In Vivo, In Vitro, In Silico: Computational Tools for Product and Process Design in Tissue Engineering - Computational Modeling in Tissue Engineering - page 4

the chondrogenic lineage (all the way up to hypertrophy) will result in bone
formation after implantation in vivo has been delivered by several groups [ 19 - 21 ].
3 Computational Tools for Product and Process Design
in Tissue Engineering
Engineered products will only be a viable and competitive alternative to upcoming
off-the-shelf innovations in regenerative medicine if they are manufactured with
reproducible properties, a prerequisite for consistent clinical outcomes. This
important target is mainly challenged by the intrinsic variability in the behaviour
of human cells from different batches or donors as well as by the sensitivity of
cells to perturbations in the culture environment [ 22 ].
Although research-oriented systems are generally too complex, user-unfriendly,
unsafe and expensive for direct use in clinical applications, their underlying
principles could nevertheless lay a solid foundation for more clinically compliant
manufacturing systems. This will require not only the optimization of the TE
product itself but also the identification of only the most essential processes,
culture parameters and construct parameters that must be monitored and controlled
to standardise production and provide meaningful quality and traceability data, at
the same time minimise risks, costs and user complexity [ 22 ].
Below we describe a number of computational tools are being used to optimize
the design of both TE products and processes as well as the in vivo result. These
tools use a variety of modelling techniques building on physical, mechanical or
(bio)chemical laws/equations and/or experimental data. The models can range from
mechanistic (hypothesis-driven, white box) to phenomenological (data-driven,
black box) and, depending on the specific application, range from the gene/protein
level over the cellular level up to the tissue/organ level. Figure 1 shows an overview
figure of different models that have been developed in the field of bone tissue
engineering by the research group of the author. The overview in this chapter is by
no means exhaustive but serves to illustrate different aspects of product and process
design. The reader is referred to the other chapters of this topic that provide a more
in depth review on a number of the aspects mentioned here.
3.1 Computational Tools for Product Design
There are a number of aspects on the design of TE products where computational
models can make and already have made contributions, not only in the way the
carrier structure (when dealing with combination products or biomaterials only) is
designed but also the way cells are processed prior to implantation.
Obvious aspects of scaffold design include their structural, mass transport and
mechanical properties. Several chapters in this topic describe the design and