Titanium Phosphate Glass Microspheres as Microcarriers for In Vitro Bone Cell Tissue Engineering - Biointerfaces: Where Material Meets Biology - page 106

investigating biomaterials that can help combat bone loss or bone deformities
arising from trauma, disease or congenital defects. 1-4 In this context, it is
worth mentioning at the outset that research on glasses for biomedical ap-
plications is not so recent; silicate glasses have been studied for a significantly
longer period since Larry Hench developed 45S5 Bioglass in the late 1960s 5
and consequently far more literature exists on the properties and biomedical
applications of silicate glasses in comparison with phosphate glasses. How-
ever, the amount of research on biological phosphate glasses suggests that
they have now emerged as a distinct class of biomaterials in their own right.
The composition of the ternary P 2 O 5 -Na 2 O-CaO glass system can be var-
ied to control the rate at which the glass degrades; for example, an increase
in the CaO content (at the expense of Na 2 O) leads to a decrease in the
degradation rate and vice versa. However, due to the relatively high dis-
solution rate (and hence poor biocompatibility) of most compositions within
the ternary system above, most studies have focused on controlling the
degradation rate of phosphate glasses by the addition of other metal oxides
to the glass system to achieve their objective. To date, the metal oxides used
for this purpose include Fe 2 O 3 , 6-8 CuO, 9-12 Al 2 O 3 , 13 TiO 2 , 14-17 MgO, 18
ZnO, 19-23 Ag 2 O, 24-28 Ga 2 O 3 29-31 and SrO. 32-38 The purposes of metal oxide
addition to the glass structure are two-fold. First, metal oxides serve as the
most effective means to control the degradation rate by increasing the co-
valent nature of the bonds within the glass structure. Second, the metal ions
released from such glasses can exert an antimicrobial effect and/or positively
impact on cell proliferation and tissue regeneration.
The appeal of titanium phosphate glasses in biomedical research derives
essentially from the strong inter-relationships between three sets of fac-
tors: (1) the glass chemistry and glass network structure, (2) the glass
properties, and (3) the interactions between glasses and living cells or
tissues. The link between the first two factors is that subtle changes in glass
chemistry through variations in glass composition can bring about sig-
nificant changes in glass properties such as the glass transition tempera-
ture, glass density or glass degradation. A glass not containing titanium
oxide may disappear completely in a matter of a few hours when immersed
in deionised water, whereas a glass containing 5 mol% titanium oxide may
take several months to degrade completely. In turn, the glass properties
greatly influence the ability of the glass surface to provide a stable sub-
strate for cells to attach and proliferate and, in the case of stem cells, to
possibly differentiate down a specific lineage, for example osteogenic or
chondrogenic pathways. Using the same example as above, the rapid deg-
radation of the former glass would lead to considerable fluctuations in the
solution pH which would be detrimental to cells under in vitro cell culture
conditions, while the latter glass would provide the stable surface required
for the cells to flourish.
Thus, considering what is known about the strong links between struc-
ture, properties and cell-material interactions, a reasonably obvious ques-
tion arises: what biomedical applications can we develop based on this

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