Barbieri Thesis - BioMedical Materials program (BMM)

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.
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