Stem Cell Differentiation Depending on Different Surfaces - Tissue Engineering: Cell-Surface Interactions for Tissue Culture - page 268

microenvironment plays an important role in initiating and controlling MSC
differentiation [ 23 ]. The number of reports demonstrating that cellular behavior is
modulated by biomaterial properties such as pore size, topography, geometry,
and stiffness is increasing steadily. These properties are described to control
cell distribution, adhesion, migration, cell shape, proliferation, and finally differ-
entiation. Within this chapter we will focus on the optimal biomaterial parameters
for MSC differentiation into the osteogenic lineage.
4.1 Porosity and Pore Size
The porosity (percentage of void space in a solid) and the pore size of biomaterials
play a critical role in tissue formation. As stated earlier, a certain interconnected
porous network is necessary to distribute oxygen as well as nutrients and to
eliminate waste material, but optimal pore sizes for the regeneration of different
tissues have not yet been reported [ 24 ]. For bone tissue engineering applications,
pore sizes between 10 and 2250 lm have been used, resulting in various degrees of
tissue formation and ingrowth [ 24 - 26 ]. Nevertheless, early studies of Hulbert et al.
[ 27 ] showed the minimum pore size required to generate mineralized bone to be
100 lm. Matrices with a smaller pore size resulted in either ingrowth of unmin-
eralized tissue or fibrous tissue. Supposedly, too small pore sizes limit the transport
of nutrients and the cell migration [ 24 ]. It was demonstrated that only pores sizes
above 300 lm result in vascularized tissue formation [ 28 ]. Additionally, increased
porosity and pore sizes facilitate bone ingrowth [ 29 ], even though this depends on
the biomaterial [ 28 ]. In contrast, if the pores are too large, the decrease in surface
area limits cell adhesion [ 30 ] and increasing porosity affects the load-bearing
capacity [ 31 ]. Therefore, porosity and pore size have to be within a specific range
to maintain the balance between the optimal pore size for cell migration, mass
transportation, vascularization, and specific surface area for cell attachment as well
as mechanical stability.
A variety of optimal pore sizes for different tissues have been proposed
(Table 2 ). These diverse numbers for the optimal pore size and porosity might be
caused by results obtained from various cell types or MSC derived from different
origins. Another reason could be the difference in biomaterial fabrication, which
results in differing pore architectures [ 32 ].
In many cases it has been reported that for bone tissue engineering applications
pores greater than 300 lm facilitate capillary formation and therefore direct
osteogenesis [ 25 , 28 , 33 ]. To achieve osteoconduction, pore sizes between 100 and
400 lm are generally preferred [ 34 ].
Furthermore, differing porosities and pore sizes have described for bone tissue
in vivo. Human and mammalian bone is classified into two types:
1. Cortical bone, which is compact and usually located in the shaft of long bones
(diaphysis) and in the outer bone shell