Bioactive Glass-Based Scaffolds for Bone Tissue Engineering - Tissue Engineering: Cell-Surface Interactions for Tissue Culture - page 196

1 Introduction
Tissue engineering (TE) and regenerative medicine aim to restore diseased or
damaged tissue using combinations of functional cells, bioactive molecules and
biodegradable scaffolds made from engineered biomaterials [ 1 , 2 ]. Some of the
most promising biomaterials for application in bone TE are bioceramics such as
hydroxyapatite (HA), calcium phosphates, bioactive silicate glasses and related
composite materials combining bioactive inorganic materials with biodegradable
polymers [ 3 , 4 ]. Bioactive inorganic materials are capable of reacting with
physiological fluids to form strong bonds to bone through the formation of bone-
like hydroxyapatite layers, leading to effective biological interaction and fixation
of bone tissue with the implanted material surface [ 5 , 6 ]. Moreover, in the case of
silicate bioactive glasses, such as 45S5 Bioglass [ 5 ], reactions on the material
surface induce the release and exchange of critical concentrations of soluble Si,
Ca, P and Na ions, which can lead to favorable intracellular and extracellular
responses promoting rapid bone formation [ 7 - 11 ].
In 1971, Hench and colleagues discovered that rat bone can bond chemically to
certain silicate-based glass compositions [ 12 ]. This group of glasses was later
termed ''bioactive'', meaning ''a material that elicits a specific biological response
at the material surface which results in the formation of a bond between the tissues
and the materials'' [ 5 , 13 ]. Hench [ 13 ] has published the history of the develop-
ment of bioactive glass (BG), focusing on the breakthrough discovery of the
classical 45S5 Bioglass composition. This oldest BG composition consists of a
silicate network (45 wt% SiO 2 ) incorporating 24.5 wt% Na 2 O, 24.5 wt% CaO and
6 wt% P 2 O 5 . The high amounts of Na 2 O and CaO, as well as the relatively high
CaO/P 2 O 5 ratio, make the glass surface highly reactive in physiological environ-
ments [ 5 ]. A schematic diagram showing the series of events that occur on the
surface of BG in contact with a biological environment, as proposed in the liter-
ature [ 5 ], is presented in Fig. 1 .
Other bioactive glass compositions developed over the years have additional
elements incorporated in the silicate network, such as fluorine [ 14 ], magnesium
[ 15 , 16 ], strontium [ 17 - 19 ], iron [ 20 ], silver [ 21 - 24 ], boron [ 25 - 28 ], potassium
[ 29 ], or zinc [ 30 , 31 ]. The biological response to the different ion dissolution
products released from BG has recently been reviewed by Hoppe et al. [ 9 ].
The typical characteristic of all bioactive glasses, which are usually fabricated
by melting or sol-gel methods (see Sect. 3 ), is the ability to form a strong bond to
bone and in some cases soft tissues [ 32 , 33 ]. It is now widely accepted that for
establishing a bond with bone, a biologically active apatite surface layer must form
at the material/bone interface [ 1 , 5 , 12 , 34 - 36 ]. Early clinical applications of
bioactive glasses were in the form of solid pieces for small bone replacement,
e.g. in middle ear surgery [ 1 , 5 , 13 ]. Later, other clinical applications of bioactive
glasses were proposed, for example as coatings on metallic orthopedic implants or
in periodontology [ 5 , 13 , 32 ].