Bioactive Glass-Based Scaffolds for Bone Tissue Engineering - Tissue Engineering: Cell-Surface Interactions for Tissue Culture - page 212

theories based on the combination of the Ishai-Cohen [ 160 ] and Gibson-Ashby
models [ 161 ]. The modulus-density (pore volume fraction) relationship was
characterized by a power-law function with exponents between 2 and 3. This is
close to the exponents found for similar relationships valid for human bone (2-3.2)
[ 129 , 130 ].
Extensive work has been also carried out to investigate the cellular response to
polymer/bioactive glass composites concerning composition, particle concentra-
tion and particle size effect in vitro and in vivo, as discussed in Ref. [ 128 ]. Some
key findings are included here. For example, Lu et al. [ 162 ] showed that for
PLGA/bioactive glass films (0, 10, 25, 50 wt%), the growth, mineralization
and differentiation of human osteoblast-like SaOS-2 cells as well as the kinetics of
Ca-P layer formation and the resulting Ca-P chemistry were dependent on BG
content. The 10 and 25 wt% BG composite supported greater osteoblast
growth and differentiation than the 50 wt% BG group. Such bioactive glass dose-
dependent cell proliferation and alkaline phosphatase (ALP) synthesis were also
reported by Yang et al. [ 158 ], Verrier et al. [ 153 ] and Tsigkou et al. [ 150 ]. Tsigkou
et al. [ 150 ] observed, for example, that human fetal osteoblasts were less spread
and elongated on PDLLA and PDLLA/5 wt% BG, whereas cells on PDLLA/40
wt% BG were elongated but with multiple protrusions spreading over the BG
particles. However, when differentiation and maturation of fetal osteoblasts were
examined, incorporation of 45S5 Bioglass particles within the PDLLA matrix
was found to significantly enhance ALP and osteocalcin protein synthesis
compared to PDLLA alone. Alizarin red staining indicated extracellular matrix
mineralization on 5 and 40 wt% BG-containing films, with significantly more bone
nodules formed than on neat PDLLA films. Yang et al. [ 158 ] pre-treated 45S5 BG
containing (0, 5, 40 wt%) PDLLA scaffolds with serum and found a significant
increase in ALP activity in human bone marrow mesenchymal stem cells in 5 wt%
Bioglass composites relative to the 0 and 40 wt% Bioglass groups, whereas in
vivo studies indicated significant new bone formation throughout all the scaffolds.
The results of numerous studies [ 150 , 153 , 158 , 162 ] have confirmed the osteo-
genic potential of BG-containing scaffolds and suggest that there is a critical
threshold range of BG content (5-40 wt%) which is optimal for osteoblast growth
and Ca-P formation. This finding is also relevant for the vascularization and
angiogenic properties of composite scaffolds, as discussed in Sect. 6 .
Several cell culture studies (see Ref. [ 49 , 128 ]) have demonstrated the pro-
angiogenic potential of bioactive glass over a limited range of concentrations,
implying that dose-dependent effects are also involved in angiogenesis similar to
those shown for osteogenic differentiation (e.g., ALP synthesis) and cellular
behavior (adhesion, proliferation, mineralization). BG has been reported to have
pro-angiogenic potential over a limited range of lower concentrations and greater
osteogenic potential at higher concentrations [ 50 , 163 ]. To our knowledge, Misra
et al. [ 45 ] were the first to incorporate bioactive glass nanoparticles (30-50 nm) of
composition matching the 45S5 BG composition into degradable matrices (in their
case P(3HB) was used) and compared their thermal, mechanical, microstructural,
bioactive and cell biological properties with those of conventional, micron-sized