Barbieri Thesis - BioMedical Materials program (BMM)

Chapter 8 – General discussion
ceramic surface with a slowly dissolvable polymer (hydro)gel would inhibit or delay
cell adhesion and thus osteoinduction. To evaluate this, we used polymer binders with
different dissolution rates and studied their effect on bone induction when combined
with micro–structured ceramics and after ectopic implantation. Our results indicated
that the availability of the ceramic micro–structured surface to the surrounding tissue
in early post–implantation time is crucial. Moreover, free space between granules is
likely necessary for vasculature formation and soft tissue infiltration, which may be
obstructed with slower degrading (hydro)gels reducing, or even nullifying, the chances
of stem cell migration into the implant. It was concluded in Chapter 2 that designing
instructive putties (or injectable pastes) implies careful choice of the binder, whose
chemistry and dissolution rate are crucial factors for its in vivo performance.
8.1.4. Manufacturing nano–composites: considerations
As mentioned earlier, the intrinsic brittleness of (commercially available) ceramic
materials restricts their use as fillers to mechanically non–loaded sites. Thus
scientists strive to design biologically active composite materials that may bear
mechanical loads. At the same time, to favor bone growth and full replacement of
the implant with new tissue over time, controllable degradation rate is a crucial
property as well. Adding (micro– or nano–) (hydroxy)apatite particulate or fibres into
polylactide led to porous materials with improved mechanical properties. [239, 240] In
particular, composites containing more than 40%wt. hydroxyapatite resulted also
osteoconductive, [241] with enhanced protein adsorption and osteoblast adhesion in
vitro. [241–243] In some cases, such porous composites fabricated with solvent–methods
were reported to be osteoinductive as well. [235] However, to support (physiological)
cyclic stresses, composites may need dense bulk with homogeneous distribution of
calcium phosphate particulate in the polymer matrix, which relies on the
manufacturing method. We observed that, despite the occurrence of thermal and
frictional degradation of the polymer phase, extrusion could be used to make highly
homogeneous composites with mechanical characteristics similar to those of dry bone
(Chapter 4). Consistently with literature results, [336] we observed that extrusion
decreased the molecular weight of the polymer. In particular, this effect was
dependent on the starting molecular weight of the used polymers and on the filler
content (Chapters 4, 5). On the contrary, a solvent–based method did not have
degrading effects on the polymer but led to inhomogeneous porous materials and
issues such as incomplete solvent evaporation (Chapter 3). This fact has
consequences on the mechanical and degradation features of the composite. It was
therefore concluded that the manufacturing method is a crucial factor to be
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