Barbieri Thesis - BioMedical Materials program (BMM)

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Chapter 1 – Introduction 1.11. Rationale and aims of the thesis Based on the aforementioned introductory review, it can be said that guiding the regeneration of injured body tissues might be possible through the control of various material parameters that eventually instruct cells. In particular, biomaterials should actively interact with the biological surrounding evoking a cascade of specific phenomena that will lead to the full regeneration of the required tissue. In bone tissue regeneration, the most promising instructive materials (i.e. micro–structured calcium phosphate ceramics) already showed their tissue regenerative potential but can only be used as fillers for bone voids where no mechanical stresses act. Therefore for bone regeneration in load–bearing sites, the sole instructive characteristic may not be sufficient. Designing materials that, besides controlling cellular fate in vivo, also have improved mechanical performances is a key request. Further, most calcium phosphate ceramics are prepared in block or particulate forms making their handling properties not optimal with risks of incomplete defect filling or granule dispersion during surgery. Consequently, developing bone instructive materials with improved handling properties would be desired. Combining polymers with calcium phosphate granules or powders has been suggested as possible solution to have improved biomaterials that might be used in bone sites, either with or without mechanical stresses. For these reasons, many groups have already proposed moldable putties of calcium phosphate granules with polymeric gels, or composites of hydroxyapatite with either degradable and not polymers. However, to the best of our knowledge, none reported or studied the impact of polymer and calcium phosphate phases on the instructive properties of the resulting composites. Therefore, the objective of this thesis was to evaluate the influence of polymer and calcium phosphate phases when designing instructive composite materials for bone tissue regeneration. 1.12. Outlines of the thesis The effect of polymer gels on the osteoinductive potential of calcium phosphate granules in putties and injectable pastes is studied in Chapter 2, which is based on the assumption that fast dissolution and clearance of the gel is a crucial factor. Thereafter, Chapter 3 introduces a pilot study on the feasibility to design osteoinductive composites. This Chapter puts the basis for further studies on the effects of manufacturing methods and choice of polymer phase features (i.e. molecular weight, monomer chemistry) on the osteoinductivity, mechanical and degradation properties of composites (Chapters 4–7). Further, the importance of role of body fluid uptake by biomaterials is also hypothesized and studied using, besides composites, also calcium phosphate ceramics (Chapter 7). Finally, a general discussion and conclusion are reported in Chapter 8. 24
CHAPTER 2 The role of gels in bone instructive putties The results described in this Chapter are published in: <strong>Barbieri</strong> D, Yuan H, de Groot F, Walsh WR, de Bruijn JD. Influence of different polymeric gels on the ectopic bone forming ability of an osteoinductive biphasic calcium phosphate ceramic. Acta Biomater. 2011, 7, 2007.
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CHAPTER 5 Effects of alkali surface
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Chapter 6 - Flu uid uptake as insst
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Figure 7. Mass left (a) annd fluid
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Chapter 7 - Polymer molecular weigh
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ūapatite = 100 · mdry · pap Chap
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CHAPTER 8 General discussion
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Chapter 8 - General discussion 8.1.
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References [1] Waggoner B. Eukaryot
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References induction of rank in ost
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References [72] Kokovay E, Wang Y,
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References [102] McBeath R, Pirone
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References molecule-mediated TGF- t
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References [159] Autumn K, Sitti M,
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References [189] Teixeira AI, McKie
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References [215] Tang L, Jennings T
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References [242] Wei G, Ma PX. Stru
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References [270] Atkinson BL, Hanks
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References [297] Sato I, Akizuki T,
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References hematopoietic stem cell
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References [352] Cullinane DM, Sali
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References [382] Norde W, Giacomell
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References differentiation of rat B
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Acknowledgments thank you for all t
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Acknowledgments desidero tutto il m
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