Biomedical Engineering Reference
In-Depth Information
2.2 SCAFFOLDDESIGN
2.2.1 I
NTRODUCTION
It is important to emphasize, at the outset, that the fi eld of scaffold-based tissue engineering is still
in its infancy, and many different approaches are under experimental investigation. Thus, it is by no
means clear what defi nes an ideal scaffold/cell or scaffold/neotissue construct, even for a specifi c
tissue type. Indeed, since some tissues perform multiple functional roles, it is unlikely that a single
scaffold would serve as a universal foundation for the regeneration of even a single tissue. Hence,
the considerations for scaffold design are complex. They include material composition, porous
architecture, structural mechanics, surface properties, degradation properties and their products
(degradation rate strongly depends on polymer type, impurities, manufacturing process, steriliza-
tion, device size, and the local environment), together with the composition of any biological com-
ponent that may have been added to the scaffold to improve function. Furthermore one must also
consider the behaviors and the consequences of how all the aforementioned factors may change
with time.
Hollister
17
stated that approaches in scaffold design must be able to create hierarchical porous
structures to attain desired mechanical function and mass-transport (permeability and diffusion)
properties and to produce these structures within arbitrary and complex 3-D anatomical shapes.
Hierarchical refers to the fact that features at scales from the nanometer to millimeter level will
determine how well the scaffold meets confl icting mechanical function and mass-transport needs.
Material chemistry together with processing determines the maximum functional properties that
a scaffold can achieve, as well as how cells interact with the scaffold. However, mass-transport
requirements for cell nutrition, pore interconnections for cell migration, and surface features for cell
attachment necessitate a minimal requirement for scaffold morphology. The porous structure dic-
tates that achievable scaffold properties fall between the theoretical maximum set by the material
and the theoretical minimum of zero predicted by composite theories. The critical issue for design
is then to compute the precise value of mechanical as well as mass-transport properties at a given
scale based on more microscopic properties and structure.
Hence, for each envisioned application, successful TECs have certain minimum requirements
from a biochemical, chemical, and physical perspective as described previously. Scaffolds are
normally required to provide suffi cient initial mechanical strength and stiffness to substitute for
the mechanical function of the diseased or damaged tissue, which the TEC aims at repairing
or regenerating. Scaffolds may not necessarily be required to provide a complete mechanical
equivalence to a healthy tissue; indeed the variability in architecture for a single tissue type is so
extensive that it is inconceivable that a single TEC would serve universal applications for even
a single tissue. Nevertheless, stiffness and strength should be suffi cient to at least either permit
prerequisite cell seeding of the scaffold
in vitro
without compromising scaffold architecture or
support and transmit forces in an
in vivo
healing site. Thus, in the context of skin tissue engineer-
ing the scaffold material should be suffi ciently robust not only to resist change in shape as a result
of the introduction of cells into the scaffold, each of which would be capable of exerting tractional
forces, but also to withstand the wound contraction forces, which will be invoked during tissue
healing
in vivo.
The same general rules would apply to bone engineering, although the external
and internal fi xation systems, or other supports or restrictions on patient activity during the early
stage recovery, may lessen the importance of scaffold mechanical considerations during the
in vivo
phase.
Cell and tissue remodeling is important for achieving stable biomechanical conditions and vas-
cularization at the host site. Hence, the 3-D scaffold/tissue construct should maintain suffi cient
structural integrity during the
in vitro
and/or
in vivo
growth and remodeling processes.
Scaffold architecture has to allow for initial cell attachment and subsequently migration into
and throughout the matrix. It must enable mass transfer of nutrients and metabolites, provision
of suffi cient space for development, and later remodeling of organized tissue. The porosity and
