Barbieri Thesis - BioMedical Materials program (BMM)

Summary
Summary
Developing new biomaterials for tissue regeneration requires careful balance
between many factors, which is challenging because, on one side, such materials
must provide complex information, through their physicochemical properties to
actively interact with the biological surroundings and induce tissue regeneration. On
the other side, regulatory issues, costs and ease of use of the final device, require
low system complexity. For this reason, an emerging strategy is not attempting to
recreate the complexity of tissues in vitro, but to focus on synthetic materials that
have ‘intrinsic’ features that can instruct cells in vivo finally determining their fate.
Therefore, newly developed biomaterials should be carefully designed to have
specific local characteristics (e.g. surface stiffness, chemistry and topography) that
can induce controlled cellular behaviors ultimately leading to tissue regeneration. In
bone tissue regeneration by biomaterials, such instructing phenomenon is referred as
‘osteoinduction’.
In this thesis we aimed to develop simple biomaterial systems, i.e. composites of
two phases (i.e. polymer and calcium phosphate) that could be able to interact with
the biological system. In particular, we have striven to understand the role of some
‘intrinsic’ characteristics of the composite phases (e.g. calcium phosphate content,
polymer molecular weight and monomer chemistry) in determining crucial phenomena
occurring at the interface between biomaterial and biological environment. Such
surface processes, e.g. surface mineralization and protein adsorption, play key roles
in instructing (stem) cells leading to bone tissue regeneration. Besides this, we also
studied how the mechanical and physical properties of the composites were
affected by the two phases and tried to develop a material with as close properties as
possible to those of bone tissue.
Adding a polymer (hydro)gel to osteoinductive ceramic granules leads to putties
and/or injectable pastes with improved handling properties. However, covering the
micro–structured ceramic surface with a slowly dissolvable polymer (hydro)gel could
inhibit or delay cell adhesion and thus osteoinduction. To verify this hypothesis, we
studied the effect of various polymer binders on the bone induction of their putties
comprising micro–structured ceramics in Chapter 2. Our results indicated that
(hydro)gels with a slow dissolution rate not only hinder the contact between the
ceramic micro–structured surfaces and cells from the surroundings, but may also
obstruct vasculature formation and soft tissue infiltration. It was therefore concluded
that the binder chemistry and dissolution rate are crucial parameters to allow
material-directed osteoinduction of putties and injectable pastes.
The brittleness of ceramics restricts their use as fillers in mechanically non–loaded
sites, thus there is need of biologically active composites that allow load bearing.
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