Barbieri Thesis - BioMedical Materials program (BMM)

Summary
containing 96%mol. L–lactide), which led to excessively slow degradation. In vitro
results indicated that surface roughness is a parameter affecting the final material
properties with implications on its biological performances, but we should consider the
limitation of in vitro systems and thus be careful in the extrapolation to the complex
in vivo environment.
We studied the role of two intrinsic properties of the polymer phase, i.e. the
molecular weight and the choice of monomer, on osteoinduction. We observed that
polymers with low molecular weight or containing D,L–lactide monomer led to larger
fluid uptake in their composites (Chapters 6, 7), indirectly enhancing their biological
properties. In particular, composites containing such polymers activated a cascade of
surface events where nano–structured mineralized surfaces formed on which
serum proteins were adsorbed. Cell colonization and differentiation on such
mineralized surface may have been guided by the adsorbed protein motifs, leading
later to heterotopic bone formation. Larger fluid uptake also caused more
degradation, which released ions and increased the available space for bone
ingrowth. Further, increased stiffness and decreased damping were seen for those
composites with high molecular weight or low D,L–lactide containing polymers.
To examine whether a common general link between material properties and
osteoinduction exists (Chapter 6), we observed that hydrophilicity, in general,
improved the contact between fluids and biomaterials leading to larger fluid uptake.
Since fluids carry various molecules and ions, such improved contact enhanced
biomolecule adsorption and surface mineralization. Thus, the early cell response
upon implantation may have been improved; triggering cytokine production by
macrophages and eventually inducing bone formation. Further, absorbed fluids
enhanced biomaterial degradation and facilitated the release of calcium and
phosphate ions together with changes at the surface structure, for example by
generating nano– or micro–porosity. The combination of such phenomena triggered
by fluid uptake contributed to heterotopic bone formation. Although it was possible to
apply this general hypothesis only to each class of biomaterial separately, it was not
valid under a more general ‘biomaterial’ view (Chapter 6).
In this thesis we evaluated some crucial factors in the design of instructive composite
biomaterials. However, other factors that were not evaluated in this work, such as the
monomer content after extrusion, or changes in polymer crystallinity, should not be
excluded from having an effect on the biological properties of instructive composites.
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