Bioactive Glass-Based Scaffolds for Bone Tissue Engineering - Tissue Engineering: Cell-Surface Interactions for Tissue Culture - page 216

cortical bone defects and capable of functioning under relevant loads. Although a
number of bioactive glass and glass-ceramic scaffolds with favorable properties
are available, as comprehensively discussed in this chapter, several issues need to
be addressed prior to clinical application, such as mechanical reliability of scaf-
folds, tailored degradability, and induction of vascularization. A major challenge
remains the proper cellularization and controlled vascularization of 3D scaffolds.
For successful bone regeneration, there is a need for functional, mature vessels
promoting functionality to the intrinsically ''inactive'' man-made TE constructs.
Angiogenesis requires that capillaries develop and stabilize before differentiating
into arterioles and venules by the appearance of circumferentially located smooth
muscle cells, and may ultimately mature into arteries and veins [ 174 ]. A stable
vasculature is important for the long-term success of TE constructs and bone
regeneration [ 175 ].
One alternative to accelerate osteogenesis and angiogenesis is the incorporation
of active biomolecules such as growth factors into the scaffold structure [ 176 - 181 ].
However, the short half-life and uncontrolled release of growth factors from
scaffolds associated with possible toxicity effects may be a problem or limitation of
current drug delivery scaffolds. The use of bioactive glass as a filler in degradable
matrices might offer a promising strategy for the regulated in situ secretion/
expression of angiogenic growth factors (e.g., VEGF) and osteogenic markers
(e.g., ALP) at therapeutic levels, leading to successful vascularization and bone
formation (mineralization) of TE scaffolds.
Further improvement in scaffold function is related to surface modification,
e.g., through the control of specific/non-specific protein adsorption [ 182 ], plasma
treatment [ 183 , 184 ] or enzyme grafting [ 185 ], to provide biofunctional groups for
cell attachment and response, thus making the scaffold more surface-compatible.
There is still limited understanding of the long-term in-vivo behavior of bioactive
glass-based scaffolds and polymer/BG composite scaffolds, particularly regarding
their degradation rate, ion release kinetics, variation in mechanical properties and
angiogenic effect. In this context, it has to be pointed out that the influence of
sterilization on the cytotoxic, mechanical (e.g., compressive strength, fracture
toughness) and physical properties (glass transition temperature, crystallinity) of
biodegradable composites has often been overlooked in the past. This is particu-
larly important for scaffolds incorporating a polymeric phase. Sterilization issues
have to be considered and monitored in parallel to the design and development
stages of scaffolds because standard medical product sterilization techniques
(gamma irradiation, ethylene oxide gas exposure) have shown to reduce the
molecular weight of resorbable polymers by a factor of 2-3 [ 186 - 188 ].
Moreover, more focus on in-vivo studies is required and there is need for further
research on the evaluation of scaffolds in realistic biological systems. Engineered
scaffolds from silicate amorphous or partially crystallized glasses, combined with
biodegradable polymers, will continue to be improved and optimized. These
scaffolds constitute attractive alternative approaches in future developments and
their combination with stem cells is of great interest [ 57 , 189 - 191 ]. The use of
bioactive glass and glass-ceramic nanoparticles and carbon nanotubes (CNTs)