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Role of physiochemical parameters in the osteogenic potential of calcium phosphate biomaterialsCampion, Charlie January 2015 (has links)
The number of clinical procedures performed in the USA using bone graft substitutes was estimated at 1.1 million in 2010 and is projected to reach 1.3 million in 2015. This increasing demand for bone graft substitutes is a result of an ever-ageing population coupled with recent reports in the clinical literature of concerns regarding the safety of allograft and recombinant bone morphogenetic proteins such as rh- BMP-2 and the supply of autograft, which has led to an increased clinical interest in synthetic alternatives to allograft; autograft; and recombinant growth factors. One such synthetic material is silicate-substituted hydroxyapatite (SiCaP). Mechanical testing revealed SiCaP to have similar mechanical behaviour to morcellised cancellous bone. In computated spinal and hip models the simulated stresses in SiCaP were determined to be low when in situ, indicating a stressshielding effect from the implanted metalwork and surrounding bone. We also found an inverse relationship between porosity and Young's Modulus. Our results indicated that the strut-porosity of a material substrate should be increased to maximise the potential for formation of a precursor to bone-like apatite after implantation in osseous defects and further confirmed previous reports that betatricalcium phosphate is less bioactive than hydroxyapatite. We demonstrated a direct link between the amount of strut-porosity and the osteoinductivity of SiCaP. We learned that adding a resorbable carrier phase did not impair the osteoinductive potential of SiCaP, suggesting that osteoinductivity is not necessarily determined in the first 24-48 hours post implantation. Most notably from our studies we determined that the osteoinductivity of SiCaP correlated with its performance in orthotopic defects. Our research confirmed our hypothesis that modifying the micron-scale physical structure of a hierarchical porous SiCaP based biomaterial influences its functional performance in vitro and such modifications can be applied to improve its performance outcomes in ectopic and orthotopic treatment sites in vivo.
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The minimization of morbidity in cranio-maxillofacial osseous reconstruction:bone graft harvesting and coral-derived granules as a bone graft substituteSándor, G. K. (George Kálmán Béla) 25 April 2003 (has links)
Abstract
Reduction of morbidity in osseous reconstruction of cranio-maxillofacial bony defects could come from development of less invasive bone graft harvesting techniques or by elimination of bone graft donor sites using a bone graft substitute. This work studies outcomes and morbidity associated with these two approaches.
A power-driven trephine was used to harvest bone from the anterior iliac crest using a minimally invasive surgical technique. Initially the safety of the technique was evaluated in a cadaver model. Twenty-five freshly preserved adult cadavers had a total of 250 cancellous cores of bone harvested from 50 anterior iliac crest sites. Twenty intentional perforations were made to the maximum depth possible with the instrumentation tested. No encroachment upon the peritoneum was found.
A total of 84 patients had 333 cores of cancellous bone harvested using the same approach with a complication rate of 3.6% and a patient satisfaction rate of 98.8%. In a further 76 patients the motorized trephine method was compared to traditional open iliac crest corticocancellous block harvesting. The trephine group ambulated earlier, required fewer days of hospital stay and had significantly lower pain scores than the open iliac crest group.
Coral-derived granules were used as a xenograft bone graft substitute to treat bony defects in the cranio-maxillofacial skeletons of 36 patients with 54 sites and followed for 12 to 36 months. The augmentations produced satisfactory results with the following complications noted: overt wound infection 1.8%, wound irritation 3.8% and clinically evident resorption in 9.3% of augmented sites.
Coral-derived granules were then used to treat 48 dento-alveolar defects in 21 growing patients with trauma induced tooth-loss in the anterior maxilla and elective ankylosed tooth removal in the posterior maxilla and mandible. Coral granules were significantly more efficacious in reconstructing alveolar defects in the posterior maxilla or mandible (93.5%), than the anterior maxilla (17.6%).
The minimally invasive technique using a power driven trephine was successful at reducing morbidity from bone graft harvesting at the anterior iliac crest. Coral-derived granules can be used in selected situations as a bone graft substitute and minimize post surgical morbidity by eliminating the bone graft donor site.
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Calcium phosphate substrate-directed osteogenic differentiation of mesenchymal stem cellsCameron, Katherine Rachel January 2013 (has links)
An increase in degenerative bone disease in an ageing population, combined with a rise in the number of patients suffering from bone defects caused by physical trauma, makes the repair of bone an issue of growing clinical relevance. Current treatments such as autografts and allografts have major drawbacks, including donor site morbidity, limited availability, disease transmission and immune rejection. To overcome these issues synthetic bone grafts have been developed to mimic the mineral phase of bone. Given the significant roles of silicon in bone growth and development there has been great interest in introducing silicon into synthetic bone grafts to enhance their bioactivity. Calcium phosphate based silicate containing grafts have demonstrated enhanced bioactivity, improved physical properties, enhanced protein adsorption and greater bone formation, when compared to non-silicated calcium phosphates such as hydroxyapatite. However, is not clear whether the increased bone formation associated with these materials is the result of greater osteoblast activity or a rise in numbers of osteoblasts resulting from activation and differentiation of stem/ progenitor cells. To answer this question, multipotent stem cells were cultured on silicate substituted calcium phosphate (Si-CaP) and hydroxyapatite (HA). Si-CaP promoted greater cell adhesion and enhanced proliferation when compared to HA. Cells differentiated along the osteogenic lineage on both substrates as evidenced by up regulation of osteoblast specific genes and proteins. However, cells on Si-CaP showed earlier and greater gene expression of all osteoblast genes examined, and greater protein production as detected by immunohistochemistry. Integrin gene expression analysis revealed up regulation of α an d β subunits on both substrates during differentiation. Integrins α5 and β1 expression were greater on Si-CaP than on HA, suggesting preferential binding of fibronectin. The implication of these findings for tissue engineering is clear, suggesting these substrates may be utilized to control stem cell fate in vivo and in vitro without the need for osteogenic supplementation. Furthermore, the increased rate of differentiation seen on Si-CaP may enable the development of novel substrates for osteogenic differentiation of MSC, which may have significant impact in regenerative medicine.
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Efeito do substituto ósseo particulado associado ou não ao MTA na citotoxicidade, resposta tecidual e reparo ósseo em defeitos críticos em calvária de ratos /Machado, Thiago. January 2019 (has links)
Orientador: Wirley Gonçalves Assunção / Resumo: A utilização de biomateriais que visam devolver o volume ósseo perdido após a perda dentária tem se expandido. O osso é um tecido conjuntivo altamente especializado, possuindo dinâmica aposicional onde o equilíbrio entre neoformação e reabsorção envolve a interação de fatores endócrinos, parácrinos e autócrinos. Diversas associações de materiais diversos e substitutos ósseos têm sido estudadas, porém, o MTA (Agregado Trióxido Mineral) ainda carece de informações acerca da sua utilização como substituto ósseo ou em associação com demais substitutos. Assim, o objetivo deste estudo foi avaliar a influência da presença do MTA Angelus Branco® nas proprorções de 5%, 10% e 15% em associação com substituto ósseo de Hidroxiapatita e β- Tricálcio Fosfato na citotoxicidade, resposta tecidual e reparo ósseo, em defeito crítico em calvária de ratos. Para tanto, utilizou-se cultura celular da SAOS-2 para avaliação citológica e ensaio MTT do contato direto e eluentes. Também foram utilizados 112 ratos machos Wistar distribuídos em 7 grupos e avaliados em 2 tempos (7 e 28 dias). Após eutanasiados foram submetidos à microtomografia e por coloração de hematoxilina e eosina para análise histológica e histomorfométrica. A análise da homocedasticidade foi realizada pelo teste Shapiro-Wilk, para distinção dos dados paramétricos e não paramétricos. Para análise dos dados paramétricos, foi realizada análise de variância One-Way (ANOVA One-Way) e realizado o pós-teste de Tukey para os parâmetros micr... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The use of biomaterials that aim to return lost bone volume after tooth loss has expanded. Bone is a highly specialized connective tissue with appositional dynamics where the balance between neoformation and resorption involves the interaction of endocrine, paracrine and autocrine factors. Several associations of different materials and bone substitutes have been studied. However, the MTA (Mineral Trioxide Aggregate) still lacks information about its use as bone substitute or in association with other substitutes. Thus, the aim of this study was to evaluate the influence of presence of MTA Angelus Branco® in the 5%, 10% and 15% proportions in association with Hydroxyapatite and β-Tricalcium Phosphate bone substitute in cytotoxicity, tissue response and bone repair in critical defect in rat calvaria. For this, SAOS-2 cell culture was used for cytological evaluation and MTT assay of direct contact and eluents. We also used 112 male Wistar rats distributed into 7 groups and evaluated at 2 distinct times (7 and 28 days). After euthanasia, the specimens were submitted to microtomography and hematoxylin and eosin staining for histological and histomorphometric analysis. The analysis of homoscedasticity was performed by the Shapiro-Wilk test for distinction of parametric and non-parametric data. For analysis of parametric data, one-way analysis of variance (One-Way ANOVA) was performed and Tukey's post-test was performed for the microtomographic parameters and for the cytotoxicity t... (Complete abstract click electronic access below) / Mestre
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Bone tissue regeneration indento-alveolar surgery : clinical and experimental studies on biomaterials and bone graft substitutesSahlin-Platt, Annika January 2011 (has links)
Pathological processes in the alveolar and facial bones can lead to bone loss that may not heal with complete regeneration. Biomaterials can be used to facilitate the healing process and/or as a bone substitute, but the mechanisms are not fully understood. Persistent leakage of bacteria/bacterial toxins, after root canal treatment, may lead to a residual bone defect. The healing is dependent on a placed dental biomaterial providing a tight seal. The composition of the filling material may also influence the healing process. The general aim of this study is to investigate surface properties and biological interactions of biomaterials used in dento-alveolar surgery. A dental biomaterial, a bonded compomer (DAP) containing a corroding glass filler, was used as a root end filling material, promoting a new operation technique. The healing (assessed according to Molven´s x-ray criteria) demonstrates a significant improvement in healing results for the compomer group, compared to a commonly used technique. The surface properties and biological interactions of DAP were analyzed. ICP-OES of DAP cell culture medium extract demonstrated a significant release of Sr, Si and F from the dental biomaterial. Human periodontal ligament (PDL) cells grew on and around DAP specimens without any sign of toxic reactions. DAP extract stimulated proliferation of PDL cells, but caused an inhibition of osteoblastic gene expression in mouse bone marrow cells. The surface properties of the glass containing compomer may contribute to improved healing of the periapical lesions. A bovine inorganic bone graft substitute (BO) is commonly used as a treatment option in dento-alveolar surgery with new bone formation in immediate close contact with BO material. ICP-OES dissolution analysis of cell culture media, after incubation with BO particles, demonstrated a dosedependent release of Si and a decrease of Ca and P. An uptake of Ca from the medium to the BO particle was demonstrated with calcium-45 labeling. The Si dissolution varied between different batches, possibly reflecting a variation in food intake in the animals. Stimulated osteogenic response was seen in close contact to the BO particles in cell cultures. Furthermore, it was clearly demonstrated that the study design is a critical factor for correctly understanding biomaterials’ biological interactions. The surface properties of three bone graft substitutes reported to have good results in dento-alveolar surgery were investigated, in order to establish whether or not dissolution-precipitation reactions could contribute to the bone healing. Dissolution-precipitation extracts of BO, bioactive glass 45S5 (BG) and a marine algae hydroxyl apatite (AP) in cell culture media were analyzed. Dissolution of Si at significant levels was detected for BO and 45S5 over time. Significant uptake levels of Ca and P from the culture were seen for both 45S5, BO and AP but at different times. Surface analysis of the biomaterials with SEM/EDAX, before and after immersion in cell culture media, revealed a smoothing of the surface morphology for 45S5 over time. No obvious alterations for BO and AP were detected. Ca/P ratio decreased significantly for 45S5, but no major changes were detected by XPS for BO or AP. XPS further demonstrated a surface charge for BO, changing from negatively to positively charged when exposed to serum. 45S5 and AP had positive surface charges, both in the absence and the presence of serum. These demonstrated surface changes in biomaterials could contribute to adherence of cells and subsequently affect bone healing. Conclusion: Biomaterials used in dento-alveolar surgery interact with biological surroundings through surface and dissolution-precipitation reactions which may have implications for bone healing.
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Bio-inspired structured composites for load-bearing bone graft substitutionGalea, Laetitia 21 May 2015 (has links) (PDF)
Natural composites, in particular nacre, often combine high strength and toughness thanks to highly ordered architectures and controlled geometries of the reinforcement components. However, combining strength, toughness and resorbability in synthetic materials remains a challenge in particular in the field of bone graft substitutes. In the present study, calcium phosphate-(CaP-)based materials with designed architectures inspired from natural composite materials were achieved. CaP platelets obtained by precipitation in organic medium were first aligned in chitosan matrices by solvent casting in ambient conditions. Efficient strengthening was obtained with 15 vol-% ceramic, reaching cortical bone strength (150 MPa) and preserving good ductility (5 % deformation). In a weak magnetic field, high spatial arrangement without percolation was maintained up to 20 vol-%. With directional freezing, good alignment of the platelets could be pushed up to 50 vol-%. In parallel, in situ recrystallization of CaP blocks in hydrothermal conditions led to hierarchical structures. The strength and the work-of-fracture were enhanced (300%) thanks to a change of failure mode.
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Bio-inspired structured composites for load-bearing bone graft substitutionGalea, Laetitia 03 March 2015 (has links)
Natural composites, in particular nacre, often combine high strength and toughness thanks to highly ordered architectures and controlled geometries of the reinforcement components. However, combining strength, toughness and resorbability in synthetic materials remains a challenge in particular in the field of bone graft substitutes. In the present study, calcium phosphate-(CaP-)based materials with designed architectures inspired from natural composite materials were achieved. CaP platelets obtained by precipitation in organic medium were first aligned in chitosan matrices by solvent casting in ambient conditions. Efficient strengthening was obtained with 15 vol-% ceramic, reaching cortical bone strength (150 MPa) and preserving good ductility (5 % deformation). In a weak magnetic field, high spatial arrangement without percolation was maintained up to 20 vol-%. With directional freezing, good alignment of the platelets could be pushed up to 50 vol-%. In parallel, in situ recrystallization of CaP blocks in hydrothermal conditions led to hierarchical structures. The strength and the work-of-fracture were enhanced (300%) thanks to a change of failure mode.:Acknowledgements v
Summary vii
Background vii
Thesis outline viii
Part I: “Brick-and-mortar” structures with discrete reinforcement components ix
Part II: “Textured” structures with continuous reinforcement components x
Zusammenfassung xi
Hintergrund xi
Doktorarbeit Gliederung xii
Teil I: “Ziegelmauer-Architektur” mit diskreten Verstärkungskomponenten xiii
Teil II: “ Texturierte” Strukturen mit kontinuierlichen Verstärkungskomponenten xiv
Chapter 1: General introduction 1
Bone grafting 1
CaP ceramics 1
How to improve toughness of CaP ceramics? 2
Importance of structure design: bio-inspiration 2
What mechanical properties should be reached? 5
Specific aims 5
Two general approaches to reach the goal 6
Nacre-inspired “brick-and mortar” structures (Part I) 6
Textured ceramic monoliths (Part II) 6
References 7
Chapter 2: Theoretical calculations 11
Introduction 12
Theoretical tensile strength of β-TCP platelets and critical size for flaw tolerance 13
Optimal aspect ratio 15
Composite strength and stiffness 17
Limitations 19
References 19
PART I: NACRE-INSPIRED “BRICK-AND-MORTAR” STRUCTURES
Chapter 3: Synthesis of sub-micrometer calcium phosphate platelets 23
Introduction 24
ii
Materials and Methods 25
Precipitation method 25
Reaction parameters 25
Characterization 26
Statistical analysis of results 28
Results 28
Reproducibility of standard experiments 28
Increase of the reagent volume to increase the productivity 30
Increase of the precursors concentration to increase the productivity and modify the
particles 30
Increase of titration rate to simplify the process 32
Influence of temperature on the particles 35
Effect of the pH value on the particles 37
Effect of a longer reaction time on the particle stability 40
Study of the influence of variations of the Ca/P molar ratio 42
Discussion 43
Reproducibility 43
Productivity 44
CaP crystal shape 45
Crystal purity 47
Aspect ratio 48
Critical thickness 49
Uniformity of primary particles 50
Non agglomerated 51
General points 52
Conclusions 52
References 53
Chapter 4: Kinetics study of the calcium phosphate platelets growth 57
Introduction 58
Theory 58
Materials and methods 60
Materials and sample preparation 60
Characterization methods 61
Results 62
Visual observations during manipulations 62
SEM observations 62
XRD results 66
Size measurements 68
Kinetics calculations 70
Discussion 74
Nucleation and assembly mechanism 74
Reaction kinetics 76
Control of size and aspect ratio 76
Conclusions 77
References 78
Chapter 5: Structural design of bio-inspired composites by solvent casting 81
Foreword 82
Introduction 82
Experimental section 84
iii
Synthesis of resorbable ceramic platelets 84
Solvent casting to prove the reinforcement efficiency of DCP platelets 84
Magnetization of the platelets 85
Maintaining the orientation during drying of an hydrogel matrix 86
Results 87
Synthesis of resorbable ceramic platelets 87
Solvent casting to prove the reinforcement efficiency of CaP platelets 87
Magnetization of the platelets 91
Maintaining the orientation during drying of an hydrogel matrix 93
Discussion 95
Detrimental effect of β-TCP platelets in chitosan 95
Efficient reinforcement with DCP platelets up to a given volume fraction 96
Threshold value for strength improvement 97
Fitting the experimental results with theoretical equations 98
Conclusions 101
References 101
Chapter 6: Biodegradable, strong and tough nacre-inspired structures obtained by freezecasting
105
Introduction 106
Experimental section 108
Synthesis of resorbable ceramic platelets 108
Preliminary freeze-casting tests with β-TCP-based slurries 108
Determination of adequate freeze-casting parameters for hydrogels-CaP slurries 108
Integration of CaP platelets and local planar alignment 109
Attempts to globally align porosity in two directions 109
Densification and consolidation 110
Tensile testing 110
Results 111
Preliminary freeze-casting tests with β-TCP-based slurries 111
Determination of adequate freeze-casting parameters for hydrogels-CaP slurries 112
Integration of CaP platelets and local planar alignment 113
Attempts to globally align porosity in two directions 119
Densification and consolidation 121
Tensile testing 121
Discussion 122
Conclusions 124
References 125
PART II: TEXTURED CERAMIC MONOLITHS
Chapter 7: Micro-texturing by recrystallization of calcium phosphate blocks in hydrothermal
conditions 127
Introduction 128
Materials and Methods 130
Samples characterization 132
Results 133
Macroscopic observations 133
Microstructural changes (SEM) 133
Crystalline phase conversion (XRD) 139
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Mechanical properties 142
Fractured surfaces 142
Discussion 145
Conclusions 150
References 150
Chapter 8: Toughening of textured calcium phosphate blocks by polymer impregnation 155
Foreword 156
Introduction 156
Materials and Methods 157
Samples preparation 157
Characterization 158
Results 158
Porosity and microstructure 158
Composition 161
Mechanical properties 161
Discussion 162
Conclusions 164
References 164
Chapter 9: Synthesis and outlook 167
Curriculum Vitae 171
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BIOERODIBLE CALCIUM SULFATE BONE GRAFTING SUBSTITUTES WITH TAILORED DRUG DELIVERY CAPABILITIESOrellana, Bryan R 01 January 2014 (has links)
Bone regeneration or augmentation is often required prior to or concomitant with implant placement. With the limitations of many existing technologies, a biologically compatible synthetic bone grafting substitute that is osteogenic, bioerodible, and provides spacing-making functionality while acting as a drug delivery vehicle for bioactive molecules could provide an alternative to ‘gold standard’ techniques.
In the first part of this work, calcium sulfate (CS) space-making synthetic bone grafts with uniformly embedded poly(β-amino ester) (PBAE) biodegradable hydrogel particles was developed to allow controlled release of bioactive agents. The embedded gel particles’ influence on the physical and chemical characteristics of CS was tested. Namely, the compressive strength and modulus, dissolution, and morphology, were studied. All CS samples dissolved via zero-order surface erosion consistent to one another. Compression testing concluded that the amount, but not size, of embedded gel particles significantly decreased (up to 75%) the overall mechanical strength of the composite. Release studies were conducted to explore this system’s ability to deliver a broad range of drug types and sizes. Lysozyme (model protein for larger growth factors like bone morphogenic protein [BMP]) was loaded into PBAE particles embedded in CS matrix. The release of simvastatin, a small molecule drug capable of up regulating BMP production, was also examined. The release of both lysozyme and simvastatin was governed by dissolution of CS.
The second part of this work proposed a bilayered CS implant. The physical and chemical properties were characterized similarly to the CS composites above. Release kinetics of directly loaded simvastatin in either the shell, core, or both were investigated. A sequential release of simvastatin was witnessed giving foresight of the composite’s tunability. The sequential release of an antibacterial, metronidazole, loaded into poly(lactic-co-glycolic acid) (PLGA) particles embedded into the shell along with directly loaded simvastatin either in the shell, core, or both layers was also observed. Through controlled release of bioactive agents, as well as a tunable layered geometry, CS-based implants have the potential to be optimized in order to help streamline the steps required for the healing and regeneration of compromised bone tissue.
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