In Silico Biology of Bone Regeneration Inside Calcium Phosphate Scaffolds - Tissue Engineering: Computer Modeling, Biofabrication and Cell Behavior - page 32

promotes local bone repair or regeneration [ 14 , 19 ]. Bone formation is a very com-
plex physiological process, involving the participation of many different cell types
and regulated by countless biochemical and mechanical factors. Therefore, mathe-
matical models can make a significant contribution in further unraveling the interac-
tions between the different influential factors. Thus, in silico experimentation seeks
to explain and understand the underlying principles of the biological phenomenon.
Moreover, mathematical models can be used to design and test possible experimen-
tal and therapeutic strategies in silico before they are tested in vitro or in vivo . These
experimental results will, in turn, guide further model building.
This topic chapter will start with an overview of the biology of bone regenera-
tion inside calcium phosphate (CaP) scaffolds. Then some mathematical models of
bone regeneration inside (CaP) scaffolds will be discussed, indicating clearly the
opportunities of an integrative approach that combines mathematical modeling with
experimental research. Finally, some future prospects are presented.
2 Biology of Bone Regeneration Inside CaP Scaffolds
Tissue engineering aims to develop biological substitutes that restore, maintain or
improve tissue function. Two main strategies have been developed to regenerate
bone tissue: the use of biomaterials to induce bone formation chemically and the
construction of hybrid implants composed of a biomaterial scaffold seeded with
osteogenic cells [ 19 , 25 ]. Delayed and non-unions are characterized by an in vivo
micro-environment that fails to support bone repair or tissue regeneration. Hence,
the micro-environment found at a non-union could be considered as an ectopic site
[ 14 ]. Consequently, the tissue engineering constructs should display osteoinduc-
tive properties. CaP bioceramics are then interesting candidates, because of their
biocompatibility, bioactivity and osteoinductive characteristics. It has been clearly
shown that CaP induces bone formation, but the exact mechanism is still largely
unknown [ 2 , 10 , 14 , 20 , 35 , 46 ]. There are, however, several mechanisms proposed
in literature to explain the influence of CaP particles on bone formation as observed
in many experiments.
It has been stated that a high local concentration of growth factors and proteins
can be achieved by adsorption on the biomaterial substrate, thereby creating a fa-
vorable micro-environment for bone formation [ 28 , 35 , 46 ]. Another explanation for
the osteoinductive properties of CaP biomaterials is given by the surface topogra-
phy, since it influences the osteoblastic guidance and attachment and can cause the
asymmetrical division of MSCs [ 1 , 2 ]. Barrère et al. [ 2 ] also suggest that the surface
charge of the substrate can play a key role by triggering cell differentiation. Further-
more, negative charges distributed on the surface of the biomaterial can be an ob-
stacle for cell-material adhesion, because the cell surface is also negatively charged
[ 40 , 47 ]. The bioapatite layer, formed in vivo , might also be recognized by MSCs
[ 19 ]. A low oxygen tension in the central region of the biomaterial, which triggers
the pericytes of microvessels to differentiate in osteoblasts, is another mechanism