Barbieri Thesis - BioMedical Materials program (BMM)

Chapter 6 – Fluid uptake as instructive factor
adsorbed would play important roles in osteoinduction as well, [153, 250, 251, 346] and thus
there is need of further studies.
Upon implantation of biomaterials, a cascade of reactions is triggered by the initial
injury of the vascularized tissue and by interactions between ECF and the
material. [216] During the earliest period following surgery, the contact between ECF
and the surface of biomaterials allows quick adsorption of biomolecules occurs.
Further to this, the injury of the surrounding tissues and vessels triggers the
coagulation and complement systems leading to temporary thrombus–like layers onto
the biomaterial surface. [216] Such layers contain structural, biochemical and cellular
elements necessary for foreign body reaction and wound healing. In particular, they
release biomolecules such as growth factors, chemo–attractans and cytokines into
the ECF, which are then diffused towards the surrounding tissues. These molecules
recruit phagocytes, including macrophages, to the implant site and modulate their
activity. [215] Once macrophages reach the biomaterial, they can adhere and colonize
its surface. At this point, it is interesting to observe that the initial inflammation
provoked by biomaterials has been suggested to trigger osteoinduction, where the
colonization of the material by macrophages is considered a prerequisite. When
cultured on osteoinductive biomaterials, macrophages synthesized and secreted
cytokines, like prostaglandin E2, [386] that may help recruiting stem cells from the
vicinity and induce their osteogenic differentiation. This may happen also in vivo
since, iIn the specific case of instructive ceramics, upon their implantation monocytes
and macrophages colonize their surface at early moments, while bone is formed
later. [218–220] Besides inflammation, calcium and phosphate ions dissolved in ECF can
precipitate and nucleate onto the biomaterial surface generating nano–structured
mineralized layers that may promote, besides protein adsorption by virtue of the large
surface area, also cell adhesion, proliferation and osteogenic differentiation. [152, 153, 195,
234, 245, 246, 248–250] After heterotopic implantation of osteoinductive calcium phosphate–
based materials, an adequate and quick ECF uptake would improve the contact
between biomolecules and the material. This will favor coagulation, protein
adsorption, ion (re)–precipitation and their mineralization into layers. At the same
time, large uptake of body fluids would trigger the dissolution of calcium phosphate
components that will release ions, which may act as ‘attractant’ for inflammatory
cells. [254] Such cells would later secrete cytokines attracting un–differentiated (stem)
cells towards the biomaterial. [217] The presence of previously adsorbed proteins and
mineralized surface would help their adhesion and differentiation into osteogenic
phenotypes initiating bone formation. To summarize, ECF may have key roles in the
cellular response to implants and could have an indirect ‘instructive’ action during the
subsequent tissue healing and regeneration processes.
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