Barbieri Thesis - BioMedical Materials program (BMM)

Chapter 8 – General discussion
can induce various and controlled cellular behaviors ultimately leading to new tissue
synthesis. [103, 152–154]
8.1.2. Instructive biomaterials in bone tissue engineering
In bone tissue regeneration, a subgroup of instructive biomaterials has the potential to
favor undifferentiated stem cells to differentiate into bone phenotype without addition
of (osteogenic) factors or cells (i.e. biomaterial–directed osteoinduction
phenomenon). [86] It has been suggested that the micro–structured surface of certain
calcium phosphate ceramics may be a key factor inducing and supporting heterotopic
bone growth in large animals (e.g. dog and sheep), [86, 228, 236, 237] and such
osteoinductive ceramics demonstrated to be effective alternatives to autologous bone
grafts in critical–sized bone defects. [86, 238] Besides the clear biological benefits such
ceramics bring, they have two main drawbacks: their handling characteristics and
their brittleness. In this thesis we evaluated the material factors to be considered
when designing instructive and improved calcium phosphate–based materials by
means of composites. According to the European Composites Industry Association
(EuCIA), [404] composite materials are the combination of two or more materials to
reinforce their properties making them mechanically, chemically, physically or
biologically better together than they are apart. Thus, to improve the handling or
mechanical performances of osteoinductive calcium phosphates we added a polymer
component to obtain composite materials. The calcium phosphate phase would
contribute to the biological (i.e. osteoinductive) properties of the composite whereas
the polymer phase would have roles in the handling and mechanical properties.
However, adding a polymer may have effects or even take actively part in the
material–directed osteoinductive phenomenon. The challenge in this thesis was to
develop composite biomaterials that are, at the same time, degradable to leave
room to the growing tissue, mechanically suitable for the required clinical application
in load–bearing sites, have good handling properties and still be osteoinductive. In
particular, we evaluated the design factors involved when designing such instructive
composite biomaterials for bone tissue regeneration.
8.1.3. Dissolution rate of (hydro)gels and osteoinduction
Most osteoinductive calcium phosphate ceramics are manufactured in block or
particular forms, which have poor handling properties. Adding a polymer (hydro)gel to
ceramic particulate has been proposed as a way to prepare putties and/or injectable
pastes with better handling properties. Initial (stem) cell adhesion on the surface of
osteoinductive ceramics appears to be the first step to trigger osteoinduction
phenomenon. [86] Therefore, we hypothesized that covering the micro–structured
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