eduardo Blumer Rosa / Resumo: Esta pesquisa avaliou o efeito do uso local do residronato de sódio, em diferentes concentrações molares, no processo de reparação de defeitos ósseos em fêmures de ratas. Foi confeccionado no fêmur de 60 ratas um defeito ósseo medindo 2,5 mm de diâmetro. Estes animais foram divididos em grupos: controle (C), amido (Am), residronato 0,25 mol (Res 0,25), residronato 0,5 mol (Res 0,50), residronato 0,75 mol (Res 0,75) e residronato 1 mol (Res 1), de acordo com o material de preenchimento utilizado. Nos animais do grupo controle o defeito ficou preenchido apenas pelo coágulo. Os animais foram eutanasiados aos sete e 21 dias, e o fêmur foi removido, fixado e descalcificado, para a confecção de lâminas histológicas. Foram realizadas análises histológica e histomorfométrica, e os dados obtidos foram submetidos à análise estatística ANOVA. Histologicamente, as principais diferenças ocorreram após 21 dias. Os grupos C e Am apresentaram fechamento em extensão do defeito ósseo em todos os espécimes e a maioria dos animais dos grupos tratados com residronato em diferentes concentrações molares não exibiu neoformação óssea na região central do defeito, permanecendo este preenchido por tecido conjuntivo. Nos períodos de sete e 21 dias não houve diferença estatística significante entre os grupos C e Am em relação a neoformação óssea. Estatisticamente, não houve diferença entre os grupos Res 0,25; Res 0,50; Res 0,75 e Res 1 no período de sete dias. Já no período de 21 dias o grupo Res 0,25 apresentou a maior média, mas não diferiu estatisticamente do grupo Res 0,75. Concluiu-se que o residronato de sódio em todas as concentrações molares, prejudicou a reparação óssea nesse modelo experimental. No entanto, foi observada uma neoformação óssea extra-cortical subperiosteal nos grupos que receberam residronato. / Abstract: This work evaluated the action of sodium residronate, in different molars concentrations, in the repair of bone defects in femurs of rats. A bone defect measuring 2,5 mm in diameter was made in the femur of 60 rats. These animals were divided in groups: control (C), starch (Am), residronate 0,25 mol (Res 0,25), residronate 0,50 mol (Res 0,50), residronate 0,75 mol (Res 0,75), residronate 1 mol (Res 1), in accordance with the material of fill used. In the animals of the control group, the defect was just filled by the clot originating from the defect. The animals were euthanized at seven and 21 days, when the femur was removed, fixed and decalcified, to make histologicals laminae. Histological and histomorphometric analyses were performed and the results obtained were submitted to statistical analysis ANOVA. Histologically, the principal differences occurred after 21 days. The groups C and Am, showed an extension closure of bone defect in every specimen and most animals in groups treated with residronate in different molar concentrations did not show bone neoformation in the central region of the bone defects, which remained filled with connective tissue. After seven and 21 days, there was no significant statistical difference among groups C and Am in relation to bone neoformation. Statistically, there were no differences among the groups Res 0,25; Res 0,50; Res 0,75 e Res 1 in the period of seven days. In the period of 21 days, the group Res 0,25 had the highest average, but did not differ statistically from the Res 0,75. It was concluded that the sodium residronate in all the molar concentrations, harmed the bone repair in this experimental model. However, there was an extracortical subperiosteal bone neoformation in groups receiving residronate. / Mestre

There exists a dire need for improved therapeutics to achieve predictable and effective bone regeneration. Non-viral gene therapy is a safe method that can efficiently transfect target cells, therefore is a promising approach to overcoming the drawbacks of protein delivery of growth factors. The goal of this study was to employ cost-effective biomaterials to deliver genetic materials (DNA or RNA) in a controlled manner in order to address the high cost issues, safety concerns, and lower transfection efficiencies that exist with protein and gene therapeutic approaches. To achieve our goal, we set several aims: 1) To assess the bone regeneration capacity of polyethylenimine (PEI)-chemically modified ribonucleic acid (cmRNA) (encoding bone morphogenetic protein-2 (BMP-2)) activated matrices, compared to PEI-plasmid DNA (BMP-2)-activated matrices. 2) To explore the osteogenic potential of cmRNA-encoding BMP-9, in comparison to cmRNA-encoding BMP-2. 3) To use collagen membranes as integral components of a guided bone regeneration protocol and to enhance the bioactivity of collagen membranes by incorporating plasmid DNA (pDNA) or cmRNA encoding bone morphogenetic protein-9 (BMP-9). 4) To test whether the delivery of pDNA encoding BMP-2 (pBMP-2) and fibroblast growth factor-2 (pFGF-2) together can synergistically promote bone repair in a leporine model of diabetes mellitus, a condition that is known to be detrimental to union. 5) To investigated whether there is a synergistic effect on bone regeneration following delivery of pBMP-2 and pFGF-2, insulin and/or vitamin D. These investigations together provided new insights regarding the appropriate treatment methods for patients with fractures. Here we develop and test a non-viral gene delivery system for bone regeneration in challenging animal models utilizing a scaffold carrying PEI-nucleic acid complexes. We utilized three kinds of pDNA encoding either BMP-2, BMP-9 or FGF-2 as well as two kinds of cmRNA encoding either BMP-2 or BMP-9 formulated into PEI complexes. The fabricated nanoplexes were assessed for their size, charge, in vitro cytotoxicity, and capacity to transfect human bone marrow stromal cells (BMSCs). The in vivo functional potency of different nanoplexes embedded in scaffolds was evaluated using a calvarial bone defect model in rats, diaphyseal long bone radial defects in a diabetic rabbit model and intramuscular implantation in a diabetic rat. The results indicate that our non-viral gene delivery system induced migration and differentiation of resident cells to enhance bone regeneration. Together these findings suggest that scaffolds loaded with non-viral vectors harboring cmRNA or pDNA encoding osteogenic proteins may be a powerful tool for stimulating bone regeneration with significant potential for clinical translation.

Repair of large bone defects remains a clinical challenge for orthopedic surgeons. Current treatment strategies such as autograft and allograft are limited by the amount of available tissue in the case of the former, and failure of revascularization effecting engraftment in the case of the latter. Tissue engineering offers an alternative approach to this challenging clinical problem. The general principle of tissue engineering for bone regeneration prescribes delivery of osteoinductive factors to induce an endogenous response within the host to repair a defect that will not normally heal. One such tissue engineering approach is cell based therapy and this is attractive in the cases of patients with a lack of endogenous osteoprogenitors cells due to volumetric loss of tissue/ageing. Stem cell therapy has emerged as a possible alternative to current treatment modalities, however many challenges to clinical translation remain. Central to these challenges for bone tissue engineering are lingering questions of which cells to use and how to effectively deliver those cells. The goal of this thesis was to elucidate more effective ways to enhance bone repair utilizing adult stem cells. First, we investigated adipose derived stem cells (ADSCs) as a viable cell source for bone tissue engineering. Upon isolation, adipose derived stem cells are a heterogeneous population of multipotent cells predisposed to adipogenic differentiation. We developed an enrichment protocol that demonstrated the osteogenic potential of ADSCs can be enhanced in a dose dependent manner with resveratrol, which had been demonstrated to up-regulate Runx-2 expression. This enrichment strategy produced an effective method to enhance the osteogenic potential of ADSCs while avoiding cell sorting and gene therapy techniques, thus bypassing the use of xenogenic factors to obtain an enriched source of osteoprogenitor cells. This protocol was also used to investigate differences between human and rat ADSCs and demonstrated that rat ADSCs have a higher osteogenic potential than human ADSCs in vitro. The second major thrust of this thesis was to develop an injectable hydrogel system to facilitate bone formation in vivo. Both a synthetic and a naturally based polymer system was investigated, the results of which demonstrated that the naturally based alginate hydrogel was a more effective vehicle for both cell viability in vitro and bone formation in vivo. Our results also demonstrated that despite the ability to increase the osteogenic potential of ADSCs in vitro with resveratrol treatment, this was insufficient to induce bone formation in vivo. However, the inclusion of bone marrow mesenchymal stem cells (BMMSCs) in BMP-2 functionalized alginate hydrogels resulted in significantly greater mineralization than acellular hydrogels. Finally, the effect of timing of delivery of therapeutics to a non-healing segmental bone defect in the femur was investigated. We hypothesized that delivery of biologics after the initial inflammation response caused by injury to the host tissue would result in greater regeneration of tissue in terms of newly formed bone. Contrary to our initial hypothesis, these experiments demonstrated that delayed implantation of therapeutics has a detrimental effect on the overall healing response. It was, however, demonstrated that the inclusion of BMMSCs results in greater bone volume regenerated in the defect site over acellular hydrogels. In conclusion, this work has rigorously investigated the use of adipose derived stem cells for bone tissue engineering, and further produced an injectable hydrogel system for stem cell based bone tissue engineering. This work also demonstrated that the inclusion of adult stem cells, specifically BMMSCs, can enhance the regeneration response in a non-healing bone defect model relative to acellular hydrogel.

A new model of a critically-sized segmental femoral bone defect in rats was developed to enable in vivo imaging and facilitate post-mortem mechanical testing of samples. The critically-sized nature of the model was assessed and confirmed. The efficacy of sustained co-delivery of osteogenic (BMP-2 and TGF- Ò3) and angiogenic (VEGF) growth factors in promoting functional bone repair was assessed. Effects of scaffold modification in terms of geometry and composition were evaluated. The results indicated that co-delivery of BMP-2 and TGF- Ò3 resulted in a dose-dependent improvement in functional bone repair. Modification of the polylactide scaffold to include an absorbable ceramic component and a cored out geometry enhanced rate of union. Addition of VEGF to the scaffold treatment did not significantly impact revascularization of the defect site or functional repair of the bone defect. These data demonstrate that the complex environment of an acute bone defect requires different treatment strategies than simple ectopic models would suggest. A positive predictive correlation between bone repair parameters measured in vivo and mechanical functionality was established. The novel defect model demonstrated robustness and reproducibility. Implications for further research are discussed.

Non-healing bone defects have a significant socioeconomic impact in the U.S. with approximately 600,000 bone grafting procedures performed annually. Autografts and allografts are clinically the most common treatments; however, autologous donor bone is in limited supply, and allografts often have poor mechanical properties. Therefore, tissue engineering and regenerative medicine strategies are being developed to address issues with clinical bone grafting. The overall objective of this work was to develop bone tissue engineering strategies that enhance healing of orthotopic defects by targeting specific osteogenic cell signaling pathways. The general approach included the investigation of two different tissue engineering strategies, which both focused on directed osteoblastic differentiation to promote bone formation. In the first cell-based strategy, we hypothesized that constitutive overexpression of the osteoblast-specific transcription factor, Runx2, in bone marrow stromal cells (BMSCs) would promote orthotopic bone formation in vivo. We tested this hypothesis by delivering Runx2-modified BMSCs on synthetic scaffolds to critically-sized defects in rats. We found that Runx2-modified BMSCs significantly increased orthotopic bone formation compared to empty defects, cell-free scaffolds and unmodified BMSCs. This gene therapy approach to bone regeneration provides a mineralizing cell source which has clinical relevance. In the second biomaterial-based strategy, we hypothesized that incorporation of the collagen-mimetic peptide, GFOGER, into synthetic bone scaffolds would promote orthotopic bone formation in vivo without the use of cells or growth factors. We tested this hypothesis by passively adsorbing GFOGER onto poly-caprolactone (PCL) scaffolds and implanting them into critically-sized orthotopic defects in rats. We found that GFOGER-coated scaffolds significantly increased bone formation compared to uncoated scaffolds in a dose dependent manner. Development of this cell-free strategy for bone tissue engineering provides an inexpensive therapeutic alternative to clinical bone defect healing, which could be implemented as a point of care application. Both strategies developed in this work take advantage of specific osteoblastic signaling pathways involved in bone healing. Further development of these tissue engineering strategies for bone regeneration will provide clinically-relevant treatment options for healing large bone defects in humans by employing well-controlled signals to promote bone formation and eliminating the need for donor bone.

Thesis (Ph.D.)--University of Alabama at Birmingham, 2007. / Title from PDF title page (viewed on Feb. 19, 2010). Includes bibliographical references.