Barbieri Thesis - BioMedical Materials program (BMM)

Chapter 1 – Introduction
developed materials may offer, besides instructive cues, also mechanical
characteristics close to those of the considered tissue. For example, the natural
intrafibrillar collagen mineralization, which occurs during bone tissue development,
has been replicated in vitro to produce composite materials that chemically and
hierarchically mimic the bone tissue. [213] Other groups successfully mimicked the
macro–structure of bone obtaining similar mechanical strength by producing macro–
porous blocks with silk fibers and calcium phosphate. [214]
1.9. Instructive biomaterials for bone tissue regeneration
In bone tissue regeneration a subgroup of instructive biomaterials exists that
have osteoinductive potential. These materials, following injury and
colonization of inflammatory cells [215, 216] are capable of inducing stem cell
differentiation into osteogenic phenotypes. [217–220] This has been demonstrated in
implantation sites where bone is normally not present (e.g. muscle, skin) without
the support of exogenously added bone growth factors or (osteogenic) cells
(Figure 6). [86] Since the Sixties, when osteoinductivity of biomaterials was
observed for the first time in a polymer, [221] this process has been reported for
various materials, mainly sintered calcium phosphate ceramics, [222–228] but also in
calcium phosphate cements, [229, 230] coatings, [231, 232] porous Bioglass TM , [233]
surface–treated titanium. [234] More recently, bone induction was shown also in a
composite of hydroxyapatite and polylactide. [235] So far, under certain
physicochemical characteristics it seems that all types of materials can potentially
be osteoinductive. Although the process underlying bone induction by these
materials has not yet been fully elucidated, [86] numerous hypotheses have been
formulated to explain it. For example, surface microstructural features such as
grain and micro–pore size have been shown to play a crucial role in several studies.
When hydroxyapatite (HA) with and without micro–structured surface was implanted
in muscles of dogs, only those possessing micro–structure could induce ectopic bone
formation. [236, 237] Similar results were shown in studies where HA and biphasic
calcium phosphate (BCP) ceramics with various micro–porosities were compared. [228]
Thus the surface structure and, to a lesser extent, the chemistry have been
proposed as key actors in osteoinduction since they may control (specific) protein
adsorption and may also induce an inflammatory response that eventually lead to
bone formation. More detailed description of the current hypotheses on
osteoinduction–related phenomena will be given in §1.10. When used for the repair of
critical sized bone defects (e.g. 17 mm diameter in goats), micro–structured
osteoinductive calcium phosphate ceramics have shown high bone forming
potential, [86] superior to non–osteoinductive ceramics. [238] Further, recently these
20